Factors influencing the choice of biologic therapy following Rituximab in patients with rheumatoid arthritis: A retrospective study using propensity score.

OBJECTIVES: To assess factors influencing the choice and effectiveness of biological disease-modifying antirheumatic drugs (DMARDs) following failure of rituximab (RTX) in rheumatoid arthritis (RA), taking patient profile into account. METHODS: In a retrospective, multicenter study, data about RA patients starting a new biologic during the year after RTX discontinuation were collected at baseline (when the biologic was introduced after RTX), and during follow-up (3, 6, and 12 months). Characteristics of patients receiving tocilizumab (TCZ), abatacept (ABA), or a TNFα inhibitor (TNFi), EULAR response, and retention rate were compared using multidimensional factorial analysis for patient profiles and multivariate analysis including propensity score built on the patient profile. RESULTS: Among 152 patients analyzed (37.5% TCZ, 31.6% ABA, 30.9% TNFi), sex, disease characteristics and activity, concomitant DMARDs or glucocorticoids, and previous use of RTX and TNFi were similar at baseline. Patients receiving ABA were slightly older. Multimorbidity index was higher but not significantly different. Multidimensional factorial analysis showed a distinct profile of patients receiving ABA, characterized by older age, more men, more smokers, more comorbidities, and higher anti-cyclic citrullinated peptide antibody. At 1 year, drug retention was higher for ABA than TNFi after adjustment for disease duration, concomitant DMARDs, glucocorticoids, and propensity score (P=0.04). Tolerance and serious infections were similar among groups. CONCLUSIONS: The profile of patients receiving ABA following failure of RTX differed from TNFi and TCZ using multidimensional factorial analysis. After adjustment for propensity score, drug retention rate remained higher with ABA than TNFi.

Diosgenin, a plant steroid, induces apoptosis in human rheumatoid arthritis synoviocytes with cyclooxygenase-2 overexpression.

In the present study, we have shown for the first time that a plant steroid, diosgenin, causes an inhibition of the growth of fibroblast-like synoviocytes from human rheumatoid arthritis, with apoptosis induction associated with cyclooxygenase-2 (COX-2) up-regulation. Celecoxib, a selective COX-2 inhibitor, provoked a large decrease in diosgenin-induced apoptosis even in the presence of exogenous prostaglandin E2, whereas interleukin-1beta, a COX-2 inducer, strongly increased diosgenin-induced apoptosis of these synoviocytes. These findings suggest that the proapoptotic effect of diosgenin is associated with overexpression of COX-2 correlated with overproduction of endogenous prostaglandin E2. We also observed a loss of mitochondrial membrane potential, caspase-3 activation, and DNA fragmentation after diosgenin treatment.