Biologic therapy in refractory neurobehçet's disease: a multicentre study of 41 patients and literature review.

OBJECTIVES: To assess efficacy and safety of biologic therapy (BT) in neurobehçet's disease (NBD) refractory to glucocorticoids and at least one conventional immunosuppressive drug. METHODS: Open-label, national, multicentre study. NBD diagnosis was based on the International Consensus Recommendation criteria. Outcome variables were efficacy and safety. Main efficacy outcome was clinical remission. Other outcome variables analysed were glucocorticoid-sparing effect and improvement in laboratory parameters. RESULTS: We studied 41 patients [21 women; age 40.6 (10.8) years]. Neurological damage was parenchymal (n = 33, 80.5%) and non-parenchymal (n = 17, 41.5%). First BTs used were infliximab (n = 19), adalimumab (n = 14), golimumab (n = 3), tocilizumab (n = 3) and etanercept (n = 2). After 6 months of BT, neurological remission was complete (n = 23, 56.1%), partial (n = 15, 37.6%) and no response (n = 3, 7.3%). In addition, median (IQR) dose of oral prednisone decreased from 60 (30-60) mg/day at the initial visit to 5 (3.8-10) mg/day after 6 months (P < 0.001). It was also the case for mean erythrocyte sedimentation rate [31.5 (25.6)-15.3 (11.9) mm/1st h, P = 0.011] and median (IQR) C-reactive protein [1.4 (0.2-12.8) to 0.3 (0.1-3) mg/dl, P = 0.001]. After a mean follow-up of 57.5 months, partial or complete neurological remission persisted in 37 patients (90.2%). BT was switched in 22 cases (53.6%) due to inefficacy (n = 16) or adverse events (AEs) (n = 6) and discontinued due to complete prolonged remission (n = 3) or severe AE (n = 1). Serious AEs were observed in two patients under infliximab treatment. CONCLUSIONS: BT appears to be effective and relatively safe in refractory NBD.

Long-term survival of biological therapy in psoriatic arthritis: 18-year analysis of a cohort in a tertiary hospital.

To study retention of biologic disease-modifying anti-rheumatic drugs (bDMARDs) or apremilast and potential predictors of lack of response in patients with psoriatic arthritis (PsA). A single-center retrospective analysis of PsA patients who received ≥ 1 bDMARD or apremilast during 2000-2018. The main endpoint was lack of response (primary or secondary failure). Analyses included retention of DMARDs (Kaplan-Meier curves) and potential predictors of lack of response (bivariate and multivariate logistic regression models). A total of 159 patients with PsA received up to 8 DMARDs: etanercept (34%), adalimumab (30%), infliximab (9%), golimumab (9%), apremilast (7%), ustekinumab (5%), certolizumab (4%), and secukinumab (2%). Therapy was discontinued in 96 cases (60%), mainly owing to secondary failure (37%), followed by primary failure (25%) and adverse effects (24%). Retention was analyzed based on 313 units of analysis. Duration of follow-up was 846.1 treatment-years (maximum 14.8 years, median 2.75 years). A total of 172 DMARDs were discontinued. The probability of continuing the initial treatment was 37% at 5 years, 22% at 10 years, and 12% at 14 years. The longest medium retention time was observed for infliximab (6.2 years) and etanercept (4.5 years). Predictors of lack of response included male sex, number of swollen joints, and, especially, depression (OR = 35.2). The sensitivity and specificity of the model were 86.4% and 85.7%, respectively, with a coefficient of determination (R2) of 45.6 (ROC, 0.912). Rates of discontinuation due to primary and secondary failure are high in PsA. Retention is better for anti-TNF agents than for other agents.

Imbalance Between Omega-6- and Omega-3-Derived Bioactive Lipids in Arthritis in Older Adults.

Elderly-onset rheumatoid arthritis (EORA) and polymyalgia rheumatica (PMR) are common rheumatic diseases in older adults. Oxylipins are bioactive lipids derived from omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) that serve as activators or suppressors of systemic inflammation. We hypothesized that arthritis symptoms in older adults were related to oxylipin-related perturbations. Arthritis in older adults (ARTIEL) is an observational prospective cohort with 64 patients older than 60 years of age with newly diagnosed arthritis. Patients' blood samples at baseline and 3 months posttreatment were compared with 18 controls. A thorough clinical examination was conducted. Serum oxylipins were determined by mass spectrometry. Data processing and statistical analysis were performed in R. Forty-four patients were diagnosed with EORA and 20 with PMR. At diagnosis, EORA patients had a mean DAS28CRP (Disease Activity Score 28 using C-reactive protein) of 5.77 (SD 1.02). One hundred percent of PMR patients reported shoulder pain and 90% reported pelvic pain. Several n-6- and n-3-derived oxylipin species were significantly different between controls and arthritis patients. The ratio of n-3/n-6 PUFA was significantly downregulated in EORA but not in PMR patients as compared to controls. The top two candidates as biomarkers for differentiating PMR from EORA were 4-HDoHE, a hydroxydocosahexaenoic acid, and 8,15-dihydroxy-eicosatrienoic acid (8,15-diHETE). The levels of n-3-derived anti-inflammatory species increased in EORA after treatment. These results suggest that certain oxylipins may be key effectors in arthrtis in older adults and that the imbalance between n-6- and n-3-derived oxylipins might be related to pathobiology in this population.