A PHASE 2A, PLACEBO-CONTROLLED, RANDOMIZED STUDY OF ABT-981, AN ANTI-INTERLEUKIN-1ALPHA AND -1BETA DUAL VARIABLE DOMAIN IMMUNOGLOBULIN, TO TREAT EROSIVE HAND OSTEOARTHRITIS (EHOA)

Background: No approved OA therapies reduce pain and slow joint damage. Mouse data suggested that inhibiting IL-1α and -1β with ABT-981 would reduce pain and slow structural progression in EHOA. Objectives: To test the efficacy and safety of ABT-981 in EHOA. Methods: Subjects with HOA per ACR criteria, ≥3 inflamed IP joints (tender, swollen, or both), hand pain ≥6 (scale 0–10), and ≥1 erosive IP joint on X-ray (Verbruggen-Veys) were randomized to placebo (PBO) or ABT-981 200 mg SC every 2 wk for 26 wk. The primary outcome was AUSCAN hand pain at 16 wk. Subjects had radiographs of both hands and MRI of the index hand at baseline and 26 wk. Both radiographs (Verbruggen-Veys, GUSS™, OARSI, Kellgren-Lawrence [KL]) and MRIs (HOAMRIS) were read by 2 independent central readers. A modified intent-to-treat population (ie, randomized and treated) was analyzed. Continuous efficacy endpoints were assessed using ANCOVA models with treatment and country as main factors and baseline measurements as covariates with LOCF imputation for the primary endpoint. Results: Of 131 treated subjects (85% women; mean age 66 y), 61/67 randomized to PBO and 49/64 to ABT-981 completed the study; subject characteristics were well matched. AUSCAN pain was not significantly different vs PBO at wk 16 (P=0.39; Table 1, Figure); X-ray data and other endpoints also were not statistically different vs PBO (Table 1). ABT-981 significantly decreased hsCRP, neutrophils, IL-1α, and IL-1β. Immunogenicity had no impact on ABT-981 pharmacokinetics. Besides injection site reactions and neutropenia, ABT-981 was well tolerated and safety was similar vs PBO, with no serious infections (Table 2). Table 1 PBOABT-981PBOABT-981P 1° EndpointBaseline, mean±SDLS, mean change±SE at Wk 16 AUSCAN pain (0–50)39±738±6−10.7±2.4−9.2±2.30.39 2° EndpointsBaseline, mean±SDLS, mean change±SE at Wk 26 AUSCAN function (0–90)69±1571±13−14.3±4.2−16.4±4.00.49 Tender joints (0–30)12±612±7−4.7±1.2−5.8±1.20.32 Swollen joints (0–30)6±66±5−1.8±0.8−2.2±0.90.64 X-ray erosive joints (0–16)2±2*3±2*0.26±0.080.18±0.080.33 KL score (0–80)41±1346±130.13±0.190.10±0.190.87 OARSI JSN (0–58)28±1032±90.14±0.190.03±0.190.51 OARSI osteophytes (0–58)23±1126±100.25±0.150.14±0.160.45 HOAMRIS synovitis (sum score; 0–52.5)11±410±40.92±0.480.85±0.510.89 HOAMRIS erosive damage (sum score; 0–105)18±917±100.26±0.640.10±0.670.80 HOAMRIS BML (sum score, 0–105)7±55±40.11±0.640.44±0.660.60 *Verbruggen-Veys, erosive phase (E) + erosive with remodeling (E/R) ornew E or E/R or R. Table 2 PBO (n=67)ABT-981 (n=64) Any AE/serious AE, %88/391/3 Death, %00 Infection/serious infection, %51/041/0 Injection site reaction, %1636 Neutropenia by NCI CTCAE grade, n  G2 (1000 to <1500/mm)09  G3 (500 to <1000/mm)03  G4 (<500/mm)00 Conclusions: Despite adequate pharmacodynamics results, targeting IL-1 may be ineffective in EHOA, as ABT-981 did not improve outcomes. Acknowledgements: AbbVie funded the study (NCT02384538); participated in study design, data collection, analysis, and interpretation and in abstract writing, review, and approval; and funded writing support by M. Theisen of CPS. Disclosure of Interest: M. Kloppenburg Grant/research support from: Pfizer, Consultant for: AbbVie, GlaxoSmithKline, Merck, Levicept, C. Peterfy Shareholder of: Spire Sciences, Inc. (which provides imaging services for clinical trials to multiple pharmaceutical companies), Employee of: Spire Sciences, Inc. (which provides imaging services for clinical trials to multiple pharmaceutical companies), Speakers bureau: Amgen, I. Haugen Consultant for: AbbVie, F. Kroon: None declared, S. Chen Shareholder of: AbbVie, Employee of: AbbVie, L. Wang Shareholder of: AbbVie, Employee of: AbbVie, W. Liu Shareholder of: AbbVie, Employee of: AbbVie, G. Levy Shareholder of: AbbVie, Employee of: AbbVie, R. Fleischmann Grant/research support from: AbbVie, Consultant for: AbbVie, F. Berenbaum Consultant for: AbbVie, Pfizer, Regeneron, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB, Employee of: Director of Imaging Rheumatology bv., J. Medema Shareholder of: AbbVie, Employee of: AbbVie, M. Levesque Shareholder of: AbbVie, Employee of: AbbVie DOI: 10.1136/annrheumdis-2017-eular.4947Citation: Annals of the Rheumatic Diseases, volume 76, supplement 2, year 2017, page 122Session: Osteoarthritis: new horizons for treatment (Oral Presentations )