Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials.

BACKGROUND: Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status. METHODS: STRAP and STRAP-EU were two parallel, open-label, biopsy-driven, stratified, randomised, phase 3 trials done across 26 university centres in the UK and Europe. Biologic-naive patients aged 18 years or older with rheumatoid arthritis based on American College of Rheumatology (ACR)-European League Against Rheumatism classification criteria and an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (DMARDs) were included. Following ultrasound-guided synovial biopsy, patients were classified as B cell poor or B cell rich according to synovial B cell signatures and randomly assigned (1:1:1) to intravenous rituximab (1000 mg at week 0 and week 2), subcutaneous tocilizumab (162 mg per week), or subcutaneous etanercept (50 mg per week). The primary outcome was the 16-week ACR20 response in the B cell-poor, intention-to-treat population (defined as all randomly assigned patients), with data pooled from the two trials, comparing etanercept and tocilizumab (grouped) versus rituximab. Safety was assessed in all patients who received at least one dose of study drug. These trials are registered with the EU Clinical Trials Register, 2014-003529-16 (STRAP) and 2017-004079-30 (STRAP-EU). FINDINGS: Between June 8, 2015, and July 4, 2019, 226 patients were randomly assigned to etanercept (n=73), tocilizumab (n=74), and rituximab (n=79). Three patients (one in each group) were excluded after randomisation because they received parenteral steroids in the 4 weeks before recruitment. 168 (75%) of 223 patients in the intention-to-treat population were women and 170 (76%) were White. In the B cell-poor population, ACR20 response at 16 weeks (primary endpoint) showed no significant differences between etanercept and tocilizumab grouped together and rituximab (46 [60%] of 77 patients vs 26 [59%] of 44; odds ratio 1·02 [95% CI 0·47-2·17], p=0·97). No differences were observed for adverse events, including serious adverse events, which occurred in six (6%) of 102 patients in the rituximab group, nine (6%) of 108 patients in the etanercept group, and three (4%) of 73 patients in the tocilizumab group (p=0·53). INTERPRETATION: In this biologic-naive population of patients with rheumatoid arthrtitis, the dichotomic classification into synovial B cell poor versus rich did not predict treatment response to B cell depletion with rituximab compared with alternative treatment strategies. However, the lack of response to rituximab in patients with a pauci-immune pathotype and the higher risk of structural damage progression in B cell-rich patients treated with rituximab warrant further investigations into the ability of synovial tissue analyses to inform disease pathogenesis and treatment response. FUNDING: UK Medical Research Council and Versus Arthritis.

Method of nutrition of patients after major oral and craniofacial surgery and its effects on BMI changes during a half-year period of observation.

UNLABELLED: Injuries, deformations and tumours of the facial part of skull, oral cavity or neck often hamper or prevent normal food consumption. After surgery of these structures food intake may be decreased due to postoperative wounds, pain, swelling and trismus. The aim of the study was to evaluate nutritional state of patients treated surgically in the craniomaxillo- facial surgery department and determination of factors affecting body weight changes after surgery. MATERIAL AND METHODS: The study included 83 patients operated between 2008 and 2010 in the department of cranio-maxillo-facial surgery, due to: maxillo-facial defects (30 individuals), malignant tumours (23 individuals), injuries (19 individuals), benign tumours (11 individuals). The study was prospective. A method of nutrition during the observation period and BMI (Body Mass Index) value on the first day of hospitalization and after 10, 60, 180 days after hospital admission were considered. For statistical analysis of results a general regression analysis was used. RESULTS: Significant reduction of BMI was observed in all patients after 10 and 60 days from the start of hospitalization. A significant increase of this parameter was observed between Day 60 and Day 180 of observation, however the BMI values after 180 days were still significantly lower than the baseline. A dependency between these changes and a cause of hospitalization as well as nutrition during and after the stay at hospital has been shown. CONCLUSIONS: There is a distinct relationship between the worsening of nutritional state after craniofacial surgery and nutrition during and after hospitalization, and therefore special attention should be paid to the issue of nutrition during this period.