Background/Purpose: Adalimumab (ADA) is indicated for treatment of ankylosing spondylitis (AS) and was also effective in a pilot study of patients (pts) with non-radiographic axial spondyloarthritis (axSpA).1 ABILITY 1, the first pivotal trial to use the ASAS axSpA criteria, was designed to evaluate the efficacy and safety of ADA in axSpA pts without radiographic sacroiliitis.2
Method: ABILITY 1 is an ongoing multi-country, phase 3 study. Eligible pts fulfilled the ASAS axSpA criteria but not modified NY criteria for AS, had BASDAI ≥4 cm, total back pain VAS ≥40 mm, and inadequate response/intolerance/contraindication for NSAIDs. Pts were randomized 1:1 to ADA (40 mg every other wk) or placebo (PBO) for 12 wks followed by a 92-wk open-label extension. Primary endpoint was ASAS40 response at wk 12. Subgroup analyses were performed to evaluate the impact of the following baseline conditions on the primary endpoint: sex, race, age, weight, CRP, HLA-B27, sacroiliitis by MRI, history of IBD or uveitis, and concomitant DMARD or NSAID use. Logistic model was performed to assess treatment and subgroup interaction, with significant interaction defined as Pvalue £0.10.
Result: Of the 192 randomized pts, 7 pts (4 ADA, 3 PBO) were excluded from efficacy analyses due to investigator noncompliance, leaving 91 randomized to ADA and 94 to PBO. Baseline demographics/disease characteristics were comparable between ADA and PBO groups (% or mean): females (52/57), age (38/38 yrs), symptom duration (10/10 yrs), duration since diagnosis (3/3 yrs), BASDAI (6.4/6.5), elevated CRP (32/39) and history of HLA-B27 positivity (79/71). Positive MRI fulfilling the imaging arm of the ASAS criteria was present in 51% of ADA and 46% of PBO pts. Baseline BASDAI was comparable regardless of which arm of the ASAS criteria pts fulfilled (MRI/HLA-B27): 6.4 (+/–), 6.2 (+/+) and 6.6 (–/+). A significantly higher percentage of ADA pts achieved the primary endpoint and other clinical and imaging outcomes compared to PBO (Table). The only significant interaction terms in the subgroup analyses for wk 12 ASAS40 were for the age and CRP subgroups (Table). Response rates were similar between MRI positive and negative pts. During the double-blind period, safety analyses for all 192 randomized pts revealed comparable results for ADA and PBO (%): AEs (57.9/58.8), serious AEs (3.2/1.0), and infectious AEs (29.5/28.9); there were no serious infections, TB, malignancies, or demyelinating disease.
Conclusion: Adalimumab significantly improved the signs and symptoms of pts with active non-radiographic axSpA. Pts <40 yrs or with elevated baseline CRP were more likely to achieve ASAS40 with ADA, consistent with a previously published report.1 ABILITY 1 results suggest a favorable benefit-risk profile for ADA as treatment for non-radiographic axSpA pts.
References: 1. Haibel H, et al. Arthritis Rheum 2008;58:1981. 2. Rudwaleit M, et al. Ann Rheum Dis 2009;68:777
Disclosure: J. Sieper, Abbott, Merck, Pfizer, UCB, 2, Abbott, Merck, Pfizer, UCB, 5, Abbott, Merck, Pfizer, UCB, 8 ; D. van der Heijde, Abbott, Amgen, AstraZeneca, BMS, Centocor, Chugai, Eli-Lilly, GSK, Merck, Novartis, Otsuka, Pfizer, Roche, Sanofi-Aventis, Schering-Plough, UCB, Wyeth, 5 ; M. Dougados, ABBOTT,PFIZER,ROCHE,UCB,BMS,MERCK, 2, ABBOTT,PFIZER,ROCHE,UCB,BMS,MERCK, 5 ; P. J. Mease, Abbott Immunology Pharmaceuticals, 2, Amgen, 2, Bristol Myers Squibb, 2, Novartis Pharmaceutical Corporation, 2, Centocor, Inc., 2, Genentech and Biogen IDEC Inc., 2, Lilly , 2, Pfizer Inc, 2, U C B, 2, Abbott Immunology Pharmaceuticals, 5, Amgen, 5, Bristol Myers Squibb, 5, Centocor, Inc., 5, Genentech and Biogen IDEC Inc., 5, Lilly, 5, Novartis Pharmaceutical Corporation, 5, Pfizer Inc, 5, U C B, 5, Abbott Immunology Pharmaceuticals, 8, Amgen, 8, Bristol Myers Squib, 8, Centocor, Inc., 8, Genentech and Biogen IDEC Inc., 8, Lilly, 8, Pfizer Inc, 8, U C B, 8 ; L. S. Brown, Abbott , 3, Abbott , 1 ; T. F. Nicholson, Abbott, 3 ; A. Pangan, Abbott Laboratories, 1, Abbott Laboratories, 3 .