Efficacy of Adalimumab in the treatment of Preradiographic Axial Spondyloarthritis: Results of a 20-Week, Randomized controlled trial with an Open-Lable extension phase - OP0043
Authors: H. Haibel, M. Rudwaleit, A. Amtenbrink, F. Heldmann, J. Listing, R. Wong, H. Kupper, J. Braun, J. Sieper
Background:
Ankylosing Spondylitis is a disease in which TNF antagonists have proven their efficacy in terms of symptomatic outcomes. Both soluble receptor constructs and monoclonal antibodies that inhibit TNF are efficacous and approved for treating AS. Most recently Adalimumab has been approved in US and EU for the treatment of AS. The results of the pivotal 52 week ATLAS study were presented at ACR2006 and have also been published (van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J, Dougados M, Reveille JD, Wong RL, Kupper H, Davis JC Jr; ATLAS Study Group. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006 Jul;54(7):2136-46). Ankylosing Spondylitis represents one end of a spectrum of spondyloarthropaties in which patients may have inflammatory disease, yet not meet criteria that would qualify them for clinical trials. One of these criteria is the presence of radiographic sacroileitis. Determining if adalimumab will be effective in patients with axial complaints of Spondyloarthropathy who are refractory to NSIADS in controlling their symptoms, but in patients who do not yet have Spondylitis on plain radiography, or early AS.
Methods:
This was a placebo-controlled trial conducted at 2 centers of 46 patients with NSAID-refractory preradiographic axial SpA who were randomized to placebo or adalimumab 40 mg subcutaneously every other week for 12 weeks, followed by an open-label extension. A diagnosis of preradiographic axial SpA required at least 2 of the following: inflammatory back pain, HLA-B27 positivity, and an MRI showing acute inflammation of spine or sacroiliac joints. The primary endpoint was a 40% improvement in the ASessments in Ankylosing Spondylitis criteria (ASAS40). Other clinical outcome assessments included ASAS20, ASAS criteria for partial remission, disease activity (BASDAI), function (BASFI), patient's global assessment of disease activity (numerical rating system), and C-reactive protein (CRP) concentration.
Results:
A total of 22 patients (mean age 38 years, 59% female, mean disease duration 7 years, 59% HLA-B27 positive) received adalimumab 40 mg eow, and 24 patients (mean age 37 years, 50% female, mean disease duration 8 years, 75% HLA-B27 positive) received placebo. All patients completed the 12-week trial, and 43 patients completed Week 20. Among patients who initially received placebo and were switched to open label adalimumab, after 8 weeks of adalimumab treatment, the percentages of patients who achieved ASAS20, ASAS40, and ASAS partial remission at Week 20 were 70.8%, 58.3%, and 41.7%, respectively. The efficacy achieved in the adalimumab group over the initial 12 weeks remained stable after an additional 8 weeks of open label treatment. In addition, the BASFI, patient's global assessment, general assessment of pain (NRS), and morning stiffness all showed significant improvements from baseline.
12 Week Results |
ASAS 20 |
ASAS 40 |
ASAS Partial Remission |
ADA 40 mg every other wk |
68.2% |
54.5% |
22.7% |
PBO |
20.8% |
12.5% |
0.0% |
Conclusion:
This is the first study to demonstrate the efficacy of a TNF antagonist in patients with early preradiographic axial SpA (early AS). In this patient group, adalimumab had a good safety profile. The substantial percentage of patients who achieved partial remission is especially encouraging and might indicate that TNF antagonists may be even more effective in early forms of axial SpA.
Editorial Comment:
In rheumatoid arthritis, MRI and ultrasound are more sensitive in detecting early changes indicative of inflammation and that ultimately precede changes detectable on plain radiography. We have also adopted treatment strategies that move toward more aggressive treatment algorithms in an early “window of opportunity” to improve long term prognosis and potentially to decrease radiographic damage. Similar studies to understand the stages of Ankylosing Spondylitis are currently lacking. Most studies to date for AS have required patients to fulfill criteria that include the presence of radiographic sacroileitis or spondylitis. However, as in the case of RA, disease may exist long before the advent of these plain radiographic changes, and in a period in which patients may be quite symptomatic and unresponsive to NSAIDS. Previous reports have been reviewed showing that MRI inflammatory changes may be precedent to later radiographic findings. The current study addresses this important group of Spondylitis patients commonly seen in clinical practice. This group of patients with inflammatory back pain is increasingly recognized earlier with the increasing attention paid to spondyloarthritis in the community as effective therapies have been introduced. This small, but very well conducted study shows that adalimumab is an effective option at substantially reducing signs and symptoms of back pain in patients with early AS who are refractory to NSAIDS.