Improvements in health-related quality of life after treatment with tocilizumab in patients with rheumatoid arthritis refractory to tumour necrosis factor inhibitors: results from the 24-week randomized controlled RADIATE study

Abstract

Objective. To investigate the effect of tocilizumab on patient-reported outcomes (PROs) in RA patients with inadequate responses to TNF inhibitors (TNFis).Methods. In a Phase III randomized controlled trial, 489 patients received 4 or 8 mg/kg tocilizumab or placebo every 4 weeks plus MTX for 24 weeks. Mean changes from baseline over time and proportions of patients reporting improvements greater than or equal to minimum clinically important differences (MCIDs) in PROs were analyzed.Results. At week 24, 8 mg/kg resulted in significantly greater improvements vs placebo in pain, global assessment of disease activity (P = 0.001), Health Assessment Questionnaire-Disability Index (HAQ-DI; P < 0.0001), Functional Assessment of Chronic Illness Therapy-Fatigue (P = 0.0150) and Medical Outcomes Survey Short Form 36 (SF-36 v2) Physical Component Summary (PCS; P = 0.0003) scores, all greater than MCID; 4 mg/kg resulted in greater improvements in pain (P = 0.0100), HAQ-DI (P = 0.0030) and SF-36 PCS (P = 0.0020) scores. Tocilizumab-associated improvements were evident as early as week 2. At week 24, more tocilizumab-treated than control patients reported improvements greater than or equal to MCID in SF-36 domain scores and related PROs (50.9–84.9% vs 35.0–51.7%) and achieved ACR50 responses and/or Disease Activity Score 28 (DAS28) remission with PRO improvements greater than or equal to MCID (36.2–51.2% vs 10–20.7% and 10.7–37.5% vs 0.0–3.4%, respectively).Conclusion. Tocilizumab treatment in patients with inadequate responses to TNFis resulted in rapid and sustained improvements in multiple PROs that were statistically significant and clinically meaningful, consistent with previous efficacy reports.Trial Registration. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00106522.

Tofacitinib With Methotrexate in Third‐Line Treatment of Patients With Active Rheumatoid Arthritis: Patient‐Reported Outcomes From a Phase III Trial

“…The proportion of patients reporting improvements greater than or equal to the MCID in FACIT-F and HAQ DI after treatment with rituximab plus MTX for 6 months was similar to those reported here (38). Again, similar proportions of patients reported clinically meaningful changes in PtGA, pain, HAQ DI, SF-36v2 PCS and MCS scores, and FACIT-F, with 24 weeks of tocilizumab plus MTX (39). HAQ DI responses greater than or equal to the MCID (Ն0.3 points) were reported in 47% of patients receiving abatacept plus DMARDs for 6 months with an inadequate response to TNFi (40).…”

Poststroke Fatigue: Emerging Evidence and Approaches to Management: A Scientific Statement for Healthcare Professionals From the American Heart Association

“…96 Finally, modulation of inflammation with cytokine antagonists improves fatigue in several different diseases. [97][98][99][100][101][102] Actual data to support a role for inflammation in PSF are more limited. Most attempts at identifying biological markers of PSF are based on small patient cohorts and have serious methodological issues.…”

Inflammation and the Silent Sequelae of Stroke

“…And, as with depression, the administration of proinflammatory cytokines [e.g., interleukin (IL)-6] is associated with the perception of fatigue [49]. Further, treatment with cytokine antagonists is associated with a decrease in fatigue-administration of exogenous IL-1ra (anakinra) decreases fatigue in patients with Sjögren's syndrome [50], and the tumor necrosis factor (TNF)-α receptor antagonist infliximab and the IL-6 receptor antagonist toclizumab reduce fatigue in patients with cancer and autoimmune diseases [51][52][53][54][55].…”

“…Treatment with exogenous IL-1ra (anakinra), for instance, decreases fatigue in patients with Sjögren's syndrome [50]. Similarly, the TNF-α receptor antagonist infliximab and the IL-6 receptor antagonist tocilizumab reduce fatigue in patients with cancer [51] and a variety of autoimmune diseases [52][53][54][55]. Fatigue is a particularly prevalent problem for patients with multiple sclerosis (MS) [117].…”