46 Digestive Disorders FAMILY P RACTICE N EWS • December 15, 2005 Adalimumab Maintains Crohn’s Disease Remission

The subcutaneously injected drug is currently compared with 44% of those on placebo, Of the patients who entered the open- a statistically significant difference. Re- label phase, 43% were in remission after a approved by the FDA for the treatment of arthritis. mission was maintained in 74% of pa- year of treatment, Dr. Sandborn said in a tients who received the drug every other separate report at the meeting. ARTICLES BY maintain remission in patients with mod- week, which was not significantly differ- Serious adverse events occurred in 17% MITCHEL L. ZOLER erately to severely active Crohn’s disease ent from placebo. of patients, including 5% who had an in- Philadelphia Bureau began with a study of 299 patients who re- The failure to reach statistical signifi- fection while receiving treatment. Anti- ceived two doses of the drug to induce re- cance was probably due to the small num- bodies to the drug were measured in six C OPENHAGEN — Regular treatment mission, defined as a Crohn’s Disease Ac- ber of patients in the study, said Dr. Sand- patients. with adalimumab maintained remission in tivity Index score of less than 150. born, a professor of medicine at the Mayo The first phase of this study showed that patients with Crohn’s disease during a After induction efficacy was assessed 2 Medical School, Rochester, Minn. adalimumab was more effective than year of follow-up, in a controlled study weeks following the second dose, patients Serious adverse events occurred in two placebo for inducing an initial remission. with 55 patients. were given the option of receiving two patients in the placebo group, in one pa- The 299 patients enrolled in the induction A larger study that’s powered to defin- more doses on an open-label basis. tient who got adalimumab every other phase were randomized to receive 160 itively assess the long-term efficacy of Fifty-five patients were in clinical re- week, and in no patients who got the mg, 80 mg, 40 mg, or placebo as their ini- adalimumab is in progress, William J. mission at both the start and end of the 4- drug weekly. tial dose. For their second induction dose, Sandborn, M.D., said at the 13th United week open-label phase, and these patients Antiadalimumab antibodies were found these groups received 80 mg, 40 mg, 20 European Gastroenterology Week. were then rerandomized for the long- in one patient in the placebo group and one mg, or placebo, respectively. Adalimumab is a fully humanized, term maintenance phase. in the group that received adalimumab Two weeks after the second dose, 36% anti–tumor necrosis factor monoclonal Another 221 patients who were not in every other week. Injection-site reactions of patients in the highest-dose group were antibody that’s administered by subcuta- remission after both the induction phase occurred in three patients, one of whom in remission, compared with 24% in the 80 neous injection. It’s currently approved in and the open-label phase were continued was in the placebo group. No patient in the mg/40 mg group and 12% in the placebo the United States for treating rheumatoid on long-term, open-label treatment. study had an opportunistic infection. group. arthritis and psoriatic arthritis, and is mar- In the randomized group, 18 patients re- Among the 221 patients who received The remission rate in the highest-dose keted as Humira by Abbott Laboratories, ceived 40 mg of adalimumab once a week long-term treatment with adalimumab on group (160 mg followed by 80 mg) was sig- which is sponsoring development of the for 1 year. Nineteen patients received the an open-label basis, 131 (59%) remained nificantly higher than that in the placebo drug for Crohn’s disease. Dr. Sandborn is same dose every other week, and 18 pa- on the drug after 1 year. Seventy of these group. The response rate in the 80 mg/40 a consultant to Abbott and several other tients received placebo. patients were receiving one dose of adal- mg group just missed statistical signifi- companies. After a year, remission continued in imumab every 2 weeks, and 60 patients cance, compared with the control group Assessment of adalimumab’s ability to 83% of patients on the weekly dose, were receiving it weekly. (P = .06). ■ Natalizumab Boosts Quality of Life in Crohn’s Disease

C OPENHAGEN — Maintenance therapy These primary end point results were In addition, the analysis showed no sig- and general health, Dr. Feagan reported. with natalizumab in patients with Crohn’s reported last month (New Engl. J. Med. nificant differences between individual In contrast, the scores of patients in the disease led to improved quality of life 2005;353:1912-25). component scores for patients in the ac- placebo arm were consistently and sig- compared with placebo, and normalized Natalizumab was approved by the Food tive-treatment arm and scores from an nificantly lower than scores of the nor- quality of life measures in a study with 339 and Drug Administration in late 2004 for age-adjusted sample of normal Ameri- mal, general population, he noted in his patients. treating multiple sclerosis, and then was cans, except for the categories of vitality presentation. ■ “We’re trying to normalize” patients withdrawn from the U.S. market in Feb- with Crohn’s disease, Brian G. Feagan, ruary following reports that associated its M.D., said at the 13th United European use with cases of multifocal leukoen- A Promising Future, Despite Safety Issues Gastroenterology Week. cephalopathy. Maintenance therapy with natalizum- In September, the companies submitted espite natalizumab’s safety issues, back for Crohn’s disease? Yes I do,” he ab produced quality of life scores that a supplemental application to the FDA in Dthe drug remains a viable option said. were similar to scores measured in nor- a move to resume selling the drug for for treating selected patients with In an editorial that accompanied the mal populations. treating multiple sclerosis. Crohn’s disease, Dr. Feagan said at the published report of the primary effica- Dr. Feagan presented findings from a Natalizumab is a humanized, IgG mon- meeting. cy and safety data for natalizumab in secondary analysis of data collected in oclonal antibody that binds alpha-4 inte- After Tysabri was withdrawn from 905 patients with Crohn’s disease, the pivotal, phase III trial for natalizumab grin and thereby blocks the adhesion of the market, the two companies that Daniel K. Podolsky, M.D., wrote that in patients with active Crohn’s disease— leukocytes to the gut and the migration of comarket it offered an extensive safety natalizumab treatment may interfere the Efficacy of Natalizumab as Active these cells into the gut. evaluation to the more than 3,500 pa- with immune control of the endemic Crohn’s Therapy (ENACT) trial. The quality of life analysis led by Dr. tients who had participated in the JC virus, and that this may be the trig- This study had an induction phase, EN- Feagan used data collected on the in- drug’s trials. ger for progressive, multifocal ACT-1, with 905 patients randomized to flammatory bowel disease questionnaire This offer was accepted by about leukoencephalopathy (New Engl. J. natalizumab or placebo, and a mainte- (IBDQ) and on the Short Form–36 (SF- 90% of all patients in the multiple scle- Med. 2005; 353:1965-8). nance phase, ENACT-2, that included the 36). rosis, rheumatoid arthritis, and Dr. Podolsky suggested that natal- 339 patients who had a response to the Starting with the first maintenance Crohn’s disease trials—a total of more izumab therapy be targeted to pa- drug in ENACT-1. dose, patients receiving natalizumab had than 3,000 patients—said a spokes- tients with frequent and debilitating The studies were sponsored by Elan significantly higher IBDQ scores than did woman for Biogen Idec. recurrences of inflammatory bowel Pharmaceuticals and Biogen Idec, the two those treated with placebo. The investigation turned up no addi- disease, in concert with close surveil- companies that jointly market natalizum- After 1 year of treatment, patients who tional cases beyond the three patients lance by MRI, which may be able to ab (Tysabri). took natalizumab had an average score of that had been reported previously, not- identify the leukoencephalopathy Dr. Feagan has served as a consultant to 181, compared with an average score of ed Biogen Idec and Elan Pharmaceuti- complication at an early stage in pa- Elan Pharmaceuticals. 157 in the placebo group, a statistically sig- cals in written statements. tients who are still asymptomatic for The results from ENACT-1 failed to nificant difference, said Dr. Feagan, a pro- That’s good news,” said Dr. Feagan. this adverse effect. show an advantage for natalizumab over fessor of medicine at the University of “What it comes down to is, will we, The precedent exists for treating pa- placebo for producing clinical responses, Western Ontario, London. as physicians, accept this rare but seri- tients with more severe inflammatory but the ENACT-2 data showed that con- After 1 year, patients on maintenance ous and often fatal complication? I bowel disease with other agents that tinued treatment with 300 mg natalizum- therapy with natalizumab also showed think we will pick our spots, and fo- can cause potentially life-threatening ab once every 4 weeks led to a 61% rate significantly better scores than did place- cus on patients who fail other treat- immunodeficiency, such as infliximab, of sustained responses during 36 weeks of bo patients for all physical and mental ments, at least until there are more said Dr. Podolsky, chief of gastroen- follow-up, significantly higher than the component scores of the SF-36, including safety data.” terology at Massachusetts General 28% rate of sustained responses in the bodily pain, social function, and mental “Do I think that the drug will come Hospital in Boston. placebo group. health.