THU0439 EFFICACY AND SAFETY OF ANAKINRA IN THE TREATMENT OF RECURRENT GOUT FLARES: RESULTS FROM THE EXTENSION PHASE OF THE ANAGO STUDY

Background: The anaGO (anakinra in gout) study was a multi-center, randomized, double-blind, double-dummy, phase 2 study investigating the efficacy and safety of anakinra for recurrent gout flares. Results from subsequent flares (extension phase) are presented in relation to the previously reported results from the 1st flare (flare at study enrollment). Objectives: The objective of the extension phase was to evaluate the efficacy, safety and immunogenicity of two anakinra regimens (100 or 200 mg daily s.c. injections for 5 days) compared to triamcinolone (single i.m. injection 40 mg) for subsequent flares after initial study enrollment flare. The primary endpoint of the study was change in patient-assessed flare pain intensity from baseline to 24-72 hours (average of 24, 48 and 72 hours) in the most affected joint measured on a visual analogue scale (0-100 VAS). Secondary endpoints included: patient’s and physician’s assessments of global response, anti-drug antibodies (ADA) and safety. Methods: The study included patients with acute gout (ACR/EULAR 2015 gout classification criteria) unsuitable for anti-inflammatory therapy with NSAIDs and colchicine due to contraindication, intolerance or inefficacy. Patients were eligible for treatment of subsequent flares for up to 2 years. Each patient received the same treatment for all flares, starying with the flare at enrollment. Results: 161 patients were treated for 1 flare, 61 patients for 2 flares, 31 patients for 3, and 20 patients for 4 or more flares with 1 patient treated for 9 flares. In total, 300 flares were treated in the full study; anakinra 100 mg and 200 mg, 107 and 106 flares, respectively; and triamcinolone, 87 flares. Both anakinra doses and triamcinolone provided a clinical meaningful reduction in patient-assessed pain intensity in both the 1st and subsequent flares. Mean changes in pain intensity from baseline to 24–72 hours for total anakinra and triamcinolone were: 1st flare -41.2 and -39.4; 2nd flare -33.9 and -31.1; 3rd flare -31.8 and -51.2, respectively. Mean differences in pain reduction between anakinra and triamcinolone treatment groups were (negative value favors anakinra): 1st flare -1.8, 2nd flare -2.8 3rd flare 19.4. The majority of secondary endpoints favored anakinra, including patient’s and physician’s global assessement of response and physician’s assessement of the joint. No unexpected safety findings during subsequent flares were identified. 21 patients (19.6%) developed ADA to anakinra in low titers at some time point; 7 (6.5%) had pre-existing ADA at baseline and 12 (11.2%) developed treatment induced ADA. 2 patients had pre-existing ADA to triamcinolone at baseline. 4 patients on anakinra (3.7%) developed neutralizing antibodies (NAbs). Pre-dose 72 hour anakinra serum concentrations were in similar range for ADA+ and ADA- patients. Presence of ADA was not associated with adverse events or had an impact on pain reduction. Conclusion: The efficacy and safety of anakinra and triamcinolone in subsequent flares were similar to the findings from 1st flare in patients with acute gout. Patient-assessed pain in the 1st and 2nd flare was reduced to similar degrees in all treatment groups, but to a larger extent in the 3rd flare in the small triamcinolone group. Secondary endpoints were in favor of anakinra across flares 1 to 3. The overall incidence of ADA and NAb was low also after repeated anakinra dosing and did not appear to impact exposure, efficacy or safety. In conclusion, anakinra was shown to be an option in the treatment of recurrent gout flares in patients for whom conventional therapy is unsuitable. Disclosure of Interests: : Kenneth Saag Grant/research support from: Horizon, Sobi, Shanton, Grant/research support from: Horizon Pharma, Sobi, Shanton, Consultant of: Horizon and Sobi, Consultant of: Horizon Pharma, Amgen, Radius, LG-Pharma, Takeda, Sobi, Atom, Arthrosi, Puja Khanna Grant/research support from: Dyve, Selecta, Sobi, Consultant of: Sobi, Horizon, Robert Keenan Consultant of: Sobi, Selecta, Horizon, Sven Ohlman Shareholder of: Sobi, Employee of: Former employee of Sobi, Erik Sparve Shareholder of: Sobi, Employee of: Sobi, Daniel Lindqvist Employee of: Sobi, Ann-Charlotte Akerblad Shareholder of: Sobi, Employee of: Sobi, Margareta Wiken Shareholder of: Sobi, Employee of: Former employee of Sobi, Alexander So Consultant of: Sobi, Grunenthal, Michael H. Pillinger Grant/research support from: Horizon, Hikma, Consultant of: Sobi, Horizon, Robert Terkeltaub Consultant of: Sobi, Selecta, Horizon, Astra-Zeneca