Background Canakinumab, a fully human anti-IL-1β monoclonal antibody, selectively targets IL-1β and may be an alternative treatment to NSAIDs or colchicine in patients (pts) presenting with acute gouty arthritis (GA), in whom standard care is inappropriate or ineffective. The ideal qualities of such a treatment should include fast and potent pain relief and reduction of the risk of a new flare. When treating pts with biologic therapy, it is important to develop criteria for response-guided retreatment decisions to reduce risk of futile treatment and potential exposure to an unnecessary safety risk.
Objectives To explore the rapidity of response to treatment, defined as ≥50% pain reduction within 7 days, as a potential surrogate marker of time to new flare.
Methods A good concordance between prevention of flare and 50% pain reduction on a 0-100 mm visual analogue scale (VAS) was detected in a retrospective pooled analysis of two 12-week studies (β-RELIEVED, N=230; β-RELIEVED-II, N=226) in pts treated with a single dose of canakinumab 150mg sc or triamcinolone acetonide (TA) 40 mg im. The 12-week extension studies allowed evaluation of early pain response as a predictor of delay to new flare. The predictive value of the response was studied using a Cox model with response as a time-dependent covariate and the number of flares in the previous year as baseline predictor.
Results 50% pain reduction within 7 days of treatment was confirmed to be a highly significant predictor of time to new flare (p<0.0001). The hazard ratio for responders vs non-responders was 0.47 (95% CI, 0.32 – 0.67). The baseline number of flares was also significant (p=0.0011) confirming the temporal aspect of disease severity as intensity of recurrent disease. A similar result was obtained for time from response (or Day 7 for non-responders) to new flare using Kaplan-Meier technique (log-rank test, p<0.0001) with median time 100 days for non-responder and non-estimable yet for responders within 6 month study (Figure).
Conclusions These results demonstrate that a 50% pain reduction by VAS within 7 days of treatment in acute GA pts is associated with delay of new flare and can be used as a surrogate marker of time to new flare.
Disclosure of Interest A. So Grant/Research support from: Novartis, Consultant for: Novartis, Ardea, Speakers Bureau: Novartis, Ardea, Menarini, T. Bardin Grant/Research support from: Menarini, Consultant for: Novartis, Ipsen, Menarini, Ardea, Biocryst, M. Bloch Grant/Research support from: Novartis, A. Shpilsky Shareholder of: Novartis, Employee of: Novartis, T. Kiechle Shareholder of: Novartis, Employee of: Novartis, N. Schlesinger Grant/Research support from: Novartis, Consultant for: Novartis, URL Pharma, Savient, Takeda, Rx Ensyme, Speakers Bureau: Takeda, Savient, Novartis