Relative Impact of Pain and Disease Activity on Improvements in Fatigue

Abstract

Background/Objective Fatigue is common in patients with rheumatoid arthritis (RA). We assessed the relative impact of pain and disease activity on improvements in fatigue in 2 phase 3 baricitinib clinical trials. Methods RA-BEAM (NCT01710358) and RA-BEACON (NCT01721044) were randomized, double-blind, placebo-controlled studies in adults with moderate to severe RA. RA-BEAM assessed baricitinib + methotrexate (MTX) and adalimumab + MTX in patients with prior inadequate response/intolerance (IR) to MTX (MTX-IR). RA-BEACON assessed patients with IR to ≥1 biologic disease-modifying antirheumatic drug (bDMARD-IR). Measures included the Functional Assessment of Chronic Illness Therapy—Fatigue scale, Clinical Disease Activity Index (CDAI) for RA, and pain visual analog scale (VAS). Analyses were implemented separately for each study. Results Significant improvements were seen in disease activity and pain, which were greater with baricitinib versus adalimumab. A statistically significant improvement was seen in fatigue with both active treatments versus placebo. Moderate correlations were observed between improvements in disease activity and fatigue and between improvements in pain and fatigue in both MTX-IR and bDMARD-IR patients. Reductions in pain (≥50%) and remission or low disease activity (CDAI ≤10) had significant associations with fatigue improvement at week 24. In mediation analysis, improvements in fatigue attributable to CDAI and pain VAS in MTX-IR patients were 31% and 52%, respectively, for baricitinib, and 30% and 47%, respectively, for adalimumab. In bDMARD-IR patients, improvement in fatigue was attributed 48% to CDAI and 48% to pain VAS. Conclusions In both MTX-IR and bDMARD-IR patients, a large proportion of improvements in fatigue across treatment arms were accounted for by improvements in pain and disease activity.

Potential Mechanism of Fatigue Induction and Its Management by JAK Inhibitors in Inflammatory Rheumatic Diseases

“…It is worth noting that, mediation analysis showed that the large majority of the improvement in FACIT-F was explained by changes in pain and disease activity for both BARI and ADA in MTX-IR patients, and these factors explained almost all of the improvements in FACIT-F in the bDMARD experienced population. 117 …”

“…115,116 It is worth noting that, mediation analysis showed that the large majority of the improvement in FACIT-F was explained by changes in pain and disease activity for both BARI and ADA in MTX-IR patients, and these factors explained almost all of the improvements in FACIT-F in the bDMARD experienced population. 117 In summary, addressing fatigue in RA patients undergoing baricitinib treatment is crucial for optimizing treatment outcomes, monitoring disease activity, improving quality of life, and promoting patient adherence. By recognizing and managing fatigue, health-care providers can support patients in achieving better symptom control and overall disease management.…”