GO-DACT: a phase 3b randomised, double-blind, placebo-controlled trial of GOlimumab plus methotrexate (MTX) versus placebo plus MTX in improving DACTylitis in MTX-naive patients with psoriatic arthritis.

OBJECTIVES: To assess the efficacy of golimumab in combination with methotrexate (MTX) versus MTX monotherapy in psoriatic arthritis (PsA) dactylitis. METHODS: Multicentre, investigator-initiated, randomised, double-blind, placebo-controlled, parallel-design phase 3b trial in 11 Portuguese rheumatology centres. Patients with PsA along with active dactylitis and naive to MTX and biologic disease-modifying antirheumatic drugs (bDMARDs) were randomly assigned to golimumab or placebo, both in combination with MTX. The primary endpoint was Dactylitis Severity Score (DSS) change from baseline to week 24. Key secondary endpoints included DSS and Leeds Dactylitis Index (LDI) response, and changes from baseline in the LDI and MRI dactylitis score. Analysis was by intention-to-treat for the primary endpoint. RESULTS: Twenty-one patients received golimumab plus MTX and 23 MTX monotherapy for 24 weeks. One patient from each arm discontinued. Patient inclusion was halted at 50% planned recruitment due to a favourable interim analysis. Median baseline DSS was 6 in both arms. By week 24, patients treated with golimumab plus MTX exhibited significantly greater improvements in DSS relative to MTX monotherapy (median change of 5 vs 2 points, respectively; p=0.026). In the golimumab plus MTX arm, significantly higher proportions of patients achieved at least 50% or 70% improvement in DSS and 20%, 50% or 70% improvement in LDI in comparison to MTX monotherapy. CONCLUSIONS: The combination of golimumab and MTX as first-line bDMARD therapy is superior to MTX monotherapy for the treatment of PsA dactylitis. TRIAL REGISTRATION NUMBER: NCT02065713.

Predictors and causes of first-line biologic agent discontinuation in rheumatoid arthritis: data from Reuma.pt.

OBJECTIVES: To assess the discontinuation of first-line biological treatment and to evaluate the reasons and predictors thereof in patients with rheumatoid arthritis (RA) from daily clinical practice. METHODS: RA patients registered in the Rheumatic Diseases Portuguese Register (Reuma.pt) starting treatment with biologic DMARDs (bDMARDs) were included in this prospective observational study. The main outcome was the time to discontinuation (in years) due to any cause. Discontinuation was defined as a 90-day discontinuation of treatment or the occurrence of any switch to another bDMARD during follow-up. Baseline and time-varying sociodemographic and clinical characteristics were tested as possible predictors of discontinuation using multivariable Cox models. RESULTS: Of the 1,851 RA patients included in the study, 871 (47%) discontinued their first bDMARD. The median overall persistence of the first bDMARD was 5.5 years and the leading cause of discontinuation was inefficacy [N=476 (55%)], followed by adverse events [N=262 (30%)], other causes [N=69, (8%)] and unknown causes [N=64 (7%)]. Patients with a higher HAQ score (more disability) at baseline were more likely to discontinue their first bDMARD [hazard ratio (HR):1.39 (95% CI: 1.17-1.64)], as were patients with a higher number of comorbidities [HR: 1.17 (1.05-1.29)] and patients starting treatment from 2007 onwards [HR:1.89 (1.5-2.38)]. On the contrary, receiving TNFi bDMARD [HR:0.74 (0.57-0.94)] as opposed to non-TNFi was associated with less discontinuation. Expectedly, the higher the DAS28 during follow-up the higher the likelihood to discontinue bDMARD [HR:1.08 (1.06-1.1)]. No other time-varying predictor was found. CONCLUSION: In the Portuguese RA population, maintenance of first-line bDMARD was shown to be relatively high. Inefficacy was the leading cause of discontinuation. Features found to predict drug discontinuation (e.g. baseline disability) may contribute to inform clinician's decisions in clinical practice.

Translation, cross-cultural adaptation and validation of the Osteoarthritis Quality of Life (OAQoL) questionnaire for use in Portugal.

Osteoarthritis (OA) is the most prevalent rheumatic disease and is a leading cause of decreased quality of life (QoL). The OA Quality of Life questionnaire (OAQoL) is an OA-specific patient-reported outcome measures. The aim of this study was to translate and validate the original UK English version of the Osteoarthritis Quality of Life (OAQoL) questionnaire into European Portuguese. The translation of the questionnaire was carried out according to a dual panel methodology (bilingual panel followed by lay panel). This was followed by cognitive debriefing interviews (CDIs) with OA patients to assess comprehension and relevance of the translated questionnaire. Finally, a validation survey was conducted to assess its psychometric properties. The Portuguese OAQoL, a comparator scale (the Nottingham Health Profile-NHP) as well as questions relating to demographic and disease information were administered to OA patients. A sub-sample of patients also completed the Portuguese OAQoL two weeks later, to assess test-retest reliability. The internal consistency, construct validity and known group validity (according to perceived OA severity) of the scale was also assessed. Both the bilingual and lay panels consisted of five individuals and no major difficulties relating to the translation process were identified. A total of ten patients with OA participated in the CDIs. The mean time to complete the questionnaire was 5 min. These interviews revealed that the Portuguese version of the OAQoL was clear, relevant and easy to complete. Finally, 53 OA patients (44 females; mean age of 67.6 years) completed the validation survey. Cronbach's alpha coefficient was 0.87, demonstrating high internal consistency. Test-retest reliability, assessed by Spearman's rank correlation coefficient, was 0.86. Moderate correlations were found with the majority of the NHP sections, providing evidence of construct validity. Significant differences in OAQoL scores were found between patients who differed according to their perceived OA severity, providing evidence of known group validity. The Portuguese version of the OAQoL is a valid and reliable questionnaire that can be used to assess QoL in OA, both in clinical practice and for research purposes.

Portuguese recommendations for the use of biological therapies in patients with axial spondyloarthritis - 2016 update.

OBJECTIVE: To update the recommendations for the treatment of axial spondyloarthritis (axSpA) with biological therapies, endorsed by the Portuguese Society of Rheumatology. METHODS: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting, the 7 recommendations included in this document were discussed and updated. A draft of the full text of the recommendations was then circulated and suggestions were incorporated. A final version was again circulated before publication and the level of agreement among Portuguese Rheumatologists was anonymously assessed using an online survey. RESULTS: A consensus was achieved regarding the initiation, assessment of response and switching of biological therapies in patients with axSpA. In total, seven recommendations were produced. The first recommendation is a general statement indicating that biological therapy is not a first-line drug treatment option and should only be used after conventional treatment has failed. The second recommendation is also a general statement about the broad concept of axSpA adopted by these recommendations that includes both non-radiographic and radiographic axSpA. Recommendations 3 to 7 deal with the definition of active disease (including the recommended threshold of 2.1 for the Ankylosing Spondylitis Disease Activity Score [ASDAS] or the threshold of 4 [0-10 scale] for the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), conventional treatment failure (nonsteroidal anti-inflammatory drugs being the first-line drug treatment), assessment of response to treatment (based on an ASDAS improvement  of at least 1.1 units or a BASDAI improvement of at least 2 units [0-10 scale] or at least 50%), and strategy in the presence of an inadequate response (where switching is recommended) or in the presence of long-term remission (where a process of biological therapy optimization can be considered, either a gradual increase in the interval between doses or a decrease of each dose of the biological therapy). CONCLUSION: These recommendations may be used for guidance in deciding which patients with axSpA should be treated with biological therapies. They cover a rapidly evolving area of therapeutic intervention. As more evidence becomes available and more biological therapies are licensed, these recommendations will have to be updated.