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

Contains fulltext : 96669.pdf (publisher's version ) (Open Access)INTRODUCTION: Identifying ankylosing spondylitis (AS) patients who are likely to benefit from tumor necrosis factor-alpha (TNF-alpha) 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-alpha blocking therapy are lacking. The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-alpha blocking therapy in AS patients in daily clinical practice. METHODS: AS outpatients who started TNF-alpha 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-alpha treatment. Predictor analyses of response and treatment discontinuation were performed using logistic and Cox regression models, respectively. RESULTS: Between 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-alpha blocking agent with a median follow-up of 33.1 months (range 2.4 to 68.2). Baseline predictors of discontinuation of TNF-alpha blocking therapy were female gender, absence of peripheral arthritis, higher BASDAI, lower ESR level, and lower CRP level. CONCLUSIONS: Besides 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-alpha 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-alpha treatment

Daily physical activity in ankylosing spondylitis:validity and reliability of the IPAQ and SQUASH and the relation with clinical assessments

Introduction: The aim of this study was to investigate the construct validity and test-retest reliability of the International Physical Activity Questionnaire (IPAQ; long form) and the Short QUestionnaire to Assess Health-enhancing physical activity (SQUASH) and to investigate the relation between daily physical activity and clinical assessments in patients with ankylosing spondylitis (AS). Methods: For validity, the self-report questionnaires IPAQ and SQUASH were compared with daily physical activity assessed with the ActiGraph accelerometer during 7 consecutive days in 63 AS outpatients. For reliability, the IPAQ and SQUASH were administered twice approximately 1 week apart in 52 AS outpatients. In all 115 patients, clinical assessments were performed at the outpatient clinic. Results: IPAQ and SQUASH total scores correlated significantly with accelerometer outcome: rho = 0.38 and r = 0.35, respectively. Intraclass correlation coefficients between first and second assessments of the IPAQ and SQUASH were 0.83 and 0.89, respectively. Bland-Altman analyses showed no systemic bias, but in particular for the IPAQ the 95% limits of agreement were wide. Daily physical activity assessed by accelerometer, IPAQ, and SQUASH correlated significantly with disease activity, physical activity, and quality of life. A relation with spinal mobility was found only for the accelerometer and SQUASH. The direction of these correlations indicates that higher daily physical activity is related to lower disease activity and better physical function, spinal mobility and quality of life. Conclusions: Both physical activity questionnaires showed modest construct validity. The SQUASH showed good test-retest reliability, superior to the IPAQ. These results indicate that the SQUASH is more suitable than the IPAQ to assess daily physical activity in AS population studies. However, it is desirable to add questions on AS-specific physical activity. Further studies are needed to investigate the causality of the relation between daily physical activity and clinical assessments

A comparison of an interferon-gamma release assay and tuberculin skin test in refractory inflammatory disease patients screened for latent tuberculosis prior to the initiation of a first tumor necrosis factor α inhibitor

Treatment with TNFα inhibitors increases risk of reactivating a latent tuberculosis\infection (LTBI). Therefore screening, prior to therapy with TNFα inhibitors, has been recommended, even in low-endemic areas such as well-developed Western Europe countries. We evaluated interferon-gamma release assay (IGRA), as opposed to tuberculin skin test (TST), for detection of LTBI in refractory inflammatory disease patients prior to the initiation of a first TNFα inhibitor. In addition, we evaluated the impact of impaired cellular immunity on IGRA. Patients starting on TNFα inhibition were screened for LTBI by TST and IGRA (Quantiferon-TB Gold). Data on tuberculosis exposure and Bacillus Calmette–Guérin (BCG) vaccination were obtained. Cellular immunity was assessed by CD4+ T lymphocyte cell count. Nine out of 56 patients (16.1%) tested positive for LTBI. A concordant positive result was present in three patients with a medical history of tuberculosis exposure. Six patients with discordant test results had either: (1) a negative TST and positive IGRA in combination with a medical history of tuberculosis exposure (n = 1) or (2) a positive TST and negative IGRA in combination with BCG vaccination (n = 3) or a medical history of tuberculosis exposure (n = 2). CD4+ T lymphocyte cell counts were within normal limits, and no indeterminate results of IGRA were present. IGRA appears reliable for confirming TST and excluding a false positive TST (due to prior BCG vaccination) in this Dutch serie of patients. In addition, IGRA may detect one additional case of LTBI out of 56 patients that would otherwise be missed using solely TST. Immune suppression appears not to result significantly in lower CD4+ T lymphocyte cell counts and indeterminate results of IGRA, despite systemic corticosteroid treatment in half of the patients. Confirmation in larger studies, including assessment of cost-effectiveness, is required

The prevalence of clinical remission in RA patients theated with anti-TNF: results from the Dutch Rheumatoid Arthritis Monitoring (DREAM) registry

Objectives. To evaluate the prevalence of clinical remission and minimal disease activity according to the ACR/European League Against Rheumatism (EULAR) remission, DAS-28 <2.6 and minimal disease activity (MDA) criteria, and to compare the extent of residual disease activity with disability in RA patients after 6 months of treatment with anti-TNF. \ud \ud Methods. In the Dutch Rheumatoid Arthritis Monitoring (DREAM) biologic registry the prevalence of DAS-28 <2.6, MDA and ACR/EULAR remission criteria was assessed. Residual disease activity during MDA or remission was assessed as the percentage of patients with swollen and tender joints, elevated acute-phase reactants and general health on a visual analogue scale (VAS). Disability was evaluated with the HAQ score. \ud \ud Results. Prevalence of DAS-28 <2.6 was 27%, prevalence of MDA was 34% and ACR/EULAR remission was reached by 6% of patients. Residual disease activity was present mostly in the most lenient criteria and occurred most frequently on the level of swollen joint count and VAS score: at least one swollen joint in DAS-28 <2.6, MDA and ACR/EULAR remission was present in, respectively, 51, 54 and 34% of the patients. VAS >1 occurred in, respectively, 67, 69 and 0% of the patients. Modification of the cut-point of the patient-reported outcome increased the prevalence of ACR/EULAR remission, but also the level of disability. \ud \ud Conclusion. MDA and DAS-28 <2.6 are reachable treatment targets in RA with anti-TNF, although residual disease activity might still be present. In turn, ACR/EULAR remission criteria leave little residual disease activity, but might be too stringent for use in daily clinical practice due to the strict cut-point in the patient-reported outcom

Convergent validity of the PsAQoL.

<p>PsAQoL, psoriatic arthritis quality of life; HAQ, health assessment questionnaire; Skin-17, Skindex-17.</p>*<p>P<0.01.</p

Characteristics of the psoriatic arthritis (PsA) study population.

<p>Data obtained from self-reports.</p>A<p> = responders 1^st series of questionnaires;</p>B<p> = 1^st series PsAQoL complete; used for internal con- sistency assessment;</p>C<p> = 1^st and 2^nd series PsAQoL complete; used for calculating test-retest reliability;</p>D<p> = 1^st series PsAQoL, HAQ and Skindex complete; used for convergent validity analyses.</p><p>PsA, psoriatic arthritis; n, number; y, years; SD, standard deviation; DMARD, disease-modifying antirheumatic drugs; anti-TNFα, anti-tumor necrosis factor α; NSAID, non-steroidal anti- inflammatory drug; PsAQoL, psoriatic arthrtitis quality of life; HAQ, health assessement questionnaire.</p

Bland-Altman plot PsAQoL.

<p>Difference between the 1^st and 2^nd PsAQoL plotted against the mean of both assessments. PsAQoL, Psoriatic Arthritis Quality of Life; LOA, limits of agreement; CI, confidence interval.</p

Scores on the PsAQoL, HAQ and Skindex-17 at first and second assessment.

<p>PsAQoL, psoriatic arthritis quality of life; HAQ, health assessment questionnaire; Skin-17, Skindex-17; N, number of patients.</p