Anti-IP-10 antibody (BMS-936557) for ulcerative colitis: a phase II randomised study.

OBJECTIVE: Interferon-γ-inducible protein-10 (IP-10 or CXCL10) plays a role in inflammatory cell migration and epithelial cell survival and migration. It is expressed in higher levels in the colonic tissue and plasma of patients with ulcerative colitis (UC). This phase II study assessed the efficacy and safety of BMS-936557, a fully human, monoclonal antibody to IP-10, in the treatment of moderately-to-severely active UC. DESIGN: In this 8-week, phase II, double-blind, multicentre, randomised study, patients with active UC received placebo or BMS-936557 (10 mg/kg) intravenously every other week. The primary endpoint was the rate of clinical response at Day 57; clinical remission and mucosal healing rates were secondary endpoints. Post hoc analyses evaluated the drug exposure-response relationship and histological improvement. RESULTS: 109 patients were included (BMS-936557: n=55; placebo: n=54). Prespecified primary and secondary endpoints were not met; clinical response rate at Day 57 was 52.7% versus 35.2% for BMS-936557 versus placebo (p=0.083), and clinical remission and mucosal healing rates were 18.2% versus 16.7% (p=1.00) and 41.8% versus 35.2% (p=0.556), respectively. However, higher BMS-936557 steady-state trough concentration (Cminss) was associated with increased clinical response (87.5% vs 37.0% (p<0.001) for patients with Cminss 108-235 µg/ml vs placebo) and histological improvements (73.0% vs 41.0%; p=0.004). Infections occurred in 7 (12.7%) BMS-936557-treated patients and 3 (5.8%) placebo-treated patients. 2 (3.6%) BMS-936557 patients discontinued due to adverse events. CONCLUSIONS: Anti-IP-10 antibody, BMS-936557, is a potentially effective therapy for moderately-to-severely active UC. Higher drug exposure correlated with increasing clinical response and histological improvement. Further dose-response studies are warranted. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00656890.

Immune responses following administration of influenza and pneumococcal vaccines to patients with rheumatoid arthritis receiving adalimumab.

OBJECTIVE: This study compared the immunogenicity of influenza and pneumococcal vaccines in adult patients with rheumatoid arthritis (RA) receiving adalimumab or placebo. METHODS: In this double-blind, randomized, multicenter study, patients received adalimumab or placebo on Days 1, 15, and 29. Pneumococcal and influenza vaccines were administered on Day 8 (vaccine baseline). Vaccine response (> or = 2-fold titer increase from baseline in > or = 3 of 5 pneumococcal antigens and > or = 4-fold titer increase from baseline in > or = 2 of 3 influenza antigens) and protective antibody titers (> or = 1.6 microg/ml pneumococcal antibody concentration to > or = 3 of 5 antigens and > or = 1:40 influenza antibody titer to > or = 2 of 3 antigens) were analyzed 4 weeks' postvaccination. RESULTS: Following pneumococcal vaccination, percentages of patients achieving a vaccine response were similar in the adalimumab and placebo groups [37.4% and 40.4%, respectively; 95% CI (confidence interval) -16.2%, 10.3%]. Percentages of patients with protective antibody titers were similar in both treatment groups (adalimumab: 85.9%, placebo: 81.7%). Following influenza vaccination, percentages of patients achieving a vaccine response were lower with adalimumab than placebo (51.5% and 63.3%, respectively; 95% CI -25.2%, 1.6%)--a result explained by the subgroup of patients with preexisting protective antibody titers at baseline. For patients without protective antibody titers at baseline, response rates were similar in the 2 groups (adalimumab: 73.3%, placebo: 73.9%). Percentages of patients with protective antibody titers were similar in both treatment groups (adalimumab: 98%, placebo: 94.5%). CONCLUSION: Patients with RA treated with adalimumab can be effectively and safely immunized with pneumococcal and influenza vaccines.