OBJECTIVE:Rheumatoid arthritis (RA) features sporadic symptoms that intensify during flares, significantly affecting the quality of life. This study aimed to (1) characterize flare frequency and severity, (2) assess if short-term changes in patient-reported outcomes (PROs) signal RA flares, and (3) examine the relationship between passive smartphone data and self-reported flares. METHODS:Participants from FORWARD Databank completed PROs in two phases: conditional (flare questions triggered by PRO changes) and fixed (biweekly flare assessments). Passive smartphone data, including mobility and communication patterns, were collected alongside PROs and flares (binary outcome). Adjusting for demographic and seasonal confounders, we assessed associations between smartphone data, PROs, and flares using logistic generalized estimating equation models, multivariate analyses with backward selection, and kappa statistics. RESULTS:The study included 292 adults with RA. In the conditional phase, 71% reported greater than or equal to one flare over 441 days (2.9 per participant), while 76% reported flares in the fixed phase over 172 days (3.7 per participant). Flares were linked to worse PROs. Increased mobility and longer texts were associated with fewer flares, whereas slower reaction times and shorter texts were associated with more flares. Flares were less common in the summer. Lower mobility radius (odds ratio [OR] 0.88), younger age, workdays, and lower educational level were associated with flare in the conditional phase. Worse patient global (OR 1.25) and pain (OR 1.30) were associated with flaring in the fixed phase. CONCLUSION:Integrating PROs with passive smartphone data demonstrates novel associations with flare occurrence and highlights the potential for future predictive modeling. These findings suggest that, with further validation, personalized algorithms may one day support the earlier recognition of flares and improved disease management.

Background: Older age is a risk factor for serious infection (SI) associated with biologic or targeted synthetic DMARDs (b/tsDMARDs) use in rheumatoid arthritis (RA). Among older adults with RA, one-third are diagnosed at ⩾60 years (late-onset RA, LORA), while others are diagnosed earlier (young-onset RA, YORA). LORA is characterized by a more acute onset and heightened inflammatory burden due to age-related immune dysregulation. Whether RA onset age independently affects infection risk with b/tsDMARDs remains unclear. Objective: Evaluate SI risk in older adults with RA initiating b/tsDMARDs, stratified by RA onset age: LORA versus YORA. Design: Retrospective cohort study using prospectively collected registry data. Methods: From FORWARD, the National Databank for Rheumatic Diseases (2001–2019), we identified RA patients aged ⩾60 years who initiated (1) anti–TNF then (2) subsequent non-TNF b/tsDMARDs. Patients were categorized as LORA versus YORA and matched using kernel-based propensity scores. SI was defined as an infection requiring hospitalization, intravenous antibiotics, or death. Multivariable Cox models estimated the risk of SI in LORA versus YORA. Results: Among 1379 LORA and 2727 weighted YORA patients initiating anti-TNF therapy, the crude incidence of SI was 28.2 and 20.5 per 1000 person-years. In adjusted models, LORA was not associated with increased anti-TNF-related SI risk compared to YORA (HR 0.82, 95% CI 0.63–1.02). Among 198 LORA and 675 weighted YORA patients subsequently initiating non-TNF b/tsDMARDs, the crude incidence of SI was 17.3 versus 19.5 per 1000 person-years. In adjusted models, LORA was not associated with increased non-TNF related SI risk (aHR 0.81, 95% CI 0.31–2.12). Across cohorts, older age was independently associated with increased SI risk. For anti-TNF, prior SI and recent long-term glucocorticoid use, and for non-TNF, HAQ disability were also associated with SI. Conclusion: Age at RA onset was not independently associated with SI risk following b/tsDMARD initiation. Risk stratification should prioritize functional status and treatment history.

OBJECTIVE:Despite advances in rheumatoid arthritis (RA) treatment, a considerable proportion of patients exhibit refractory disease, prompting the need for a comprehensive understanding of refractory RA. We aimed to analyze the burden and patient experiences associated with initiation of a third biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) (BT3-RA) in a large observational cohort. METHODS:Data were obtained from participants with RA in the FORWARD Databank from 1999 to 2019. Participants, stratified into BT3-RA and a comparator BT1-RA (first initiation of a b/tsDMARD) cohorts, were matched based on key demographic and disease-specific parameters. Demographics, patient-reported outcomes (PROs), comorbidities, and health care interactions were assessed at initiation of first advanced therapy and at the time of meeting BT3-RA criteria. RESULTS:After matching, 1,384 participants were included in the study (692 each for BT3-RA and BT1-RA). The BT3-RA cohort had worse PROs, greater comorbidity burden, and lower health satisfaction than BT1-RA controls. Those with BT3-RA had significantly higher odds of having a greater number of rheumatology visits in the previous six months than controls (>4 visits, 0-2 visit reference, odd ratio [OR] 3.8 [95% confidence interval (CI) 2.7-5.4], P < 0.001; 3-4 visits, 0-2 visit reference, OR 1.9 [95% CI 1.5-2.5]; P < 0.001). Those with BT3-RA also had higher odds of concomitant glucocorticoid use (OR 1.5 [95% CI 1.2-2.0], P < 0.001) and gastrointestinal disorders (OR 1.5 [95% CI 1.1-1.9], P < 0.01). CONCLUSION:Exposure to three advanced RA therapies was associated with significant disease burden and unmet health care needs. These findings underscore the importance of well-defined refractory criteria and the need for further investigation into this RA phenotype to identify targeted treatment strategies and ultimately improve outcomes.

OBJECTIVES:Postmenopausal women with RA experience worsening functional decline, independent of disease activity. Estrogen replacement therapy (ERT) has been proposed to mitigate musculoskeletal deterioration, but its role in RA remains unclear. This study investigated the association between ERT use and physical function in postmenopausal women with RA. METHODS:This longitudinal study analysed data from 'Forward, the National Databank for Rheumatic Diseases' (2000-22). Postmenopausal women with RA who initiated ERT were matched 1:1 to non-users based on menopause year or ERT initiation. The primary outcome was physical function, assessed using the HAQ. Generalized estimating equations (GEE) were used to evaluate the association between ERT and HAQ scores, adjusting for demographics, reproductive history, RA duration, comorbidities and medication use. Sensitivity analyses with propensity score matching were conducted. RESULTS:A total of 8246 women were included, with 4123 ERT users matched to non-users. ERT use was associated with modestly improved HAQ scores (β = -0.02, 95% CI -0.03, -0.01; P < 0.001). Later menopause correlated with better function (β = -0.008 per year after menopause, 95% CI -0.03, -0.01; P < 0.001). Women initiating ERT within 5 years of menopause demonstrated greater benefits. Sensitivity analyses using propensity score adjustment confirmed these findings and revealed additional improvements in patient-reported outcomes. CONCLUSION:ERT use was modestly associated with improved physical function and other patient-reported outcomes in postmenopausal women with RA, with the greatest benefits seen in early postmenopausal initiation. No excess crude rates of cardiovascular or cancer events were observed. Further research is needed to determine the clinical implications of ERT in RA management.

Objective:To describe Raynaud phenomenon (RP) management practices for systemic sclerosis (SSc) patients among US community-based rheumatologists.Methods:We identified all adult SSc patients, diagnosed by a rheumatologist, from the FORWARD Databank between 1999 and 2023. We evaluated longitudinal RP medication use, from data collected by semiannual questionnaires. We evaluated factors associated with RP medication use with multivariable Andersen and Gill Cox proportional models.Results:Of the 270 SSc patients, 61% received a medication for RP over the median (interquartile range) follow-up of 3.4 (1.3-7.8) years. Calcium-channel blockers were the most chosen overall (48%) and first-line (75%) medication, followed by renin-angiotensin system inhibitors (18% [23%]). The use of RP medications persistently (29%), combination regimens (20%), and advanced therapies (15%; phosphodiesterase-5 inhibitors [PDE5i], endothelin receptor antagonists, or prostaglandin analogs) throughout the follow-up was low. Whereas calcium-channel blocker use has declined, PDE5i use has increased since 2019. Factors associated with initiating medications for RP were hypertension (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.25-1.98), pulmonary disease (HR, 1.25; 95% CI, 1.04-1.52), immunomodulatory use (HR, 1.32; 95% CI, 1.04-1.68), higher annual income (HR, 1.33; 95% CI, 1.02-1.73), and having an insurance (HR, 2.37; 95% CI, 1.04-5.44).ConclusionOverall use of RP medication was low with poor maintenance rates in less than one-third of the patients from this community sample. The pattern of RP medication use changed over time with increasing use of PDE5i use since 2019. Although socioeconomic factors had impact on RP medication initiation, there is also a need for education and guideline recommendations to assist community-based rheumatologists in RP management.

OBJECTIVE:To quantify the degree of financial distress and identify its determinants in adults with rheumatoid arthritis (RA) given the frequent prolonged use of expensive disease-modifying therapies. METHODS:We identified adults enrolled in the FORWARD databank with either RA or noninflammatory musculoskeletal disease (NIMSKD) completing the Functional Assessment of Chronic Illness Therapy-Comprehensive Score for Financial Toxicity (FACIT-COST) questionnaire. In this cross-sectional study, FACIT-COST was analyzed as a continuous (higher score indicates less financial distress) and binary variable (presence of financial distress with threshold <26). Least Absolute Shrinkage and Selection Operator (LASSO) was applied to linear and logistic regression to select covariates for inclusion in multivariable models. RESULTS:Participants with RA (n = 2,277) had lower FACIT-COST scores, indicating greater financial distress, than those with NIMSKD (n = 1,340) (mean of 30.2 ± SD 9.4 vs mean of 34.0 ± SD 8.4; unadjusted P < 0.001). Assessed as a binary outcome, financial distress was more frequent in participants with RA than participants with NIMSKD (29% vs 15%; unadjusted P < 0.001). Differences in financial distress by diagnosis persisted following multivariable adjustment. Among those with RA, determinants identified in multivariable models included depression (adjusted odds ratio 1.12; 95% confidence interval 1.09-1.16) and disease severity. CONCLUSION:Financial distress is prevalent in adults with RA and appears to be greatest in those with comorbidities, specifically depression, identifying a potential area for intervention. Notably, expensive biologic or targeted synthetic disease-modifying antirheumatic drugs were not associated with FACIT-COST scores.

Older age increases the risk of serious infections (SI) in rheumatoid arthritis (RA) patients using biologics like anti-TNFs. About one-third of older adults are diagnosed with RA between ages 60-65, classified as late-onset RA (LORA). LORA exhibits more acute symptoms and faster disease progression compared to young-onset RA (YORA), possibly due to age-related immune changes. This study utilized data from the FORWARD-The National Databank for Rheumatic Diseases (2001-2019) to assess SI risk differences in older adults with LORA versus YORA starting anti-TNF therapy. Patients aged ≥60 years, categorized by age at RA diagnosis (LORA ≥60; YORA < 60), were propensity-matched for demographics and health factors. Exclusions applied to those with other rheumatic diseases, cancer, or HIV preceding SI. SI was defined as infections requiring hospitalization, IV antibiotics, or causing death, linked to anti-TNF within three months after treatment cessation. The study included 1,219 LORA and 6,030 weighted YORA patients. LORA patients had fewer previous infections, lower glucocorticoid (GC) use, but higher methotrexate use. Although LORA had a higher crude SI incidence (3.6/1000 patient-years) than YORA (2.7/1000 patient-years), SI risk did not significantly differ (aHR 0.85, 95% CI 0.58-1.25). Adjusting for prior SI, smoking, and methotrexate use did not alter outcomes. Long-term GC use and older age were independent risk factors for increased SI risk. These findings indicate that SI risk from anti-TNFs does not vary by RA onset age but highlight the risky and often suboptimal reliance on long-term GC use in LORA patients, suggesting a need for improved treatment strategies.

OBJECTIVE:To describe Raynaud phenomenon (RP) management practices for systemic sclerosis (SSc) patients among US community-based rheumatologists. METHODS:We identified all adult SSc patients, diagnosed by a rheumatologist, from the FORWARD Databank between 1999 and 2023. We evaluated longitudinal RP medication use, from data collected by semiannual questionnaires. We evaluated factors associated with RP medication use with multivariable Andersen and Gill Cox proportional models. RESULTS:Of the 270 SSc patients, 61% received a medication for RP over the median (interquartile range) follow-up of 3.4 (1.3-7.8) years. Calcium-channel blockers were the most chosen overall (48%) and first-line (75%) medication, followed by renin-angiotensin system inhibitors (18% [23%]). The use of RP medications persistently (29%), combination regimens (20%), and advanced therapies (15%; phosphodiesterase-5 inhibitors [PDE5i], endothelin receptor antagonists, or prostaglandin analogs) throughout the follow-up was low. Whereas calcium-channel blocker use has declined, PDE5i use has increased since 2019. Factors associated with initiating medications for RP were hypertension (hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.25-1.98), pulmonary disease (HR, 1.25; 95% CI, 1.04-1.52), immunomodulatory use (HR, 1.32; 95% CI, 1.04-1.68), higher annual income (HR, 1.33; 95% CI, 1.02-1.73), and having an insurance (HR, 2.37; 95% CI, 1.04-5.44). CONCLUSION:Overall use of RP medication was low with poor maintenance rates in less than one-third of the patients from this community sample. The pattern of RP medication use changed over time with increasing use of PDE5i use since 2019. Although socioeconomic factors had impact on RP medication initiation, there is also a need for education and guideline recommendations to assist community-based rheumatologists in RP management.

Background: Cognitive symptoms such as forgetfulness or "brain fog" are frequently reported by individuals with systemic lupus erythematosus (SLE) and are reported to be among the most distressing symptoms of lupus. Less well understood is how these self-reported symptoms compared to those experienced by individuals with other rheumatic or musculoskeletal conditions and what the relationship of cognitive symptoms may be to disease status. Cognitive symptoms are also more commonly reported among older adults, but little information is available about cognitive symptoms in older people with SLE compare to those of similar ages with other rheumatic or musculoskeletal conditions. Objectives: We examined self-reported cognitive function among an older cohort of individuals with SLE to individuals with rheumatoid arthritis (RA), osteoarthritis (OA), and fibromyalgia (FM) of similar ages, and the association of cognitive function with self-perceptions of disease status and satisfaction with health. Methods: Data were drawn from FORWARD, The National Databank for Rheumatic Diseases, a longitudinal observational cohort. Data are collected biannually via questionnaires. Cognitive symptoms were assessed with the 8-item NeuroQoL Cognitive Function Short Form (NCF)1. NCF items query cognitive symptoms and perceived ability to complete everyday tasks. Raw scores range from 8-40 and can be transformed to standardized T-scores with a population mean of 50 and standard deviation of 10. The NCF was administered in 3 biannual surveys. We compared scores of individuals with physician-confirmed SLE and no other rheumatic diagnosis to individuals with RA, OA, FM, and SLE + FM using generalized estimating equation (GEE) modeling, adjusting for age, education, pain, fatigue, sleep disturbance, and depressive symptoms. Among the SLE-only group, we compared self-reported lupus disease activity (0-10 scale, 0 = not at all active, 10 = extremely active), organ damage (using the validated Brief Index of Lupus Damage, BILD), and the occurrence of flares in the past 3 months between those with low NCF T-scores (below 40, i.e., 1 SD below mean) and those with higher scores. We also compared health satisfaction (rated on 5-point Likert scale, 0 = very satisfied, 4 = very dissatisfied; low scores = more satisfaction) for those with and without low NCF scores, in both unadjusted t-tests and multivariable regression analysis adjusting for age, education, pain, fatigue, sleep disturbance, depressive symptoms, self-rated lupus activity, and BILD. Results: 142 SLE, 6742 RA, 1018 OA, 298 FM, and 42 SLE+FM questionnaires were completed over 3 periods. Characteristics of each group are shown in Table 1. After adjustment, NCF scores of individuals with SLE alone and SLE +FM were significantly lower than other groups (Table 1). Over a quarter of the SLE group had low NCF scores; almost half of the SLE + FM had low NCF scores (Table 1). Low NCF scores were associated with significantly higher self-reported disease activity and damage, and a greater occurrence of recent flares (Table 2). Health satisfaction was significantly lower among individuals with low NCF in both unadjusted analyses (not low: 1.6 ± 1.2; low: 2.2 ± 1.2; p <0.0001) and adjusted analyses (β = 0.92, p=0.0059). Conclusion: Cognitive symptoms are significantly worse among older individuals with SLE compared to individuals of similar age with other rheumatic or musculoskeletal conditions. Worse perceived cognitive function is, in turn, associated with worse self-reported disease status. Perceptions of cognitive function are associated with less satisfaction with health, even after controlling for disease status. Results confirm that the burden of cognitive symptoms continues into older age for individuals with SLE, is significantly greater than for older individuals with other rheumatic/musculoskeletal conditions, and has an important impact on quality of life, above and beyond lupus disease status. REFERENCES: [1] Iverson GL et al. Arch Clin Neuropsychol 2021; 36:126-134. Acknowledgements: NIL. Disclosure of Interests: None declared.

ObjectiveOpioid use among individuals with spondyloarthritis is common; however, data on whether these individuals have higher utilization of the healthcare system are lacking. We examined the association between opioid use and healthcare utilization and costs among patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS).MethodsWe included adults with PsA or AS enrolled in the FORWARD registry, with ≥ 1 completed disease activity or disability questionnaire between 2010 and 2019. The exposure was patient-reported opioid use, and the outcomes were annualized healthcare utilization and prescription costs. We used negative binomial regression to assess the association between opioid use and the utilization outcomes, and generalized linear models with γ-distribution and log link function for the association between opioid use and costs. Models were adjusted for age, sex, and hospitalization. AS and PsA were studied separately.ResultsAmong 828 patients with PsA, 21.4% used opioids; for those with AS, 27.2% of 334 patients reported opioid use. Opioid users had higher healthcare utilization and costs, including increased medical visits, diagnostic tests, direct medical costs, and pharmacy expenses. Opioid users had 32-33% more medical visits annually vs nonusers. Patients using opioids spent more on medical visits annually compared to nonusers (US $3464 vs $2706 for PsA; US $4500 vs $3660 for AS).ConclusionCompared to patients not using opioids, patients with PsA and AS who used opioids had higher healthcare utilization and higher health-related costs. New care pathways are needed to improve care and reduce costs.

Objectives This study aims to evaluate non-melanoma skin cancer (NMSC) risk associated with abatacept treatment for rheumatoid arthritis (RA). Methods This evaluation included 16 abatacept RA clinical trials and 6 observational studies. NMSC incidence rates (IRs)/1000 patient-years (p-y) of exposure were compared between patients treated with abatacept versus placebo, conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biological/targeted synthetic (b/ts)DMARDs. For observational studies, a random-effects model was used to pool rate ratios (RRs). Results ~49 000 patients receiving abatacept were analysed from clinical trials (~7000) and observational studies (~42 000). In randomised trials (n=4138; median abatacept exposure, 12 (range 2–30) months), NMSC IRs (95% CIs) were not significantly different for abatacept (6.0 (3.3 to 10.0)) and placebo (4.0 (1.3 to 9.3)) and remained stable throughout the long-term, open-label period (median cumulative exposure, 28 (range 2–130 months); 21 335 p-y of exposure (7044 patients over 3 years)). For registry databases, NMSC IRs/1000 p-y were 5–12 (abatacept), 1.6–10 (csDMARDs) and 3–8 (other b/tsDMARDs). Claims database IRs were 19–22 (abatacept), 15–18 (csDMARDs) and 14–17 (other b/tsDMARDs). Pooled RRs (95% CIs) from observational studies for NMSC in patients receiving abatacept were 1.84 (1.00 to 3.37) vs csDMARDs and 1.11 (0.98 to 1.26) vs other b/tsDMARDs. Conclusions Consistent with the warnings and precautions of the abatacept label, this analysis suggests a potential increase in NMSC risk with abatacept use compared with csDMARDs. No significant increase was observed compared with b/tsDMARDs, but the lower limit of the 95% CI was close to unity.

ObjectiveGlucocorticoids (GCs) can be beneficial from both clinical and patient perspectives, but side effects are well documented. We examined patterns of GC use over 15 years (2006–2021) and occurrence of adverse health conditions (AHCs) and health care use by GC exposure in two longitudinal cohorts with systemic lupus erythematosus (SLE).MethodsData from the Lupus Outcomes Study (LOS; 2003–2015) and FORWARD cohort (2015–2021) were used. AHCs examined were diabetes, osteoporosis, nontraumatic fractures, cataracts, and infections. Health care use measures examined were the number of rheumatology and other provider visits, hospitalizations, and specific diagnostic tests. Kaplan–Meier analyses examined time to occurrence of each AHC. Cox regression analyses estimated the risk of occurrence of AHCs, controlling for covariates by GC use and by GC dose (0, 1–5, 5–7.5, and ≥7.5 mg).ResultsGC use was relatively consistent over time. At baseline, individuals who used GCs in the LOS were more likely to report osteoporosis (adjusted odds ratio [aOR] 1.7, 95% confidence interval [CI] 1.2–2.6) and cataracts (aOR 1.6, 95% CI 1.04–2.6); individuals who used GCs in the FORWARD cohort were more likely to report diabetes (aOR 5.1, 95% CI 2.2–12.0), osteoporosis (aOR 4.5, 95% CI 2.6–8.0), and fractures (aOR 6.5, 95% CI 3.8–11.1). Individuals who used high doses of GCs in the LOS had greater incidence of osteoporosis, fracture, and cataracts. In the FORWARD cohort, a significant difference in incidence was noted only for infections. In both cohorts, individuals who used GCs had more rheumatology and other physician visits, and greater risk of hospitalization.ConclusionDespite recommendations on steroid sparing, a large portion of people with SLE appear to remain on steroids. These analyses provide additional evidence of the potential health and health care burden of GC use, underscoring the need for other effective treatments for individuals with SLE.