Benefit-risk profile of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: pooled analysis across six clinical trials.

BACKGROUND: Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate-to-severe chronic plaque psoriasis. OBJECTIVES: To consider the benefits and risks of tofacitinib in patients with moderate-to-severe psoriasis. METHODS: Data were pooled from one phase II, four phase III and one long-term extension study comprising 5204 patient-years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of 'clear' or 'almost clear', ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure. RESULTS: Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients' quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID. CONCLUSIONS: Tofacitinib has a benefit-risk profile in moderate-to-severe psoriasis consistent with that of other systemic treatments.

Factors influencing choice of surgical route of repair of genitourinary fistula, and the influence of route of repair on surgical outcomes: findings from a prospective cohort study.

OBJECTIVE: The abdominal route of genitourinary fistula repair may be associated with longer term hospitalisation, hospital-associated infection and increased resource requirements. We examined: (1) the factors influencing the route of repair; (2) the influence of the route of repair on fistula closure 3 months following surgery; and (3) whether the influence of the route of repair on repair outcome varied by whether or not women met the published indications for abdominal repair. DESIGN: Prospective cohort study. SETTING: Eleven health facilities in sub-Saharan Africa and Asia. POPULATION: The 1274 women with genitourinary fistula presenting for surgical repair services. METHODS: Risk ratios (RRs) and 95% confidence intervals (95% CIs) were generated using log-binomial and Poisson (log-link) regression. Multivariable regression and propensity score matching were employed to adjust for confounding. MAIN OUTCOME MEASURES: Abdominal route of repair and fistula closure at 3 months following fistula repair surgery. RESULTS: Published indications for abdominal route of repair (extensive scarring or tissue loss, genital infibulation, ureteric involvement, trigonal, supratrigonal, vesico-uterine or intracervical location or other abdominal pathology) predicted the abdominal route [adjusted risk ratio (ARR), 15.56; 95% CI, 2.12-114.00]. A vaginal route of repair was associated with increased risk of failed closure (ARR, 1.41; 95% CI, 1.05-1.88); stratified analyses suggested elevated risk among women meeting indications for the abdominal route. CONCLUSIONS: Additional studies powered to test effect modification hypotheses are warranted to confirm whether the abdominal route of repair is beneficial for certain women.