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Abstract
Background Patients with active ankylosing spondylitis (AS) experience fatigue which frequently leads to reduced health-related quality of life (HRQoL). Secukinumab (SEC) treatment results in rapid improvements in signs and symptoms, physical functioning and HRQoL in patients with active AS versus placebo (PBO) in the phase 3 studies MEASURE 1 (M1) and MEASURE 2 (M2).
Objectives To assess the impact of SEC on fatigue in patients with AS, including biologic-naïve patients and those with an inadequate response to TNF therapy (TNF-IR) and to investigate correlations between fatigue and baseline characteristics or clinical endpoints.
Methods The two phase 3 studies involved patients with active AS (M1, N=371; M2, N=219). Patients were randomized to receive subcutaneous SEC 150 mg or 75 mg or PBO administered every 4 weeks after initiating therapy. Patients randomized to PBO who did not meet predefined response criteria at week 16 were re-randomized at week 24 to SEC 150 mg or 75 mg. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. The FACIT-F response analyses were based on observed data with no imputation. A change in FACIT-F score of ≥4 from baseline was used to define fatigue response. Possible correlations between baseline characteristics or clinical response criteria and improvements in fatigue at weeks 16 and 52 were investigated using a logistical regression model.
Results From week 4 onwards, greater improvements in fatigue response were observed for both SEC groups compared with PBO. At week 16, 66.4% (M1) and 77.6% (M2) of patients receiving SEC 150 mg achieved a fatigue response, compared with 47.7% (M1) and 50.0% (M2) for PBO (p <0.05 for both comparisons; see figure). Response rates for SEC 150 mg at week 16 were numerically higher in biologic-naïve patients (M1, n=271; M2, n=134) than in TNF-IR patients (M1: 68.9% vs 59.4%; M2: 86.0% vs 62.5%, respectively). Responses were sustained at week 52 in both studies (M1, 73.6%; M2, 80.6%) and at week 104 in M1 (71.3%; see figure for M1 data) in the overall population, and in the two subgroups according to prior biologic therapy status. Correlation analyses based on pooled data from both studies did not identify any baseline factors that consistently predicted an improvement or worsening of FACIT-F score at week 16 or 52. Achieving a fatigue response was strongly positively correlated at weeks 16 and 52 with clinical response (ASAS20, 40, 5/6 responses, ASAS partial remission, ASDAS-CRP major improvement and BASDAI 50 response).
Conclusions SEC 150 mg provided rapid improvement in fatigue, regardless of prior biologic therapy, and response was sustained up to 104 weeks. Fatigue response showed a strong correlation with improvement in clinical response criteria, indicating a relationship between fatigue and disease activity in AS and is an important treatment goal for patients with AS.
Disclosure of Interest T. K. Kvien Grant/research support from: AbbVie, BMS, MSD, Pfizer, Roche and UCB, Consultant for: AbbVie, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira, Merck-Serono, MSD, Novartis, Orion Pharma, Pfizer, Roche, Sandoz and UCB, P. Conaghan Speakers bureau: Abbvie, Janssen, Lilly, Novartis, Pfizer and Roche, A. Deodhar Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Janssen, Novartis, Pfizer and UCB, Consultant for: AbbVie, Amgen, Boehringer Ingelheim, Janssen, Novartis, Pfizer and UCB, L. Gossec Consultant for: Abbvie, Celgene, Janssen, Novartis, Pfizer, Roche and UCB, M. Østergaard Grant/research support from: Abbvie, BMS, Janssen, Merck, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Centocor, GSK, Hospira, Janssen, Merck, Mundipharma, Novartis, Novo, Orion, Pfizer, Regeneron, Schering-Plough, Roche, Takeda, UCB, and Wyeth., J. Cañete Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Biogen, Janssen, Merck, Novartis, Pfizer and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Biogen, Janssen, Merck, Novartis, Pfizer and UCB, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, H. Richards Shareholder of: Novartis, Employee of: Novartis, N. Williams Consultant for: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis