Background Fatigue is a major issue for patients (pts) with RA. Biologic DMARDs including abatacept (ABA) have shown efficacy in improving fatigue in randomized controlled trials (RCTs),1–3 but questions remain.
Objectives We explored the effects of ABA on fatigue versus on pain in RA.
Methods This was a post hoc analysis of 3 RCTs of ABA in RA: AIM1 and ATTAIN2 in established RA, and AGREE3 in early RA. Pts were randomized to ABA versus placebo (pbo), with concomitant MTX in both treatment arms in most cases. Fatigue and pain were assessed by visual analogue scales (VAS, 0–10 cm) at baseline (BL), Days 29, 85 and 169; mean changes from BL were analysed using an ANCOVA model with treatment as a factor and BL value as a covariate. Associations between fatigue VAS score and pain score were evaluated using Pearson correlation coefficients at BL and Days 29, 85 and 169. Agreement of reporting minimum clinically important differences (MCID; improvement of ≥10 mm from BL to 169 day) for fatigue and pain was evaluated using Kappa coefficients, MCID was cross-tabulated for fatigue and pain. Data from each trial were analysed separately.
Results Data were available for 1536 pts (women: 78–79%, mean age: 50–53 years across RCTs). Mean disease duration was 8.5–12.2 years (AIM and ATTAIN) and 6.2–6.7 months (AGREE). ABA was efficacious relieving fatigue, with mean relative decreases from BL to day 169 of 30–44%. Benefit on fatigue was reported early, decreasing by 18–24% at Day 29, indicating that ∼50% of the mean decrease in fatigue was already achieved by this time point. Results were consistent across RCTs, although the effect of ABA on fatigue was greater in pts with shorter versus longer disease duration. ABA also significantly reduced pain: mean decreases were 29–49% across trials. There was an association between treatment effects on fatigue and pain: Pearson correlation coefficients were 0.69–0.72 at Day 169. Agreement between MCID improvements in pain and fatigue were, however, moderate: kappas ranged from 0.30–0.51 across RCTs and time points. Cross-tabulation indicated most pts who reported improvements ≥MCID in fatigue also did so in pain (795/903 pts; 88.0%), and vice versa (795/1004 pts; 79.2%) at Day 169.
Conclusions ABA led to a rapid improvement in both fatigue and pain in pts with active RA. However, agreement between clinically meaningful improvements in these outcomes was only moderate, suggesting that the pathways of fatigue and pain in RA represent different domains of response. Fatigue should be further studied in RA.
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Disclosure of Interest L. Gossec Grant/research support from: UCB France, Consultant for: AbbVie, Bristol-Myers Squibb, Celgene, Chugai, Janssen, MSD, Novartis, Pfizer, Roche, UCB, S. Ahdjoudj Employee of: Bristol-Myers Squibb, E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, V. Strand Consultant for: AbbVie, Alder, Amgen Corporation, AstraZeneca, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, CORRONA, Crescendo/Myriad Genetics, EMD Serono, Genentech/Roche, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer, Regeneron, Sandoz, Sanofi, UCB