OBJECTIVE: Clazakizumab is a humanized monoclonal antibody that binds to the @entity650 ( @entity650 ) cytokine. This study was undertaken to evaluate the efficacy and safety of clazakizumab in combination with @entity1499 ( @entity6822 ) or clazakizumab monotherapy versus @entity6822 alone in @entity1 with @entity309 ( @entity309 ) and an inadequate response to @entity6822 . METHODS: In this multinational, phase IIb, randomized, double-blind, placebo-controlled, dose-ranging study, @entity1 were randomized to receive 1) once-monthly subcutaneous (SC) clazakizumab at 25, 100, or 200 mg plus @entity6822 , 2) once-monthly SC clazakizumab at 100 mg or 200 mg as monotherapy, or 3) @entity6822 plus placebo (i.e., @entity6822 alone). Adalimumab (40 mg) plus @entity6822 was included as an active reference. The primary end point was the American College of Rheumatology 20% (ACR20) improvement response rate at week 12. Secondary end points included ACR20, ACR50, and ACR70 response rates as well as protocol-defined remission rates and Health Assessment Questionnaire disability index scores at weeks 12 and 24. RESULTS: In total, 418 @entity1 were randomized, and baseline characteristics were balanced across the treatment groups. @entity1 receving clazakizumab had significantly greater ACR20 response rates at week 12 compared with @entity1 receiving @entity6822 alone (76.3%, 73.3%, and 60.0% of @entity1 in the clazakizumab 25, 100, and 200 mg plus @entity6822 groups, respectively, and 55.0% and 61.0% of @entity1 in the clazakizumab 100 and 200 mg monotherapy groups, respectively, versus 39.3% of @entity1 receiving @entity6822 alone; P < 0.05 for all comparisons). At week 24, all clazakizumab groups had higher ACR20, ACR50, and ACR70 response rates and higher remission rates compared with @entity6822 alone. Rates of serious adverse events ranged from 8.3% to 13.6% in the clazakizumab treatment groups, compared with 3.3% in the @entity6822 alone group. Changes in laboratory data were consistent with the pharmacologic effects of @entity650 blockade. CONCLUSION: In @entity1 with @entity309 and an inadequate response to @entity6822 , treatment with clazakizumab in combination with @entity6822 or clazakizumab monotherapy was well tolerated, and @entity1 achieved significant improvements in disease activity, including higher rates of remission, as compared with @entity1 receiving @entity6822 alone.

The efficacy and safety of subcutaneous clazakizumab in XXXX with moderate-to-severe @entity309 and an inadequate response to @entity1499 : results from a multinational, phase IIb, randomized, double-blind, placebo/active-controlled, dose-ranging study.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity650 :: ('3569', 'Gene') :: ['IL-6', 'interleukin-6'] @entity6822 :: ('D008727', 'Chemical') :: ['MTX'] @entity1499 :: ('MESH:D008727', 'Chemical') :: ['methotrexate'] @entity309 :: ('MESH:D001172', 'Disease') :: ['rheumatoid arthritis', 'RA']
@entity1 :: (9606,Species) :: ['patients']
