Interstitial lung disease (ILD) affects up to half of individuals with systemic sclerosis (SSc), within which it is a major cause of disease-related morbidity and a leading cause of mortality. Forced vital capacity (FVC) has been endorsed as a primary outcome measure for randomised controlled trials (RCT) assessing the efficacy of novel treatments for SSc-ILD. The FVC is considered a suitable surrogate biomarker, although does not directly capture information on how patients ‘feel’ and ‘function’, which regulators consider essential for marketing authorisation. Only patient-reported outcome (PRO) instruments can provide this insight. This review aims to systematically examine the inclusion, validity and performance of respiratory-specific PRO instruments used in SSc-ILD RCTs, using the COnsensus based Standards for the selection of health Measurement INstruments (COSMIN) framework and regulatory guidance.Our search identified 10 respiratory-specific PRO instruments used in SSc-ILD RCTs. Of these, 4 are single-item instruments and 2 were developed with any ILD patient input. Seventeen studies assessing the measurement properties of respiratory-specific PRO instruments within an SSc-ILD population were identified, with varying methodologies.The findings of this review highlight the lack of consensus for the use of respiratory-specific PRO instrument use in SSc-ILD RCTs. Identified instruments have unproven content validity within this population and limited evidence for other measurement properties, primarily derived from post hoc analyses of RCT data or cross-sectional studies. Future work should prioritise assessing the content validity and measurement properties of existing ILD specific instruments according to COSMIN guidance.
OBJECTIVES:Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS:In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS:Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS:ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.
BACKGROUND:Rheumatoid arthritis (RA) is an inflammatory autoimmune disease in which the immune system attacks joint tissues. Identifying predictors of RA diagnoses may enable earlier detection and opportunities for prevention. METHODS:We applied a hypothesis-free data-driven machine learning approach using 445,515 UK Biobank participants, including 4,510 incident cases (8.4 median years follow-up, IQR 5.3 - 10.9). From 2,898 baseline input features, those identified as potentially important by the machine learning model were taken forward to logistic regression analyses, adjusting for known confounders. We used a Bonferroni corrected p-value of p<3.0 × 10-4. RESULTS:The model identified 200 features as potentially important for prediction of RA diagnosis. Epidemiological analyses confirmed associations with known RA risk factors (older age, female sex, smoking, and physical inactivity) and some indicators of low socioeconomic status and psychosocial well-being (e.g. highest vs lowest neuroticism score OR 1.44, 95% CI 1.24-1.67). History of joint disorder, osteoporosis, hypothyroidism, diverticular disease, and emphysema/chronic bronchitis were each associated with a 48% to 230% higher odds of RA. Markers of inflammation (e.g. C-reactive protein Q5 vs Q1 OR 1.92, 95% CI 1.71-2.16), altered liver and kidney function (e.g. cystatin C Q5 vs Q1 OR 1.55, 95% CI 1.38-1.74), and a range of blood cell markers were also found to associate with the odds of RA. CONCLUSION:Our data-driven analyses identified lifestyle, psychosocial, clinical and biomarker features predictive of RA years before diagnosis. While external validation is required, many identified candidate predictors likely reflect prodromal RA and may aid earlier disease detection, while modifiable lifestyles could support prevention. Further studies are required to confirm causality and clinical relevance.
OBJECTIVE:To characterize the clinical phenotype and disease burden in patients with concomitant spondyloarthritis (SpA) and hidradenitis suppurativa (HS) versus patients with SpA alone. METHODS:We conducted a multicenter, retrospective and matched case-control study. Cases were adults with SpA and dermatologist‑confirmed HS; controls had SpA without HS. Data from the preceding three years were extracted from electronic medical records. RESULTS:We included 39 cases and 111 controls. Among cases, 64% had axial SpA (axSpA) and 36% peripheral SpA (pSpA). Compared with controls, patients with axSpA+HS had less HLA-B27 positivity (46%vs. 79%, p = 0.002), less radiographic sacroiliitis (60%vs. 86%, p = 0.007), and more frequent arthritis (40%vs. 23%; p = 0.081). Several comorbidities were more prevalent in axSpA+HS: active smoking (68%vs. 35%; p = 0.006), hypertension (44%vs. 17%; p = 0.011), and anxiety-depressive disorders (36%vs. 16%; p = 0.046). Among EMM, IBD was more frequent in axSpA+HS than in controls (20%vs. 3%; p = 0.020). Patients with axSpA+HS presented higher disease activity (ASDAS-CRP: 3.0 vs. 2.1, p = 0.003; CRP: 11.3 vs. 3.3 mg/L, p = 0.001), had received a greater number of different biologic agents (p = 0.028), showed more frequent csDMARD use (52%vs. 28%; p = 0.018), and had more rheumatology visits (median 9.0 vs. 7.0; p = 0.050). CONCLUSIONS:Concomitant SpA and HS appears to be associated with a distinct clinical phenotype and higher disease burden that translates into greater therapeutic complexity and healthcare utilization. These findings support the hypothesis that HS may form part of the broader spectrum of immune-mediated manifestations associated with SpA, although further investigation is required.
OBJECTIVE:Immune checkpoint inhibitors (ICIs) may induce rare immune-related vascular toxicities, but evidence on ICI-associated aortitis and classical large-vessel vasculitis remains limited. This study characterized clinical features and disproportionality signals using the FDA Adverse Event Reporting System (FAERS). METHODS:FAERS reports from 2011 Q1 to 2025 Q3 were retrospectively analyzed. Cases were identified using the MedDRA Preferred Terms "Aortitis," "Giant cell arteritis," and "Takayasu's arteritis." ICI exposure was defined as an ICI recorded as the primary or secondary suspect drug. Clinical characteristics were summarized descriptively. Disproportionality was assessed using reporting odds ratio (ROR), proportional reporting ratio, information component, and empirical Bayesian geometric mean, with subgroup analyses by ICI class, individual agent, regimen, and event subtype. RESULTS:We identified 83 reports of ICI-associated aortitis and classical large-vessel vasculitis. The median age was 68 years, and 57.8% of patients were male. Hospitalization and death were reported in 34.9% and 2.4% of cases, respectively. Among reports with available onset data, the median time to onset was 105.5 days. ICIs showed a positive disproportionality signal overall (ROR, 4.45; 95% CI, 3.57-5.55). Signals were most evident for anti-PD-1 agents (ROR, 4.32; 95% CI, 3.27-5.71), nivolumab, pembrolizumab, ipilimumab, and ipilimumab plus nivolumab. At the event-subtype level, aortitis and giant cell arteritis showed positive signals, whereas Takayasu's arteritis was rarely reported. CONCLUSION:This FAERS analysis identified disproportionate reporting signals for ICI-associated aortitis and classical large-vessel vasculitis. Clinicians should consider this rare but potentially serious toxicity in patients with unexplained inflammatory symptoms or abnormal vascular imaging during ICI therapy. These findings are hypothesis-generating and require validation, and they cannot be used to infer incidence or causality.
OBJECTIVE:To characterize malignancy patterns in Chinese patients with idiopathic inflammatory myopathies (IIM) and evaluate the real-world applicability of the International Myositis Assessment and Clinical Studies Group (IMACS) cancer screening guideline. METHODS:This multi-centre retrospective study included adult patients with IIM from five tertiary referral centers in China between January 2010 and December 2024. Cancer-associated myositis (CAM) was defined as malignancy diagnosed within 3 years before or after IIM onset. Logistic regression analyses were performed to identify factors associated with malignancy, and a simplified refinement score was developed to assess its incremental value beyond the IMACS guideline. RESULTS:Among 1980 eligible patients with IIM, 176 (8.9%) had CAM. Lung cancer (18.2%), breast cancer (14.8%), and thyroid cancer (11.9%) were the most common malignancies. Overall, 76.1% of cancers occurred within 1 year before or after IIM onset. According to the IMACS guideline, 65.9% of CAM patients were classified as high-risk, whereas 65.4% of non-CAM patients were also assigned to the moderate-risk category. Multivariable analysis identified anti-TIF1γ antibody positivity, anti-SAE antibody positivity, elevated C-reactive protein, and elevated CA125 as independent risk factors, whereas interstitial lung disease was inversely associated with malignancy. A refinement score incorporating anti-SAE antibody positivity, elevated C-reactive protein, elevated CA125, and absence of interstitial lung disease further stratified malignancy risk within IMACS categories and improved discrimination compared with IMACS alone (AUC 0.762 vs. 0.699, P < 0.001). CONCLUSION:The IMACS guideline effectively identifies patients at increased malignancy risk, and a simple refinement score may further improve risk stratification.
OBJECTIVE:To systematically review the (1) timeliness of publication of randomized controlled trials (RCTs) in rheumatology, (2) impact of the COVID-19 pandemic on time to publication, and (3) factors associated with publication delays. METHODS:We searched Medline, Embase, EBM Reviews, Cochrane Central Register of Controlled Trials, and Scopus from January 1, 2018, to June 30, 2023 for Phase 3, superiority, parallel-design RCTs that evaluated any treatment for a rheumatologic illness or a rheumatologic treatment for COVID-19 and reported clinical primary efficacy outcome. Outcomes of interest were time to publication after trial completion and publication delay of >2 years after trial completion. RESULTS:448 RCTs were included in this systematic review. Median time from completion to publication was 549 days and 65.9 % RCTs were published within 2 years of completion. Compared with RCTs on rheumatologic diseases, RCTs on COVID-19 were published sooner (253 vs. 549 days; p < 0.001) and were more likely to be published within 2 years (adjusted OR 9.49, 95 % CI 2.07 to 43.61). Compared with RCTs completed before March 1, 2020, RCTs completed after March 1, 2020, were published sooner (327 vs. 724 days; p < 0.001) and were more likely to be published within 2 years (adjusted OR 9.40, 95 % CI 5.14 to 17.21). Time from RCT completion to submission accounted for most (67 %) of the time to publication. CONCLUSIONS:Publication delay continues to be an important concern in dissemination of clinical research. Most of the delays in publication were attributable to delays in submission to journals after trial completion.
OBJECTIVE:This retrospective study investigated the efficacy and safety of upadacitinib in adult patients with dermatomyositis (DM). METHODS:Adult patients with DM who received upadacitinib between January 2024 and April 2025 were included and followed up for 6 months. Clinical data and complications were collected. RESULTS:The cohort included 40 adult patients with DM, of whom 21 (52.5%) were female. The mean age was 46.93 ± 11.04 years. The median disease duration was 14 (8.25, 31) months. At baseline, the mean disease visual analog scale (VAS) score was 3.93 ± 1.75, and the mean daily glucocorticoid (GC) dose was 29.03 ± 17.02 mg. By the 3-month follow-up, the mean VAS score decreased to 2.57 ± 1.56 (p < 0.001), with significant improvements in cutaneous involvement, interstitial lung disease and manual muscle test 8 score (all p < 0.05). The mean daily GC dose was reduced to 17.66 ± 10.35 mg (p < 0.001). At 6 months, the mean VAS score further decreased to 1.74 ± 1.46 (p < 0.001). The mean daily GC dose was further reduced to 10.65 ± 5.97 mg (p < 0.001). Only four patients with anti-MDA5 antibody showed disease aggravation or relapsed in the cohort. Infection was the most common complication affecting 17 patients, including 6 patients with CMV viraemia and 3 patients with herpes zoster. CONCLUSION:Upadacitinib may be a promising treatment option for adult DM, contributing to clinical improvement and GC dose reduction.
OBJECTIVES:To characterize the clinical profile of patients with anti-synthetase syndrome (ASyS) presenting with dermatomyositis (DM)-type skin lesions (ASyS-DM-skin) and compare them with patients with ASyS without DM-type skin lesions (ASyS-nonDM-skin) and patients with DM. METHODS:We performed a cross-sectional study of baseline data from the Spanish registry of patients with IIM (Myo-Spain). Patients with ASyS (classified as ASyS-DM-skin or ASyS-nonDM-skin) and DM were included. We compared characteristics between groups using univariable analysis. Two multivariable logistic regression models were evaluated: (1) factors associated with DM-type skin lesions among ASyS patients; and (2) factors associated with an ASyS diagnosis among patients with DM-type skin lesions. RESULTS:We included 194 patients with ASyS (61 [31.4%] ASyS-DM-skin) and 116 with DM. In the multivariable model restricted to patients with ASyS, DM-type skin lesions were positively associated with periungual capillary alterations (OR 2.49, 95% CI 1.10-5.65), and negatively associated with age at diagnosis (OR 0.97, 95% CI 0.94-0.99) and arthralgia (OR 0.39, 95% CI 0.15-1.00). Among patients with DM-type skin lesions, ASyS diagnosis was positively associated with Raynaud's phenomenon (OR 6.84, 95% CI 1.04-44.81), mechanic's hands (OR 12.60, 95% CI 1.55-102.7), and interstitial lung disease (OR 27.83, 95% CI 4.55-170.5), and negatively associated with heliotrope rash or Gottron sign/papules (OR 0.10, 95% CI 0.01-0.73) and muscle weakness at diagnosis (OR 0.11, 95% CI 0.01-0.83). Malignancy was less frequent in ASyS-DM-skin than in DM. CONCLUSION:ASyS-DM-skin patients displayed a distinct clinical phenotype, characterized by DM-type cutaneous involvement while retaining ASyS features, particularly interstitial lung disease, Raynaud's phenomenon, and mechanic's hands.
BACKGROUND:Rheumatoid arthritis (RA) and calcium pyrophosphate deposition (CPPD) disease are forms of inflammatory arthritis which may have similar presentations. There is growing recognition that these conditions can coexist, especially in elderly patients. This systematic literature review aims to examine the epidemiology and clinical characteristics of patients with both RA and CPPD disease. METHODS:A systematic literature search was performed from database inception to 31st January 2026 using the databases EMBASE, MEDLINE, Scopus, PubMed, CINAHL, and Cochrane. Keywords relating to RA, CPPD and chondrocalcinosis were used. Inclusion criteria were studies published in English and those that addressed the co-occurrence of RA and CPPD. RESULTS:The search yielded 24 studies comprising 12 cross-sectional studies, 2 case series, and 10 case reports published between 1965 and 2026. A total of 404 patients had both RA and CPPD, with 397/404 (98.3%) aged over 60 years old. Of 365 patients with serostatus data, 204/339 (60.2%) were seronegative for both rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA). Radiographic chondrocalcinosis was evident in 271/287 (94.4%). Of 271 patients with chondrocalcinosis, 162 (59.8%) were seronegative for both RF and ACPA. The most prescribed medications were methotrexate and prednisolone, in 75/205 (36.6%) and 64/205 (31.2%) patients, respectively. Colchicine was prescribed for 24/205 (11.7%). CONCLUSION:While the studies were small, RA, which is commonly seronegative, and CPPD can co-exist in the elderly. Higher-quality studies are required to determine the prevalence of co-existent RA and CPPD, thereby improving insight into the epidemiology and potentially enhancing outcomes of these patients.
INTRODUCTION/OBJECTIVES:We aimed to investigate associations between menopausal characteristics, including age at menopause and cause (natural vs. artificial), with long-term outcomes in women with rheumatoid arthritis (RA), incident Alzheimer's disease and related dementias (ADRD), RA severity, and overall mortality. We hypothesized that atypical menopausal characteristics increase ADRD risk and disease severity. METHODS:Women with incident RA in 1980-2014 who were ≥50 years of age at RA incidence were included. Menopause cause and age at menopause (categorized as <45, 45-54, ≥55 years) were abstracted from medical records. Associations between menopausal characteristics and ADRD, extra-articular manifestations (ExRA), erosions, cardiovascular events, and mortality were evaluated using Cox models. Associations with clinic visits for flares and remissions were assessed using mixed-effects models. Data were collected using the Rochester Epidemiology Project medical records-linkage system. RESULTS:Both early/premature and late menopause were associated with nonsignificant near two-fold increases in ADRD risk. In addition, early/premature (HR 2.40; 95% CI 1.15-5.01) and late menopause (HR 2.17; 95% CI 1.01-4.66) significantly increased severe ExRA risk. Menopausal characteristics were not associated with presence of erosions or mortality. Artificial menopause was associated with fewer cardiovascular events and fewer visits for RA remission. Early/premature menopause was associated with fewer remission visits (OR 0.50; 95% CI 0.29-0.87). CONCLUSION:Women with early/premature and late menopause had nonsignificant, increased risk of incident ADRD. Menopausal characteristics had significant associations with RA severity and cardiovascular events, and may be relevant contextual factors in long-term risk assessment for women with RA.
OBJECTIVES:To estimate the prevalence and incidence of eosinophilic granulomatosis with polyangiitis (EGPA) in Northern Italy using multi-source capture-recapture methodology. METHODS:We conducted a population-based study in Reggio Emilia area from 1991 to 2022. Cases fulfilling the 2022 ACR/EULAR classification criteria were identified through seven independent sources: outpatient vasculitis and asthma clinic records, centralized laboratory databases for ANCA testing, drug prescription records for IL-5 inhibitors, hospital discharge data, day service admissions database and the regional rare disease registry. Capture-recapture models were fitted to estimate the total number of cases, including those not identified by any source. RESULTS:Forty patients with EGPA were identified (mean age 55 years, 75% female). On January 1, 2023, 36 prevalent cases were alive and resident. The best-fitting capture-recapture model estimated 0 missed cases (95% CI 0 to 2), yielding a crude prevalence of 68 per million inhabitants (95% CI 68-72). Between 2001 and 2022, 37 incident cases were identified. Capture-recapture analysis estimated complete case ascertainment in both periods 2001-2011 and 2012-2022 (0 missed cases in both periods, 95% CI 0-3 and 0-2, respectively). The age- and sex-standardized incidence was 3.31 per million inhabitants (95% CI 2.24-4.37), increasing from 2.83 (95% CI 1.39-4.27) in 2001-2011 to 3.59 (95% CI 2.08-5.09) in 2012-2022. Hospital discharge data identified only 25% of prevalent cases, while the exemption registry captured 86%. CONCLUSIONS:EGPA prevalence in Northern Italy is among the highest reported in Europe, likely reflecting near-complete case ascertainment through integrated health data sources rather than true geographic variation.
BACKGROUND:Fibromyalgia (FM) is a common, multifaceted condition with evolving diagnostic criteria and limited effective treatment. Data on long-term trends in incidence, patient characteristics, healthcare utilization, and medication use remain limited. PURPOSE:To assess temporal trends in the incidence and prevalence of diagnosed FM and to evaluate changes in patient characteristics, healthcare utilization, and medication use between 2009 and 2024. METHODS:This retrospective cohort study used the centralized database of Clalit Health Services in southern Israel. Patients aged 12-90 years diagnosed with FM between 2009 and 2024 were included. The study period was divided into eight two-year intervals. Trends in incidence, prevalence, sociodemographic characteristics, comorbidities, healthcare utilization, and medication use were analyzed. RESULTS:Both incidence and prevalence increased significantly, with prevalence rising from 1.04% to 3.88%. The largest increases in incidence were observed among individuals aged 30-59 years, whereas rates declined among adolescents. The proportion of male patients increased, mean age at diagnosis decreased, and the proportion of patients without comorbid rheumatic disease increased. Psychiatric comorbidities, including anxiety, depression, and PTSD, increased, whereas the overall comorbidity burden remained stable. Healthcare utilization shifted toward fewer hospitalizations and specialist visits but increased imaging. Use of recommended medications remained limited, although prescriptions for pregabalin, duloxetine, and gabapentin increased, while amitriptyline and NSAID use declined. Opioid use increased until 2019-2020 and subsequently decreased. CONCLUSIONS:FM diagnoses have increased substantially over time, accompanied by evolving clinical and treatment patterns. Despite improved recognition, management remains suboptimal, highlighting the need for more effective and comprehensive strategies.
OBJECTIVES:This study aimed to elucidate the epidemiological and clinical characteristics of patients with polyarteritis nodosa (PAN) in Japan. METHODS:We sent a secondary questionnaire to facilities randomly selected from a nationwide list of hospitals treating patients with PAN in the first nationwide epidemiological survey. RESULTS:We analyzed data from 547 patients out of the 868 reported in the first survey. Of these, 233 were male and 314 were female (male-to-female ratio, 1:1.3), with a mean age at diagnosis of 51.7 ± 17.6 years. Fever was observed in 43.4% of cases. Among organ manifestations, skin involvement (82.4%) and joint/muscle involvement (51.6%) were the most frequently reported. Most patients (95.4%) were prescribed oral glucocorticoids, and concomitant immunosuppressants were used in 78.6%. Frequently administered agents included azathioprine (59.3%) and cyclophosphamide (49.3%). Remission was achieved in 91.2% of cases, but relapse occurred in 47.8%. Skin involvement was identified as a risk factor for relapses, while fever was associated with a lower risk. Of the 547 patients, 14.4% met the diagnostic criteria for cutaneous arteritis; the male-to-female ratio was 1:3.9, and the mean age at onset was 47.5 ± 14.5 years. Additionally, 22 patients had pediatric-onset PAN, defined as disease onset at age 18 years or younger, exhibiting a higher male ratio (1.8:1), and a higher frequency of fever and skin involvement. CONCLUSIONS:This epidemiological study revealed the number and sex ratio of patients with PAN in Japan, along with their clinical characteristics. It also detailed the features of cutaneous arteritis.
BACKGROUND:Familial Mediterranean Fever (FMF) is a monogenic autoinflammatory disease commonly treated with lifelong colchicine therapy. Although colchicine is considered safe, its long-term hepatic effects remain debated. Distinguishing liver injury attributable to FMF itself from that induced by colchicine is essential for guiding clinical management. OBJECTIVES:To determine whether FMF or colchicine exposure are independently associated with liver cirrhosis and fatty liver disease. METHODS:This retrospective cohort study utilized electronic medical records from a tertiary care centre in Israel. Patients diagnosed with FMF, gout, pseudogout, or pericarditis were included. Liver injury outcomes were assessed via ICD codes, imaging, and biopsy data. Propensity score matching was applied to isolate the effects of FMF diagnosis and colchicine treatment, and multivariate logistic regression models were constructed to adjust for relevant confounders. RESULTS:Among 19,231 patients, FMF diagnosis was significantly associated with increased risk of cirrhosis (OR = 4.00; 95% CI: 2.78-5.75) and fatty liver (OR = 2.03; 95% CI: 1.57-2.61), both in unmatched and matched cohorts. In contrast, colchicine treatment was not associated with elevated OR for either condition (Cirrhosis OR = 0.92 [95% CI: 0.69-1.22]; Fatty Liver OR = 1.01 [95% CI: 0.85-1.21]). CONCLUSIONS:FMF is independently associated with increased hepatic injury risk, while colchicine treatment does not appear to confer additional liver toxicity. These findings underscore the importance of controlling FMF-related inflammation to prevent hepatic complications, and support the continued use of colchicine as a safe therapeutic agent in this population.
Objective : Knee osteoarthritis (KOA) causes pain and progressive disability, but pharmacologic treatments are limited. Colchicine inhibits inflammation that might modulate KOA, but efficacy trials have yielded mixed results. We tested whether colchicine, without concurrent NSAIDs, improved KOA pain, function, synovial effusion size, and OA-associated inflammatory serum biomarkers. Methods : Participants with symptomatic KOA and radiographic Kellgren-Lawrence grades 2/3 were randomized to receive three months of daily colchicine or placebo in a double-blind manner, with no concurrent NSAID use. The primary outcome was between-group change in visual analog score (VAS) for index knee pain. Secondary outcomes included changes in Knee Osteoarthritis Outcome Scores (KOOS), size (depth in millimeters) of sonographically-identified effusions, acetaminophen use, and changes in OA-related serum biomarkers. Results : From baseline to end of study of 120 enrolled participants, no significant differences were observed in improvement of VAS pain, KOOS scores or effusion size. Subsets of participants with more severe VAS pain, worse radiographic disease, or higher hsCRP or serum urate levels at baseline also showed no significant clinical benefit from colchicine compared to placebo. In contrast to the clinical outcomes, colchicine treatment was associated with significant or trending improvement in multiple OA-related serum biomarkers including hsCRP and β-NGF (p<0.05) and PGE2, IL-1ra, IL-8, and VEGF (p<0.16). Conclusion : This double-blind placebo-controlled trial of colchicine for KOA failed to demonstrate improvement in pain, function, or synovial effusion size in comparison to placebo at three months. Early improvement in OA-associated inflammatory biomarkers suggests a possible longer-term clinical benefit. Clinical Trials Registration No NCT03913442.
Background/aimsGlucocorticoids (GCs) are widely used to treat autoimmune rheumatic diseases (AIRDs). Despite well-recognised adverse effects (AEs) including osteoporosis, diabetes, infection and psychiatric comorbidities, GC impact has not been well quantified in clinical trials nor standardised across indications for use. The OMERACT GC Impact Working Group established a core domain outcome set in 2021. Further work was required to establish appropriate measurement instruments for these core domains. This scoping review aims to identify clinician reported outcome measures (ClinROs) of GC-related AEs in patients with inflammatory conditions treated with GCs.MethodsMedline, EMBASE, CINHAL and CENTRAL were searched (from inception to August 2024) along with hand search of abstracts presented at major rheumatology meetings (between August 2019 and August 2024), for studies referring to the use of exogenous GCs and reporting a clinician or patient reported outcome measure (PRO). Data was extracted for each OMERACT GC domain. Results57 studies included ClinROs, 20 (35.1%) in an AIRD population. In the majority (48/57, 84.2%) GCs were delivered systemically. Bone fragility (n=31 studies) and mood disturbance (n=20) were frequently assessed, while fatigue (n=0), sleep disturbance (n=2) and appearance (n=1) were infrequently assessed. 31 individual or grouped candidate ClinROs were identified. Conclusion31 candidate ClinROs were identified for measurement of physiological and psychosocial impact domains of GC impact. These findings will inform selection of a core set of measurement instruments for future trials and clinical practice.
OBJECTIVES:to evaluate interobserver agreement in synovial tissue (ST) biopsy histology and immunohistochemistry (IHC) analysis across expert centers, and the influence of observers' experience on interobserver agreement. METHODS:ST slides, collected from 38 biologic-naïve rheumatoid arthritis patients, stained for H&E, FVIII, CD68, CD3 and CD19/20, were uploaded to an online platform. Using semiquantitative analysis, independent observers scored ST slides for immune and vascularity markers (0 to 4), and Krenn's synovitis score (0 to 9). Presence of lymphoid aggregates and synovial pathotype were also recorded. After the initial scoring, a modified eDelphi process was conducted to reach consensus on a shared scoring approach among observers, followed by a second scoring. Interobserver agreement was assessed with Kappa coefficients. RESULTS:Initial scoring showed variability across observers and centres, with higher agreement for immune markers (e.g. kappa for CD19/20=0.737; CD3=0.713) compared to vascular ones (FVIII=0.392, H&E = 0.316). Stratifying by observers' experience revealed lower agreement among highly experienced observers compared with low and intermediate-experienced observers on specific markers. After discussion, a modified eDelphi process was conducted, and consensus on adopting a maximum-score approach (the highest score observable on the slide as the final scoring) for semiquantitative parameters was reached. A rescoring exercise, applying this principle, demonstrated improved agreement among observers, across most parameters (CD68= 0.684, Krenn's score 0.545), although variability persists for certain parameters. CONCLUSION:This study demonstrates that consensus-based methods can improve interobserver agreement in ST histology and IHC scoring across centres. Adoption of a maximum-score approach among observers represents a further step toward standardization of ST biopsy analysis, and may support its broader application STATEMENT OF CLINICAL SIGNIFICANCE: Histological and immunohistochemical analysis of synovial tissue (ST) biopsy is a promising tool in rheumatoid arthritis (RA), both in translational and clinical research. Notably, the differences in ST biopsy evaluation and interpretation persist across different centres of excellence hampers its widespread clinical application and use in multicentre trials. Our study demonstrates that consensus-based approaches, particularly the adoption of a maximum-score principle, can improve interobserver agreement of ST scoring across centres. Our findings represent a critical step toward the standardization of ST biopsy analysis.
