Prior Tumor Necrosis Factor Inhibitor Research Articles

Safety and Effectiveness of Rituximab in Patients with Rheumatoid Arthritis Following an Inadequate Response to 1 Prior Tumor Necrosis Factor Inhibitor: The RESET Trial

To evaluate the safety and effectiveness of rituximab (RTX) in combination with methotrexate in patients with active rheumatoid arthritis (RA) after failure of a single tumor necrosis factor-α (TNF-α) inhibitor. Changes in patient-reported outcomes after primary treatment or retreatment with RTX and factors determining retreatment in clinical practice were also evaluated. In this phase 3b open-label, multicenter trial, patients received 2 slow infusions of RTX 1000 mg 14 days apart after premedication (primary treatment). Patients with a clinically relevant response could receive retreatment between 24 and 48 weeks. The primary endpoint was evaluation of safety. Secondary outcomes were safety of retreatment, effectiveness of primary treatment and retreatment, and changes in patient-reported outcomes after primary treatment or retreatment. Of 120 patients enrolled at 36 centers and receiving primary RTX treatment, 77 received retreatment, 112 completed the 24-week primary treatment period, and 25 completed the 48-week primary treatment and retreatment period following a single course of RTX. The most common adverse events were mild to moderate nausea, vomiting, nasopharyngitis, and headache. No infections or infusion reactions were considered life-threatening. At 24 weeks, 58%, 27%, and 7% of patients achieved American College of Rheumatology 20, 50, and 70 improvements, respectively, and similar improvements were seen after retreatment. RTX was well tolerated, with a low incidence of infusion reactions and infections. Efficacy results, including enhanced response in rheumatoid factor-positive patients, were comparable to those reported in the literature. Based on its efficacy and safety profile and retreatment schedule, RTX is an attractive treatment option for patients that have not responded to a single TNF-α inhibitor.

Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: An open‐label extension analysis

To determine the safety and efficacy of additional courses of rituximab in patients with rheumatoid arthritis (RA). An open-label extension analysis of RA patients previously treated with rituximab was conducted. Patients who had participated in any of 3 double-blind trials were eligible for additional courses (2 infusions of 1,000 mg given 2 weeks apart) if they exhibited a swollen joint count and tender joint count of > or =8 with > or =16 weeks elapsing after the previous course. Safety was assessed in patients receiving all or a portion of a rituximab course. Efficacy was assessed 24 weeks after each course, using the American College of Rheumatology 20% criteria for improvement (ACR20), ACR50, ACR70, European League Against Rheumatism (EULAR) response criteria, Disease Activity Score in 28 joints, the disability index of the Health Assessment Questionnaire, and Short Form 36 scores, stratified according to prior tumor necrosis factor (TNF) inhibitor exposure. A total of 1,039 patients received > or =1 course of rituximab. Of these, 570 received 2 courses, 191 received 3 courses, and 40 received 4 courses, for a total of 1,669 patient-years. Irrespective of prior TNF inhibitor exposure, ACR20 responses were comparable at week 24 after course 1 and at week 24 after course 2 (65% versus 72%), as were ACR50 and ACR70 responses. EULAR moderate/good responses were also comparable in course 2 relative to course 1 (88% versus 79%), with EULAR remission occurring in a 2-fold higher proportion of patients after course 2 than after course 1 (13% versus 6%). The most common adverse events, which were mild-to-moderate acute infusion-related events, decreased with each course. The serious infection rate after course 1 (5.1 per 100 patient-years) remained stable through additional courses. The proportion of patients with circulating IgM and IgG levels below the lower limit of normal (LLN) increased with subsequent courses; however, serious infection rates in these patients (5.6 per 100 patient-years in patients with low IgM levels and 4.8 per 100 patient-years in patients with low IgG levels were comparable with those in patients with immunoglobulin levels above the LLN (4.7 per 100 patient-years). Patients with human antichimeric antibody (9.2%) did not exhibit decreasing efficacy or present additional safety concerns. These findings indicate that patients treated with repeated courses of rituximab have sustained clinical responses with no new adverse events.

Assessment of rituximab’s immunomodulatory synovial effects (ARISE trial). 1: clinical and synovial biomarker results

Objective:Treatment with the anti-CD20 monoclonal antibody (mAb) rituximab is effective in rheumatoid arthritis (RA). Marked depletion of circulating B cells, seen in almost all patients, does not correlate with efficacy....