Does a short course of etanercept influence disease progression and radiographic changes in patients suspected of non-radiographic axial spondyloarthritis? Three -years follow- up of a placebo-controlled trial.

OBJECTIVE: To study the long-term effect of 16 weeks of etanercept treatment on disease activity and radiographic changes in patients with suspected non-radiographic axial spondyloarthritis (nr-axSpA). METHOD: Eighty patients with inflammatory back pain and suspected nr-axSpA, with a Bath Ankylosing Disease Activity Index (BASDAI) ≥ 4, received etanercept (n = 40) 25 mg twice weekly or placebo (n = 40) for 16 weeks. They were followed without treatment restrictions after 24 weeks, for up to 3 years. Comparisons were made between patients who received etanercept or placebo in the first period, and changes in BASDAI, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Metrology Index (BASMI), function, and radiographic changes in the spine [according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS)] and sacroiliac joints (Bath Ankylosing Spondylitis Radiology Index (BASRI). RESULTS: After 3 years of follow-up, 84% of the patients were diagnosed with SpA, predominantly axSpA. Biological treatment was started after 24 weeks in 30% of patients. Disease activity scores after 3 years did not reveal significant differences between the initial randomization groups in mean BASDAI scores (mean difference 0.9, 95% CI -1.1;0.7, p = 0.6) and ASDAS (mean ASDAS 0.3, 95% CI 0.6;3.1, p = 0.5). BASMI and function scores remained stable over 3 years. No differences in radiographic changes of the sacroiliac joints or spine were observed over 3 years between the two groups. CONCLUSION: A short course of etanercept in patients with suspected nr-axSpA did not affect disease activity, the chance of biological treatment, or radiographic progression after 3 years of follow-up.

Disease activity in women with ankylosing spondylitis remains higher under Tumour Necrosis Factor inhibitor treatment than in men: a five-year observational study.

OBJECTIVE: To assess sex differences in response, level of disease activity, and drug survival in tumour necrosis factor inhibitor (TNFi)-naïve ankylosing spondylitis (AS) patients. METHOD: Consecutive AS patients, fulfilling the modified New York criteria, were included in a prospective cohort study at initiation of the first TNFi and followed until this medication was stopped (drug survival). Disease activity scores [AS Disease Activity Score using C-reactive protein (ASDAS-CRP), Bath AS Disease Activity Index (BASDAI), and CRP] were measured at 3, 6, and 12 months, and every subsequent year, up to 5 years. The response was defined by the ASDAS-CRP response criteria (clinically important improvement: ASDAS-CRP decrease ≥ 1.1). Analyses included regression methods for repeated measurements and survival analyses. RESULTS: Overall, 356 patients were included (34% women, mean ± sd age 46 ± 12 years), with a median disease duration of 12 (interquartile range 6;20) years. Women were less likely than men to achieve a clinically important response after 6 months of TNFi treatment (47% vs 64%; relative risk 1.4, 95% confidence interval (CI) 1.1;1.9, p = 0.02], despite a lack of sex differences in mean ASDAS-CRP levels over 5 year follow-up. Adjusted models for BASDAI over 5 years showed that women had a 0.6 point higher BASDAI score than men (ß = 0.6 0.1;1.1 <0.02). Numerically, more women than men discontinued treatment over a period of 5 years (hazard ratio = 1.5, 95% CI 0.9;2.5, p = 0.15). CONCLUSION: Female AS patients show a lower response to TNFi and a higher disease activity compared to men.

Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To study the effect of folates on discontinuation of methotrexate (MTX) as single-drug antirheumatic treatment due to toxicity, to determine which type of adverse events are reduced, to study the effects on the efficacy of MTX, and to compare folic with folinic acid supplementation in a 48-week, randomized, double-blind, placebo-controlled trial. METHODS: Patients with active RA (n = 434) were randomly assigned to receive MTX plus either placebo, folic acid (1 mg/day), or folinic acid (2.5 mg/week). The initial MTX dosage was 7.5 mg/week; dosage increases were allowed up to a maximum of 25 mg/week for insufficient responses. Folate dosages were doubled once the dosage of MTX reached 15 mg/week. The primary end point was MTX withdrawal because of adverse events. Secondary end points were the MTX dosage and parameters of efficacy and toxicity of MTX. RESULTS: Toxicity-related discontinuation of MTX occurred in 38% of the placebo group, 17% of the folic acid group, and 12% of the folinic acid group. These between-group differences were explained by a decreased incidence of elevated liver enzyme levels in the folate supplementation groups. No between-group differences were found in the frequency of other adverse events or in the duration of adverse events. Parameters of disease activity improved equally in all groups. Mean dosages of MTX at the end of the study were lower in the placebo group (14.5 mg/week) than in the folic and folinic acid groups (18.0 and 16.4 mg/week, respectively). CONCLUSION: Both folate supplementation regimens reduced the incidence of elevated liver enzyme levels during MTX therapy, and as a consequence, MTX was discontinued less frequently in these patients. Folates seem to have no effect on the incidence, severity, and duration of other adverse events, including gastrointestinal and mucosal side effects. Slightly higher dosages of MTX were prescribed to obtain similar improvement in disease activity in the folate supplementation groups.