Background In patients (pts) with ankylosing spondylitis (AS), fatigue is a common symptom negatively affecting health-related quality of life (HRQoL) and social functioning. Secukinumab (SEC), a fully human anti–IL-17A mAb, rapidly improved signs and symptoms, physical functioning, and HRQoL in pts with AS.1,2
Objectives To assess the long-term effects of SEC on fatigue in TNF inhibitor (TNF)-naïve and TNF inhibitor inadequate responder/intolerant (TNF-IR) AS pts in MEASURE 1 and MEASURE 2.
Methods 371 and 219 pts were randomized to SEC or placebo (PBO) in MEASURE 1 (10 mg/kg IV followed by 150 or 75 mg SC) and MEASURE 2 (150 or 75 mg SC), respectively. At Week (Wk) 16, non-responder PBO pts were re-randomized to SEC 150 or 75 mg SC (in MEASURE 1, PBO pts achieving ASAS20 response at Wk 16 were switched to SEC at Wk 24). Fatigue was measured at baseline (BL) and Wks 4, 8, 12, 16, 24, 52, 104 and 156 using FACIT-F, which assesses fatigue in the previous 7 days using 13 questions graded on a 0–4 scale (higher scores=less fatigue). An increase from BL in FACIT-F score of ≥4 points (based on MCID) was used to define “response”. Approximately 69% of pts were TNF-naïve and 31% were TNF-IR across both trials. Analyses were based on the full analysis set and subgroups stratified by prior TNF therapy. Correlations between BL characteristics and improvements in fatigue were investigated using a logistical regression model. Only data from the approved dose (SEC 150 mg) are presented.
Results FACIT-F was 24.5–25.6 and 22.6–24.3 at BL across groups in MEASURE 1 and 2, respectively. Improvements in FACIT-F with SEC at Wk 16 were sustained through Wk 156 in MEASURE 1 and Wk 104 in MEASURE 2 (Table). Rapid and sustained fatigue responses were also seen in subgroups stratified by prior TNF use. In the overall population, LS mean changes (±SEM) from BL in FACIT-F scores were significantly greater with SEC vs PBO at Wk 16 in both MEASURE 1 (7.60±0.99 vs 3.34±1.00, P=0.002) and MEASURE 2 (8.10±1.09 vs 3.27±1.09, P=0.018); reductions in fatigue were sustained throughout the entire follow up in both trials (MEASURE 1 Wk 156: 9.81±0.95; MEASURE 2 Wk 104: 9.27±1.13). Similar results were reported in both TNF-naïve and TNF-IR pts. Correlational analyses based on pooled data from both trials did not identify any BL factors that consistently predicted improvement in fatigue response at Wks 16, 52, and 104. A one-unit increase in BL BASDAI score (i.e. worsening) was a significant factor for achieving FACIT-F response at Wk 104 (P=0.02).
Conclusions SEC provided sustained improvements in fatigue for up to 156 wks in both TNF-naïve and TNF-IR pts with AS. Fatigue response was generally higher in TNF-naïve pts.
Baeten. NEJM 2015;373:2534–48.
Kvien. ARD 2016;75(Suppl2):823.
Disclosure of Interest T. Kvien Consultant for: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz and UCB, Speakers bureau: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celltrion, Eli Lilly, Epirus, Janssen, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz and UCB, A. Deodhar Grant/research support from: Eli Lilly, Janssen, Novartis, Pfizer, UCB, Abbvie, Amgen, GSK, L. Gossec Grant/research support from: BMS, Lippy, Pfizer, Consultant for: Abbvie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche and UCB, P. Conaghan Consultant for: Abbvie, BMS, Lilly, Novartis, Pfizer, Roche, Speakers bureau: Abbvie, BMS, Lilly, Novartis, Pfizer, Roche, V. Strand Consultant for: AbbVie, Amgen, BMS, Celgene, Celltrion, CORRONA, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sanofi, and UCB, M. Østergaard Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Janssen, Merck, Novartis, Orion, Pfizer, Regeneron, Roche, UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Janssen, Merck, Novartis, Orion, Pfizer, Regeneron, Roche, UCB, N. Williams Employee of: RTI Health Solutions, B. Porter Shareholder of: Novartis, Employee of: Novartis, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis