Association of anti-citrullinated vimentin and anti-citrullinated ?-enolase antibodies with subsets of rheumatoid arthritis.

[EN] Objective. To determine whether the anti? citrullinated vimentin peptide 60?75 (anti?Cit-vimentin) and the immunodominant anti?citrullinated -enolase peptide 1 (anti?CEP-1) antibodies are associated with subsets of patients with rheumatoid arthritis (RA) independently of the associations between anti?cyclic citrullinated peptide (anti-CCP) antibodies and clinical features of RA. Methods. The 3 antibody types were quantified by enzyme-linked immunosorbent assay (ELISA) in serum samples from 521 patients with RA and 173 healthy controls of Spanish ancestry. Genotypes for HLA?DRB1 alleles and rs2476601 in PTPN22 were available for these patients and controls plus an addi- tional 106 healthy controls. A combined analysis of the 3 antibodies was conducted using stratified contingency tables and logistic regression models. Results. A differential, particularly strong, and independent association was observed between the pres- ence of anti?Cit-vimentin antibodies and the presence of shared epitope (SE) alleles, specifically in patients carrying 2 SE alleles, and between the presence of anti? Cit-vimentin antibodies and the prevalence of joint erosion. Associations were observed between anti? CEP-1 positivity and the presence of HLA?DRB1 and PTPN22 risk alleles and their additive interaction. These associations were not accounted for by the anti- CCP status. Conclusion. Our results indicate that the 2 anti- bodies against citrullinated peptides analyzed in this study add specific information beyond that obtained with the anti-CCP status. They define subgroups of patients with RA in which genetic factors have different weight and there is an observed difference in the prev- alence of erosions.Fondo de Investigaci?n Sanitaria del Instituto de Salud Carlos III (ISCIII)European Regional Development Fund of the European UnionXunta de GaliciaFundaci?n Espa?ola de Reumatolog?

Network Meta-Analysis of Tofacitinib, Biologic Disease-Modifying Antirheumatic Drugs, and Apremilast for the Treatment of Psoriatic Arthritis

Background: Tofacitinib and other new treatments approved for use in psoriatic arthritis have only recently been included in psoriatic arthritis treatment guidelines, and studies evaluating the relative efficacy of available therapies are important to inform treatment decisions by healthcare professionals. Objective: To perform a network meta-analysis to evaluate the efficacy and safety profiles of tofacitinib, biologic disease-modifying antirheumatic drugs (bDMARDs), and apremilast in patients with psoriatic arthritis naive to tumor necrosis factor inhibitor therapy (TNFi-naive) or with an inadequate response (TNFi-IR). Methods: A systematic literature review used searches of MEDLINE, Embase, and The Cochrane Library on October 9, 2017. Randomized controlled trials including adult patients with psoriatic arthritis receiving treatment administered as monotherapy or with conventional synthetic DMARDs were selected. Efficacy outcomes included American College of Rheumatology 20 response, change from baseline in Health Assessment Questionnaire-Disability Index, >/=75% improvement in Psoriasis Area and Severity Index, and change from baseline in Dactylitis Severity Score and Leeds Enthesitis Index. Treatment effects were evaluated during placebo-controlled phases, using a binomial logit model for binary outcomes and a normal identify link model for other outcomes. Discontinuations due to adverse events and serious infection events were assessed as safety outcomes. Results: The network meta-analysis included 24 published randomized controlled trials, of which 13 enrolled TNFi-naive patients only, 3 enrolled TNFi-IR patients only, and 8 enrolled both TNFi-naive and TNFi-IR patients. Placebo-controlled treatment durations ranged from 12 to 24 weeks. Indirect comparisons showed tofacitinib 5 and 10 mg BID to have similar efficacy compared with most bDMARDs and apremilast in improving joint symptoms (based on American College of Rheumatology 20 response), and with some bDMARDs in improving skin symptoms (based on Psoriasis Area and Severity Index) (tofacitinib 10 mg BID only in TNFi-IR) in patients with psoriatic arthritis who were TNFi-naive or TNFi-IR. Results also showed that, compared with placebo, the improvement in physical functioning (based on Health Assessment Questionnaire-Disability Index) with tofacitinib 5 and 10 mg BID was similar to that observed with most bDMARDs and apremilast in TNFi-naive patients, and similar to that observed with all bDMARDs with available data in the TNFi-IR population. Improvements in Dactylitis Severity Score and Leeds Enthesitis Index scores were comparable between treatments. Tofacitinib 5 and 10 mg BID were median-ranked 8 and 15, respectively, for discontinuation due to any adverse events, and 5 and 16, respectively, for a serious infection event out of a total of 20 treatments in the network (lower numbers are more favorable). Conclusions: Tofacitinib provides an additional treatment option for patients with psoriatic arthritis, both in patients naive to TNFi and in those with TNFi-IR. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX)

FCGR polymorphisms in the treatment of rheumatoid arthritis with Fc-containing TNF inhibitors

[EN] Objectives: Reproducible association of a functional polymorphism in FCGR2A with response to a TNF inhibitor (TNFi) in patients with rheumatoid arthritis (RA) led us to explore other Fc?R functional polymorphisms. Methods: Functional polymorphisms FCGR3A F158V, FCGR2B I223T and promoter VNTR in FCGRT were analyzed in up to 429 patients with RA. Response to TNFi was recorded during standard care at 3, 6 and 12 months of follow-up. Fixed effects meta-analysis of studies addressing FCGR3A F158V polymorphism, which is the most studied of these polymorphisms, was conducted with inverse variance weighting. Results: None of the functional polymorphisms were associated with change in DAS28. Meta-analysis of the seven studies (899 patients) with available data addressing association of FCGR3A F158V with response to TNFi in RA showed no association (OR: 1.11, 95% CI: 0.8-1.5; p = 0.5). Conclusion: None of the three functional polymorphisms in Fc?R genes showed association with response to TNFi in patients with RA. These negative results were obtained in spite of the larger size of this study relative to previous studies addressing the same polymorphisms. In addition, meta-analysis of FCGR3A F158V was also negative against the results provided by previous studies

Adherence to Treatment in Patients with Rheumatoid Arthritis from Spain

Objective: To evaluate adherence to treatment in a cohort of patients with rheumatoid arthritis in Spain and to identify potential predictors of adherence. Methods: An observational, cross-sectional, multicenter study in outpatient clinics of Rheumatology Departments from 41 centers was conducted. A validated Spanish version of the compliance questionnaire in Rheumatology was used to measure adherence in a cohort of patients with rheumatoid arthritis, representative of the Spanish population. Univariate and multivariate analyses were performed to detect predictors of adherence. Results: A total of 859 patients were recruited. An adherence rate of 79% was established. No differences were detected in adherence in patients receiving biologic disease-modifying antirheumatic drugs compared to conventional disease-modifying antirheumatic drugs, in patients receiving intravenous therapies compared to other routes of administration and in patients treated in specific day hospitals compared to polyvalent day hospitals. The number of drugs and cohabitation were independent predictors of adherence. Conclusion: An inexpensive and useful method was used to measure adherence in Spanish population. The adherence rate in rheumatoid arthritis is still suboptimal. Simpler, more convenient dosing regimens may improve compliance. Increased knowledge of compliance in patients with rheumatoid arthritis and the identification of possible predictors of adherence will allow to develop effective intervention strategies

Effect of lysophosphatidic acid receptor inhibition on bone changes in ovariectomized mice

[EN] Pharmacological inhibition of signaling through lysophosphatidic acid (LPA) receptors reduces bone erosions in an experimental model of arthritis by mechanisms involving reduced osteoclast differentiation and bone resorption and increased differentiation of osteoblasts and bone mineralization. These results led us to hypothesize that LPA receptor inhibition would be beneficial in osteoporosis. Our aim was to test this hypothesis with the LPA receptor antagonist, Ki16425, in ovariectomized mice, a model of postmenopausal osteoporosis. Ovariectomized mice treated with Ki16425 showed bone loss similar to that observed in the controls. Osteoblast markers, Alpl, Bglap and Col1a1, were increased at the mRNA level but no changes were detected in serum. No additional difference was observed in the Ki16425-treated mice relative to the ovariectomized controls with regard to osteoclast function markers or assays of matrix mineralization or osteoclast differentiation. Thus, pharmacological inhibition of LPA receptor was not beneficial for preventing bone loss in ovariectomized mice, indicating that its favorable effect on bone remodeling is less general than hypothesized

Changing pattern of the use of biologic disease modifying antirheumatic drugs in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis

Background: During the last 15 years, the comprehensive understanding of the safety, effectiveness, expanding access, and availability of new biologic disease-modifying antirheumatic drugs (bDMARDs) has likely contributed to the pattern of use of these compounds in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Objectives: To assess changes in the baseline characteristics of patients who underwent biological therapy from 2007 to 2018 in a real world setting. Methods: Data were obtained from BIOBADASER, the Spanish registry of biologics. Recorded data is obtained from routine clinical practice. Patients diagnosed with RA, PsA and AS and who started biological treatment from 2007 to 2018 were included. Sociodemographic and clinical variables, as well as first bDMARD used, were stratified by the starting year period (2007-2009; 2010-2012; 2013-2015; 2016-2018) and compared using Anova and Chi-square tests. Results: 6943 patients (2827 RA patients, 1274 PsA and 1261 AS) were included in this analysis (Table 1). Patient age at the beginning of the first biologic was significantly higher during the period 2016-2018 than in 2007-2009 (48.3 vs 50.6). Disease duration until the use of biologics decreased from 8.6 to 8.1 years. In RA patients, disease activity, as assessed by DAS28 at the start of the biological treatment, was significantly higher in the 2007-2009 period than in the last period analyzed (5.1 vs 4.7). The use of TNF inhibitor as a first option also changed significantly (94.6% vs 58.5%). Regarding comorbidities, the number of rheumatic patients treated with biologics and a past history of cancer (1.8% vs 3.7%), ischemic heart disease (1.8% vs 3.1%), hypercholesterolemia (13.6% vs 26.1%), or hypertension (21.7% vs 23.7%) has increased significantly. Conclusion: Our data show that during the last decade the pattern of use of biologics in patients with rheumatic diseases has changed. Nowadays these compounds are used in older patients, with shorter disease duration, with lower disease activity in RA, and with more comorbidities

Factors associated to persistence of treatment with golimumab in the biobadaser registry, with up to 6 years of follow-up

Background: Survival, or persistence in treatment with a biological drug can be considered an indirect measure of efficacy, safety and tolerability Objectives: We assessed the probability of persistence (survival) of treatment with golimumab in patients with rheumatic diseases and the factors associated to persistence with up to 6 years of follow-up. Methods: BIOBADASER is the Spanish registry of biological drugs of the Spanish Society of Rheumatology and the Spanish Medicines Agency. A data-base analysis was done in December 2018 on all the patients aged 18 years or more who had initiated golimumab for one of the approved indications (rheumatoid arthritis [RA], axial spondyloarthritis [SpA] or psoriatic arthritis [PsA]). The probability of persistence was calculated with a Kaplan-Meier test. Factors related to persistence were analyzed with a Cox-regression model. Results: 581 patients were included (165 [28.4%] RA, 249 [42.9%] axial SpA and 167 [28.7%] PsA), mean age 51 [12] years, 53% women). Median duration of disease at the onset of golimumab was 8.0 (3.0-14.7) years. Golimumab was prescribed as first biological drug in 37.9% of the patients, as second in 32.1% and as third or further in 30.0%. Concomitant medications at golimumab initiation included steroids (28.2%), methotrexate (MTX) (35.5%), sulphasalazine (7.2%) and leflunomide (13.9%). The probability of persistence of treatment with golimumab since treatment initiation was 74.3% at year 1 (95% CI 70.3 ? 77.8), 63.5% at year 2 (59.0 ? 67.6), 60.5% at year 3 (55.9 ? 65.8), 54.5% (49.1 ? 59.7) at year 4 and 5, and 52.1% (44.9 ? 57.7) at year 6. Persistence was higher when golimumab was used as first biological agent (p log-rank <0.001) and for the treatment of axial SpA or PsA compared to RA (p log-rank <0.001). As first biological drug the probability of persistence was 82.8% (year 1) and 66.5% at year 4. At year 5, survival rates (all lines of therapy) were 59.7%, 63.4% and 37.3% for axial SpA, PsA and RA respectively. Cox-regression analysis (table) showed that the probability of persistence in treatment with golimumab therapy was higher in first vs second or third biological line patients (Hazard Ratio [HR] for discontinuation: 1.78 for second and 2.41 for third or further line versus first line), in SpA and PsA patients (HR discontinuation of RA patients: 1.94 versus PsA), and lower in women (HR: 1.62), in those needing steroids (HR: 1.47) or DMARDs different to MTX (HR: 2.17). Patients treated with MTX had higher but non-significant persistence rate (HR discontinuation 0.79, table). Conclusion: The probability of persistence (survival) on therapy with golimumab was high up to 6 years of follow-up and was higher in patients treated with golimumab as first biological drug or for PsA and SpA, and lower in those needing steroids, DMARDs different to MTX and in women