2.133 infliximab (remicade)...2014/01/28 · plaque psoriasis treatment of adult patients with...

MEDICAL POLICY

POLICY TITLE INFLIXIMAB (REMICADE)

POLICY NUMBER MP-2.133

[Note: Final page is signature page and is kept on file, but not issued with Policy.]

Original Issue Date (Created): August 1, 2008

Most Recent Review Date (Revised): January 28, 2014

Effective Date: April 1, 2014

I. POLICY

Note: Infliximab (Remicade) requires preauthorization. Requests for Infliximab (Remicade)

must be accompanied by a completed preauthorization form prior to treatment, at 12

weeks, and every 6 months during treatment. Various index tools have been developed to

assess the severity and monitor the efficacy of treatment for the following diseases, and

any appropriate index form may be used providing improvement can be measured.

Note: Patients must be tested for latent tuberculosis prior to receiving Infliximab (Remicade); if

positive, treatment for TB should be started prior to starting Remicade.

Note: The only FDA-approved pediatric indication for Infliximab (Remicade) is for the

treatment of Crohn’s disease and Ulcerative Colitis. There are no FDA approved

self-administered biologics for pediatric patients for the treatment of Crohn’s

disease.

Initial Authorization

If the patient has been maintained on successful treatment with Infliximab (Remicade) for at

least six months prior to this initial authorization with Capital BlueCross, Infliximab

(Remicade) may be considered medically necessary.

Infliximab (REMICADE) is a tumor necrosis factor (TNF) blocker and U.S. Food and Drug

Administration (FDA)-approved for the following indications:

Crohn’s Disease Reducing signs and symptoms and inducing and maintaining clinical remission in adult

and pediatric patients with moderately to severely active disease who have had an

inadequate response to conventional therapy.

Reducing the number of draining enterocutaneous and rectovaginal fistulas and

maintaining fistula closure in adult patients with fistulizing disease.

Ulcerative Colitis reducing signs and symptoms, inducing and maintaining clinical remission and mucosal

healing, and eliminating corticosteroid use in patients with moderately to severely active

disease who have had an inadequate response to conventional therapy.

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Rheumatoid Arthritis in combination with methotrexate: Reducing signs and symptoms, inhibiting the progression of structural damage, and

improving physical function in patients with moderately to severely active disease.

Ankylosing Spondylitis Reducing signs and symptoms in patients with active disease.

Psoriatic Arthritis Reducing signs and symptoms of active arthritis, inhibiting the progression of structural

damage, and improving physical function.

Plaque Psoriasis Treatment of adult patients with chronic severe (i.e., extensive and /or disabling) plaque

psoriasis who are candidates for systemic therapy and when other systemic therapies are

medically less appropriate.

Infliximab (Remicade) may be considered medically necessary for the following conditions:

Crohn’s Disease

As first-line therapy (i.e., initial treatment) for adult patients with fistulizing Crohn’s

Disease.

As second-line therapy for treatment of moderate to severe active disease in adult and

pediatric patients (aged 6 to 17) with evidence of inflammation when the following

criteria are met:

Initial Therapy

Consulting gastrointestinal (GI) specialist recommends treatment with Infliximab; AND

The patient has not responded adequately to, or cannot tolerate, a trial of conventional

therapies, such as aminosalicylates, corticosteroids, and /or immunomodulators (e.g.,

azathioprine, methotrexate and cyclosporine); AND

The adult patient has had an inadequate response to a therapeutic trial of self-

administered biologic therapy (e.g. Adalimumab (Humira®), or similar self-administered

injectable or oral medication).

Note: Pediatric patients do not need to meet this requirement before being treated with

Infliximab for Crohn’s disease.) There are no FDA approved self-administered

biologics for pediatric patients for the treatment of Crohn’s disease.

Maintenance Therapy

Infliximab (Remicade) maintenance therapy may be considered medically necessary

when therapy has demonstrated efficacy as evidence by an improvement in disease

activity * at 12 weeks and maintenance of at least that improvement at each six month re-

evaluation.

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*As measured by a standardized disease activity tool (e.g, Crohn’s Disease Activity Index

[CDAI], Harvey Bradshaw Index [HBI])

Ulcerative Colitis

Diagnosis of moderate to severe ulcerative colitis with inflammation.

Initial Therapy

Consulting gastrointestinal (GI) specialist recommends treatment with Infliximab; AND

The patient has not responded adequately to, or cannot tolerate a trial of conventional

therapies such as aminosalicylates, corticosteroids, antibiotics and /or immunomodulators

(e.g., cyclosporine)

Maintenance Therapy




evaluation.

*As measured by a standardized disease activity tool (e.g., UC: Modified Truelove and Witts

Severity Index (MTWSI).

Ankylosing Spondylitis

To reduce signs and symptoms in patients with active disease of the spine (axial) and/or

peripheral joints.

Note: There is no evidence for the efficacy of disease modifying antirheumatic drugs

(DMARDs), including sulfasalazine and methotrexate, for the treatment of axial disease.

However, sulfasalazine may be considered in patients with peripheral arthritis.

Initial Therapy

Consulting Rheumatologist recommends treatment with Infliximab; AND

The patient has not responded to non-steroidal anti-inflammatory drugs (NSAIDs) (e.g.,

indomethacin)

Maintenance Therapy




evaluation.

*As measured by a standardized disease activity tool (e.g., Bath Ankylosing Spondylitis Disease

Activity Index (BASDI)

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Psoriatic Arthritis

To reduce signs and symptoms of active arthritis, inhibiting the progression of structural

damage, and improving physical function

Initial Therapy


The patient has not responded to non-steroidal anti-inflammatory drugs (NSAIDs) (e.g.,

Ibuprofen); AND

The patient has not responded to a therapeutic trial of the non-biologic DMARDs (e.g.,

methotrexate, sulfasalazine).AND

The patient has not responded to a therapeutic trial of a biologic DMARD (e.g.

Adalimumab (Humira®), Etanercept (Enbrel), or similar self-administered injectable or

oral DMARD

Maintenance Therapy




evaluation.

* As measured by a standardized disease activity tool (e.g., Clinical Disease Activity Index

[CDAI], Simplified Disease Activity Index [SDAI], Disease Activity Score based on 28-joint

evaluation [DAS28] score).

Plaque Psoriasis

To treat adult patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis

who are candidates for systemic therapy and when other systemic therapies are medically less

appropriate.

Initial Therapy

Consulting Dermatologist recommends treatment with Infliximab; AND

The patient has not responded to systemic therapies; (e.g., methotrexate, azathioprine,

cyclosporine); AND

The patient has not responded to phototherapy; (e.g., ultraviolet B (UVB) or oral

methoxsalen plus UVA light (PUVA) for psoriasis. AND

The patient has not responded to a therapeutic trial of a biologic DMARD (e.g.

Adalimumab (Humira®), Etanercept (Enbrel), or similar self-administered injectable or

oral DMARD

Maintenance Therapy



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evaluation.

*As measured by a standardized disease activity tool (e.g. Simplified Psoriasis Area Severity

Index (SPASI), Psoriasis Area Severity Index (PASI)

Rheumatoid Arthritis Infliximab may be medically necessary in combination with methotrexate for the reduction of

signs and symptoms, inhibiting the progression of structural damage, and improving physical

function in patients with moderately to severely active rheumatoid arthritis.

Initial Therapy


The patient has not responded to a therapeutic trial of non-biologic disease modifying

antirheumatic drugs (DMARDs) (e.g., methotrexate, leflunomide, azathioprine, alone or

in combination with corticosteroids; AND

The patient has not responded to a therapeutic trial of self-administered biologic

DMARD therapy (e.g. Adalimumab (Humira®), Entanercept (Enbrel), Golimumab

(Simponi), or similar self-administered injectable or oral medication.)

Maintenance Therapy


when therapy has demonstrated efficacy as evidence by an improvement in * disease

activity at 12 weeks and maintenance of at least that improvement at each six month re-

evaluation.

*As measured by a standardized disease activity tool (e.g. Clinical Disease Activity Index

[CDAI], Simplified Disease Activity Index [SDAI], Disease Activity Score based on 28-joint

evaluation [DAS28] score).

Other Indications Other uses of infliximab are considered investigational, including but not limited to the

following:

age-related macular degeneration;

alcoholic hepatitis;

arthritis (other than rheumatoid arthritis and psoriatic arthritis);

Behcet syndrome;

Behcet syndrome uveitis;

cancer cachexia;

depression;

diabetic macular edema;

endometriosis;

erythrodermic or exfoliative psoriasis;

giant cell arteritis;

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graft-versus-host disease;

intraarticular injections;

juvenile idiopathic arthritis ;

juvenile idiopathic arthritis-associated uveitis;

Kawasaki syndrome;

polyarteritis nodosa;

polymyalgia rheumatica;

renal cell carcinoma;

sacroilitis;

sarcoidosis;

sclerosing cholangitis;

Sjogren syndrome;

systemic lupus erythematosis;

systemic necrotizing vasculitides

systemic sclerosis

Wegener’s granulomatosis.

There is insufficient evidence to support a conclusion concerning the health outcomes or

benefits associated with this procedure for the above indications.

Cross-reference

MP-2.103 Off-Label Use of Prescription Drugs

II. PRODUCT VARIATIONS [N] = No product variation, policy applies as stated

[Y] = Standard product coverage varies from application of this policy, see below

[N] Capital Cares 4 Kids [N] Indemnity

[N] PPO [N] SpecialCare

[N] HMO [N] POS

[N] SeniorBlue HMO [Y] FEP PPO *

[N] SeniorBlue PPO

**Refer to FEP Medical Policy Manual MP-10.04.10 Infliximab. The FEP Medical Policy manual

can be found at: www.fepblue.org

III. DESCRIPTION/BACKGROUND

Tumor necrosis factor (TNF) is a cytokine produced by macrophages and T cells. Its name is

based on the original observations 25 years ago that TNF killed tumor cells in vitro. Further

research has revealed that TNF has a broad spectrum of biologic activities; in particular, it is a

http://www.fepblue.org/

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key mediator of inflammation and is produced in response to infection and immunologic

injury.

There are a number of TNF alpha blocking agents; Etanercept (ENBREL®, Amgen);

Adalimumab (HUMIRA®, Abbott); Certolizumab (CIMZIA®, UCB) administered via

subcutaneous injection and infliximab (REMICADE® Centocor) administered via an

intravenous (IV) infusion in the physician's office, outpatient setting, or infusion center.

Infliximab (Remicade®) is a chimeric immunoglobulin monoclonal antibody that binds to

and neutralizes the effects of tumor necrosis factor-alpha (TNF-a), a naturally occurring

cytokine that plays a role in inflammatory and immune responses.

Infliximab contains anti-TNF-a antibodies that reduce infiltration of inflammatory cells and

TNF-a production in affected areas. Infliximab also initiates healing in areas of erosion and

inflammation caused by diseases such as ulcerative colitis and Crohn's disease. In summary,

there have been no head-to-head comparative trials that have evaluated the relative efficacy of

the TNF-blocking agents in the treatment of the above conditions. Frequency of monitoring

should be decided on an individual basis depending on symptoms, severity and drug

treatment.

The initial labeled indications for infliximab by the U.S. Food and Drug Administration

(FDA) included treatment of rheumatoid arthritis, fistulizing Crohn's disease, and inducing

remission in patients with moderately to severely active Crohn's disease that has had an

inadequate response to conventional therapy. In 2002, the FDA approved an additional

indication for maintaining clinical remission in Crohn’s disease. Maintenance therapy is

designed to prevent disease flares in patients with quiescent disease; the drugs most

commonly used are azathioprine and 6-mercaptopurine. This new, labeled indication

markedly broadens the clinical indications for patients with Crohn's disease. In December

2004, the FDA approved infliximab for the treatment of ankylosing spondylitis, and in early

2005, the FDA approved infliximab for the treatment of psoriatic arthritis. In September

2005, the FDA approved infliximab for the treatment of “reducing signs and symptoms,

achieving clinical remission and mucosal healing, and eliminating corticosteroid use in

patients with moderately to severely active ulcerative colitis who have had an inadequate

response to conventional therapy.” In May 2006, the FDA approved infliximab for use in

pediatric patients with moderately to severely active Crohn’s disease who have had an

inadequate response to conventional therapy. In September 2006, FDA approved infliximab

for patients with chronic severe (i.e., extensive and/or disabling) plaque psoriasis who are

candidates for systemic therapy and when other systemic therapies are medically less

appropriate.

Infliximab (Remicade) Administration:

Infliximab is administered via an intravenous infusion in the physician’s office or outpatient

hospital setting and should only be administered to patients who will be closely monitored and

have regular follow-up visits with a physician.

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Crohn’s disease (CD) is characterized by a transmural inflammatory process that can affect

any area of the gastrointestinal (GI) tract, from the mouth to the anus, but it most commonly

affects the lower part of the ileum. The disease also can lead to abnormal connections (fistulas)

leading from the intestine to the skin or internal organs.

Ulcerative Colitis is characterized by an inflammatory process involving the colonic mucosa.

It may involve all or part of the large intestine and results in ulcerations that may produce

bloody or purulent drainage.

Ankylosing spondylitis (AS) is a chronic, painful, degenerative inflammatory arthritis

primarily affecting the spine and sacroiliac joints, and eventually resulting in fusion of the

spine. It is a member of the group of the autoimmune spondyloarthropathies with a probable

genetic predisposition.

Psoriatic arthritis is a chronic systemic rheumatic disease characterized by inflammation of

the skin (psoriasis) and joints (arthritis). About 10% of patients with psoriasis also develop

psoriatic arthritis. Psoriasis precedes the arthritis in nearly 80% of patients, while the arthritis

precedes the psoriasis in up to 15% of patients.

Plaque Psoriasis is a chronic relapsing disease of the skin characterized by scaling and

inflammation. Psoriasis is an autoimmune disease in which skin cells multiply ten (10) times

faster than the normal rate, causing excess cells to pile on the surface of the skin resulting in

raised scaly patches that can be disfiguring. Symptoms of psoriasis include pain, itching,

restricted joint motion, and emotional distress.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown etiology.

It has been theorized that unknown genetic and environmental factors activate an autoimmune

response .The resulting cytokine production (e.g., tumor necrosis factor alpha [TNF-a] and

interleukin-1) causes inflammation of synovial membranes and articular structures that leads to

joint damage and disability. RA disease activity can be classified as mild, moderate or severe.

Due to the systemic nature of the disease, other organs may also be affected.

Consistent with FDA-approved product labeling, Infliximab may be considered in combination

with a non-biologic DMARD, methotrexate, to reduce disease signs and symptoms, inhibit the

progression of structural damage, and improve physical function in individuals with

moderately to severely active rheumatoid arthritis.

Black Box Warnings

Serious Infections

Patients treated with Infliximab are at increased risk for serious infections, leading to

hospitalization or death, including bacterial sepsis, tuberculosis (TB), and invasive fungal

infections (such as histoplasmosis) and infections due to other opportunistic pathogens.

Remicade should be discontinued if a patient develops sepsis during treatment. During

treatment with Remicade, the patient should be tested for latent TB; if positive treatment for

TB should be started prior to starting Remicade. The patient should be monitored for TB

during treatment, even if the initial TB test is negative.

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Malignancy

Lymphoma and other malignancies some fatal, have been reported in children and adolescent

patients treated with TNF blockers, including Remicade. Post marketing cases of hepatosplenic

T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients

treated with TNF blockers including Remicade. All cases were reported in patients with

Crohn’s disease and ulcerative colitis, the majority of whom were adolescent or young adult

males. This rare, aggressive T-cell lymphoma is fatal. All of these patients received treatment

with azathioprine or 6-mercaptopurine concomitantly with Remicade at or prior to diagnosis.

The labels’ boxed warnings also specify that an increased risk of lymphoma and other cancers

have been found in children and adolescents who receive the therapies. This was the

conclusion of an investigation that began in June 2008 and showed that TNF blockers

increased the risk of cancer in pediatric patients. The analysis of reported U.S. cases revealed

that the cancers occurred after 30 months of treatment, on average, and some of the cases were

fatal. Approximately half of the cancers were lymphomas.

IV. RATIONALE

Crohn’s Disease

Active Crohn’s Disease

The safety and efficacy of single and multiple doses of REMICADE were assessed in 2

randomized, double-blind, placebo-controlled clinical studies in 653 patients with moderate to

severely active Crohn’s disease [Crohn’s Disease Activity Index (CDAI) ≥220 and ≤400] with

an inadequate response to prior conventional therapies. Concomitant stable doses of

aminosalicylates, corticosteroids and/or immunomodulatory agents were permitted and 92% of

patients continued to receive at least one of these medications.

In the single-dose trial of 108 patients, 16% (4/25) of placebo patients achieved a clinical

response (decrease in CDAI ≥70 points) at Week 4 vs. 81% (22/27) of patients receiving 5

mg/kg REMICADE (p<0.001, two-sided, Fisher’s Exact test). Additionally, 4% (1/25) of

placebo patients and 48% (13/27) of patients receiving 5 mg/kg REMICADE achieved clinical

remission (CDAI<150) at Week 4.

In a multidose trial (ACCENT I [Study Crohn’s I]), 545 patients received 5 mg/kg at Week 0 and

were then randomized to one of three treatment groups; the placebo maintenance group received

placebo at Weeks 2 and 6, and then every 8 weeks; the 5 mg/kg maintenance group received 5

mg/kg at Weeks 2 and 6, and then every 8 weeks; and the 10 mg/kg maintenance group received

5 mg/kg at Weeks 2 and 6, and then 10 mg/kg every 8 weeks. Patients in response at Week 2

were randomized and analyzed separately from those not in response at Week 2. Corticosteroid

taper was permitted after Week 6.

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At Week 2, 57% (311/545) of patients were in clinical response. At Week 30, a significantly

greater proportion of these patients in the 5 mg/kg and 10 mg/kg maintenance groups achieved

clinical remission compared to patients in the placebo maintenance group (Table 3).

Additionally, a significantly greater proportion of patients in the 5 mg/kg and 10 mg/kg

REMICADE maintenance groups were in clinical remission and were able to discontinue

corticosteroid use compared to patients in the placebo maintenance group at Week 54 (Table 3).

Patients in the REMICADE maintenance groups (5 mg/kg and 10 mg/kg) had a longer time to

loss of response than patients in the placebo maintenance group (Figure 1). At Weeks 30 and 54,

significant improvement from baseline was seen among the 5 mg/kg and 10 mg/kg REMICADE-

treated groups compared to the placebo group in the disease-specific inflammatory bowel disease

questionnaire (IBDQ), particularly the bowel and systemic components, and in the physical

component summary score of the general health-related quality of life questionnaire SF-36.

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In a subset of 78 patients who had mucosal ulceration at baseline and who participated in an

endoscopic substudy, 13 of 43 patients in the REMICADE maintenance group had endoscopic

evidence of mucosal healing compared to 1 of 28 patients in the placebo group at Week 10. Of

the REMICADE-treated patients showing mucosal healing at Week 10, 9 of 12 patients also

showed mucosal healing at Week 54.

Patients who achieved a response and subsequently lost response were eligible to receive

REMICADE on an episodic basis at a dose that was 5 mg/kg higher than the dose to which they

were randomized. The majority of such patients responded to the higher dose. Among patients

who were not in response at Week 2, 59% (92/157) of REMICADE maintenance patients

responded by Week 14 compared to 51% (39/77) of placebo maintenance patients. Among

patients who did not respond by Week 14, additional therapy did not result in significantly more

responses.

Fistulizing Crohn’s Disease

The safety and efficacy of REMICADE were assessed in 2 randomized, double-blind, placebo-

controlled studies in patients with fistulizing Crohn’s disease with fistula(s) that were of at least

3 months duration. Concurrent use of stable doses of corticosteroids, 5-aminosalicylates,

antibiotics, MTX, 6-mercaptopurine (6-MP) and/or azathioprine (AZA) was permitted.

In the first trial, 94 patients received 3 doses of either placebo or REMICADE at Weeks 0, 2 and

6. Fistula response (≥50% reduction in number of enterocutaneous fistulas draining upon gentle

compression on at least 2 consecutive visits without an increase in medication or surgery for

Crohn’s disease) was seen in 68% (21/31) of patients in the 5 mg/kg REMICADE group

(P=0.002) and 56% (18/32) of patients in the 10 mg/kg REMICADE group (P=0.021) vs. 26%

(8/31) of patients in the placebo arm. The median time to onset of response and median duration

of response in REMICADE-treated patients was 2 and 12 weeks, respectively. Closure of all

fistulas was achieved in 52% of REMICADE-treated patients compared with 13% of placebo-

treated patients (P<0.001).

In the second trial (ACCENT II [Study Crohn’s II]), patients who were enrolled had to have at

least 1 draining enterocutaneous (perianal, abdominal) fistula. All patients received 5 mg/kg

REMICADE at Weeks 0, 2 and 6. Patients were randomized to placebo or 5 mg/kg REMICADE

maintenance at Week 14. Patients received maintenance doses at Week 14 and then every 8

weeks through Week 46.Patients who were in fistula response (fistula response was defined the

same as in the first trial) at both Weeks 10 and 14 were randomized separately from those not in

response. The primary endpoint was time from randomization to loss of response among those

patients who were in fistula response.

Among the randomized patients (273 of the 296 initially enrolled), 87% had perianal fistulas and

14% had abdominal fistulas. Eight percent also had rectovaginal fistulas. Greater than 90% of the

patients had received previous immunosuppressive and antibiotic therapy.

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At Week 14, 65% (177/273) of patients were in fistula response. Patients randomized to

REMICADE maintenance had a longer time to loss of fistula response compared to the placebo

maintenance group (Figure 2). At Week 54, 38% (33/87) of REMICADE-treated patients had no

draining fistulas compared with 22% (20/90) of placebo-treated patients (P=0.02). Compared to

placebo maintenance, patients on REMICADE maintenance had a trend toward fewer

hospitalizations.

Patients who achieved a fistula response and subsequently lost response were eligible to receive

REMICADE maintenance therapy at a dose that was 5 mg/kg higher than the dose to which they

were randomized. Of the placebo maintenance patients, 66% (25/38) responded to 5 mg/kg

REMICADE, and 57% (12/21) of REMICADE maintenance patients responded to 10 mg/kg.

Patients who had not achieved a response by Week 14 were unlikely to respond to additional

doses of REMICADE.

Similar proportions of patients in either group developed new fistulas (17% overall) and similar

numbers developed abscesses (15% overall).

Pediatric Crohn’s Disease

The safety and efficacy of REMICADE were assessed in a randomized, open-label study (Study

Pads Crohn’s) in 112 pediatric patients aged 6 to 17 years old with moderately to severely active

Crohn’s disease and an inadequate response to conventional therapies. The median age was 13

years and the median Pediatric Crohn’s Disease Activity Index (PCDAI) was 40 (on a scale of 0

to 100). All patients were required to be on a stable dose of 6-MP, AZA, or MTX; 35% were also

receiving corticosteroids at baseline

All patients received induction dosing of 5 mg/kg REMICADE at Weeks 0, 2, and 6.At Week

10, 103 patients were andomized to a maintenance regimen of 5 mg/kg REMICADE given either

every 8 weeks or every 12 weeks.

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At Week 10, 88% of patients were in clinical response (defined as a decrease from baseline in

the PCDAI score of ≥15 points and total PCDAI score of ≤ baseline 59% were in clinical

remission (defined as PCDAI score of ≤10 points).

The proportion of pediatric patients achieving clinical response at Week 10 compared favorably

with the proportion of adults achieving a clinical response in Study Crohn’s I. The study

definition of clinical response in Study Peds Crohn’s was based on the PCDAI score, whereas

the CDAI score was used in the adult Study Crohn’s I. At both Week 30 and Week 54, the

proportion of patients in clinical response was greater in the every 8-week treatment group than

in the every 12-week treatment group (73% vs. 47% at Week 30, and 64% vs. 33% at Week 54).

At both Week 30 and Week 54, the proportion of patients in clinical remission was also greater

in the every 8-week treatment group than in the every 12-week treatment group (60% vs.35% at

Week 30, and 56% vs. 24% at Week 54), (Table 4).

For patients in Study Peds Crohn’s receiving corticosteroids at baseline, the proportion of

patients able to discontinue corticosteroids while in remission at Week30 was 46% for the every

8-week maintenance group and 33% for the every 12-week maintenance group. At Week 54, the

proportion of patients able to discontinue corticosteroids while in remission was 46% for the

every 8-week maintenance group and 17% for the every 12-week maintenance group.

Ulcerative Colitis


controlled clinical studies in 728 patients with moderately to severely active ulcerative colitis

(UC) (Mayo score5 6 to 12 [of possible range 0 to 12], Endoscopy subscore ≥ 2) with an

inadequate response to conventional oral therapies (Studies UC I and UC II). Concomitant

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treatment with stable doses of aminosalicylates, corticosteroids and/or immunomodulatory

agents was permitted. Corticosteroid taper was permitted after Week 8. Patients were

randomized at week 0 to receive either placebo, 5 mg/kg REMICADE or 10 mg/kg REMICADE

at Weeks 0, 2, 6, and every 8 weeks thereafter through Week 46 in Study UC I, and at Weeks 0,

2, 6, and every 8 weeks thereafter through Week 22 in Study UC II. In Study UC II, patients

were allowed to continue blinded therapy to Week 46 at the investigator’s discretion.

Patients in Study UC I had failed to respond or were intolerant to oral corticosteroids, 6-MP, or

AZA. Patients in Study UC II had failed to respond or were intolerant to the above treatments

and/or aminosalicylates. Similar proportions of patients in Studies UC I and UC II were

receiving corticosteroids (61% and 51%, respectively), 6-MP/AZA (49% and 43%) and

aminosalicylates (70% and 75%) at baseline. More patients in Study UC II than UC I were

taking solely aminosalicylates for UC (26% vs. 11%, respectively). Clinical response was

defined as a decrease from baseline in the Mayo score by ≥ 30% and ≥ 3 points, accompanied by

a decrease in the rectal bleeding subscore of ≥ 1 or a rectal bleeding subscore of 0 or 1.

Clinical Response, Clinical Remission, and Mucosal Healing

In both Study UC I and Study UC II, greater percentages of patients in both REMICADE groups

achieved clinical response, clinical remission and mucosal healing than in the placebo group.

Each of these effects was maintained through the end of each trial (Week 54 in Study UC I, and

Week 30 in Study UC II). In addition, a greater proportion of patients in REMICADE groups

demonstrated sustained response and sustained remission than in the placebo groups (Table 5).

Of patients on corticosteroids at baseline, greater proportions of patients in the REMICADE

treatment groups were in clinical remission and able to discontinue corticosteroids at Week 30

compared with the patients in the placebo treatment groups (22% in REMICADE treatment

groups vs. 10% in placebo group in Study UC I; 23% in REMICADE treatment groups vs. 3% in

placebo group in Study UC II). In Study UC I, this effect was maintained through Week 54 (21%

in REMICADE treatment groups vs. 9% in placebo group). The REMICADE-associated

response was generally similar in the 5 mg/kg and 10 mg/kg dose groups.

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Pediatric Ulcerative Colitis

The safety and effectiveness of REMICADE for reducing signs and symptoms and inducing and

maintaining clinical remission in pediatric patients aged 6 years and older with moderately to

severely active ulcerative colitis who have had an inadequate response to conventional therapy

are supported by evidence from adequate and well-controlled studies of REMICADE in adults.

Additional safety and pharmacokinetic data were collected in an open-label pediatric UC trial in

60 pediatric patients aged 6 through 17 years (median age 14.5 years) with moderately to

severely active ulcerative colitis (Mayo score of 6 to 12; Endoscopic subscore Mayo score was 8,

53% of patients were receiving immunomodulator therapy (6-MP/AZA/MTX), and 62% of

patients were receiving corticosteroids (median dose 0.5 mg/kg/day in prednisone equivalents).

Discontinuation of immunomodulators and corticosteroid taper were permitted after Week 0.

All patients received induction dosing of 5 mg/kg REMICADE at Weeks 0, 2, and 6. Patients

who did not respond to REMICADE at Week 8 received no further REMICADE and returned

for safety follow-up. At Week 8, 45 patients were randomized to a maintenance regimen of 5

mg/kg REMICADE given either every 8 weeks through Week 46 or every 12 weeks through

Week 42. Patients were allowed to change to a higher dose and/or more frequent administration

schedule if they experienced loss of response.

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Clinical response at Week 8 was defined as a decrease from baseline in the Mayo score by ≥30%

and ≥3 points, including a decrease in the rectal bleeding subscore by ≥1 points or achievement

of a rectal bleeding subscore of 0 or 1.

Clinical remission at Week 8 was measured by the Mayo score, defined as a Mayo score of ≤2

points with no individual subscore >1. Clinical remission was also assessed at Week 8 and Week

54 using the Pediatric Ulcerative Colitis Activity Index (PUCAI)6 score and was defined by a

PUCAI score of <10 points.

Endoscopies were performed at baseline and at Week 8. A Mayo endoscopy subscore of 0

indicated normal or inactive disease and a subscore of 1 indicated mild disease (erythema,

decreased vascular pattern, or mild friability).

Of the 60 patients treated, 44 were in clinical response at Week 8. Of 32 patients taking

concomitant immunomodulators at baseline, 23 achieved clinical response at Week 8, compared

to 21 of 28 of those not taking concomitant immunomodulators at baseline. At Week 8, 24 of 60

patients were in clinical remission as measured by the Mayo score and 17 of 51 patients were in

remission as measured by the PUCAI score.

At Week 54, 8 of 21 patients in the every 8-week maintenance group and 4 of 22 patients in the

every 12-week maintenance group achieved remission as measured by the PUCAI score.

During maintenance phase, 23 of 45 randomized patients (9 in the every 8-week group and 14 in

the every 12-week group) required an increase in their dose and/or increase in frequency of

REMICADE administration due to loss of response. Nine of the 23 patients who required a

change in dose had achieved remission at Week 54. Seven of those patients received the 10

mg/kg every 8-week dosing.

Rheumatoid Arthritis

The safety and efficacy of REMICADE were assessed in 2 multicenter, randomized, double-

blind, pivotal trials: ATTRACT (Study RA I) and ASPIRE (Study RA II). Concurrent use of

stable doses of folic acid, oral corticosteroids (≤ 10 mg/day) and/or non-steroidal anti-

inflammatory drugs (NSAIDs) was permitted.

Study RA I was a placebo-controlled study of 428 patients with active rheumatoid arthritis

despite treatment with MTX. Patients enrolled had a median age of 54 years, median disease

duration of 8.4 years, median swollen and tender joint count of 20 and 31 respectively, and were

on a median dose of 15 mg/wk of MTX. Patients received either placebo + MTX or one of 4

doses/schedules of REMICADE + MTX:3 mg/kg or 10 mg/kg of REMICADE by IV infusion at

Weeks 0, 2 and 6 followed by additional infusions every 4 or 8 weeks in combination with MTX.

Study RA II was a placebo-controlled study of 3 active treatment arms in 1004 MTX naive

patients of 3 or fewer years’ duration active rheumatoid arthritis. Patients enrolled had a median

age of 51 years with a median disease duration of 0.6 years, median swollen and tender joint

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count of 19 and 31, respectively, and >80% of patients had baseline joint erosions. At

randomization, all patients received MTX (optimized to 20 mg/wk by Week 8) and either

placebo, 3 mg/kg or 6 mg/kg REMICADE at Weeks 0, 2, and 6 and every 8 weeks thereafter.

Data on use of REMICADE without concurrent MTX are limited.

Clinical response

In Study RA I, all doses/schedules of REMICADE + MTX resulted in improvement in signs and

symptoms as measured by the American College of Rheumatology response criteria (ACR 20)

with a higher percentage of patients achieving an ACR 20, 50 and 70 compared to placebo +

MTX (Table 7). This improvement was observed at Week 2 and maintained through Week 102.

Greater effects on each component of the ACR 20 were observed in all patients treated with

REMICADE + MTX compared to placebo + MTX (Table 8). More patients treated with

REMICADE reached a major clinical response than placebo-treated patients (Table 7).

In Study RA II, after 54 weeks of treatment, both doses of REMICADE + MTX resulted in

statistically significantly greater response in signs and symptoms compared to MTX alone as

measured by the proportion of patients achieving ACR 20, 50 and 70 responses (Table 7). More

patients treated with REMICADE reached a major clinical response than placebo-treated patients

(Table 7).

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Radiographic response

Structural damage in both hands and feet was assessed radiographically at Week 54 by the

change from baseline in the van der Heijde-modified Sharp (vdH-S) score, a composite score of

structural damage that measures the number and size of joint erosions and the degree of joint

space narrowing in hands/wrists and feet.3 In Study RA I, approximately 80% of patients had

paired X-ray data at 54 weeks and approximately 70% at 102 weeks. The inhibition of

progression of structural damage was observed at 54 weeks (Table 9) and maintained through

102 weeks.

In Study RA II, >90% of patients had at least 2 evaluable X-rays. Inhibition of progression of

structural damage was observed at Weeks 30 and 54 (Table 9) in the REMICADE + MTX

groups compared to MTX alone. Patients treated with REMICADE + MTX demonstrated less

progression of structural damage compared to MTX alone, whether baseline acute-phase

reactants (ESR and CRP) were normal or elevated: patients with elevated baseline acute-phase

reactants treated with MTX alone demonstrated a mean progression in vdH-S score of 4.2 units

compared to patients treated with REMICADE + MTX who demonstrated 0.5 units of

progression; patients with normal baseline acute phase reactants treated with MTX alone

demonstrated a mean progression in vdH-S score of 1.8 units compared to REMICADE + MTX

who demonstrated 0.2 units of progression. Of patients receiving REMICADE + MTX, 59% had

no progression (vdH-S score ≤0 unit) of structural damage compare to 45% of patients receiving

MTX alone. In a subset of patients who began the study without erosions, REMICADE + MTX

maintained an erosion-free state at 1 year in a greater Proportion of patients than MTX alone,

79% (77/98) vs. 58% (23/40), respectively (P<0.01). Fewer patients in the REMICADE + MTX

groups (47%) developed erosions in uninvolved joints compared to MTX alone (59%).

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Physical function response

Physical function and disability were assessed using the Health Assessment Questionnaire

(HAQ-DI) and the general health-related quality of life questionnaire SF-36.

In Study RA I, all doses/schedules of REMICADE + MTX showed significantly greater

improvement from baseline in HAQ-DI and SF-36 physical component summary score averaged

over time through Week 54 compared to placebo + MTX, and no worsening in the SF-36 mental

component summary score. The median (interquartile range) improvement from baseline to

Week 54 in HAQ-DI was 0.1 (-0.1, 0.5) for the placebo + MTX group and 0.4 (0.1, 0.9) for

REMICADE + MTX (p<0.001). Both HAQ-DI and SF-36 effects were maintained through

Week 102. Approximately 80% of patients in all doses/schedules of REMICADE + MTX

remained in the trial through 102 weeks.

In Study RA II, both REMICADE treatment groups showed greater improvement in HAQ-DI

from baseline averaged over time through Week 54 compared to MTX alone;0.7 for

REMICADE + MTX vs. 0.6 for MTX alone (P≤0.0001). No worsening in the SF-36 mental

component summary score was observed.

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Ankylosing Spondylitis

The safety and efficacy of REMICADE were assessed in a randomized, multicenter, double-

blind, placebo-controlled study in 279 patients with active ankylosing spondylitis. Patients were

between 18 and 74 years of age, and had ankylosing spondylitis as defined by the modified New

York criteria for Ankylosing Spondylitis.4 Patients were to have had active disease as evidenced

by both a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >4 (possible

range 0-10) and spinal pain >4 (on a Visual Analog Scale [VAS] of 0-10). Patients with

complete ankylosis of the spine were excluded from study participation, and the use of

Disease Modifying Anti-Rheumatic Drugs (DMARDs) and systemic corticosteroids were

prohibited. Doses of REMICADE 5 mg/kg or placebo were administered ntravenously at Weeks

0, 2, 6, 12 and 18.

At 24 weeks, improvement in the signs and symptoms of ankylosing spondylitis, as measured by

the proportion of patients achieving a 20% improvement in ASAS response criteria (ASAS 20),

was seen in 60% of patients in the REMICADE-treated group vs. 18% of patients in the placebo

group (p<0.001). Improvement was observed at Week 2 and maintained through Week 24

(Figure 3 and Table 10).

At 24 weeks, the proportions of patients achieving a 50% and a 70% improvement in the signs

and symptoms of ankylosing spondylitis, as measured by ASAS response criteria (ASAS 50 and

ASAS 70, respectively), were 44% and 28%, respectively, for patients receiving REMICADE,

compared to 9% and 4%, respectively, for patients receiving placebo (P<0.001, REMICADE vs.

placebo). A low level of disease activity (defined as a value <20 [on a scale of 0-100 mm] in

each of the 4 ASAS response parameters) was achieved in 22% of REMICADE-treated patients

vs. 1% in placebo-treated patients (P<0.001).

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Results of this study were similar to those seen in a multicenter double-blind, placebo-controlled

study of 70 patients with ankylosing spondylitis.

Psoriatic Arthritis

Safety and efficacy of REMICADE were assessed in a multicenter, double-blind, placebo-

controlled study in 200 adult patients with active psoriatic arthritis despite DMARD or NSAID

therapy (≥ 5swollen joints and ≥ tender joints) with 1or more of the following subtypes: arthritis

involving DIP joints (n=49), arthritis mutilans (n=3),asymmetric peripheral arthritis (n=40),

polyarticular arthritis (n=100), and spondylitis with peripheral arthritis (n=8). Patients also had

plaque psoriasis with a qualifying target lesion ≥ target lesion ≥g subtypes: arthritis involving

DIP joints (n=49), arthritis mutilans (n=3),asymmetric peripheral arthritis (n=40), polyarticular

arthritis (n=100), and spondylitis with peripheral arthritis (n=8). Patients also had plaque

psoriasis target lesion ≥2 cm in diameter. Forty-six percent of patients continued on stable doses

of methotrexate (≤25mg/week). During the 24-week double –blind phase patients received

either 5 mg/kg REMICASE or placebo at Weeks), 2< 6, 14, and 22 (100patients in each group).

At week 16, placebo patients with <10% improvement from baseline in swollen and tender joint

counts were switched to REMICADE induction (early escape). At Week 24, all placebo –treated

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patients crossed over to REMICADE inductin. Dosing continued for all patients through Week

46. .

Clinical response

Treatment with REMICADE resulted in improvement in signs and symptoms, as assessed by the

ACR criteria, with 58% of REMICADE-treated patients achieving ACR 20 at Week 14,

compared with 11% of placebo-treated patients (P< 0.001). The response was similar regardless

of concomitant use of methotrexate. Improvement was observed as early as Week 2. At 6

months, the ACR 20/50/70 responses were achieved by 54%, 41%, and 27%, respectively, of

patients receiving REMICADE compared to 16%, 4%, and 2%, respectively, of patients

receiving placebo. Similar responses were seen in patients with each of the subtypes of psoriatic

arthritis, although few patients were enrolled with the arthritis mutilans and spondylitis with

peripheral arthritis subtypes.

Compared to placebo, treatment with REMICADE resulted in improvements in the components

of the ACR response criteria, as well as in dactylitis and enthesopathy (Table 11). The clinical

response was maintained through Week 54. Similar ACR responses were observed in an earlier

randomized, placebo-controlled study of 104 psoriatic arthritis patients, and the responses were

maintained through 98 weeks in an open-label extension phase.

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Improvement in Psoriasis Area and Severity Index (PASI) in psoriatic arthritis patients with

baseline body surface area (BSA) ≥3% (n=87 placebo, n=83 REMICADE) was achieved at

Week 14, regardless of concomitant methotrexate use, with 64% of REMICADE-treated patients

achieving at least 75% improvement from baseline vs. 2% of placebo-treated patients;

improvement was observed in some patients as early as Week 2. At 6 months, the PASI 75 and

PASI 90 responses were achieved by 60% and 39%, respectively, of patients receiving

REMICADE compared to 1% and 0%, respectively, of patients receiving placebo. The PASI

response was generally maintained through Week 54.

Radiographic response

Structural damage in both hands and feet was assessed radiographically by the change from

baseline in the van der Heijde-Sharp (vdH-S) score, modified by the addition of hand DIP joints.

The total modified vdH-S score is a composite score of structural damage that measures the

number and size of joint erosions and the degree of joint space narrowing (JSN) in the hands and

feet. At Week 24, REMICADE-treated patients had less radiographic progression than placebo-

treated patients (mean change of -0.70 vs. 0.82, P<0.001). REMICADE-treated patients also had

less progression in their erosion scores (-0.56 vs 0.51) and JSN scores (-0.14 vs 0.31).

The patients in the REMICADE group demonstrated continued inhibition of structural damage at

Week 54. Most patients showed little or no change in the vdH-S score during this 12-month

study (median change of 0 in both patients who initially received

REMICADE or placebo). More patients in the placebo group (12%) had readily apparent

radiographic progression compared with the REMICADE group (3%).

Physical function

Physical function status was assessed using the HAQ Disability Index (HAQ-DI) and the SF-36

Health Survey. REMICADE-treated patients demonstrated significant improvement in physical

function as assessed by HAQ-DI (median percent improvement in HAQ-DI score from baseline

to Week 14 and 24 of 43% for REMICADE-treated patients vs 0% for placebo-treated patients).

During the placebo-controlled portion of the trial (24 weeks), 54% of REMICADE treated

patients achieved a clinically meaningful improvement in HAQ-DI (≥0.3 unit decrease)

compared to 22% of placebo-treated patients. REMICADE-treated patients also demonstrated

greater improvement in the SF-36 physical and mental component summary scores than placebo-

treated patients. The responses were maintained for up to 2 years in an open-label extension

study.

Plaque Psoriasis


controlled studies in patients 18 years of age and older with chronic, stable plaque psoriasis

involving ≥ 10% BSA, a minimum PASI score of 12, and who were candidates for systemic

therapy or phototherapy. Patients with guttate, pustular, or erythrodermic psoriasis were

excluded from these studies. No concomitant anti-psoriatic therapies were allowed during the

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study, with the exception of low-potency topical corticosteroids on the face and groin after Week

10 of study initiation.

Study I (EXPRESS) evaluated 378 patients who received placebo or REMICADE at a dose of 5

mg/kg at Weeks 0, 2, and 6 (induction therapy), followed by maintenance therapy every 8 weeks.

At Week 24, the placebo group crossed over to REMICADE induction therapy (5 mg/kg),

followed by maintenance therapy every 8 weeks. Patients originally randomized to REMICADE

continued to receive REMICADE 5 mg/kg every 8 weeks through Week 46. Across all treatment

groups, the median baseline PASI score was 21 and the baseline Static Physician Global

Assessment (sPGA) score ranged from moderate (52% of patients) to marked (36%) to severe

(2%). In addition, 75% of patients had a BSA >20%. Seventy-one percent of patients previously

received systemic therapy, and 82% received phototherapy.

Study II (EXPRESS II) evaluated 835 patients who received placebo or REMICADE at doses of

3 mg/kg or 5 mg/kg at Weeks 0, 2, and 6 (induction therapy). At Week 14,

within each REMICADE dose group, patients were randomized to either scheduled (every 8

weeks) or as needed (PRN) maintenance treatment through Week 46. At Week 16, the placebo

group crossed over to REMICADE induction therapy (5 mg/kg), followed by maintenance

therapy every 8 weeks. Across all treatment groups, the median baseline PASI score was 18, and

63% of patients had a BSA >20%. Fifty-five percent of patients previously received systemic

therapy, and 64% received a phototherapy

Study III (SPIRIT) evaluated 249 patients who had previously received either psoralen plus

ultraviolet A treatment (PUVA) or other systemic therapy for their psoriasis. These patients were

randomized to receive either placebo or REMICADE at doses of 3 mg/kg or 5 mg/kg at Weeks 0,

2, and 6. At Week 26, patients with a sPGA score of moderate or worse (greater than or equal to

3 on a scale of 0 to 5) received an additional dose of the randomized treatment. Across all

treatment groups, the median baseline PASI score was 19, and the baseline sPGA score ranged

from moderate (62% of patients) to marked (22%) to severe (3%). In addition,75% of patients

had a BSA >20%. Of the enrolled patients, 114 (46%) received the Week 26 additional dose.

In Studies I, II and III, the primary endpoint was the proportion of patients who achieved a

reduction in score of at least 75% from baseline at Week 10 by the PASI (PASI 75). In Study I

and Study III, another evaluated outcome included the proportion of patients who achieved a

score of “cleared” or “minimal” by the sPGA. The sPGA is a 6-category scale ranging from “5 =

severe” to “0 = cleared” indicating the physician’s overall assessment of the psoriasis severity

focusing on induration, erythema, and scaling. Treatment success, defined as “cleared” or

“minimal”, consisted of none or minimal elevation in plaque, up to faint red coloration in

erythema, and none or minimal fine scale over <5% of the plaque.

Study II also evaluated the proportion of patients who achieved a score of “clear” or “excellent”

by the relative Physician’s Global Assessment (rPGA). The rPGA is a 6-category scale ranging

from “6 = worse” to “1 = clear” that was assessed relative

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to baseline. Overall lesions were graded with consideration to the percent of body involvement

as well as overall induration, scaling, and erythema. Treatment success, defined as “clear” or

“excellent,” consisted of some residual pinkness or pigmentation to marked improvement (nearly

normal skin texture; some erythema may be present). The results of these studies are presented in

Table 12.

In Study I, in the subgroup of patients with more extensive psoriasis who had previously

received phototherapy, 85% of patients on 5 mg/kg REMICADE achieved a PASI 75 at Week 10

compared with 4% of patients on placebo.

In Study II, in the subgroup of patients with more extensive psoriasis who had previously

received phototherapy, 72% and 77% of patients on 3 mg/kg and 5 mg/kg REMICADE achieved

a PASI 75 at Week 10 respectively compared with 1% on placebo. In Study II, among patients

with more extensive psoriasis who had failed or were intolerant to phototherapy, 70% and 78%

of patients on 3 mg/kg and 5 mg/kg REMICADE achieved a PASI 75 at Week 10 respectively,

compared with 2% on placebo.

Maintenance of response was studied in a subset of 292 and 297 REMICADE-treated patients in

the 3 mg/kg and 5 mg/kg groups; respectively, in Study II. Stratified by

PASI response at Week 10 and investigational site, patients in the active treatment groups were

re-randomized to either a scheduled or as needed maintenance (PRN) therapy, beginning on

Week 14.

The groups that received a maintenance dose every 8 weeks appear to have a greater percentage

of patients maintaining a PASI 75 through week 50 as compared to patients who received the as-

needed or PRN doses, and the best response was maintained with the 5 mg/kg every 8-week

dose. These results are shown in Figure 4. At Week 46, when REMICADE serum concentrations

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were at trough level, in the every 8-week dose group, 54% of patients in the 5 mg/kg group

compared to 36% in the 3 mg/kg group achieved PASI 75. The lower percentage of PASI 75

responders in the 3 mg/kg every 8-week dose group compared to the 5 mg/kg group was

associated with a lower percentage of patients with detectable trough serum infliximab levels.

This may be related in part to higher antibody rates

In addition, in a subset of patients who had achieved a response at Week 10, maintenance of

response appears to be greater in patients who received REMICADE every 8 weeks at the 5

mg/kg dose. Regardless of whether the maintenance doses are PRN or every 8 weeks, there is a

decline in response in a subpopulation of patients in each group over time. The results of Study I

through Week 50 in the 5 mg/kg every 8 weeks maintenance dose group were similar to the

results from Study II.

Efficacy and safety of REMICADE treatment beyond 50 weeks have not been evaluated in

patients with plaque psoriasis.

V. DEFINITIONS

MONOCLONAL ANTIBODY is a type of antibody, specific to a certain antigen, created in the

laboratory.

OFF LABEL refers to the use of a drug to treat a condition for which it has not been approved by

the U.S. Food and Drug Administration (FDA), especially when such may relieve unpleasant

symptoms or prove compassionate. Drug effects that have been observed, but not specifically

proven (and for which no application has been made) may be exploited for unproven or “off-

label” uses by licensed medical practitioners.

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DISEASE-MODIFYING ANTIRHEUMATIC DRUG (DMARD) refers to medicines classified as

disease-modifying anti-rheumatic drugs (DMARDs) have the potential to reduce or prevent joint

damage and preserve joint integrity and function. Commonly used traditional DMARDs include,

but are not limited to, leflunomide, sulfasalazine, hydroxychloroquine, azathioprine, and

methotrexate.

VI. BENEFIT VARIATIONS

The existence of this medical policy does not mean that this service is a covered benefit under

the member's contract. Benefit determinations should be based in all cases on the applicable

contract language. Medical policies do not constitute a description of benefits. A member’s

individual or group customer benefits govern which services are covered, which are excluded,

and which are subject to benefit limits and which require preauthorization. Members and

providers should consult the member’s benefit information or contact Capital for benefit

information.

VII. DISCLAIMER

Capital’s medical policies are developed to assist in administering a member’s benefits, do not constitute medical

advice and are subject to change. Treating providers are solely responsible for medical advice and treatment of

members. Members should discuss any medical policy related to their coverage or condition with their provider

and consult their benefit information to determine if the service is covered. If there is a discrepancy

between this medical policy and a member’s benefit information, the benefit information will

govern. Capital considers the information contained in this medical policy to be proprietary and

it may only be disseminated as permitted by law.

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Journal of clinical psychopharmacology 2010; 30(3):343-5.

MacDermott R, Lichenstein G. Infliximab in Crohn’s Disease. In: UpToDate Online Journal [serial

online]. Waltham, MA: UpToDate; updated June 1, 2011. [Website]: www.uptodate.com. Accessed

January 31, 2012.

Malottki K, Barton P, Tsourapas A et al. Adalimumab, etanercept, infliximab, rituximab and abatacept

for the treatment of rheumatoid arthritis after the failure of a tumour necrosis factor inhibitor: a

systematic review and economic evaluation. Health Technol Assess 2011; 15(14):1-278.

MedlinePlus. Medical Encyclopedia. Ulcerative Colitis. [Website]:

http://www.nlm.nih.gov/medlineplus/ency/article/000250.htm. Accessed . October 16, 2013.

Mosby’s Medical, Nursing & Allied Health Dictionary, 6th edition.

Menter A, Gottlieb A, Feldman SR et al. Guidelines of care for the management of psoriasis and psoriatic

arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with

biologics. Journal of the American Academy of Dermatology 2008; 58(5):826-50.

National Institute for Health and Clinical Excellence. March 2010... Infliximab for subacute

manifestations of ulcerative colitis. [Website]: http://www.nice.org.uk/guidance/index.jsp. Accessed

October 16, 2013.

National Institute for Health and Clinical Excellence. Technology Appraisal (TA) 195: Rheumatoid

arthritis - drugs for treatment after failure of a TNF inhibitor. August 2010. [Website]:

http://www.nice.org.uk/guidance/index.jsp?action=byID&o=13108 .Accessed October 16, 2013.

Nussenblatt RB, Byrnes G, Sen HN et al. A randomized pilot study of systemic immunosuppression in the

treatment of age-related macular degeneration with choroidal neovascularization. Retina 2010;

30(10):1579-87.

Pavelka K, Jarosova K, Suchy D et al. Increasing the infliximab dose in rheumatoid arthritis patients: a

randomised, double blind study failed to confirm its efficacy. Annals of the rheumatic diseases 2009;

68(8):1285-9.

Peppercorn M, Farrell R Medical management of ulcerative colitis.Updated April 12, 2010. In:

UpToDate Online Journal [serial online]. Waltham, MA: UpToDate; updated August 22, 2013.

[Website]: www.uptodate.com. Accessed October 16, 2013.

Peyrin-Biroulet L, Deltenre P, de Suray N et al. Efficacy and safety of tumor necrosis factor antagonists

in Crohn's disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol. 2008;

6(6):644-53.

Phumethum V, Jamal S, Johnson SR. Biologic therapy for systemic sclerosis: a systematic review. The

Journal of rheumatology 2011; 38(2):289-96.

Ramos-Casals M, Tzioufas AG, Stone JH et al. Treatment of primary Sjogren syndrome: a systematic

review. JAMA: the journal of the American Medical Association 2010; 304(4):452-60.

Rodgers M, Epstein D, Bojke L et al. Etanercept, infliximab and adalimumab for the treatment of

psoriatic arthritis: a systematic review and economic evaluation. Health Technol Assess 2011;

15(10):i-xxi, 1-329.

Rosenbach M, Hsu S, Korman NJ et al. Treatment of erythrodermic psoriasis: from the medical board of

the National Psoriasis Foundation. Journal of the American Academy of Dermatology 2010;

62(4):655-62.

http://www.nlm.nih.gov/medlineplus/ency/article/000250.htm

http://www.nice.org.uk/guidance/index.jsp?action=download&o=40365

http://www.nice.org.uk/guidance/index.jsp?action=byID&o=13108


MEDICAL POLICY




Ruperto N, Lovell DJ, Cuttica R et al. Long-term efficacy and safety of infliximab plus methotrexate for

the treatment of polyarticular-course juvenile rheumatoid arthritis: findings from an open-label

treatment extension. Annals of the rheumatic diseases 2010; 69(4):718-22.

Sandborn WJ. Initial combination therapy in early Crohn’s disease. Lancet 2008; 371(9613):635-6.

Schmitz S, Adams R, Walsh CD et al. A mixed treatment comparison of the efficacy of anti-TNF agents in

rheumatoid arthritis for methotrexate non-responders demonstrates differences between treatments: a

Bayesian approach. Annals of the rheumatic diseases 2011.

Sfikakis PP, Grigoropoulos V, Emfietzoglou I et al. Infliximab for diabetic macular edema refractory to

laser photocoagulation: a randomized, double-blind, placebo-controlled, crossover, 32-week study.

Diabetes care 2010; 33(7):1523-8.

Sharma P, Kumar A, Sharma BC et al. Infliximab monotherapy for severe alcoholic hepatitis and

predictors of survival: an open label trial. Journal of hepatology 2009; 50(3):584-91.

Shenoi S, Wallace CA. Tumor necrosis factor inhibitors in the management of juvenile idiopathic

arthritis: an evidence-based review. Paediatric drugs 2010; 12(6):367-77.

Singh JA, Christensen R, Wells GA, et al. Biologics for rheumatoid arthritis: an overview of Cochrane

reviews. Cochrane Database of Systematic Reviews 2009, Issue 4. Art. No.: CD007848. DOI:

10.1002/14651858.CD007848.pub2.

Singh JA, Wells GA, Christensen R et al. Adverse effects of biologics: a network meta-analysis and

Cochrane overview. Cochrane Database Syst Rev 2011; (2):CD008794.

Stone, John H. Tumor Necrosis Factor-Alpha Inhibitors.Updated September 25, 2013. In: UptoDate

Online Journal [Website] : www.uptodate.com . Accessed October 16, 2013.

Takeuchi T, Miyasaka N, Inoue K et al. Impact of trough serum level on radiographic and clinical

response to infliximab plus methotrexate in patients with rheumatoid arthritis: results from the

RISING study. Modern rheumatology / the Japan Rheumatism Association 2009; 19(5):478-87.

Takeuchi T, Miyasaka N, Tatsuki Y et al. Baseline tumour necrosis factor alpha levels predict the

necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis. Annals of the

rheumatic diseases 2011; 70(7):1208-15.

Turkstra E, Ng SK, Scuffham PA. A mixed treatment comparison of the short-term efficacy of biologic

disease modifying anti-rheumatic drugs in established rheumatoid arthritis. Current medical research

and opinion 2011; 27(10):1885-97.

Turner D, Griffiths AM. Acute severe ulcerative colitis in children: a systematic review. Inflammatory

bowel diseases 2011; 17(1):440-9.

Turner D, Mack D, Leleiko N et al. Severe pediatric ulcerative colitis: a prospective multicenter study of

outcomes and predictors of response. Gastroenterology 2010; 138(7):2282-91.

Tynjala P, Vahasalo P, Tarkiainen M et al. Aggressive combination drug therapy in very early

polyarticular juvenile idiopathic arthritis (ACUTE-JIA): a multicentre randomised open-label

clinical trial. Annals of the rheumatic diseases 2011; 70(9):1605-12.

van der Bijl AE, Teng YK, van Oosterhout M et al. Efficacy of intraarticular infliximab in patients with

chronic or recurrent gonarthritis: a clinical randomized trial. Arthritis and rheumatism 2009;

61(7):974-8.

Visvanathan S, Rahman MU, Hoffman GS et al. Tissue and serum markers of inflammation during the

follow-up of patients with giant-cell arteritis--a prospective longitudinal study. Rheumatology

(Oxford) 2011; 50(11):2061-70.


MEDICAL POLICY




United States Food and Drug Administration. GI Advisory Committee Meeting. 2011. [Website:

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Gastrointes

tinalDrugsAdvisoryCommittee/UCM266697.pdf. Accessed October 16, 2013.

Uppal SS, Hayat SJ, Raghupathy R. Efficacy and safety of infliximab in active SLE: a pilot study. Lupus

2009; 18(8):690-7.

Veres G, Baldassano RN, Mamula P. Infliximab therapy in children and adolescents with inflammatory

bowel disease. Drugs. 200767(12):1703-23.

Wells AU. Infliximab in extrapulmonary sarcoidosis: tantalising but inconclusive. The European

respiratory journal: official journal of the European Society for Clinical Respiratory Physiology

2008; 31(6):1148-9.

Yu, David T. Treatment and Prognosis of Ankylosing Spondylitis in Adults. Updated October8, 2013. In:

UpToDate Online Journal [Website] : www.uptodate.com. Accessed October 16, 2013.

IX. CODING INFORMATION

Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The

identification of a code in this section does not denote coverage as coverage is determined by the

terms of member benefit information. In addition, not all covered services are eligible for

separate reimbursement.

Covered when medically necessary:

HCPCS

Code Description

J1745 INJECTION, INFLIXIMAB, 10 MG

ICD-9-CM

Diagnosis

Code*

Description

555.0 REGIONAL ENTERITIS OF SMALL INTESTINE

555.1 REGIONAL ENTERITIS OF LARGE INTESTINE

555.2 REGIONAL ENTERITIS OF SMALL INTESTINE WITH LARGE INTESTINE

555.9 REGIONAL ENTERITIS OF UNSPECIFIED SITE

556.0 ULCERATIVE (CHRONIC) ENTEROCOLITIS

556.1 ULCERATIVE (CHRONIC) ILEOCOLITIS

556.5 LEFT SIDED ULCERATIVE (CHRONIC) COLITIS

556.6 UNIVERSAL ULCERATIVE (CHRONIC) COLITIS

556.8 OTHER ULCERATIVE COLITIS

556.9 UNSPECIFIED ULCERATIVE COLITIS

696.0 PSORIATIC ARTHROPATHY

696.1 OTHER PSORIASIS AND SIMILAR DISORDERS

696.2 PARAPSORIASIS

714.0 RHEUMATOID ARTHRITIS

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/GastrointestinalDrugsAdvisoryCommittee/UCM266697.pdf

http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/GastrointestinalDrugsAdvisoryCommittee/UCM266697.pdf


MEDICAL POLICY




ICD-9-CM

Diagnosis

Code*

Description

714.1 FELTY'S SYNDROME

714.2 OTHER RHEUMATOID ARTHRITIS WITH VISCERAL OR SYSTEMIC INVOLVEMENT

720.0 ANKYLOSING SPONDYLITIS

*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.

The following ICD-10 diagnosis codes will be effective October 1, 2014

ICD-10-CM

Diagnosis

Code*

Description

K50.00 Crohn's disease of small intestine without complications

K50.10 Crohn's disease of large intestine without complications

K50.80 Crohn's disease of both small and large intestine without complications

K50.90 Crohn's disease, unspecified, without complications

K51.80 Other ulcerative colitis without complications

K51.50 Left sided colitis without complications

K51.00 Ulcerative (chronic) pancolitis without complications

K51.90 Ulcerative colitis, unspecified, without complications

L40.54 Psoriatic juvenile arthropathy

L40.59 Other psoriatic arthropathy

L40.0 Psoriasis vulgaris

L40.1 Generalized pustular psoriasis

L40.2 Acrodermatitis continua

L40.3 Pustulosis palmaris et plantaris

L40.4 Guttate psoriasis

L40.8 Other psoriasis

L41.3 Small plaque parapsoriasis

L41.4 Large plaque parapsoriasis

L41.8 – L41.9 Other parapsoriasis

M05.30 Rheumatoid heart disease with rheumatoid arthritis of unspecified site

M05.60 Rheumatoid arthritis of unspecified site with involvement of other organs and systems

M06.1 Adult-onset Still's disease

M45.9 Ankylosing spondylitis of unspecified sites in spine

M05.40 Rheumatoid myopathy with rheumatoid arthritis of unspecified site

M05.411 Rheumatoid myopathy with rheumatoid arthritis of right shoulder

M05.412 Rheumatoid myopathy with rheumatoid arthritis of left shoulder

M05.419 Rheumatoid myopathy with rheumatoid arthritis of unspecified shoulder

M05.421 Rheumatoid myopathy with rheumatoid arthritis of right elbow

MEDICAL POLICY




ICD-10-CM

Diagnosis

Code*

Description

M05.422 Rheumatoid myopathy with rheumatoid arthritis of left elbow

M05.429 Rheumatoid myopathy with rheumatoid arthritis of unspecified elbow

M05.431 Rheumatoid myopathy with rheumatoid arthritis of right wrist

M05.432 Rheumatoid myopathy with rheumatoid arthritis of left wrist

M05.439 Rheumatoid myopathy with rheumatoid arthritis of unspecified wrist

M05.441 Rheumatoid myopathy with rheumatoid arthritis of right hand

M05.442 Rheumatoid myopathy with rheumatoid arthritis of left hand

M05.449 Rheumatoid myopathy with rheumatoid arthritis of unspecified hand

M05.451 Rheumatoid myopathy with rheumatoid arthritis of right hip

M05.452 Rheumatoid myopathy with rheumatoid arthritis of left hip

M05.459 Rheumatoid myopathy with rheumatoid arthritis of unspecified hip

M05.461 Rheumatoid myopathy with rheumatoid arthritis of right knee

M05.462 Rheumatoid myopathy with rheumatoid arthritis of left knee

M05.469 Rheumatoid myopathy with rheumatoid arthritis of unspecified knee

M05.471 Rheumatoid myopathy with rheumatoid arthritis of right ankle and foot

M05.472 Rheumatoid myopathy with rheumatoid arthritis of left ankle and foot

M05.479 Rheumatoid myopathy with rheumatoid arthritis of unspecified ankle and foot

M05.49 Rheumatoid myopathy with rheumatoid arthritis of multiple sites

M05.50 Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified site

M05.511 Rheumatoid polyneuropathy with rheumatoid arthritis of right shoulder

M05.512 Rheumatoid polyneuropathy with rheumatoid arthritis of left shoulder

M05.519 Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified shoulder

M05.521 Rheumatoid polyneuropathy with rheumatoid arthritis of right elbow

M05.522 Rheumatoid polyneuropathy with rheumatoid arthritis of left elbow

M05.529 Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified elbow

M05.531 Rheumatoid polyneuropathy with rheumatoid arthritis of right wrist

M05.532 Rheumatoid polyneuropathy with rheumatoid arthritis of left wrist

M05.539 Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified wrist

M05.541 Rheumatoid polyneuropathy with rheumatoid arthritis of right hand

M05.542 Rheumatoid polyneuropathy with rheumatoid arthritis of left hand

M05.549 Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified hand

M05.551 Rheumatoid polyneuropathy with rheumatoid arthritis of right hip

M05.552 Rheumatoid polyneuropathy with rheumatoid arthritis of left hip

M05.559 Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified hip

M05.561 Rheumatoid polyneuropathy with rheumatoid arthritis of right knee

M05.562 Rheumatoid polyneuropathy with rheumatoid arthritis of left knee

M05.569 Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified knee

MEDICAL POLICY




ICD-10-CM

Diagnosis

Code*

Description

M05.571 Rheumatoid polyneuropathy with rheumatoid arthritis of right ankle and foot

M05.572 Rheumatoid polyneuropathy with rheumatoid arthritis of left ankle and foot

M05.579 Rheumatoid polyneuropathy with rheumatoid arthritis of unspecified ankle and foot

M05.59 Rheumatoid polyneuropathy with rheumatoid arthritis of multiple sites

M05.70 Rheumatoid arthritis with rheumatoid factor of unspecified site without organ or systems involvement

M05.711 Rheumatoid arthritis with rheumatoid factor of right shoulder without organ or systems involvement

M05.712 Rheumatoid arthritis with rheumatoid factor of left shoulder without organ or systems involvement

M05.719 Rheumatoid arthritis with rheumatoid factor of unspecified shoulder without organ or systems

involvement

M05.721 Rheumatoid arthritis with rheumatoid factor of right elbow without organ or systems involvement

M05.722 Rheumatoid arthritis with rheumatoid factor of left elbow without organ or systems involvement

M05.729 Rheumatoid arthritis with rheumatoid factor of unspecified elbow without organ or systems

involvement

M05.731 Rheumatoid arthritis with rheumatoid factor of right wrist without organ or systems involvement

M05.732 Rheumatoid arthritis with rheumatoid factor of left wrist without organ or systems involvement

M05.739 Rheumatoid arthritis with rheumatoid factor of unspecified wrist without organ or systems

involvement

M05.741 Rheumatoid arthritis with rheumatoid factor of right hand without organ or systems involvement

M05.742 Rheumatoid arthritis with rheumatoid factor of left hand without organ or systems involvement

M05.749 Rheumatoid arthritis with rheumatoid factor of unspecified hand without organ or systems

involvement

M05.751 Rheumatoid arthritis with rheumatoid factor of right hip without organ or systems involvement

M05.752 Rheumatoid arthritis with rheumatoid factor of left hip without organ or systems involvement

M05.759 Rheumatoid arthritis with rheumatoid factor of unspecified hip without organ or systems involvement

M05.761 Rheumatoid arthritis with rheumatoid factor of right knee without organ or systems involvement

M05.762 Rheumatoid arthritis with rheumatoid factor of left knee without organ or systems involvement

M05.769 Rheumatoid arthritis with rheumatoid factor of unspecified knee without organ or systems

involvement

M05.771 Rheumatoid arthritis with rheumatoid factor of right ankle and foot without organ or systems

involvement

M05.772 Rheumatoid arthritis with rheumatoid factor of left ankle and foot without organ or systems

involvement

M05.779 Rheumatoid arthritis with rheumatoid factor of unspecified ankle and foot without organ or systems

involvement

M05.79 Rheumatoid arthritis with rheumatoid factor of multiple sites without organ or systems involvement

M05.80 Other rheumatoid arthritis with rheumatoid factor of unspecified site

M05.811 Other rheumatoid arthritis with rheumatoid factor of right shoulder

M05.812 Other rheumatoid arthritis with rheumatoid factor of left shoulder

M05.819 Other rheumatoid arthritis with rheumatoid factor of unspecified shoulder

M05.821 Other rheumatoid arthritis with rheumatoid factor of right elbow

MEDICAL POLICY




ICD-10-CM

Diagnosis

Code*

Description

M05.822 Other rheumatoid arthritis with rheumatoid factor of left elbow

M05.829 Other rheumatoid arthritis with rheumatoid factor of unspecified elbow

M05.831 Other rheumatoid arthritis with rheumatoid factor of right wrist

M05.832 Other rheumatoid arthritis with rheumatoid factor of left wrist

M05.839 Other rheumatoid arthritis with rheumatoid factor of unspecified wrist

M05.841 Other rheumatoid arthritis with rheumatoid factor of right hand

M05.842 Other rheumatoid arthritis with rheumatoid factor of left hand

M05.849 Other rheumatoid arthritis with rheumatoid factor of unspecified hand

M05.851 Other rheumatoid arthritis with rheumatoid factor of right hip

M05.852 Other rheumatoid arthritis with rheumatoid factor of left hip

M05.859 Other rheumatoid arthritis with rheumatoid factor of unspecified hip

M05.861 Other rheumatoid arthritis with rheumatoid factor of right knee

M05.862 Other rheumatoid arthritis with rheumatoid factor of left knee

M05.869 Other rheumatoid arthritis with rheumatoid factor of unspecified knee

M05.871 Other rheumatoid arthritis with rheumatoid factor of right ankle and foot

M05.872 Other rheumatoid arthritis with rheumatoid factor of left ankle and foot

M05.879 Other rheumatoid arthritis with rheumatoid factor of unspecified ankle and foot

M05.89 Other rheumatoid arthritis with rheumatoid factor of multiple sites

M05.9 Rheumatoid arthritis with rheumatoid factor, unspecified

M06.00 Rheumatoid arthritis without rheumatoid factor, unspecified site

M06.011 Rheumatoid arthritis without rheumatoid factor, right shoulder

M06.012 Rheumatoid arthritis without rheumatoid factor, left shoulder

M06.019 Rheumatoid arthritis without rheumatoid factor, unspecified shoulder

M06.021 Rheumatoid arthritis without rheumatoid factor, right elbow

M06.022 Rheumatoid arthritis without rheumatoid factor, left elbow

M06.029 Rheumatoid arthritis without rheumatoid factor, unspecified elbow

M06.031 Rheumatoid arthritis without rheumatoid factor, right wrist

M06.032 Rheumatoid arthritis without rheumatoid factor, left wrist

M06.039 Rheumatoid arthritis without rheumatoid factor, unspecified wrist

M06.041 Rheumatoid arthritis without rheumatoid factor, right hand

M06.042 Rheumatoid arthritis without rheumatoid factor, left hand

M06.049 Rheumatoid arthritis without rheumatoid factor, unspecified hand

M06.051 Rheumatoid arthritis without rheumatoid factor, right hip

M06.052 Rheumatoid arthritis without rheumatoid factor, left hip

M06.059 Rheumatoid arthritis without rheumatoid factor, unspecified hip

M06.061 Rheumatoid arthritis without rheumatoid factor, right knee

M06.062 Rheumatoid arthritis without rheumatoid factor, left knee

MEDICAL POLICY




ICD-10-CM

Diagnosis

Code*

Description

M06.069 Rheumatoid arthritis without rheumatoid factor, unspecified knee

M06.071 Rheumatoid arthritis without rheumatoid factor, right ankle and foot

M06.072 Rheumatoid arthritis without rheumatoid factor, left ankle and foot

M06.079 Rheumatoid arthritis without rheumatoid factor, unspecified ankle and foot

M06.08 Rheumatoid arthritis without rheumatoid factor, vertebrae

M06.09 Rheumatoid arthritis without rheumatoid factor, multiple sites

M06.80 Other specified rheumatoid arthritis, unspecified site

M06.811 Other specified rheumatoid arthritis, right shoulder

M06.812 Other specified rheumatoid arthritis, left shoulder

M06.819 Other specified rheumatoid arthritis, unspecified shoulder

M06.821 Other specified rheumatoid arthritis, right elbow

M06.822 Other specified rheumatoid arthritis, left elbow

M06.829 Other specified rheumatoid arthritis, unspecified elbow

M06.831 Other specified rheumatoid arthritis, right wrist

M06.832 Other specified rheumatoid arthritis, left wrist

M06.839 Other specified rheumatoid arthritis, unspecified wrist

M06.841 Other specified rheumatoid arthritis, right hand

M06.842 Other specified rheumatoid arthritis, left hand

M06.849 Other specified rheumatoid arthritis, unspecified hand

M06.851 Other specified rheumatoid arthritis, right hip

M06.852 Other specified rheumatoid arthritis, left hip

M06.859 Other specified rheumatoid arthritis, unspecified hip

M06.861 Other specified rheumatoid arthritis, right knee

M06.862 Other specified rheumatoid arthritis, left knee

M06.869 Other specified rheumatoid arthritis, unspecified knee

M06.871 Other specified rheumatoid arthritis, right ankle and foot

M06.872 Other specified rheumatoid arthritis, left ankle and foot

M06.879 Other specified rheumatoid arthritis, unspecified ankle and foot

M06.88 Other specified rheumatoid arthritis, vertebrae

M06.89 Other specified rheumatoid arthritis, multiple sites

M06.9 Rheumatoid arthritis, unspecified

M05.00 Felty's syndrome, unspecified site

M05.011 Felty's syndrome, right shoulder

M05.012 Felty's syndrome, left shoulder

M05.019 Felty's syndrome, unspecified shoulder

M05.021 Felty's syndrome, right elbow

M05.022 Felty's syndrome, left elbow

MEDICAL POLICY




ICD-10-CM

Diagnosis

Code*

Description

M05.029 Felty's syndrome, unspecified elbow

M05.031 Felty's syndrome, right wrist

M05.032 Felty's syndrome, left wrist

M05.039 Felty's syndrome, unspecified wrist

M05.041 Felty's syndrome, right hand

M05.042 Felty's syndrome, left hand

M05.049 Felty's syndrome, unspecified hand

M05.051 Felty's syndrome, right hip

M05.052 Felty's syndrome, left hip

M05.059 Felty's syndrome, unspecified hip

M05.061 Felty's syndrome, right knee

M05.062 Felty's syndrome, left knee

M05.069 Felty's syndrome, unspecified knee

M05.071 Felty's syndrome, right ankle and foot

M05.072 Felty's syndrome, left ankle and foot

M05.079 Felty's syndrome, unspecified ankle and foot

M05.09 Felty's syndrome, multiple sites

M05.20 Rheumatoid vasculitis with rheumatoid arthritis of unspecified site

M05.211 Rheumatoid vasculitis with rheumatoid arthritis of right shoulder

M05.212 Rheumatoid vasculitis with rheumatoid arthritis of left shoulder

M05.219 Rheumatoid vasculitis with rheumatoid arthritis of unspecified shoulder

M05.221 Rheumatoid vasculitis with rheumatoid arthritis of right elbow

M05.222 Rheumatoid vasculitis with rheumatoid arthritis of left elbow

M05.229 Rheumatoid vasculitis with rheumatoid arthritis of unspecified elbow

M05.231 Rheumatoid vasculitis with rheumatoid arthritis of right wrist

M05.232 Rheumatoid vasculitis with rheumatoid arthritis of left wrist

M05.239 Rheumatoid vasculitis with rheumatoid arthritis of unspecified wrist

M05.241 Rheumatoid vasculitis with rheumatoid arthritis of right hand

M05.242 Rheumatoid vasculitis with rheumatoid arthritis of left hand

M05.249 Rheumatoid vasculitis with rheumatoid arthritis of unspecified hand

M05.251 Rheumatoid vasculitis with rheumatoid arthritis of right hip

M05.252 Rheumatoid vasculitis with rheumatoid arthritis of left hip

M05.259 Rheumatoid vasculitis with rheumatoid arthritis of unspecified hip

M05.261 Rheumatoid vasculitis with rheumatoid arthritis of right knee

M05.262 Rheumatoid vasculitis with rheumatoid arthritis of left knee

M05.269 Rheumatoid vasculitis with rheumatoid arthritis of unspecified knee

M05.271 Rheumatoid vasculitis with rheumatoid arthritis of right ankle and foot

MEDICAL POLICY




ICD-10-CM

Diagnosis

Code*

Description

M05.272 Rheumatoid vasculitis with rheumatoid arthritis of left ankle and foot

M05.279 Rheumatoid vasculitis with rheumatoid arthritis of unspecified ankle and foot

M05.29 Rheumatoid vasculitis with rheumatoid arthritis of multiple sites

M45.0 Ankylosing spondylitis of multiple sites in spine

M45.1 Ankylosing spondylitis of occipito-atlanto-axial region

M45.2 Ankylosing spondylitis of cervical region

M45.3 Ankylosing spondylitis of cervicothoracic region

M45.4 Ankylosing spondylitis of thoracic region

M45.5 Ankylosing spondylitis of thoracolumbar region

M45.6 Ankylosing spondylitis lumbar region

M45.7 Ankylosing spondylitis of lumbosacral region

M45.8 Ankylosing spondylitis sacral and sacrococcygeal region

M45.9 Ankylosing spondylitis of unspecified sites in spine

*If applicable, please see Medicare LCD or NCD for additional covered diagnoses.

X. POLICY HISTORY MP-2.133 CAC 8/1/08 Biologic Therapy for Treatment of Crohn’s Disease

CAC 9/30/08 Title changed to Biologic Therapy for Treatment of Inflammatory Bowel

Disease

CAC 3/31/09

CAC 11/24/09 Policy statement revised, each disease listed that can be treated with

Infliximab. Approaching the specialty biologics from a drug perspective, rather than a

disease management perspective.

CAC 4/26/11 Full review. Requirements”3-month” trial for pre-treatment use of

conventional treatment and biologic DMARDs were removed from the policy and revised

to state “trial”. Plaque psoriasis indication revised from moderate to severe plaque

psoriasis to chronic severe plaque psoriasis. Black box warning information revised.

Requirement added for TB testing prior to initiation of treatment.

CAC 4/24/2012 added list of specific investigational indications. Previous statement

stated investigational for “all other” indications. Clarified statement regarding treatment of

Crohn’s for pediatric patients - a therapeutic trial of self-administered biologic therapy (e.g.

Adalimumab (Humira®), or similar self-administered injectable or oral medication) is not

required. Added FEP variation reference to manual MP-10.04.10 Infliximab. Posted 4/5/12

due to inquiries related to the safety for pediatric patients.

MEDICAL POLICY




CAC 1/29/13 Consensus review. References updated. No changes to the policy

statements.

Codes reviewed 1/8/13 klr

CAC 1/28/14 Consensus review. References updated. No changes to the policy

statements. Rationale added. Medicare variation removed.

Health care benefit programs issued or administered by Capital BlueCross and/or its subsidiaries, Capital Advantage Insurance Company®,

Capital Advantage Assurance Company® and Keystone Health Plan® Central. Independent licensees of the BlueCross BlueShield Association.

Communications issued by Capital BlueCross in its capacity as administrator of programs and provider relations for all companies.

2.133 infliximab (remicade)...2014/01/28 · plaque psoriasis treatment of adult patients with...

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