Objective: The aim was to report results from PERSIST, a real-life, observational, prospective cohort study of CT-P13, an infliximab (IFX) biosimilar, for treatment of patients with RA, AS or PsA who were biologic naïve or switched from an IFX reference product (IFX-RP; Remicade).

Methods: Adult patients were recruited during usual care at 38 sites in Europe and Canada and enrolled by their physicians after meeting eligibility criteria according to the country-approved label for CT-P13. Primary outcomes were to determine drug utilization and treatment persistence and to assess safety. Patients were followed for up to 2 years. Data were analysed and reported descriptively.

Results: Of 351 patients enrolled, 334 were included in the analysis (RA, 40.4%; AS, 34.7%; PsA, 24.9%). The safety analysis set comprised all 328 patients treated with CT-P13. The majority (58.2%) of patients received CT-P13 monotherapy, most (72.6%) by dosing every 6 or 8 weeks. The mean treatment persistence was 449.2 days; 62.3% of patients completed 2 years of treatment. In all, 214 treatment-emergent adverse events (TEAEs) were reported in 38.4% of patients. Most TEAEs were of mild or moderate intensity; 13 were severe. The most commonly reported TEAEs were drug ineffective (9.5%) and infusion-related reactions (5.2%). The most frequently reported infection-related TEAEs were upper respiratory tract infections (3.0%), nasopharyngitis (2.1%) and bronchitis (1.5%). No patients experienced tuberculosis.

Conclusion: Drug utilization and treatment persistence with CT-P13 were consistent with historical reports of IFX-RP in this patient population. Safety findings did not identify new concerns for CT-P13 in the treatment of patients with RA, AS or PsA.

Trial registration: ClinicalTrials.gov: NCT02605642.

In rehabilitation, four single-leg hop tests are frequently used for evaluation of ACL-injured children. However, reference values on single-leg hop performance and the corresponding limb symmetry indexes (LSIs) of healthy children younger than 15 years of age are lacking. Thus, the purpose was to describe hop performance and LSIs in healthy Danish children, and to quantify the proportion of participants passing LSI values of ≥85% as well as ≥90%. Healthy children aged 9–15 years were invited to participate in the study. Hop performance (single hop, 6-m timed hop, triple hop, and cross-over hop) was assessed for each leg for each hop test and expressed as absolute, normalized (to body height), and LSI values. Descriptive statistics were applied to calculate mean ±SD for all outcomes within age and gender groups. Further, the 95% reference interval was calculated for each age and gender group. A total of 531 healthy children (52% girls) were included in the study, representing seven age groups (9-15 years). The LSI group means across all participants for the four hop tests ranged between 84 and 95%. Between 70 and 83% of the children had an LSI of ≥85%, while 50 to 65% of the children had an LSI of ≥90%. The present reference material can be used in clinical practice when evaluating hop performance in pediatric ACL patients.

INTRODUCTION: Inflammatory arthritis (IA) conditions, including rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis, are characterised by inflammatory infiltration of the joints. Biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), respectively, reduce the effects of proinflammatory cytokines and immune cells to ameliorate disease. However, immunosuppression can be associated with high rates of serious adverse events (SAEs), including serious infections, and maybe an increased risk of malignancies and cardiovascular events. Currently, there is no empirical evidence on the extent to which contextual factors and risk of bias (RoB) domains may modify these harm signals in randomised trials.

METHODS AND ANALYSIS: We will search MEDLINE (via PubMed) for systematic reviews published since April 2015 and all Cochrane reviews. From these reviews, randomised trials will be eligible if they include patients with an IA condition with at least one group randomly allocated to bDMARD and/or tsDMARD treatments. A predefined form will be used for extracting data on population characteristics (eg, baseline characteristics or eligibility criteria, such as medication background) and specific harm outcome measures, such as number of withdrawals, numbers of patients discontinuing due to adverse events and number of patients having SAEs. RoB in individual trials will be assessed using a modified Cochrane RoB tool. We will estimate the potentially causal harm effects related to the experimental intervention compared with control comparator as risk ratios, and heterogeneity across randomised comparisons will be assessed statistically and evaluated as inconsistency using the I2 Index. Our metaregression analyses will designate population and trial characteristics and each RoB domain as independent variables, whereas the three harm domains will serve as dependent variables.

ETHICS AND DISSEMINATION: Ethics approval is not required for this study. Results will be disseminated through publication in international peer-reviewed journals.

PROSPERO REGISTRATION NUMBER: CRD42020171124.

OBJECTIVES: Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA).

METHODS: In this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26.

RESULTS: Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)).

CONCLUSIONS: In this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA.

TRIAL REGISTRATION NUMBER: NCT03058900.

BACKGROUND: Research on health effects of shift work has especially focused on somatic diseases, such as breast cancer and cardiometabolic disease, while less attention has been given to the association between shift work and mental health.

METHODS: We used information on 19 964 female nurses (≥44 years) from the Danish Nurse Cohort, who reported current work schedule (day, evening, night, or rotating) at recruitment (1993/1999). In 5102 nurses who participated in both cohort waves, we defined persistent night shift work as working night shift in 1993 and 1999. We used Cox regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for relevant confounders. Through linkage of cohort participants to national registers, we defined incidence of mood and neurotic disorders as first hospital contact or redeemed prescription until November 2018.

RESULTS: We found association between night shift work with mood disorders (HR = 1.31; 95%CI = 1.17-1.47) and neurotic disorders (1.29; 1.17-1.42), compared to day work. Associations were enhanced in nurses with persistent night shift work (1.85; 1.43-2.39 and 1.62; 1.26-2.09 for mood and neurotic disorders, respectively) and in nurses with specialist confirmed mood (1.69; 1.24-2.29) and neurotic (1.72; 1.22-2.44) disorders. Nurses with preexisting psychiatric disorders and full-time work seemed most susceptible.

CONCLUSIONS: Night shift work is associated with increased risk of major psychiatric disorders. The novel suggestive findings of vulnerable groups, including nurses with a history of psychiatric disorders and full-time workers, are based on a limited number of cases, and further research is needed to confirm the results.

To compare changes in low-density lipoprotein cholesterol and other lipids in patients with rheumatoid arthritis (RA) randomised to a 1-year treat-to-target strategy with either adalimumab plus methotrexate or placebo plus methotrexate. Prespecified secondary analyses from the OPERA trial, where 180 early and treatment-naïve RA patients received methotrexate 20 mg once weekly in combination with either placebo or subcutaneous adalimumab 40 mg every other week. Serum lipid levels were measured at baseline and after 1 year. Changes in lipid levels were analysed using mixed linear models based on the intention-to-treat (ITT) population. Overall, 174 patients were included in the ITT population (adalimumab plus methotrexate n = 86; placebo plus methotrexate n = 88). Differences between changes in lipid levels were low-density lipoprotein cholesterol 0.18 mmol/l [95% CI - 0.05 to 0.42], total cholesterol 0.27 mmol/l [- 0.002 to 0.54], high-density lipoprotein cholesterol 0.05 mmol/l [- 0.06 to 0.15], triglycerides 0.11 mmol/l [- 0.08 to 0.29], very-low-density lipoprotein cholesterol 0.03 mmol/l [- 0.05 to 0.12], and non-high-density lipoprotein cholesterol 0.22 mmol/l [- 0.02 to 0.46]. In early RA patients treated to tight control of inflammation over a period of 1 year with either adalimumab plus methotrexate or placebo plus methotrexate, changes in lipid levels were similar. Trial registration number: NCT00660647.