THU0442 Reduction in Fatigue in Patients with Active Psoriatic Arthritis Are Sustained over 2 Years: Long-Term Results of Two Phase 3 Studies with Secukinumab
Authors: L. Gossec, T.K. Kvien, P.G. Conaghan, M. Østergaard, J. Cañete, C. Gaillez, S. Mpofu, E. Davenport, S. Jugl
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Fatigue is an important symptom associated with active psoriatic arthritis (PsA) and can impact on health-related quality of life (HRQoL) and social functioning. Secukinumab (SEC) has resulted in rapid improvements in signs and symptoms, physical functioning and HRQoL in patients with active PsA vs placebo (PBO) in the FUTURE 1 (F1) and FUTURE 2 (F2) studies. Rapid improvements in fatigue were reported in F2. <h3>Objectives</h3> To assess 1- and 2-year data on the effects of SEC on fatigue in patients with PsA, including both 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. <h3>Methods</h3> Patients with active PsA (F1, N=606; F2, N=397) received SEC or PBO every 4 weeks. Patients receiving PBO who did not meet predefined response criteria at week 16 were re-randomized at week 24 to active treatment. Fatigue was assessed at baseline and weeks 4, 8, 12, 16, 24, 52 and 104 using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. A change in FACIT-F score of ≥4 from baseline was used to define fatigue response. Logistic regression was used to explore the relationship between fatigue response (weeks 16 and 52) and baseline characteristics and clinical response criteria. The FACIT-F response analyses were based on observed data with no imputation; the FACIT-F score analyses used mixed-effect model repeated measure imputation. <h3>Results</h3> Improvements in fatigue compared with PBO were observed for all SEC doses in from week 4 onwards. A fatigue response at week 16 was achieved by 58.4% (F1) and 70.0% (F2) of patients receiving SEC 150 mg, compared with 51.6% (F1) and 43.2% (F2) of those receiving PBO (see figure for F1 data). For SEC 300 mg, a 16 week response was achieved by 50.5% (F2). Responses were sustained at week 52 for 150 mg (F1, 67.2%; F2, 68.5%) and 300 mg (F2, 60.2%) and at week 104 for 150 mg (F1, 63.8%). Sustained responses were also seen in both biologic-naïve (F1, n=425; F2, n=258) and TNF-IR patients (F1, n=181; F2, n=104). Logistic regression analyses of pooled data from F1 and F2 found age and baseline HAQ-DI scores were associated with fatigue response (weeks 16 and 52). Achieving a fatigue response was moderately to strongly correlated with clinical response criteria (including ACR, HAQ-DI and PASI scores at weeks 16 and 52). <h3>Conclusions</h3> SEC provided rapid and sustained improvements in fatigue for up to 104 weeks in patients with active PsA, regardless of prior biologic exposure. Achieving a fatigue response was moderately to strongly correlated with improvement in clinical response criteria, indicating a relationship between fatigue and PsA disease activity. SEC-induced sustained improvements in fatigue may be important for improving HRQoL in patients with PsA. Analysis of factors predictive of fatigue response may help to clarify the drivers of fatigue; this study highlights the importance of age and physical functioning. <h3>Disclosure of Interest</h3> L. Gossec Consultant for: Abbvie, Celgene, Janssen, Novartis, Pfizer, Roche and UCB, 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, Roche, 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, C. Gaillez Shareholder of: Novartis, Employee of: Novartis, S. Mpofu Shareholder of: Novartis, Employee of: Novartis, E. Davenport Consultant for: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis