Optimisation of tocilizumab therapy in giant cell arteritis. A multicentre real-life study of 471 patients.

OBJECTIVES: Tocilizumab (TCZ) is the only biologic therapy approved for giant cell arteritis (GCA). There is general agreement on the initial/maintenance dose, duration of TCZ therapy is not well established. In GiACTA trial, after one year on TCZ, most patients had GCA relapse after withdrawal. The aim of this study is to assess the effectiveness and safety of TCZ therapy optimisation in a large unselected series of patients with GCA in a clinical practice scenario. METHODS: We carried out a multicentre study on 471 GCA patients treated with TCZ. Once prolonged remission was achieved (n=231) and based on a decision between patient and physician, TCZ was optimised (n=125). We compared optimised (TCZOPT) and not optimised (TCZNON-OPT) groups. Prolonged remission defined as normalisation of clinical and laboratory data for 6 months. Optimisation was carried out by decreasing TCZ dose and/or increasing dosing interval. RESULTS: We evaluated 231 GCA patients on TCZ in prolonged remission. At TCZ onset, no differences in demographic, clinical, or laboratory data were observed. First TCZ optimisation was performed after a median follow-up of 12[6-17] months. Intravenous TCZ was optimised from 8 to 4mg/kg/4weeks in 44% patients, while subcutaneous TCZ was optimised from 162mg/w to 162mg/every-other-week in 65% cases. At the end of follow-up, prolonged remission (78.2% vs. 84.2%; p=0.29) and relapses (5.6% vs. 10.4%, p=0.177) were similar in TCZOPT vs. TCZNON-OPT. Severe infections were more frequent in TCZNON-OPT (12.9% vs. 6.6%; p=0.009). CONCLUSIONS: TCZ optimisation may be done once complete remission is achieved by reducing dose or increasing dosing interval. This seems to be effective, safe and cost-effective therapeutic scheme.

Objectives and methodology of BIOBADASER phase iii. / Objetivos y metodología de la fase iii de BIOBADASER.

OBJECTIVE: Describe the objectives, methods and results of the first year of the new version of the Spanish registry of adverse events involving biological therapies and synthetic drugs with an identifiable target in rheumatic diseases (BIOBADASER III). METHODOLOGY: Multicenter prospective registry of patients with rheumatic inflammatory diseases being treated with biological drugs or synthetic drugs with an identifiable target in rheumatology departments in Spain. The main objective of BIOBADASER Phase III is the registry and analysis of adverse events; moreover, a secondary objective was added consisting of assessing the effectiveness by means of the registry of activity indexes. Patients in the registry are evaluated at least once every year and whenever they experience an adverse event or a change in treatment. The collection of data for phase iii began on 17 December 2015. RESULTS: During the first year, 35 centers participated. The number of patients included in this new phase in December 2016 was 2,664. The mean age was 53.7 years and the median duration of treatment was 8.1 years. In all, 40.4% of the patients were diagnosed with rheumatoid arthritis. The most frequent adverse events were infections and infestations. CONCLUSIONS: BIOBADASER Phase III has been launched to adapt to a changing pharmacological environment, with the introduction of biosimilars and small molecules in the treatment of rheumatic diseases. This new stage is adapted to the changes in the reporting of adverse events and now includes information related to activity scores.

Validity of the bath ankylosing spondylitis disease activity index for the evaluation of disease activity in axial psoriatic arthritis.

OBJECTIVE: To assess the validity of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for the evaluation and definition of disease activity of axial psoriatic arthritis (PsA). METHODS: Fifty-four peripheral PsA, 46 axial PsA, and 103 primary ankylosing spondylitis (AS) patients were assessed. Patients were classified as having axial PsA if they had grade 2 or higher unilateral sacroiliitis in the presence of spinal symptoms. The 3 groups of patients were evaluated using several measurements for AS. Assessments of acceptability, data quality, internal consistency, construct validity, and responsiveness of the BASDAI were undertaken. Disease activity of the disease was assessed in peripheral PsA and axial PsA patients using the BASDAI, and compared with those with AS. RESULTS: For peripheral PsA patients, the Cronbach's alpha for the BASDAI was 0.783, for axial PSA patients it was 0.647, and for AS patients it was 0.786. The analysis of convergent validity showed that in peripheral PsA and axial PsA patients, the BASDAI was significantly correlated with other subjective disease activity parameters. For responsiveness, no association was found between changes in the BASDAI and changes in disease activity either in peripheral PsA or in axial PsA. BASDAI scores were similar in axial PsA and AS. Axial PsA patients with a BASDAI score >4 cm showed significant differences with peripheral PsA in terms of disease activity and were very similar to patients with AS. CONCLUSION: The BASDAI performed similarly in evaluating disease activity in both axial and peripheral PsA. The BASDAI does not seem to be a good index for evaluating disease activity in axial PsA.

Association of interferon regulatory factor 5 haplotypes, similar to that found in systemic lupus erythematosus, in a large subgroup of patients with rheumatoid arthritis.

OBJECTIVE: Previous studies have shown either a lack of effect of IRF5 polymorphisms or an association of the IRF5 gene in only a minor subset of rheumatoid arthritis (RA) patients in whom anti-citrullinated protein antibodies (ACPAs) are absent. The present study was undertaken to investigate the role of genetic variation in IRF5 in susceptibility to RA. METHODS: Nine IRF5 single-nucleotide polymorphisms (SNPs) were studied in 1,338 patients with RA and 1,342 control subjects in analyses of exploratory and replication sample collections, with stratification according to sex and by the presence or absence of ACPAs, rheumatoid factor, the shared epitope, the 620W PTPN22 allele, and erosions. A meta-analysis that included results from previous studies was also carried out. RESULTS: Our findings together with those from previous studies, in a total of 4,620 RA patients and 3,741 controls, showed a significant association of the rs2004640 IRF5 SNP in RA patients as a whole (odds ratio [OR] 0.88, 95% confidence interval [95% CI] 0.83-0.94; P = 6.5 x 10(-5) versus controls). This association was stronger in ACPA- patients, but was also present in ACPA+ patients (from 3 sample collections). Further analysis of our exploratory sample collection showed that only patients in the ACPA+ and SE- group lacked an association with IRF5 SNPs. All of the remaining RA patients (ACPA- or SE+) showed a strong association with IRF5 SNPs, which followed a complex pattern of opposing effects mediated by independent haplotypes. The susceptibility haplotype showed an OR of 1.8 (95% CI 1.4-2.3; P = 1.2 x 10(-6) versus controls), whereas the protective haplotype showed an OR of 0.76 (95% CI 0.6-0.98; P = 0.046 versus controls). CONCLUSION: IRF5 polymorphisms seem to influence RA susceptibility in a large subgroup of patients, following a pattern of association very similar to that described in patients with systemic lupus erythematosus.

[Prevalence and risk factors in osteoarthritis]. / Prevalencia y factores de riesgo de la osteoartritis.

Osteoarthritis is one of the most common chronic conditions; it is a leading cause of disability in older adults and generates high costs. Incidence and prevalence of the disease varies according to the definition used. Diagnosis is established according to clinical or radiological, and ideally according to both. Joints most frequently affected are hands, knees and hip, although population distribution varies depending on the population studied. We review the prevalence of these three groups of osteoarthritis in the five continents, and we discuss the risk factors most frequently associated to each one.