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Clazakizumab, with or without methotrexate, was well tolerated and achieved significant improvements in disease activity, in patients with rheumatoid arthritis in this Phase IIb study.
Clazakizumab -– a monoclonal antibody that binds to interleukin-6 (IL-6) -- significantly improves disease activity in rheumatoid arthritis (RA) and produces higher rates of remission at 12 weeks than methotrexate (MTX), according to results from a multinational clinical trial.
Clazakizumab also produces rapid responses -- within a week of the first injection -- with or without MTX, the researchers report.
The Phase IIb, randomized double-blind, placebo-controlled trial randomized 418 patients with moderate to severe RA to one of three monthly subcutaneous doses of clazakizumab (with or without MTX), with a 20% response according to ACR criteria (ACR20) as its primary endpoint.
Among the patients, a majority of whom were white women around age 50, 15.4 % had been taking MTX and continued to do so during the trial.
They were randomized to 25 mg, 100 mg, or 200 mg of clazakizumab plus MTX, once-monthly clazakizumab 100 or 200 mg as monotherapy, or placebo plus MTX (at previous doses).
Clazakizumab plus MTX produced significantly greater ACR20 response rates (60% to 76%) at week 12 than MTX monotherapy (39.3%) -- including patients for whom MTX had been inadequate.
Remission rates at 12 and 24 weeks, according to disease activity scores in 28 joints (DAS28), were around 35% for clazakizumab vs 1.6% for MTX monotherapy.
By 6 months, all of the clazakizumab groups had also higher ACR20/50/70 response rates and remission rates compared with MTX alone, and function (according to HAQ-DI scores) improved as well. The drug also produced rapid and sustained reductions in CRP.
However, there were more serious adverse event rates (8.3% to 13.6%) with clazakizumab arms versus only 3.3% for MTX; clazakizumab 25 mg plus MTX had the best risk/benefit profile.
No clear dose response in effectiveness was seen with clazakizumab, but an ongoing clinical trial is currently evaluating additional dose ranges to determine optimal dosing for future studies. The only IL-6 blocker approved for RA is tocilizumab (Actemra).
Weinblatt M, Mease P, Mysler E, et al. The efficacy and safety of subcutaneous clazakizumab in patients with moderate-to-severe rheumatoid arthritis and inadequate response to methotrexate: results from a phase IIb, randomized, double-blind, placebo/active-controlled, dose-ranging, multinational study. Arthritis & Rheumatology. 2015. Accepted article. Online July 2, 2015. DOI: 10.1002/art.39249.