Introduction to Special Section: Drug Safety in theRheumatic Diseases

Patient safety is a big deal; and getting bigger. The lastfifteen years have seen incredible improvements in theability to treat a number of rheumatic diseases. Theseimprovements have been due to the introduction of bio-logic therapies into common use throughout the world.Each of these biologic therapies works by blocking a spe-cific receptor or eliminating a specific type of cell relatedto the immunologic function, or actually, at least in part,dysfunction in patients with a rheumatic disease. How-ever, this specificity is deceptive as each of these receptorsor cell types was chosen based on basic science researchshowing the relationship of the specific target of the bio-logic therapy to a broad network of inflammatory mecha-nisms. Our understanding of the impact of these biologictherapies, both good and bad, is incomplete but the focusof intense research. The depth of this research effort issupported by the submission of over 50 manuscripts forreview for this safety-themed issue. The breadth of theresearch effort is demonstrated by the scope of approachesincluded in this issue — from investigation of drug-in-duced DNA damage and repair in individual cells to verylarge international population-based efforts to describerates of very rare adverse events.

This drug safety–themed issue of Arthritis Care & Re-search is part of a large and multifaceted effort of theAmerican College of Rheumatology (ACR) to providetimely, accurate, and comprehensive information relatedto treatment safety to those taking care of individuals withrheumatic diseases. This is a large and ongoing challenge.In a survey of a random sample of ACR members and allthe nurses and physician assistant members of the Asso-ciation of Rheumatology Health Professionals performedin 2008, 85% indicated that they were either “concerned”or “very concerned” about drug safety issues. However,only 12% of those responding felt “very well” informedabout drug safety issues. This is in part an inevitableoutcome of the relatively recent and ongoing introductionof a large number of unique treatment options for rheu-matic and other inflammatory diseases. It is also a reflec-tion on the incomplete information we currently have aboutthese therapies. The articles included in this issue of ArthritisCare & Research provide much information that will behelpful in better understanding these complex issues.

The articles in this issue provide many perspectives onpatient safety. Two articles provide information relevantto many different types of therapies. Hudson and Suissaused published studies to demonstrate several types of

biases seen in observational studies, the effects of thebiases on the results of the studies, and ways to avoid orminimize the effects of biases in future observational stud-ies; and Nestoriuc et al showed that the attitude of patientsprior to initiation of new therapies (i.e., those with nega-tive attitudes about medications) was far more predictiveof the occurrence of side effects than disease severity ormedication-specific characteristics. This study by Nesto-riuc and colleagues suggested that identifying and ad-dressing patient concerns about medications prior to ini-tiation of new therapies may be helpful in decreasing theoccurrence of adverse events.

Several articles address the safety of anti–tumor necrosisfactor (anti-TNF) agents. Caporali et al demonstrated thatanti-TNF therapy did not seem to have any adverse effecton the hepatic status in individuals that had previouslybeen infected with hepatitis B. They did not detect anyevidence of reactivation of hepatitis B virus replication inpatients receiving anti-TNF therapy. Hastings et al dem-onstrated that neutropenia was not uncommon in thosereceiving anti-TNF therapy and some of the individualsdemonstrated serious infections due to neutropenia. In anovel case report, Racunica et al discussed the possibilitythat the reconstitution of the immune system after stop-ping anti-TNF therapy is associated with the developmentof new autoimmune disease manifestations. Dixon et aluse data from a large British registry to address the safetyof the use of anti-TNF therapies in rheumatoid arthritispatients who have had a prior malignancy. Their studyprovided reassuring but not definitive evidence that treat-ment of those with a prior malignancy was not associatedwith an increased risk of incident malignancy.

Several articles address issues of drug safety in children.In a prospective, interventional study, Lahdenne et aldemonstrated that the use of pretreatment with acetamin-ophen and cetirizine (an antihistamine) did not decreaseor prevent the frequency of infusion reactions to inflix-imab therapy. Smith et al described the work of a broad-based constituency to develop on an international basis aconsolidated longitudinal registry of patients with juve-nile idiopathic arthritis undergoing routine clinical care toprovide a more robust assessment of current and newtherapies in children. The development of such a consol-idated registry was stimulated by a recent meeting orga-nized by the Food and Drug Administration in May 2009,and work is ongoing at this time.

In the study by Wolfe and Marmor, the risk for developing

Arthritis Care & ResearchVol. 62, No. 6, June 2010, pp 747–748DOI 10.1002/acr.20202© 2010, American College of Rheumatology

SPECIAL ARTICLE: DRUG SAFETY IN THE RHEUMATIC DISEASES

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retinal toxicity from one of the oldest rheumatic treatments,hydroxycholoroquine, was studied in almost 4,000 patientswith rheumatoid arthritis or systemic lupus erythematosus.Retinal toxicity was found to be uncommon, especially in thefirst 5 to 7 years of therapy, but occurs in approximately 1%of those who remain on the therapy for longer than 5 years.The authors recommend that new screening guidelines bedeveloped for those receiving hydroxychloroquine.

This issue of Arthritis Care & Research provides a widevariety of approaches and useful information on the safetyof treatments in both adults and children with rheu-matic diseases. In addition, new areas of research aresuggested.

Daniel Lovell, MD, MPHAssociate Editor, Arthritis Care & Research

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