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GASTROENTEROLOGY IN THE '90s

New steroids CORTll n,Tl'Rl111\:-, AIU- USEFUi ANTI INFLAM~IATl1RY Al,ENTS

act mg ,11 multipk site·, of inl1amm,1l,>ry activity. Cort1co,tero1d, 1nhih1t the accumularinn nf leukocytes at sites <if inflammal 1<H1 h) red11 c ing c hemot ,1etic activi ty ,111,I in,lucmg pept ide mh,h,uon ol 11u::mhra111: ph,1,pholtpase A2. kading lO reduced pnld11L uon of pro,tagl;i nd ins, leukut ric'nes and plat elct act i v:u 111g facwr. Cnrt il:nstenHds suppress mtlammatory mediato r producti<•n inh ih1t-111g m,Kniphage interleukin- I :md tumour necrrn,i:, factor, and they 1nhih1t lc11koqte cnd,1t helial adhe,ion. 1 Oral stet\licb (cort is<,ne, predn,snlnne, tnamcm,ll()nc and hctamcthasone) have been in u,c ,incc the earl y '5lk Recently, new steroids have hcen developed for loc:11 u:,e tn rnpical apphcatillm. in the skin and in aero,ol formulations 1;ir treaung n,d1111;1. Thc.,e drugs include hetameth<1Mmc, bcdom..:thasnn..:, hud..:,on ,d..: and t1uticnsone. More r..:cently, s..:vcral f<•nnulat ion, of new , t no,d, hnve hecn adapted fur 11,c in inflammall>ry howcl disease (!RI)). Th..:,e d rug:, include tixoconal pivolme, hude,,1111de .ind lluuc-.1"H1l'.

T1xncllrt:1I piv,,bte 1s ,1\'ailahle tn em:ma fnnn ,1n ly for tre:11men1 of ldt-,1dcd ulcer:1t ive coltt i, (UC).2 Effic;icy 1s similar 1,i other tllpicnl C<ll'l ico,1eroid prq,arn1 i()ns; hnwevcr, the nwjm disadv,mrnge is the excessive cost. This is a major limiting factor which might limit use, pan icularly when there appears tu he no thcrapeutic advantage frnn1 1 his medic,11 iun.

Budesontdc 1, availahl<: in l(lptc:tl enema prcparnll(lns, .ind rcCl'ntly ha, heen ,kn:loped in a cap, uk' fmmulatilln cksign..:d 1,, relea,c hudc'sn111dc 111 t hl' dist:11 small howel (huJc,<1nid..:, C(lntrolled ileal rclea,c).1 Hudc,nnidc , how, much mnre affinity th,m cumparnblc glu.:ocnrucoids in tcrn1s nf rc lmive potl'ncy LO inhibit rat edema ,mJ r,,lai t\'l' affi111ty fllr rnt glucoconicrnd receptor. Budesnnide ha, ,1 ,t ruc1 ure similar t,1 predni,olonc ;ind un,lcrglles ,ixidat ive hio trnn,lormiltiPn in the liver 90% ,m the fin,t-pa:,:, ( I 0% <iral h1m1vailahili1y).4 T lw, pharmacolng,cal prnperry ~hnukl allPw an effccu,-c d<>sl' (,,r :mti- inllammatory action , with less ,ystemic :,ide ..:fleets thnn, cg, hydr\lcm1 1,nnc .mJ prL·dni,llne. Bude,onide h,1, ii w,ller ,oluhilll y 100 ume, grenl <:r 1h,111 that of flu1ica~"nc, which make, it likely to

he a 1:t,·ou1Td pn:pnration. Bude,llnidc ha, b..:cn :,hmvn to he effec ti ve in tre,11 mg p,nients wirh distal ulcernu ve procuus, 5·6 with the ,ame dt1cicy (11 nther form, of hydroconisone.7 IL b likely to he used ma In I y 1; ,r pat ic11ts wit h d 1sw I pn ,ctiu, rew,t,1111 1 u C<lrt 1custcmid.s nr am1n,1.Sa lt,yl 1, aud prl'par:11 tons ,kpending nn availahtl It y and cns1 .8

ll11d<:sun 1de, ,kvel,11wd 111 a , l,1w-rel..::1.,e form f,ir 1rc•;1ting paucni:, with Crohn\ disc·,ise (<.. '[)), ha, hc'en favuurahl y ,1,,esscd in npen ,1ud1e,-,'111 and h,1, recent ly hcl'n reported 111 two douhlc-hl1ml ,tud ie,. 12· 11

In Can.1d,1, a duuhlc-hlmd, rnndumizecl trial ha, heen cumplcLed th,, year 111 255 pauem, with acti ve en defined a, a en act ivity 111,lex (Cl)A J) nl 200 ,ir m m..:, wlw r<:ce ived pLtc<:ho or <1ra l huLk sontdl' in do,e, rnng,ng from l L<l 15 mg dai ly f1,r eight weL'ks. 12

l'atil'n1, had d1:,e;1,c limi ted to the ileum with or without cnlonic dt,c'ase tu the h..:p,lliL flexure. Vl'rili cd hy endoscopy ,ind/or radiolngy. Efficacy was measured ,1, :1 change in CDA I 10 150 or less (clmical remi,si, m). The re,11 It:, showed I hat 9 m g i, I he , mnl le,1 effecti ve dn,c, and that I 'i mg b 11111 hc·tter than 9 mg in mducmg remission. ( J!ucnconicoid side effect~ were nor :i m:1jur prohlcm.

In Eump<:, a ,louble-hlind, lO-weck trial comparing the safcty and dl 1c.1q nf9 mg/day urn! hudeS<ltltde ver:,11, 40 mg/d,1y pred111wlum:

l;,1-1rncn1c·n•l,1~y 111 1h1: \/0, "111en<.>1 of ,h"n <1mdc.1 ,u./Jres1111/.! Ct>/llcal, ctn1tro,•cr.liud 1.1i.,uc_... m the tnimm~ltt of gd.,lTomtt•.,cm,,! d1,,1rdcn. flw ,erit.', i, m,1de r,0.111/il,, thrm1Rh 1111 <.'il11ca111mal )!)·1m1 /,rnll A 1trn l'lwrma ht<'

588

wn, perfurmed in 176 patients with active C D.11

After ..:ight weeks, hudesonide was tapered LO 6 mg. Tapering of prcdnisone started after tw,i w<.:..:b. and cuntin ued graduall y down to 5 mg during the last week. EighLy-eight patient, were ,tllocmed Lo each ol the gn1ups. At l O weeks, remissi<111 (CDAI less than 50) was achieved 111 53% nf the patients tre~ned with hudesllnidc c,1mpared with 66% in the prcdnisnlnne gn1up. The CDA I decreased signtficamly 111 hnth groups, hut C<1mparis1111 bet ween the groups showed no signific::mt difference. LJ!ucoconicnid-associared side effect, were sign ificantl y less commnn 111 the hudeso111dc group than the prednisolone gl'(lup ( 12 palients versus 27 at LO weeks). Plasma cortisol wa:, significantly more depressed in the prednisolone group at 40%,vcn,us 84% 111 the hudc:s<miJe group. This compnrnt ive trial shows rhat with the doses used , hudesonidc is a, efficaci,ius as prednisolone in inducing remi,sinn in active ilcocecal C D. A greater improvement m C DA I was ach ieved with predn isolone in tlus t ime frame, hut 1h1s did not ach ieve sign ific.incc. Budesonide i,, however, assnciated with less steroid side effects ,tnd induce:, significitntl y less ad renitl suppression, as confirmed hy nthers.9 12·14

Fluticasnnc has been te,ted in enem;i form without , huwever, showing a more favournhle therapeutic effect than other preparn-. 15.16M I I . ( 11 . . llun, . ore r<:cent y, an ora preparnuon o uuca,one propnon-

a1e ha, heen studied in active UC17·18 and compared with prednisolonc tahlcts in the tremment of act ive C D. 1~ A wrnl of 156 p,11 ients wer<: entered into rhe pro,pective comrollccl study comparing 20 mg flutiec1s,mc wiLh 40 mg prednbolone. The phy'1c1<111s' ,ivernll assessmen t of remission for the Out icasone group was that ii was I..:» ..:ffective than prednisolonc at htllh two and four wceks, and ac.1 1vtt y uf CO using I he I larvcy-Bradshaw lndex dccrea,ed less 1n I he 1lu1ic 1sc,ne group than the prcdn isolonc group at Lwo we<:ks, with 11,1 difference tit four weeks. It was concluded Lhat with the dnses used, prcdni.sollllle i.s .superior l<l f\ur ic;isonc in the therapy of active CI).

Of thc new steroids, hudesonide i:, a prom bing new antiinfh11nmaw ry agent, and when approved ,md marketed - and if priced approprnncly should he a key foctor 111 reducing I he major, tmuhlcwmc, lung term, systemic side effects of corticosteroid:,.

REFERENCES I. Sawyer AM. ct al. Altmcm Plrnrmacol Thcr I \/91 ;5: 1-14. 2. Jewell l)l'.1'\t S1n:11 J Med 1990;57:29l-6. l. flrntt,and R. Can J G:btrocmcml 1990:4:407-14. 4. Ed,hachcr S. ct al. Ga.strocnLcrolngy 1991; I 04:A695. (Ah,1) 5. nan11.:b,on /\, cl al. Scand J Ga,1rocn1crol 1992;27:9-12. 6. The Danish Hudc.,onidc Study (,roup. Sc and J Uastrcx:nt<:rol

1991 : 26: 12 2 5-10. 7. Lolherg R, cl al. C,ut 1991;37:Tl62. (Suppl) H. Mulder CJ, Tyq:pt GN. Aliment l'harmarnl Thcr.tp 1991;7: 125- lO. 9. Wolm,111 SL, (,rccnhcrg GR. (,,1strnenLcr,,l, >gy 1991; I OO:A26 'l. (Ah,t)

10. Lill,crg R, ct nl. Gas1mcmcn,l,1gy l991;100:A226. (Ahst ) 11. Roth M, ct al. A111J Ga,trncntcrol 1991;8:%8-9. 12. Canadian lnfla111111,uory Bowel Dbcasc St u,ly Group. Ua,tn>l'n1crol<1gy

1991; 104:A675. (Ahsi) I l. Rutgct·rts I', ct al. Gastrocmcrnlogy J 991; I 04:A 772. (Ah,t) 14. Roth M, cl al. Gaslrocntcrology 1992;102:A688. (Ah,t) 15. De Kask, MC, t'I ;1 1. ()ur 199 1; 12:657-6 J. 16. Lynn FV, Pcppcrcurn MA. Am J Surg 1992: 164:85-9. 17. Angus P. cl al. U111 1992:rl:71 l-4. 18. I I.1w1hnm1: AR. cl al. Gut 199'l;l4:125-8. I\/. Wngh1 JI'. ct al. (.,,1,truc111crnl,,g, 199l; 104:AHOl. (Ah,1)

CN Wil/l(nm. MD, Fl<CPC I lolifcn:. N1J1>a Srntia

CAN J GASTROENTl 'Rl)L VOL 7 Nl\ 8 NOVl:MBER/DFCl'MRER 1991

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