Research in older adults diagnosed with rheumatic and musculoskeletal diseases (RMDs) comes with unique challenges, as these patients often face consequences of ageing, such as multimorbidity, polypharmacy, and geriatric syndromes (eg, frailty). In this viewpoint, we highlight various clinical, ethical, regulatory and logistical challenges, including, among others, issues with the decision-making capacity of older adults regarding study participation. We emphasise the need for feasible strategies and protocols to enhance research inclusivity in order to ultimately improve evidence-based care for the growing population of older adults with RMDs.

ObjectiveThis study evaluated the effects of a 6-week osteoarthritis (OA) exercise and education intervention on metabolic health markers, including blood pressure (BP), glycated haemoglobin (HbA1c), high-density lipoprotein (HDL), cholesterol levels and weight in individuals with both OA and diabetes.MethodsData originated from the Swedish Osteoarthritis and Diabetes cohort, which is composed of the Swedish Osteoarthritis Register (SOAR) and National Diabetes Register. We included individuals diagnosed with OA and diabetes who underwent the intervention between January 2008 and December 2019, matched with controls with diabetes who did not based on birth year, sex, OA site (hip/knee) and OA diagnosis year. Outcomes included BP, HbA1c, HDL, total cholesterol levels and weight measured up to 3 years before and after SOAR enrolment. Statistical analyses used two-way fixed-effect models.ResultsThe study included 4571 individuals with OA and diabetes (mean age: 69.5, SD: 7.8; women: 52.7%; knee OA: 71.2%) and 7925 controls. The intervention group showed a systolic BP decrease of approximately 1.0 mm Hg at 6 and 12 months compared with the control group. HDL levels increased by about 0.02 mmol/L at 12, 18 and 24 months. Weight decreased by approximately 0.5 kg at 6, 18 and 30 months. HbA1c levels increased by approximately 0.5 mmol/mol at 6 months. No essential differences were found in the total cholesterol levels.ConclusionAn OA exercise and education intervention designed following OA clinical practice guidelines led to small and unlikely clinically relevant improvements in metabolic health markers in individuals with OA and diabetes.

ObjectivesWe aimed to compare various methods for imputing disease activity in longitudinally collected observational data of patients with axial spondyloarthritis (axSpA).MethodsWe conducted a simulation study on data from 8583 axSpA patients from ten European registries. Disease activity was assessed by the Axial Spondyloarthritis Disease Activity Score (ASDAS) and the corresponding low disease activity (LDA; ASDAS<2.1) state at baseline, 6 and 12 months. We focused on cross-sectional methods which impute missing values of an individual at a particular time point based on the available information from other individuals at that time point. We applied nine single and five multiple imputation methods, covering mean, regression and hot deck methods. The performance of each imputation method was evaluated via relative bias and coverage of 95% confidence intervals for the mean ASDAS and the derived proportion of patients in LDA.ResultsHot deck imputation methods outperformed mean and regression methods, particularly when assessing LDA. Multiple imputation procedures provided better coverage than the corresponding single imputation ones. However, none of the evaluated methods produced unbiased estimates with adequate coverage across all time points, with performance for missing baseline data being worse than for missing follow-up data. Predictive mean and weighted predictive mean hot deck imputation procedures consistently provided results with low bias.ConclusionsThis study contributes to the available methods for imputing disease activity in observational research. Hot deck imputation using predictive mean matching exhibited the highest robustness and is thus our suggested approach.

ObjectivesFactors associated with peripheral arthritis and enthesitis, especially Achilles tendonitis and plantar fasciitis, were examined in a longitudinal cohort of 1075 patients with ankylosing spondylitis (AS) (also known as radiographic axial spondyloarthritis).MethodsPatients were derived from the Prospective Study of Outcomes in Ankylosing Spondylitis cohort. Disease activity and functional indices, as well as physical examination and medications used, were measured at every study visit. Univariable and multivariable analyses of the association of peripheral arthritis and enthesitis with clinical, sociodemographic factors were performed. Human leucocyte antigen (HLA)-B alleles were analysed by single-stranded conformational polymorphism analysis.ResultsThose with peripheral arthritis on examination were more likely to have psoriasis (p=0.001, OR=1.68; CI, 1.11, 2.54), greater functional impairment (p<0.001 OR=1.72; CI, 1.31, 2.27), higher erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels (p<0.001), greater tumour necrosis factor (TNF) inhibitor (p<0.001, OR=1.50; CI, 1.14, 1.97) and use methotrexate/sulfasalazine (p<0.001, OR=2.25, CI [1.57, 3.23]). Patients with enthesitis were less likely to be male (p<0.001, OR=0.57; CI, 0.43, 0.75) and have peripheral arthritis (p<0.001, OR=2.35; CI, 1.47, 3.75), greater functional impairment (p<0.001, OR=1.91; CI, 1.43, 2.55) and higher ESR/CRP levels (p<0.001). Patients with plantar fasciitis and/or Achilles’ tendonitis on examination were less likely to male (p<0.001 OR=0.57; CI, 0.43, 0.75), to have significant functional impairment (p<0.001), to be using TNF inhibitors (p<0.001, OR=1.48; CI 1.13, 1.93) and to be using either sulfasalazine or methotrexate (p<0.001, OR=1.86, CI, 1.30, 2.67). HLA-B*15 (p=0.03, OR=1.84; CI, 1.05, 3.21) and HLA-B*37 (p=0.04, OR=3.00; CI, 1.03, 8.74) were marginally increased in frequency in those with peripheral arthritis on examination compared with those without.ConclusionThere was a higher prevalence of peripheral musculoskeletal manifestations in women with AS, with significant impact on physical function and greater use of methotrexate or sulfasalazine and TNF inhibitors and enrichment for certain non-HLA-B27 HLA-B alleles.

ObjectiveThis study aimed to assess the impact of Sjögren disease (SjD) on the quality of sexual life and its determinants using the Qualisex questionnaire.MethodsThe Qualisex questionnaire was administered to participants within the ASSESS cohort, a French national multicentric prospective cohort of individuals with SjD. Patients’ characteristics and psychometric evaluations were also collected.ResultsAmong the 395 patients of the cohort, 92 (23%) completed the questionnaire, with a median age of 56 (44–59) years and a female ratio of 92% (85/92). The median Qualisex score was 3.4 (1.1–5.9).Comparing the first and last quartiles of the Qualisex score, a worst sexual satisfaction was associated with older age (median (IQR) 58 (52–65) vs 52 (41–56) years, p=0.005), higher EULAR Sjögren’s disease Patient Reported Index (ESSPRI) (6.8 (5.7–7.7) vs 4.3 (2.8–5.3), p<0.0001) lower SF-36 mental and physical scores (respectively, 43 (38–46) vs 49 (47–53), p=0.0035 and 31 (29–35) vs 35 (30–37), p=0.035), higher Depression and Anxiety scores (HADS) (respectively, 9 (7–11) vs 2 (1–4), p<0.0001 and 11 (8–14) vs 7 (4–10), p=0.006). Interestingly, EULAR Sjögren’s disease Disease Activity Index (ESSDAI) score did not differ significantly (4 (1–10) vs 2.5 (1.8–4), p=0.35). In a multivariable analysis, the Qualisex score remained strongly associated with a higher HADS depression score and, to a lesser extent, with a higher ESSPRI. The inability to obtain a score was associated with older age.ConclusionIn SjD patients, sexual satisfaction assessed with the Qualisex score, was strongly associated with depression and, to lesser extent, with ESSPRI, but not with systemic activity.

ObjectiveTo test the reliability of the Outcome Measures in Rheumatology Giant cell arteritis (GCA) Ultrasonography Score (OGUS) and other composite scores in a patient-based exercise involving experts and non-experts in vascular ultrasonography.MethodsSix GCA patients were scanned twice (two rounds separated ≥3 hours) by 12 experts and 12 non-experts. Non-experts received 90 min of theoretical and 240 min of practical training between rounds 1 and 2. Ultrasonography was conducted on temporal arteries (common superficial, frontal and parietal branches) and axillary arteries bilaterally to calculate the OGUS, the Southend score and the Halo count. Inter-reader and intra-reader reliability were assessed by intraclass correlation coefficient (ICC).ResultsMean age of GCA patients was 78±5.1 years, 2 (33.3%) were women, and all were in clinical remission. Expert inter-reader ICC of the OGUS was 0.60 in both rounds, 0.40 in round 1 and 0.51 in round 2 for the Southend score and 0.45 and 0.52, respectively, for the Halo count. Median ICCs for intra-reader reliability were 0.86, 0.73 and 0.65 for the OGUS, Southend score and Halo count, respectively.For non-experts, inter-reader ICCs in round 1 were 0.20 for the OGUS, 0.20 for a normalised Southend score (=score divided by available segments) and 0.35 for a normalised Halo count. After training, inter-reader reliability ICCs improved to 0.52, 0.29 and 0.54, respectively.ConclusionInter-reader reliability was fair to moderate, and intra-reader reliability was good for OGUS, Southend score and Halo count among experts. Inter-reader reliability of non-experts in vascular ultrasonography improved after the training.

ObjectiveRheumatoid arthritis (RA) and psoriatic arthritis (PsA) are currently treated similarly. However, it is unclear which patient-reported outcome (PRO) domains need specific attention in the management of RA and PsA. Therefore, we aimed to determine the difference in disease impact between matched RA and PsA patients at diagnosis and after 1 year in two different regions.MethodsRA patients from the treatment in the Rotterdam Early Arthritis CoHort trial (tREACH), PsA patients from the Dutch southwest Early PsA cohoRt (DEPAR) and RA and PsA patients from the Leiden Early Arthritis Clinic (EAC) were included. The difference in disease impact between RA and PsA was measured with the following PROs: pain (Visual Analogue Scale (VAS), 0–100), fatigue (VAS), activity limitation (Health Assessment Questionnaire-Disability Index) and health impact (general health (VAS) and 36-item Short-Form Health Survey (SF-36)). Propensity scores were used to match RA and PsA patients, after which inverse probability weights (IPWs) were calculated. IPW-weighted linear regression models were used to measure PRO differences.Results391 RA patients from tREACH, 416 PsA patients from DEPAR, 702 RA and 99 PsA patients from the EAC were included. At diagnosis, PsA-DEPAR patients scored 5.04 units worse (95% CI 2.21 to 7.87) on SF-36 mental health compared with RA-tREACH patients. This difference still existed after 1 year of treatment (3.88 (95% CI 1.90 to 5.86)). PsA-EAC patients had more activity limitations after 1 year of treatment compared with RA-EAC patients (−0.30 (95% CI −0.50 to −0.10)). No significant differences were present in the other PRO domains.ConclusionThe disease impact of early RA patients is similar to matched early PsA patients on most PRO domains, except for mental health and functional limitations, which were worse in PsA after 1 year of treatment.

ObjectivesDARWIN 3 (ClinicalTrials.gov: NCT02065700) assessed the safety and efficacy of filgotinib in a long-term extension (LTE) of two phase II randomised controlled rheumatoid arthritis (RA) trials.MethodsEligible patients completing the 24-week DARWIN 1 (filgotinib plus methotrexate) and DARWIN 2 (filgotinib monotherapy) trials could enrol. Patients received filgotinib 200 mg/day, except 15 men who received filgotinib 100 mg/day. The primary endpoints were safety and tolerability, which were assessed by the incidence of treatment-emergent adverse events (TEAEs). Safety and efficacy analyses included all enrolled patients who received ≥1 dose of filgotinib in DARWIN 3.Results739 patients entered the LTE. The total patient-years of exposure (PYE) to filgotinib was 3706.3 years; the mean exposure duration was 259.8 weeks. 497 patients (67.3%) discontinued prematurely (including 266 TEAEs and 172 withdrawals due to the patient’s decision or ‘sponsor request’). Overall exposure-adjusted incidence rate (EAIR) was 67 (95% CI 62 to 72.2)/100 PYE for TEAEs and 3.8 (95% CI 3.2 to 4.5)/100 PYE for serious TEAEs. EAIR of infections was 23.3 (95% CI 21.2 to 25.6)/100 PYE, 1.3 (95% CI 0.9 to 1.7)/100 PYE for serious infections and 1.3 (95% CI 0.9 to 1.7)/100 PYE for herpes zoster. EAIRs of major adverse cardiovascular events (0.19 (95% CI 0.8 to 0.39)/100 PYE) and malignancies (0.6 (95% CI 0.4 to 0.9)/100 PYE) were low. Disease response assessed using non-responder imputation plateaued at LTE week 12 before slowly declining over time, with overall American College of Rheumatology (ACR)20/50/70 response rates of 26.9%/20.2%/14.7% at week 396.ConclusionFilgotinib was well tolerated in patients with RA for up to 8 years. Safety and efficacy profiles were maintained in patients previously receiving either filgotinib plus methotrexate or filgotinib monotherapy.

ObjectiveThe objective of this study is to evaluate the efficacy and safety of jaktinib hydrochloride tablets (jaktinib), a Janus kinase inhibitor, in patients with active radiographic axial spondyloarthritis (r-axSpA).MethodsAdults with active r-axSpA who met modified New York criteria and had an inadequate response to non-steroidal anti-inflammatory drugs were randomised 1:1:1 to receive jaktinib 75 mg two times per day, 100 mg two times per day, or placebo. The primary and key secondary endpoints were Assessment of SpondyloArthritis international Society 20 (ASAS 20) and ASAS 40 responses, respectively, at week 16. Safety was evaluated by analysing adverse events.ResultsA total of 107 patients with active r-axSpA were randomised (jaktinib 75 mg two times per day, n=35; jaktinib 100 mg two times per day, n=36; placebo, n=36). In the ASAS20 response rates, the 100 mg two times per day group had the highest response at 61.1%, followed by the 75 mg two times per day group at 57.1%, and the placebo group had the lowest at 33.3% for the 16 weeks of treatment. The ASAS40 response rates were significantly higher with jaktinib (100 mg two times per day group: 47.2%, 75 mg two times per day group: 37.1%) compared with placebo (13.9%). The incidence of treatment-emergent adverse events in the 75 mg two times per day, 100 mg two times per day and placebo groups was 88.6% versus 94.4% versus 86.1%, respectively, with no statistically significant difference among the three groups. No major adverse cardiovascular events, malignancy, thromboembolism or deaths were reported.ConclusionsJaktinib showed good efficacy and tolerability in the treatment of active r-axSpA, with the 100 mg two times per day showing a trend towards better efficacy.Trial registration numberNCT04507659.

BackgroundCardiovascular disease (CVD) is a leading cause of death in ANCA-associated vasculitis (AAV). Screening and primary cardiovascular prevention may improve outcomes.MethodsWe identified patients in the 2002–2019 Mass General Brigham AAV cohort with thoracic CT scans obtained for other clinical purposes. Coronary artery calcium (CAC) scores and age, sex and race-standardised CAC percentiles were calculated. Quantile regression was used to identify differences by ANCA type, and Gray’s test examined differences in major adverse cardiac events by CAC score.ResultsOf 175 included patients, 127 (73%) were MPO-ANCA+and 48 (27%) were PR3-ANCA+. The median CAC score was 17 (IQR 0, 334) and CAC percentile was 45 (IQR 0, 78); 65 (39%) patients had CAC of ≥100. The total CAC score was higher in patients with MPO-ANCA+AAV vs PR3-ANCA+AAV (median 24 vs 1, p=0.003), as was the standardised CAC percentile (50th vs 34th, p=0.02). Of 116 (66%) patients with non-zero CAC scores, only 29 (25%) were on a statin. In a time-to-event analysis, CAC of 100 or higher trended towards association with higher risk of major adverse cardiovascular events (χ2=1.9, p=0.16).ConclusionA majority of patients with AAV had clinically significant CAC. There were differences in CAC burden among those with MPO-ANCA+AAV versus PR3-ANCA+AAV. Although CAC is associated with CVD risk and an indication for statins, the use was inconsistent. The role of CT imaging to screen for CVD and guide primary prevention in AAV requires further study.