ObjectivesTo assess the efficacy of golimumab in combination with methotrexate (MTX) versus MTX monotherapy in psoriatic arthritis (PsA) dactylitis.MethodsMulticentre, 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.ResultsTwenty-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.ConclusionsThe combination of golimumab and MTX as first-line bDMARD therapy is superior to MTX monotherapy for the treatment of PsA dactylitis.Trial registration numberNCT02065713
Introduction: The aim of this study was to conduct a systematic review in order to examine the effectiveness of ozone therapy on knee osteoarthritis. The objectives were to evaluate the effect over time of ozone therapy in terms of knee pain, functional improvement and radiographic progression.Material and Methods: A search was carried out on PubMed, Embase, Cochrane Library, Scopus and Web of Science databases to identify randomized and controlled studies focusing on this association. The following descriptors were used in English: ozone therapy, knee osteoarthritis. A descriptive summary and quality assessment was made of all studies included for analysis.Results: Six randomized and controlled studies were identified. The risk of bias assessment demonstrated that one study was considered as having a moderate risk of bias and the remainder a high risk of bias. No quantitative analysis of the data was performed, as the studies included were not sufficiently homogeneous. The participants in the studies were generally elderly patients with mild to moderate knee osteoarthritis.Discussion: The variability of ozone therapy and the comparators demonstrates that there is no standardized therapy. Few studies reported adverse effects, and where they occurred, they were mild and associated with the procedure.Conclusion: Ozone therapy proved effective in the short-term in relation to placebo and when combined with hyaluronic acid, but it was not superior to other current treatments. More randomised and controlled studies are needed to evaluate the risks/benefits of ozone therapy, both in the short term and the medium/long term.
BackgroundPain and stiffness are characteristic clinical features of axial Spondyloarthritis (axSpA), leading to functional impairment. Patients describe beneficial effects of physical activity, suggesting a possible involvement of muscle tissue. Body composition data in young axSpA patients with short disease duration are scarce and its implications in muscle strength are not yet clarified.ObjectivesThe purpose of this study is to assess the muscle strength and body composition of different body segments (trunk, upper and lower limbs), in patients with axSpA and to compare them with healthy controls.MethodsPatients with clinical diagnosis of axSpA meeting the ASAS classification criteria, aged 18 to 50 years, with symptoms duration ≤ 10 years, were included in this study. Healthy individuals matched by gender and age (1:1) were used as control group (HC). Muscle strength was measured by resisted hand-held dynamometer performed by a single reader, in three different body segments: trunk, upper and lower limbs (on both sides). The mean strength of right and left, upper and lower limbs, was calculated and used in the analysis. Strength of each body segment was also normalized to the total lean mass (LM) of the respective segment. Body composition was measured by octapolar multifrequency bioelectrical impedance analysis (InBody770). Physical activity was assessed by the International Physical Activity Questionnaire (IPAQ). Fisher’s exact test or chi-square test and Mann-Whitney U test were used to compare differences between groups.ResultsA total of 27 axSpA patients and 27 HC were included. Mean age was 36.5 ± 1.0 years, 67% were males. There was no significant difference between both groups in terms of age, gender, body mass index and physical activity. AxSpA patients had a mean symptoms duration of 7.0 ± 0.9 years.AxSpA patients had lower muscle strength in the upper limbs (50.55 ± 31.60 vs 71.70±31.41 p=0.023) and lower limbs (52.25±18.45 vs 59.83±9.75, p=0.001), compared to HC. Trunk muscle strength did not show any difference between groups (59.10±26.1 vs 56.45±11.2, p=0.856).There were no significant differences in LM and body water, between both groups, for each segment (upper limbs, lower limbs and trunk). Fat mass was significantly higher in the trunk (10.90±8.80 vs 8.10±5.83, p=0.035) and upper limbs (1.40±1.35 vs 0.88±1.0, p=0.05) of axSpA patients, but not in the lower limbs (3.10±1.90 vs 2.45±1.68, p=0.157).Normalized appendicular muscle strength was lower in axSpA patients (upper limbs: 18.63±8.25 vs 21.21±5.92, p=0.018) (Table).ConclusionYoung patients with short duration have reduced appendicular muscle strength, compared to HC, with no differences in LM, suggesting a possible muscle dysfunction. Further studies are needed to confirm these findings and understand the underlying pathophysiological mechanisms.Abstract THU0395 –Table 1Disclosure of InterestsAgna Neto: None declared, Rita Pinheiro Torres: None declared, Lucia Domingues: None declared, Diana Teixeira: None declared, Santiago Rodrigues-Man...
Background:The response to treatment in spondylarthropaties is heterogeneous, due to factors yet to be better described. For that reason, it is important to find tools that might help clinicians to decide what is the best available therapeutic option for each patient.Objectives:The goal of this study is to use comprehensive molecular profiling to characterize clinical response to therapy in a real-world setting. Specifically, to identify molecular biomarkers differentiating good responders and non-responders to TNF inhibitors (TNFi) treatment, using adalimumab, in radiographic axial spondyloarthritis | ankylosing spondylitis (r-axSpA|AS) patients context.Methods:Whole-blood mRNA and plasma proteins were measured in a cohort of biologic naïve r-axSpA|AS patients (n = 35) from the Bioefficacy study (Biomarkers identification of anti-TNF alpha agent efficacy in AS patients using RNA sequencing and mass spectrometry), pre and post (14 weeks) TNFi treatment using adalimumab. Response to treatment was categorized according to ASAS20. Results of differential expression analysis were used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi.Results:A treatment-related signature, independent of the type of response, suggests a reduction in inflammatory disease activity. We found genes and proteins robustly differentially expressed between baseline and week 14 in responders, including the GWAS AS-associated genes TNFRSF1A, FCGR2A, TYK2, TBKBP1, IL1R1, IL6R, ICOSLG, IL7R, HHAT and LTBR. Moreover, CRP and HP proteins showed strong and early decrease in the plasma of AS patients, while a cluster of apolipoproteins (APO1, APO2, APO3) showed an increased expression at week 14. Good responders to TNFi treatment tend to have higher expression of innate immunity genes at baseline, and lower expression of markers associated with adaptive immunity, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender and Gene x, the top differentially expressed gene at baseline between responders and non-responders, enabled an accurate prediction of response to adalimumab in our cohort (AUC=0.97).Conclusion:Differences in disease activity and/or innate/adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in r-axSpA|AS. Alternatively, a model including clinical and gene expression variables could be considered, particularly in patients with mild disease activity.Disclosure of Interests:None declared
BackgroundThe ASAS-EULAR recommendations for the continuation of biological Disease-Modifying Anti-rheumatic Drugs (DMARD) suggest the evaluation of patients after at least 12 weeks of treatment by either the Ankylosing Spondylitis (AS) Disease Activity Score – C reactive protein (ASDAS-CRP) or by the Bath AS Disease Activity Index (BASDAI). For ASDAS-CRP, a Minimal Clinical Important Difference (MCID) ≥1.1 is necessary, while for the total BASDAI score a 50% reduction or a change of ≥2.0 points is considered clinically relevant. In clinical trials, the Assessment in Ankylosing Spondyloarthritis (ASAS) response criteria – ASAS 20, ASAS 40 and ASAS 70 – are still the most frequent primary outcome measures to evaluate improvement in treatment response. However, in clinical practice the BASDAI is still routinely used.ObjectivesThe aim of this work was to assess the concordance/agreement between different therapeutic outcome measures, such as the ASAS response criteria, ΔASDAS-CRP and BASDAI 50.MethodsData from 54 patients who fulfilled the modified New York criteria for AS were collected at baseline, weeks 2 and 14 post-treatment with Adalimumab. Pearson’s correlation (PCCs) and the Cohen’s Kappa coefficients were calculated for the three scores.ResultsA strong correlation was found between the three scores throughout the visits: rho=−0.676 for ASDAS/ASAS, rho=−0.807 for ASAS/BASDAI, and rho=0.786 for BASDAI/ASDAS (all PCCs with p<0.001). Additionally, when the categorization in different disease activity states and response levels was performed, PCCs revealed significant concordance/agreement between the three scores’ cut-offs (see table 1).The individuals categorised as responders, by eitheir BASDAI50 or ΔASDAS ≥1.1, have shown similar clinical characteristics (Erythrocyte Sedimentation Rate, CRP, AS Quality of Life Scale and Bath AS Functional Index).Importantly, when more stringent measures of ASAS response criteria and ASDAS were used (i.e. ASAS 70 and ASDAS≥2.1) the agreement with BASDAI values decreased.Abstract AB0865 – Table 1Summary information of the Agreement and Cohen’s kappa.†p-value<0.05, n: number of visitsConclusionsOur results suggest that the ASAS response criteria, ΔASDAS-CRP and BASDAI 50 report the same clinical information. Hence, the clinician’s decision should still be consistent independently of the score adopted. However, this study also highlights the importance of establishing a new and more stringent BASDAI cut-off, in alignment with ASDAS-CRP’≥2.1 and ASAS 70.Disclosure of InterestNone declared
Background:Psoriatic arthritis (PsA) dactylitis is associated with an increased risk of erosions and higher disease activity. Dactylitis treatment strategies are however controversial due to the absence of evidence from randomized controlled trials studying dactylitis as a primary outcome.Objectives:To assess the efficacy of golimumab plus MTX versus placebo plus MTX for active dactylitis in PsA patients, in a phase 3b trial.Methods:GO-DACT was a proof-of-concept multicentric, investigator-initiated randomized, double-blind, placebo-controlled, parallel-design trial, conducted in 13 Portuguese Rheumatology Centers. PsA patients, naïve for MTX and biologic disease modifying anti-rheumatic drugs (bDMARDs), with active dactylitis, were randomly allocated to either golimumab in combination with MTX or MTX monotherapy. The primary endpoint was the change from baseline in the dactylitis severity score (DSS) assessed at week 24. Key secondary endpoints included DSS response and the magnetic resonance imaging (MRI) dactylitis score, as well as composite indexes of PsA activity.Results:44 patients were centrally randomized, 21 to golimumab plus MTX and 23 to placebo plus MTX, for 24 weeks, and 1 patient from each arm dropped out. Due to favorable results on a planned interim analysis recruitment was halted. The median MTX dose in the golimumab plus MTX group was 15mg/week and in the MTX monotherapy group 20mg/week. The median baseline DSS was 6 in each arm. Patients treated with golimumab plus MTX experienced significantly greater improvements in the DSS at week 24 (median change of 5) as compared to the MTX group (median change of 2) (p=0.026). At week 24, 12 (60.0%) patients treated with golimumab plus MTX and 4 (18.2%) with MTX, achieved the DSS70 response (p<0.05). Significant differences were also observed in the median changes from baseline to week 24 in MRI dactylitis score, Disease Activity Score 28 (DAS28), Disease Activity Index for PsA (DAPSA), PsA Disease Activity Score (PASDAS) and Target Nail Psoriasis Severity Index (tNAPSI), favoring the golimumab and MTX association arm. Likewise, higher proportions of patients treated with golimumab plus MTX achieved DSS50 responses and the American College of Rheumatology 20/50 responses, at week 24. There were no new safety issues for golimumab during this trial.Conclusion:GO-DACT suggests additional benefits from the combination of golimumab and MTX as first-line bDMARD therapy versus MTX monotherapy, in the treatment algorithm of PsA active dactylitis.ReferenceNot applicableDisclosure of Interests:Elsa Vieira-Sousa Grant/research support from: MSD, Novartis, Pedro Alves: None declared, Ana Maria Rodrigues: None declared, Filipa Teixeira: None declared, José Tavares-Costa: None declared, Alexandra Bernardo: None declared, Sofia Pimenta: None declared, Fernando Pimentel dos Santos Grant/research support from: From Abbvie and Novartis, Speakers bureau: Abbvie, Novartis, Pfizer, Biogen, João Lagoas Gomes: None declared, Renata Aguiar: None declared, Taciana Videira: None ...
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