Tumor Necrosis Factor-alpha Blocking Therapy Research Articles

Diagnosis and Management of Tuberculosis in Candidates for Tumor Necrosis Factor Alpha Antagonists: An Experts Survey

Background: There are some controversies regarding the management of latent tuberculosis infection and tuberculosis in patients with rheumatologic indications for biologic therapy. Objectives: To describe current expert opinions and preferences regarding the evaluation and management of latent tuberculosis infection and tuberculosis in candidates and recipients of tumor-necrosis factor-alpha blocking therapy. Methods: A questionnaire addressing preferences related to management and treatment of latent tuberculosis infection and active tuberculosis in tumor-necrosis factor-alpha blocking candidates was distributed to tuberculosis and rheumatology experts across the United States between August 18, 2009, and June 21, 2010. Survey responses were formulated as a 5-point Likert scale (strongly disagree to strongly agree), or as a priority rank order list (1 to 6 or 7), and data were analyzed for percent agreement and median rankings. Measurements and main results: The tuberculin skin test and interferon-gamma release assays for latent tuberculosis infection screening were highly accepted among tuberculosis and rheumatology experts. Most participants supported the use of daily isoniazid for 9 months for latent tuberculosis infection therapy, but responses were mixed regarding timing to initiation of tumor-necrosis factor-alpha blocking therapy. Most tuberculosis experts supported standard anti-tuberculosis therapy for treatment of tuberculosis, but preferences varied among rheumatologists. In contrast, most rheumatologists believed tumor-necrosis factor-alpha blocking therapy should be stopped in individuals with active tuberculosis, while opinions varied among tuberculosis experts. Conclusions: Agreement among experts was common regarding preferences for diagnosis and management of latent tuberculosis infection and tuberculosis under hypothetical but likely common clinical scenarios, but some differences exist.

THU0265 Early change in bone resorption predicts discontinuation of tumor necrosis factor-alpha blocking therapy in patients with ankylosing spondylitis

BackgroundIn ankylosing spondylitis (AS), objective measurements evaluating the effect of tumor necrosis factor-alpha (TNF-α) blocking therapy are lacking.ObjectivesTo investigate the predictive value of bone turnover markers (BTM) in relation to...

Early change in bone resorption predicts discontinuation of tumor necrosis factor-alpha blocking therapy in patients with ankylosing spondylitis

Background In ankylosing spondylitis (AS), objective measurements evaluating the effect of tumor necrosis factor-alpha (TNF-α) blocking therapy are lacking. Objectives To investigate the predictive value of bone turnover markers (BTM) in relation to discontinuation of TNF-α blocking therapy in patients with AS. Methods 111 consecutive AS outpatients from the Medical Center Leeuwarden and the University Medical Center Groningen who started TNF-α blocking therapy (infliximab n=22; etanercept n=71; adalimumab n=18) were included between November 2004 and December 2007. All patients fulfilled the modified New York criteria for AS (n=109) or the ASAS criteria for axial spondyloarthritis (n=2). Patients with recent fractures and/or use of bisphosphonates were excluded. Continuation of TNF-α blocking therapy was based on decrease in Bath AS Disease Activity Index (BASDAI) of at least 50% or 2 units compared with baseline, and/or expert opinion in favor of treatment continuation. Clinical assessments, marker of bone formation bone-specific alkaline phosphatase (BALP), and marker of bone resorption serum collagen-telopeptide (sCTX) were assessed at baseline, 3 and 6 months, and 1, 2, and 3 years. Z-scores of BTM were calculated using matched 10-years-cohorts of a Dutch reference group (200 men or 350 women) to correct for the normal influence that age and gender have on bone turnover. Results Mean age of the 111 AS patients was 42.2 years (SD ± 10.3), median disease duration was 16 years (range 1-49), and 70% were male. Mean BASDAI was 6.1 (SD ± 1.7) and mean AS disease activity index (ASDAS) was 3.8 (SD ± 0.8) at baseline. After 3 years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased BALP Z-score and significantly decreased sCTX Z-score compared to baseline. Baseline to 3 months decrease in sCTX Z-score (HR: 0.513, 95% CI: 0.367-0.717) was inversely associated with time to discontinuation of TNF-α blocking therapy in univariate Cox regression. Multivariate analysis showed that baseline to 3 months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263-0.591), ASDAS (HR: 0.488, 95% CI: 0.317-0.752), and physician’s global disease activity (GDA) (HR: 0.739, 95% CI: 0.600-0.909) were independent inversely related predictors of time to treatment discontinuation. Conclusions In addition to the ASDAS and physician’s GDA, early change in bone resorption marker sCTX after starting treatment can serve as an objective measure in the prediction of long-term continuation of TNF-α blocking therapy in AS. Disclosure of Interest None Declared

Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study

IntroductionIdentifying ankylosing spondylitis (AS) patients who are likely to benefit from tumor necrosis factor-alpha (TNF-α) blocking therapy is important, especially in view of the costs and potential side effects of these agents. Recently, the AS Disease Activity Score (ASDAS) has been developed to assess both subjective and objective aspects of AS disease activity. However, data about the predictive value of the ASDAS with respect to clinical response to TNF-α blocking therapy are lacking. The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-α blocking therapy in AS patients in daily clinical practice.MethodsAS outpatients who started TNF-α blocking therapy were included in the Groningen Leeuwarden Ankylosing Spondylitis (GLAS) study, an ongoing prospective longitudinal observational cohort study with follow-up visits according to a fixed protocol. For the present analysis, patients were excluded if they had previously received anti-TNF-α treatment. Predictor analyses of response and treatment discontinuation were performed using logistic and Cox regression models, respectively.ResultsBetween November 2004 and April 2010, 220 patients started treatment with infliximab (n = 32), etanercept (n = 137), or adalimumab (n = 51). At three and six months, 68% and 63% of patients were Assessments in Ankylosing Spondylitis (ASAS)20 responders, 49% and 46% ASAS40 responders, and 49% and 50% Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)50 responders, respectively. Baseline predictors of response were younger age, male gender, higher ASDAS score, higher erythrocyte sedimentation rate (ESR) level, higher C-reactive protein (CRP) level, presence of peripheral arthritis, higher patient's global assessment of disease activity, and lower modified Schober test. In August 2010, 64% of patients were still using their TNF-α blocking agent with a median follow-up of 33.1 months (range 2.4 to 68.2). Baseline predictors of discontinuation of TNF-α blocking therapy were female gender, absence of peripheral arthritis, higher BASDAI, lower ESR level, and lower CRP level.ConclusionsBesides younger age and male gender, objective variables such as higher inflammatory markers or ASDAS score were identified as independent baseline predictors of response and/or continuation of TNF-α blocking therapy. In contrast, higher baseline BASDAI score was independently associated with treatment discontinuation. Based on these results, it seems clinically relevant to include more objective variables in the evaluation of anti-TNF-α treatment.