The "Knowns" and "Unknowns" of Biologic Therapy in Ankylosing Spondylitis
ABSTRACT Since the first biologic agent was tested in the treatment of ankylosing spondylitis (AS), the ability of these therapies to dramatically improve the clinical symptoms and signs of the disease was very evident. Over the past decade, 4 tumor necrosis factor-alpha inhibitors have been approved by the Food and Drug Administration for the treatment of AS. Published data include randomized controlled trials, registries and observational studies. Guidelines have also been developed for the use of biologics in AS. Although a lot is known about the use of biologics in the AS, several "unknowns" remain. Whether these agents can alter the natural history of AS if started very early in the course or whether they can prevent extra-articular manifestations are among the important unanswered questions. Most of the data summarized in this review relate to tumor necrosis factor-alpha inhibitors, and other biologic agents that have been studied are included, as well. This review also summarizes what questions remain about the use of biologics in AS and what type of studies will be required to answer them.
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ABSTRACT: To analyse the impact of infliximab treatment on the number of hospital inpatient days and days of sick leave in patients with active ankylosing spondylitis (AS). The data of a 2 year open extension study of a 12 week, double blind, randomised, placebo controlled trial, in which all patients with AS were treated with 5 mg/kg infliximab, were used to investigate the effect of anti-TNF treatment on admissions to hospital and days of sick leave. All patients were interviewed at baseline and at regular intervals during the study to collect this information by questionnaires. Patients who completed 2 years of treatment (n = 49) and those who did not (n = 20) were analysed separately. Sick leave analysis was restricted to currently employed patients (n = 38). During the 12 months before the screening visit, 20/49 (41%) completers had been admitted to hospital. After 1 and 2 years of treatment this percentage was reduced to 5/49 (10%; p<0.01), corresponding to a significant decrease in the mean number of inpatient days: from 11.1 to 0.6 after 1 year (p<0.01) and 2.9 after 2 years (p<0.01), respectively. No changes were seen in the dropout group. The use of infliximab in patients with active AS reduces some important costs of AS, but additional studies with detailed cost calculations are needed.Annals of the Rheumatic Diseases 12/2004; 63(12):1670-2. DOI:10.1136/ard.2003.017327 · 9.27 Impact Factor
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ABSTRACT: To study levels of sick leave and disability pension before and after TNF-antagonist therapy in AS patients. Using the population-based South Swedish Arthritis Treatment Group register, we identified 139 AS patients (aged 18-58 years, 78% men), who between January 2002 and December 2008 started their first treatment with adalimumab, etanercept or infliximab. We linked data to the payment register by the Swedish Social Insurance Agency and calculated the proportion on sick leave in 30-day intervals from 12 months before treatment start until 12 months after. For each AS patient, we randomly selected four subjects from the general population matched for age, sex and area of residence. One to 3 months before treatment, an average of 24% of AS patients were on sick leave. During the first 6 months after treatment start, this fraction dropped to 15%, and further declined to 12% at 12 months (P < 0.001). Comparing AS patients with the general population, the relative risk of being on sick leave 3 months before treatment, treatment start and 12 months after treatment start was 8.0 (95% CI 4.6, 13.9), 9.2 (95% CI 5.4, 15.7) and 4.0 (95% CI 2.1, 6.3), respectively. The decrease in sick leave was not substantially offset by changes in disability pension. There is a decline in sick leave during the first 12 months after initiation of TNF-antagonist treatment in AS patients not explained by societal factors or secular trends. The proportion of AS patients on disability pension remained unchanged during the observation period.Rheumatology (Oxford, England) 05/2011; 51(2):243-9. DOI:10.1093/rheumatology/ker169 · 4.44 Impact Factor
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ABSTRACT: We analyzed the effects of adalimumab on biomarkers predictive of structural damage in inflammatory arthritis. In a 24-week randomized controlled trial, patients with active ankylosing spondylitis (AS) received adalimumab 40 mg or placebo every other week. Efficacy measures included ASsessment in Ankylosing Spondylitis International Working Group response, Bath AS Disease Activity Index (BASDAI), Total Back Pain, Bath AS Functional Index, C-reactive protein (CRP), and patient's global assessment of disease activity. Urinary type II collagen C-telopeptides (CTX-II), serum type I collagen N-telopeptides (NTX), and serum metalloproteinase-3 (MMP-3) were assessed using ELISA for treatment-group differences at baseline, 12, and 24 weeks. We determined correlations between changes in biomarkers and AS efficacy outcomes. A total of 82 patients (38 adalimumab, 44 placebo) enrolled. At 12 and 24 weeks, significant reductions in urinary CTX-II and MMP-3, but not NTX concentrations, were observed for adalimumab versus placebo (p<0.001). Significant baseline correlations were noted between CRP and CTX-II (r=0.71), MMP-3 (r=0.45), and NTX (r=0.37) (p<or=0.001), as well as between CTX-II and NTX (r=0.49; p<0.0001). Changes in CTX-II and MMP-3 at 12 weeks correlated significantly with changes in BASDAI (r=0.31 and 0.33), and CRP (r=0.40 and 0.43) (p<or=0.005). Change in CTX-II at 12 weeks also correlated significantly with change in MMP-3 (r=0.41; p<0.0001). Adalimumab suppresses biomarkers that reflect matrix turnover in patients with AS.The Journal of Rheumatology 10/2008; 35(10):2030-7. · 3.17 Impact Factor