Larissa Valor-Méndez

Objective: Rheumatoid arthritis (RA) is characterized by erosive joint damage, deterioration of bone mass, and biomechanics. Preclinical evidence suggests a beneficial effect of Janus kinase inhibition (JAKi) on bone properties, but clinical data are scarce to date. In this study, we evaluated the effect of JAKi through baricitinib (BARI) on 1) volumetric bone mineral density (vBMD), bone microstructure, biomechanics, and erosion repair and 2) synovial inflammation in RA patients.Methods: Prospective, single‐arm, interventional, open‐label, single‐center phase 4 study in RA patients with pathological bone status and clinical indication of JAKi (BARE BONE trial). Participants received BARI (4 mg/day) over 52 weeks. To assess bone properties and synovial inflammation, high‐resolution computed tomography scans and magnetic resonance imaging were performed at baseline (BL), week 24, and week 52. Clinical response and safety were monitored.Results: Thirty RA patients were included. BARI significantly improved disease activity (Disease Activity Score in 28 joints using the erythrocyte sedimentation rate: 4.82 ± 0.90 to 2.71 ± 0.83) and synovial inflammation (RAMRIS synovitis score: 5.3 [4.2] to 2.7 [3.5]). We observed a significant improvement in trabecular vBMD with a mean change of 6.11 mgHA/mm³ (95% confidence interval [95% CI] 0.01–12.26). Biomechanical properties also improved with mean change from baseline in estimated stiffness of 2.28 kN/mm (95% CI 0.30–4.25) and estimated failure load of 98.8 N (95% CI 15.9–181.7). The number and size of erosions in the metacarpal joints remained stable. No new safety signals with BARI treatment were observed.Conclusion: Bones of RA patients improve with BARI therapy, as shown by an increase in trabecular bone mass and an improvement of biomechanical properties.

Antisynthease syndrome (ASSD) is a rare, complex and understudied autoimmune disease. Internet-based studies can overcome barriers of traditional on-site research and are therefore very appealing for rare diseases. The aim of this study was to investigate patient-reported symptoms, diagnostic delay, symptoms, medical care, health status, working status, disease knowledge and willingness to participate in research of ASSD patients by conducting an international web-based survey. The multilingual questionnaire was created by an international group of rheumatologists and patients and distributed online. 236 participants from 22 countries completed the survey. 184/236 (78.0%) were female, mean age (SD) was 49.6 years (11.3) and most common antisynthetase antibody was Jo-1 (169/236, 71.6%). 79/236 (33.5%) reported to work full-time. Median diagnostic delay was one year. The most common symptom at disease onset was fatigue 159/236 (67.4%), followed by myalgia 130/236 (55.1%). The complete triad of myositis, arthritis and lung involvement verified by a clinician was present in 42/236 (17.8%) at disease onset and in 88/236 (37.3%) during the disease course. 36/236 (15.3%) reported to have been diagnosed with fibromyalgia and 40/236 (16.3%) with depression. The most reported immunosuppressive treatments were oral corticosteroids 179/236 (75.9%), followed by rituximab 85/236 (36.0%). 73/236 (30.9%) had received physiotherapy treatment. 71/236 (30.1%) reported to know useful online information sources related to ASSD. 223/236 (94.5%) were willing to share health data for research purposes once a year. Our results reiterate that internet-based research is invaluable for cooperating with patients to foster knowledge in rare diseases.

Larissa Valor-Méndez, Michael Sticherling, Martin Zeschick, Raja Atreya, F Daniela Schmidt, Frank Waldfahrer, Marc Saake, Ulrike Hüffmeier, Georg Schett, Juerge

Objectives To quantify tolerance to risks of preventive treatments among first-degree relatives (FDRs) of patients with rheumatoid arthritis (RA). Methods Preventive treatments for RA are under investigation. In a preference survey, adult FDRs assumed a 60% chance of developing RA within 2 years and made choices between no treatment and hypothetical preventive treatment options with a fixed level of benefit (reduction in chance of developing RA from 60% to 20%) and varying levels of risks. Using a probabilistic threshold technique, each risk was increased or decreased until participants switched their choice. Perceived risk of RA, health literacy, numeracy, Brief Illness Perception Questionnaire and Beliefs about Medicines Questionnaire-General were also assessed. Maximum acceptable risk (MAR) was summarised using descriptive statistics. Associations between MARs and participants’ characteristics were assessed using interval regression with effects coding. Results 289 FDRs (80 male) responded. The mean MAR for a 40% reduction in chance of developing RA was 29.08% risk of mild side effects, 9.09% risk of serious infection and 0.85% risk of a serious side effect. Participants aged over 60 years were less tolerant of serious infection risk (mean MAR ±2.06%) than younger participants. Risk of mild side effects was less acceptable to participants who perceived higher likelihood of developing RA (mean MAR ±3.34%) and more acceptable to those believing that if they developed RA it would last for a long time (mean MAR ±4.44%). Conclusions Age, perceived chance of developing RA and perceived duration of RA were associated with tolerance to some risks of preventive RA therapy.

Dear Editor, Infliximab, a chimeric mAb against TNF-α, is approved for PsA treatment. Infliximab is available as an originator (Remicade) and as biosimilars (CT-P13, Remsima, Inflectra; SB2, Flixabi) [ 1–4]. We present the case of a 38-year-old Caucasian female physician, who was diagnosed with PsA in 2009, with skin and peripheral joint involvement. She received treatment with MTX, which was not tolerated, before receiving adalimumab, ultimately controlling her disease. In 2010, she developed lymph node tuberculosis and was treated successfully with standard tuberculostatic treatment. After her tuberculosis was treated, she started on etanercept, which was maintained until 2013. Treatment with etanercept was stopped owing to sustained absence of symptoms related to psoriatic arthritis (PsA).

Objective: To quantify preferences for preventive therapies for rheumatoid arthritis (RA) across three countries. Methods: A web-based survey including a discrete choice experiment was administered to adults recruited via survey panels in the UK, Germany and Romania. Participants were asked to assume they were experiencing arthralgia and had a 60% chance of developing RA in the next 2 years and completed 15 choices between no treatment and two hypothetical preventive treatments. Treatments were defined by six attributes (effectiveness, risks and frequency/route of administration) with varying levels. Participants also completed a choice task with fixed profiles reflecting subjective estimates of candidate preventive treatments. Latent class models (LCMs) were conducted and the relative importance of attributes, benefit–risk trade-offs and predicted treatment uptake was subsequently calculated. Results: Completed surveys from 2959 participants were included in the analysis. Most participants preferred treatment over no treatment and valued treatment effectiveness to reduce risk more than other attributes. A five-class LCM best fitted the data. Country, perceived risk of RA, health literacy and numeracy predicted class membership probability. Overall, the maximum acceptable risk for a 40% reduction in the chance of getting RA (60% to 20%) was 21.7%, 19.1% and 2.2% for mild side effects, serious infection and serious side effects, respectively. Predicted uptake of profiles reflecting candidate prevention therapies differed across classes. Conclusion: Effective preventive pharmacological treatments for RA were acceptable to most participants. The relative importance of treatment attributes and likely uptake of fixed treatment profiles were predicted by participant characteristics.

Larissa Valor-Méndez, Bernhard Manger, Martin Winterholler, Georg Schett, Mattias Türk, Johannes Knitza; Rare meets rarer: anti-synthetase syndrome in a patient