title: Safety of rituximab in combination with other biologic disease-modifying antirheumatic drugs in rheumatoid arthritis: an open-label study.
abstract: OBJECTIVE
  To characterize the safety of rituximab (RTX) in combination with biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  We did an open-label study of the safety and efficacy of RTX in adult patients with active RA and an inadequate response to ≥ 1 biologic for ≥ 12 weeks (stable dose ≥ 4 weeks). RTX (2 × 500 mg) was added to patients' current biologic and nonbiologic DMARD treatment. After 24 weeks, patients with 28-joint Disease Activity Score ≥ 2.6 were eligible for RTX retreatment. The primary endpoint was the proportion of patients developing a serious adverse event (SAE) within 24 weeks of initiating RTX.
  
  
  RESULTS
  Patients (n = 176) received RTX with 18 different biologic/DMARD combinations. Adalimumab alone (n = 46; 26.1%) or etanercept alone (n = 37; 21.0%) plus RTX were the most common combinations. Overall, 90.9% and 76.1% of patients completed 24 and 48 weeks, respectively; 147 patients (83.5%) received a second course of RTX. Over 24 weeks, 9.1% of patients reported SAE (24.3 events/100 patient-yrs, 95% CI 15.5-38.1). The SAE rate was similar over 48 weeks (22.4 events/100 patient-yrs, 95% CI 15.9-31.5). Four serious infections were reported over 48 weeks (2.7 events/100 patient-yrs, 95% CI 1.0-7.2). No SAE occurred within 24 h of any RTX infusion. Efficacy responses improved numerically at Week 48 compared with Week 24.
  
  
  CONCLUSIONS
  The overall safety profile of RTX in combination with 1 other biologic was consistent with that previously reported for RTX plus methotrexate or other nonbiologic DMARD. (Clinicaltrials.gov NCT00443651).
authors.affiliation: Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire 03756-000, USA. william.rigby@dartmouth.edu
authors.forename: William F C
authors.initials: WF
authors.lastname: Rigby
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.forename: Ewa
authors.initials: E
authors.lastname: Olech
authors.forename: Mark
authors.initials: M
authors.lastname: Ashby
authors.forename: Swati
authors.initials: S
authors.lastname: Tole
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001424:Bacterial Infections / Q000453:epidemiology / Q000209:etiology; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000209:etiology; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor; D000069283:Rituximab; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069283:Rituximab; D000068879:Adalimumab; D000068800:Etanercept
keywords: B LYMPHOCYTES; BIOLOGICAL THERAPY; RHEUMATOID ARTHRITIS