Abstract 753: Efficacy of Adalimumab in the Treatment of Preradiographic Axial Spondyloarthritis: 52-Week Results of a Randomized Controlled Trial and Open-Label Extension
Authors
H Haibel, M Rudwaleit, A Amtenbrink, F Heldmann, J Listing, R Wong, H Kupper, J Braun, J Sieper
Background:
Adalimumab is approved in Europe and the US for active, established AS. However, there are no placebo-controlled data on its efficacy in early axial spondyloarthritis (SpA) before radiographic sacroiliitis is detected.
Objective:
To evaluate the efficacy and safety of adalimumab in patients with NSAID-refractory preradiographic axial SpA (early AS).
Methods:
46 patients with NSAID-refractory preradiographic axial SpA were randomized to placebo or adalimumab 40 mg subcutaneously every other week for 12 weeks, followed by an open-label extension up to 52 weeks. A diagnosis of preradiographic axial SpA required at least 2 of the following 3 parameters: inflammatory back pain, HLA-B27 positivity, MRI showing acute inflammation of the spine or sacroiliac joints plus 1 criterion of the following three: good response to NSAIDs; one or more of the following extraspinal manifestations (uveitis, peripheral arthritis, enthesitis), or family history. The primary endpoint was a 40% improvement in the ASessments in Ankylosing Spondylitis criteria (ASAS40).
Results:
22 patients (Group A: mean age 38 years, 59% female, mean disease duration 7 years, 59% HLA-B27 positive) received adalimumab 40 mg eow, and 24 patients (Group B: mean age 37 years, 50% female, mean disease duration 8 years, 75% HLA-B27 positive) received placebo. All 46 patients completed the 12-week trial, and 38 patients completed Week 52. After 12 weeks, 12.5% of placebo-treated patients had achieved an ASAS40, and no patients achieved the ASAS criteria for partial remission. At 12 weeks, with adalimumab, 54.5% achieved an ASAS40 (p=0.004), and 22.7% achieved partial remission (p=0.019). After 40 weeks of adalimumab therapy (through Week 52), the percentages of the originally placebo treated patients achieving ASAS40 and ASAS partial remission at Week 52 increased significantly to 50.0% (p=0.004) and 37.5% p=0.002), respectively. Improvements achieved in Group A were sustained through Week 52: ASAS40 was reached in 45.5%, and ASAS partial remission in 18.2% of patients. During the 52-week study period, serious adverse events were observed in 5 patients (4 in Group A and 1 in Group B), none of which were deemed to be related to study drug.
Conclusions:
In this study adalimumab was demonstrated to be effective for symptoms in patients with early preradiographic SpA. A substantial proportion met criteria for partial remission.
Editorial Comments:
This study is important in demonstrating that patients with spondyloarthritis who are in the pre-ankylosis phase may benefit significantly in clinical parameters from adalimumab. Similar clinical results are seen with infliximab below (Abstract L11). This study however does not include radiographic outcomes. These results suggest that, even if patients do not yet show plain radiographic sactoiliitis, MRI may be a way to identify an “inflammatory” patient population who would benefit from TNF antagonists. A more detailed discussion of this study is available from EULAR.
