Bayram Farisogullari

Treatment response and retention rates of bDMARDs in advanced spinal ankylosis or bamboo spine: Real-world data from the HUR-BIO registry - Journal of Turkish Society for Rheumatology

Objectives: To explore pregnancy outcomes in patients with axial spondyloarthritis (axSpA) in the UK. Methods: A patient-reported online survey, based on the EULAR core dataset for pregnancy registries in rheumatology, was conducted via the REDCap platform with data included between October 2022 and October 2023. Data were analysed descriptively. Results: A total of 139 pregnancies from 89 women following a diagnosis of axSpA were analysed. The mean age at pregnancy was 32.1 years (s.d. 4.3), at diagnosis was 27.6 years (s.d. 5.1) and at symptom onset was 20.8 years (s.d. 5.8). Most pregnancies were planned (90.6%) and achieved by natural conception (90.2%), with 68.3% conceiving within 1 year. Assisted conception was reported infrequently. Pre-pregnancy concerns such as pain levels increasing (74.8%), birth complications (62.6%) and passing on axSpA to a child (63.3%) were frequently reported. Flares occurred during 33.6% of pregnancies and in more than half (55.6%) during postpartum. The live birth rate was 76.4%. Rates of pre-eclampsia and congenital anomalies were 5.4% and 9.5%, respectively. Caesarean section occurred in 53.8% of pregnancies, with active disease and patient choice being core reasons. Most infants received vaccinations as scheduled (83.5%). AxSpA did not affect the decision to breastfeed for 82.5% of pregnancies, but it did affect perceived ability to care for the baby in the first 6 months (61.3%). Conclusion: Many women with axSpA experience increased time to pregnancy, disease-related pre-pregnancy worries, flares and delivery via caesarean section. Pre-pregnancy counselling may be important for women of reproductive age with axSpA.

Objectives: To investigate real-world use of Janus kinase inhibitors (JAKis) prescribed for RA and PsA. Methods: We conducted a retrospective review of all patients treated with baricitinib, filgotinib, tofacitinib and upadacitinib across six UK rheumatology centres from time of first use in routine care until November 2024. Standardised data were collected and retention was calculated using Kaplan–Meier analysis. Factors associated with JAKi discontinuation were analysed using multivariable Cox regression analyses. Results: A total of 985 patients [79.5% female, mean age 60 years, RA 849 (86.2%), PsA 136 (13.8%)] were reviewed. MTX and glucocorticoids (GCs) were co-prescribed in 43% and 33.6% of cases, respectively. Among GC users, dose reduction occurred in 18% and complete discontinuation in 61.8%. JAKis were prescribed as a first-line biologic DMARD in 7.5% and as a third-line or later in 78.8%. Median retention was 49 months (range 1–85; 95% CI 42.62, 55.37), with 52.8% remaining on treatment at censure, with no difference between RA and PsA populations. Retention on tofacitinib was significantly lower than baricitinib (P < 0.001) and upadacitinib (P = 0.007). Variables significantly associated with higher JAKi discontinuation risk were female sex [hazard ratio (HR) 1.66 (95% CI 1.28, 2.16)], increasing age [HR 1.01 (95% CI 1.00, 1.02)] and tofacitinib (vs baricitinib) treatment [HR 2.27 (95% CI 1.64, 3.14)]. Among RA patients, MTX co-prescription was associated with a lower discontinuation risk [HR 0.81 (95% CI 0.66, 0.98)]. Conclusion: In a real-world setting, JAKi demonstrated high retention in RA and PsA, with a GC-sparing effect. Retention is lower for female sex, older age, tofacitinib vs baricitinib and use without MTX in RA, whereas place in the treatment pathway did not impact retention outcomes.

Objective: To evaluate the prevalence and anatomical distribution of inflammatory and structural MRI lesions in axial spondyloarthritis (axSpA) and compare these between patients with isolated axial involvement and those with peripheral manifestations. Methods: Data from the Assessment of SpondyloArthritis International Society (ASAS) Classification Cohort were analysed. Peripheral involvement was defined as past or current arthritis/dactylitis/enthesitis. Sacroiliac joint (SIJ) and spinal MRI lesions typical of axSpA were classified per ASAS lesion definitions and centrally read with multi-reader majority agreement (lesion present if called by the majority; SIJ ≥4/7, spine ≥5/9 readers). Comparisons between patients with and without peripheral manifestations were made. Results: Among 199 axSpA patients with SIJ MRI, 67 also had spinal MRI. Subchondral SIJ bone marrow oedema (BMO) was observed in 49%, without quadrant preference or subgroup differences. Other SIJ inflammatory lesions ranged from 4%–18%. Erosions (35%) and fat lesions (22%) were the most frequent structural lesions. In the spine, BMO, fat lesions and syndesmophytes/ankylosis were detected in 38%, 25% and 5%, respectively, with similar subgroup frequencies. Among 40 patients with both SIJ and whole spine MRI, inflammatory lesions were observed in both sites in 18%, SIJ only in 38%, and spine only in 20%. Structural lesions occurred in both sites in 19%, SIJ only in 30%, and spine only in 5%, with no subgroup differences. Conclusion: The prevalence and anatomical distribution of ASAS-defined MRI lesions was similar across axSpA subgroups. Notably, 20% exhibited spine-only inflammation, suggesting potential added diagnostic and monitoring value of spinal MRI, warranting further study.

Objective: To summarise the measurement properties of instruments used to assess fatigue in people with rheumatic and musculoskeletal diseases (RMDs). Methods: A systematic review (SR) of measurement properties was conducted in children, adolescents/young adults and adults with RMDs, following Joanna Briggs Institute and COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) guidelines. Searches were performed in Medline, Embase, CINAHL and Cochrane Library. Risk of bias assessment, data extraction and synthesis were conducted independently by two reviewers. Instruments were assessed according to Outcome Measures in Rheumatology (OMERACT) criteria. Results: Out of 16 657 records, 109 articles underwent full-text review, and 60 met inclusion criteria. These studies evaluated the psychometric properties of 27 instruments. Most studies focused on construct validity (54/60, 90%) and intermethod reliability (45/60, 75%), with an overall low risk of bias. In contrast, test–retest reliability (13/60, 21.7%) and responsiveness (14/60, 23.3%) were less frequently assessed, but also with an overall low risk of bias. Evidence regarding clinical trial discrimination and thresholds of meaningful change was limited or absent, indicating the need for further research in these domains. Only five instruments—the Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue, the 36-Item Short Form Survey Instrument (SF-36) Vitality, the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ), the BRAF Numerical Rating Scales (BRAF-NRS) and the Fatigue Severity Scale (FSS)—were rated as valid, reliable and low risk of bias, fulfilling OMERACT endorsement criteria. Conclusions: This SR comprehensively supports the use of several well-validated instruments to assess fatigue, particularly FACIT-Fatigue, SF-36 Vitality, BRAF-MDQ, BRAF-NRS and FSS, in both clinical and research settings. PROSPERO registration number: CRD42024507112.

Objective To identify the best evidence on the efficacy of treatment interventions for inclusion body myositis (IBM) and to describe their safety. Methods Systematic review of randomised controlled trials (RCTs) of pharmacological treatments of adults with IBM, conducted according to the Cochrane Handbook, updating a previous Cochrane review. The search strategy was run on Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. Assessment of risk of bias, data extraction and synthesis were performed independently by two reviewers. Data pooled in statistical meta-analyses, if possible. Results From a total of 487 records, 48 were selected for full-text review, 14 fulfilled the inclusion criteria, but only 2 RCTs were included in meta-analyses due to clinical heterogeneity (different drug interventions or dosages). Treatments included various immunosuppressive and immunomodulatory agents, alongside interventions modulating muscle growth and protein homoeostasis. Efficacy was assessed across multiple outcomes, namely muscle strength, physical function, mobility and muscle trophicity. Trials of methotrexate (MTX), intravenous immunoglobulin, interferon beta-1a and MTX, MTX and anti-T-lymphocyte immunoglobulin, oxandrolone, MTX and azathioprine, bimagrumab, arimoclomol, and sirolimus provided low-quality to high-quality evidence of having no effect on the progression of IBM. Conclusions Drug interventions for IBM were not effective for most of the outcomes of interest. We observed inconsistency of outcome measures across trials. More RCTs are needed, of adequate size and duration, and using a standardised set of outcome measures.

Objectives To investigate the frequency and factors associated with disease flare following vaccination against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal diseases (I-RMDs). Methods Data from the European Alliance of Associations for Rheumatology Coronavirus Vaccine physician-reported registry were used. Factors associated with flare in patients with I-RMDs were investigated using multivariable logistic regression adjusted for demographic and clinical factors. Results The study included 7336 patients with I-RMD, with 272 of 7336 (3.7%) experiencing flares and 121 of 7336 (1.6%) experiencing flares requiring starting a new medication or increasing the dosage of an existing medication. Factors independently associated with increased odds of flare were: female sex (OR=1.40, 95% CI=1.05 to 1.87), active disease at the time of vaccination (low disease activity (LDA), OR=1.45, 95% CI=1.08 to 1.94; moderate/high disease activity (M/HDA), OR=1.37, 95% CI=0.97 to 1.95; vs remission), and cessation/reduction of antirheumatic medication before or after vaccination (OR=4.76, 95% CI=3.44 to 6.58); factors associated with decreased odds of flare were: higher age (OR=0.90, 95% CI=0.83 to 0.98), non-Pfizer/AstraZeneca/Moderna vaccines (OR=0.10, 95% CI=0.01 to 0.74; vs Pfizer), and exposure to methotrexate (OR=0.57, 95% CI=0.37 to 0.90), tumour necrosis factor inhibitors (OR=0.55, 95% CI=0.36 to 0.85) or rituximab (OR=0.27, 95% CI=0.11 to 0.66), versus no antirheumatic treatment. In a multivariable model using new medication or dosage increase due to flare as the dependent variable, only the following independent associations were observed: active disease (LDA, OR=1.47, 95% CI=0.94 to 2.29; M/HDA, OR=3.08, 95% CI=1.91 to 4.97; vs remission), cessation/reduction of antirheumatic medication before or after vaccination (OR=2.24, 95% CI=1.33 to 3.78), and exposure to methotrexate (OR=0.48, 95% CI=0.26 to 0.89) or rituximab (OR=0.10, 95% CI=0.01 to 0.77), versus no antirheumatic treatment. Conclusion I-RMD flares following SARS-CoV-2 vaccination were uncommon. Factors associated with flares were identified, namely higher disease activity and cessation/reduction of antirheumatic medications before or after vaccination.

The aim of the study is to investigate the frequency of triggering factors in colchicine-resistant and -responsive Familial Mediterranean Fever (FMF) patients as well as the effect of interleukin (IL)-1 antagonist treatment on the triggering factors. Both colchicine-resistant (patients on IL-1 antagonist treatment) and colchicine-responsive (patients on colchicine who had ≤ 3 attacks in the last year) patients were questioned for the presence of 12 different triggering factors, including exposure to cold, emotional stress, fatigue, physical activity, menstruation (for females), sleeplessness, prolonged standing, long-duration travel, high-fat diet intake, starvation, infection, and trauma. Colchicine-resistant patients were questioned for the presence of triggering factors for two time periods, before and after treatment with IL-1 antagonists. We studied 28 colchicine-resistant and 35 colchicine-responsive patients. Overall 77.8% of patients had at least one triggering factor. Triggering factors were associated with 28.5% of the total number of attacks. More than half of the patients (57.1%) declared that they had avoided these conditions. The frequency of triggering factors was higher in the colchicine-resistant group as compared to the colchicine-responsive group (89.3% vs 68.6%; p = 0.04). In colchicine-resistant FMF patients, the frequency of triggering factors (89.3% vs 32.1%) and the percentage of attacks initiated by triggering factors (27.8 vs 14.4%; p < 0.001) were decreased after treatment with IL-1 antagonists. In this study, triggering factors were more frequent in colchicine-resistant patients as compared to colchicine-responsive patients. Treatment with IL-1 antagonists seems to increase the endurance of colchicine-resistant patients in stressful conditions.

Objectives: We aimed to determine the choice of biologic/targeted synthetic disease‐modifying anti‐rheumatic drugs (b/ts‐DMARDs), factors associated with the development of chronic kidney disease (CKD), and mortality in RA patients with CKD receiving b/ts‐DMARDs.Methods: Two thousand one hundred forty‐one RA (79.4% female) patients were included in the analysis from the HUR‐BIO prospective registry. Patients were divided into the CKD group and the non‐CKD group. Age and gender‐matched patients were selected from the non‐CKD group, and then three main groups were determined. CKD was staged according to the glomerular filtration rate criteria. The clinical characteristics of the patients, disease activities, treatment choices, drug retention rate, and mortality rates were compared between the groups.Results: CKD was detected in 90/2141 (4.2%) RA patients on b/ts‐DMARDs. Forty patients (2.3%) developed CKD during follow‐up after the initiation of b/ts‐DMARDs. In the CKD group, anti‐TNF agents were chosen as the first‐line b/ts‐DMARDs therapy in 64.4% of patients, with etanercept leading in 31 (34.4%) patients. In multivariate analysis, age at the start of treatment, DAS‐28‐ESR at last visit, amyloidosis, hypertension, and history of smoking were the factors associated with the development of CKD in RA patients receiving b/ts‐DMARDs. The mortality rate in RA‐CKD patients until the onset of the pandemic was 15.41 per 1000 patient years, whereas it was 85.9 per 1000 patient years after the pandemic.Conclusion: Comorbidities and control of disease activity are critical in the development of CKD in RA patients receiving b/ts‐DMARDs. While there was no significant difference in mortality rate between CKD and non‐CKD patients, the overall mortality rate increased after the COVID‐19 pandemic duration in both groups.