Background: The potential association of long-term oral corticosteroid (OCS) use with adverse events (AEs) in patients with bullous pemphigoid (BP) is not well characterized in a real-world setting. Objective: To evaluate the effect of OCS use and treatment duration on the incident AEs in patients with BP. Methods: This retrospective cohort study used medical and pharmacy claims and patient enrollment data from IQVIA PharMetrics (R) Plus from 2006-2021. Eligible patients had a diagnosis of BP between 1 January 2006 and 30 June 2020 (>= 2 claims for BP >= 30 days apart). Patients in the OCS cohort also had a claim for OCS use, >= 7.5 mg daily dose of prednisone or equivalent, and no claims for a nonoral systemic corticosteroid (CS) at any time during the study period. A control cohort of patients with BP not using OCS was also selected. Relative risk ratios were estimated between the incidence of AEs in OCS users with different exposure durations (short-term, <30 days; medium-term, 30-90 days; long-term, >90 days) and nonusers by Poisson regression, after adjusting for age, sex, prior drug use, and baseline Charlson Comorbidity Index score within the follow-up period. Results: At the 1-year follow-up, long-term OCS users had a higher incidence of infections, cataract, osteoporosis, heart failure, depression or anxiety, and diabetes compared with OCS nonusers (p < 0.05). Furthermore, compared with nonusers, long-term users had increased 1-year risks (risk ratio; 95% confidence interval) for heart failure (2.27; 1.50-3.44), diabetes (2.05; 1.30-3.24), osteoporosis (1.72; 1.23-2.41), and infection (1.50; 1.13-1.99). Long-term OCS users also had increased 1-year risks for heart failure (2.00; 1.21-3.28) and osteoporosis (1.70; 1.16-2.50) compared with short-term OCS users. Conclusion: Long-term OCS use (>= 7.5 mg) in patients with BP was associated with an increased risk of AEs. Study findings demonstrate a need for steroid-sparing options with an improved safety profile.

OBJECTIVES:To identify the predictive factors of first hospitalization and associated variables to the main causes of hospitalizations in lupus patients from a Latin American cohort. METHODS:The first hospitalization after entry into the cohort during these patients' follow-up due to either lupus disease activity and/or infection was examined. Clinical and therapeutic variables were those occurring prior to the first hospitalization. Descriptive statistical tests, multivariable logistic, and Cox regression models were performed. RESULTS:1341 individuals were included in this analysis; 1200 (89.5%) were women. Their median and interquartile range (IQR) age at diagnosis were 27 (20-37) years and their median and IQR follow up time were 27.5 (4.7-62.2) months. A total of 456 (34.0%) patients were hospitalized; 344 (75.4%), 85 (18.6%) and 27 (5.9%) for disease activity, infections, or both, respectively. The predictors of the first hospitalization regardless of its cause were: medium (HR 2.03(1.27-3.24); p = 0.0028) and low (HR 2.42(1.55-3.79); p < 0.0001) socioeconomic status, serosal (HR 1.32(1.07-1.62); p = 0.0074) and renal (HR 1.50(1.23-1.82); p < 0.0001) involvement. Antimalarial (AM) use (HR 0.61(0.50-0.74); p < 0.0001) and achieving remission (HR 0.80(0.65-0.97); p = 0.0300) were negative predictors. CONCLUSIONS:The first hospitalization was associated with worse socioeconomic status and serosal and renal involvement. Conversely, AM use and achieving remission were associated with a lower risk of hospitalizations.

This retrospective cohort study described real-world treatment patterns and healthcare resource utilization (HCRU) of patients with warm autoimmune hemolytic anemia (wAIHA) initiating treatment with first-line (1L) oral corticosteroids (OCS) + rituximab (R) compared to 1L OCS. Patients with a wAIHA diagnosis code (D59.11) between 8/2020–3/2022 were identified using US pharmacy and medical claims databases. Patients initiating 1L OCS ± R were identified (date of initiation = ‘index date’) with a 1-year pre-index period and a variable (minimum 1-year) follow-up period. The final sample comprised 77 1L OCS + R patients and 400 1L OCS patients ( 60

Topic: 36. Ethics and health economics Background: Warm autoimmune hemolytic anemia (wAIHA) is a rare life-threatening disorder caused by autoantibodies that lead to the premature destruction of healthy red blood cells. Due to a paucity of clinical trials and no approved treatment, the First International Consensus meeting published recommendations in 2020 with goals to provide international guidelines for diagnosis and to create a framework for current treatment of autoimmune hemolytic anemia (AIHA). Oral corticosteroids (OCS) remain as first-line (1L) therapy for wAIHA, while the addition of rituximab (R) in 1L was recommended only in select patients due to limited duration of follow up and power in prospective studies evaluating the effect of 1L OCS plus rituximab (OCS+R) on the need for other treatments or inducing long-term remission. Experts highlighted the limited evidence base and recommended that clinicians should consider discussion of available clinical trials at all stages of treatment. Aims: This study described real-world treatment patterns and healthcare resource utilization (HCRU) of patients with wAIHA initiating 1L OCS+R compared to 1L OCS. Methods: A retrospective cohort study was conducted using IQVIA pharmacy and medical claims databases in the US to identify patients with a diagnosis code for wAIHA (D59.11) from 8/2020-3/2022. Patients initiating 1L OCS +/- R were identified (date of initiation = the ‘index date’) and required to have a 1-year pre-index (baseline) period and a minimum 1-year post-index (follow-up) period. Baseline clinical and demographic characteristics were collected. Treatment and utilization patterns were reported over the follow-up. Data were analysed using descriptive statistics. Study outcomes for the 1L OCS+R and 1L OCS cohorts were reported as a composite for primary and secondary wAIHA. Results: The final sample comprised 77 1L OCS+R patients and 400 1L OCS patients (~60% female and mean age >64 years). The OCS+R cohort had more patients with a hematology/oncology visit associated with the index date compared to the OCS cohort (71.4% and 55.3%, respectively). For both cohorts, hematologic malignancy was the most common associated condition (23.4% OCS+R and 19.0% OCS) followed by solid tumors (18.2% and 14.8%, respectively), and autoimmune disease (7.8% and 11.8%, respectively) (not mutually exclusive). Over the 1-year follow-up, HCRU was higher in the OCS+R cohort with higher mean number of physician office visits (22.9 and 14.4), including hematology/oncology office visits (10.7 and 5.6), and higher utilization of rescue therapy (59.7% and 33.3%), driven by higher use of injectable corticosteroids (50.6% and 24.8%). Use of outpatient red blood cell transfusion and inpatient hospitalization was comparable between groups. Patients in OCS+R and OCS groups completed 1L therapy after a similar mean duration of 103.5 and 134.6 days, respectively. In the majority of patients, treatment with OCS + R did not extend the remission period because second-line (2L) therapy was initiated at a similar timepoint: 66.2% OCS+R and 72.0% OCS cohorts initiated 2L in a mean of 218.3 and 203.2 days after the end of 1L treatment, respectively. Summary/Conclusion: Despite the addition of rituximab in 1L, duration of remission was brief in both cohorts with most patients initiating 2L therapy within less than 1 year of completing 1L treatment. In addition, substantial HCRU burden was observed among patients initiating 1L OCS+R. More effective novel therapies targeted to the underlying pathophysiology are needed to address the high unmet need to maintain long-term remission in patients with wAIHA.Keywords: Autoimmune hemolytic anemia (AIHA), Treatment, Health care

Introduction: For patients with rheumatoid arthritis (RA) with an inadequate response to tumor necrosis factor inhibitors (TNFi), main options include cycling onto a different TNFi or switching to a biologic/targeted synthetic disease-modifying antirheumatic drug with a different mechanism of action (MOA). This network meta-analysis (NMA) assessed comparative clinical efficacy of cycling versus switching. Methods: We conducted a literature search in MEDLINE, Embase, and Cochrane Library. Outcomes included proportion of patients with 20%, 50%, or 70% response to American College of Rheumatology criteria (ACR20/ACR50/ACR70 response), Disease Activity Score in 28 joints (DAS28) score below 2.6 or between 2.6 and 3.2, mean change in DAS28 score, mean reduction in and proportion of patients achieving a clinically meaningful reduction (⩾0.22) in Health Assessment Questionnaire score, number of serious adverse events (AEs), and withdrawals for any reason/due to AEs/lack of treatment efficacy. To account for the wide range of study populations and designs, we developed three models to conduct the NMA: fixed-effect, random-effects, and hierarchical Bayesian. PROSPERO ID: CRD42019122993. Results: We identified nine randomized controlled trials and 16 observational studies. The fixed-effect model suggested a 0.99 probability that switch was the better strategy for increasing odds of a clinically meaningful improvement in ACR50 [odds ratio (OR): 1.35 (95% credible interval (CI): 0.96–1.81)]. The fixed-effect model also suggested that switch was associated with lower rates of withdrawal for any reasons [OR: 0.53 (95% CI: 0.40–0.68)]. The random-effects and hierarchical Bayesian models suggested additional uncertainty as they considered more variability than the fixed-effect model. Discussion: Results suggest that switching to a drug with a different MOA is more effective and associated with lower rates of withdrawal than cycling to a different TNFi after failure of first-line TNFi. Further trials that directly compare cycling with switching are warranted to better assess comparative efficacy. Plain language summary Assessment of the effectiveness of different drug treatment strategies in patients with rheumatoid arthritis: an analysis of the published literature Rheumatoid arthritis (RA) is a chronic disease in which inflammation affects joints along with the entire body; this may cause significant pain, joint damage, physical disability, a decreased quality of life, and an increased risk of death. Tumor necrosis factor inhibitors (TNFis) are a common choice as first-line drugs to treat RA. Although they are effective in many patients, therapy with a TNFi is not successful within the first year of treatment in approximately one-third of patients due to either a lack of efficacy or safety issues. When TNFi therapy is unsuccessful, the options are to “cycle” to another TNFi or to “switch” to another drug with a different mechanism of action (MOA). Further studies are needed to help doctors decide the best treatment strategy for their patients when treatment with an initial TNFi fails. This study analyzed 25 published studies in which patients were either “cycled” to another TNFi or “switched” to a drug with a different MOA after unsuccessful treatment with an initial TNFi. The results showed that “switching” to a drug with a different MOA was a better treatment strategy than “cycling” to another TNFi; “switching” increased the chance of clinically meaningful improvement in disease status and lowered the chance of having to stop treatment for any reason.

The objective of this study was to compare rheumatoid arthritis (RA) disease activity and patient-reported outcomes (PROs) in a national sample of patients with RA with/without Sjögren’s syndrome (SS). Adults with RA from a large observational US registry (Corrona RA) with known SS status between 22 April 2010 and 31 July 2018 and a visit 12 (± 3) months after index date were identified (n = 36,256/52,757). SS status: determined from a yes/no variable reported at enrolment into the Corrona RA registry and follow-up visits. Index date: date that SS status was recorded (yes/no). Patients received biologic or targeted synthetic disease-modifying antirheumatic drugs as part of standard care. Patients with RA only were followed for ≥ 12 months to confirm the absence of SS. Patients were frequency- and propensity-score matched (PSM) 1:1 and stratified by disease duration and treatment response-associated variables, respectively. Clinical Disease Activity Index (CDAI) and PROs 12 months after index visit were compared in patients with and without SS. Baseline characteristics in 283 pairs of PSM patients were balanced. Mean change in CDAI score was numerically lower in patients with RA and SS than patients with RA only (8.8 vs 9.3). Reductions in PROs of pain, fatigue and stiffness were two- to threefold lower for patients with RA and SS versus RA only. Reductions in RA disease activity and RA-related PROs were lower in patients with RA and SS versus those with RA only. Our data indicate that SS adds to treatment challenges; physicians may wish to consider SS status when managing patients with RA.

Objective Definitions of remission in systemic lupus erythematosus (SLE; DORIS (1A/1B/2A/2B)), disease activity assessments and patient-reported outcome measures (PROMs) are useful in shared decision making between patients with SLE and physicians. We used longitudinal registry data from well-characterized Swedish patients with recent-onset SLE to explore potential correlations between DORIS status or disease activity, and PROMs. Methods Patients from the Clinical Lupus Register in North-Eastern Gothia, Sweden, who fulfilled the 1982 American College of Rheumatology and/or the 2012 Systemic Lupus International Collaborating Clinics classification criteria without prior organ damage, were enrolled at diagnosis. Data on treatments, serology, remission status (DORIS), disease activity (SLE Disease Activity Index-2000 (SLEDAI-2K)) and PROMs (quality of life: EuroQoL-5 Dimensions (EQ-5D); pain intensity, fatigue and well-being: visual analog scale (VAS) 0–100 mm) were collected during rheumatology clinic visits at months 0 (diagnosis), 6, 12, 24, 36, 48 and 60. Correlations were assessed using Pearson correlation and/or beta regression coefficients. Results A total of 41 patients were enrolled (median age = 39 years, 80% female, 85% white). Achievement of DORIS 1A and 2A (neither of which includes serology) significantly correlated with all PROMs (EQ-5D: p ≤ 0.02; pain: p = 0.0001; fatigue: p = 0.0051; well-being: p < 0.0001). Disease activity measures were correlated with VAS pain intensity ( p < 0.03) and VAS well-being ( p < 0.04). Conclusions Our findings illustrate the importance of the interplay between remission, disease activity assessments and PROMs. PROMs may be a useful tool in clinical practice, being administered prior to patient visits to streamline clinical care.

OBJECTIVE:Seropositivity for anti-citrullinated protein antibody (ACPA)/rheumatoid factor (RF) in rheumatoid arthritis (RA) is associated with increased overall mortality; however, the association between antibody titers and mortality is not well established. Investigating relationships between antibody titers and mortality may clarify their role in RA pathogenesis. This study was undertaken to evaluate the association of antibody titers with mortality and its modification by disease-modifying antirheumatic drugs (DMARDs).METHODS:Eligible patients with established RA were identified through administrative claims data linked to laboratory results (2005-2016). Patients were categorized by positivity status for ACPA, RF, or both. Patients were further divided into groups by autoantibody titers. DMARD-exposed patients were categorized into biologic DMARD (bDMARD) and conventional DMARD (cDMARD) subcohorts. Crude mortality rates/1,000 patient-years and Kaplan-Meier curves were compared between antibody categories. Adjusted Cox proportional hazards regression and sensitivity (propensity-matched patients) analyses were conducted.RESULTS:Overall, 53,849 and 79,926 patients had evaluable ACPA and RF status, respectively. For both autoantibodies, mortality rates were significantly higher in seropositive versus seronegative patients (risk increase of 48.0% and 44.0% in ACPA- and RF-positive patients, respectively; P < 0.001 each). Mortality rates were greatest in patients with higher versus lower autoantibody titers (ACPA hazard ratio [HR] 1.60 [95% confidence interval (95% CI]) 1.45-1.76]; RF HR 1.78 [95% CI 1.66-1.91]). In cDMARD-exposed patients, HRs were higher in seropositive versus seronegative cohorts; in bDMARD-exposed patients, there was no difference in mortality by serostatus.CONCLUSION:Elevated ACPA/RF titers were independently associated with increased mortality among patients with RA and persisted in patients treated with cDMARDs but not with bDMARDs.

Understanding the correlation between transplant symptoms, health-related quality of life (HRQoL), and graft outcomes is needed to support patient-focused drug development and posttransplant management. A post-hoc analysis of patient-reported outcomes from the Phase III belatacept trials was conducted in order to investigate the interrelationship between trajectories of HRQoL, symptom experience, and allograft outcomes. HRQoL and symptom experience were evaluated using Short-Form 36 Survey (SF-36) and Modified Transplant Symptom Occurrence and Distress Scale (MTSOSD-59R), respectively. HRQoL was captured in 831 eligible renal transplant patients at baseline, 12, 24, and 36 months posttransplant. Following transplantation, patients reported improvements in all SF-36 subscales compared to baseline. Latent class analysis revealed four trajectories in perceived general health, which were associated with graft failure after adjustment. Compared to patients with good perceived health, patients with fair and poor perceived health had 4.7 (95% confidence interval [CI] 1.5-14.8, P < .01) and 19.8 (95% CI 5.9-66.0, P < .01) times the risk of graft failure, respectively. Using multinomial logistic regression, different sets of symptoms were associated with perceived general health at baseline and 12 months posttransplant. The study supports monitoring HRQoL and symptom experience to capture each patient's health perspective, improve drug development, and optimize posttransplant management.

Objective. Patients with rheumatoid arthritis (RA) who also have diabetes mellitus (DM) might have worse clinical outcomes and adverse events compared to patients with RA who do not have DM. We evaluated the effects of DM on Health Assessment Questionnaire (HAQ) changes and outpatient infection rates in patients with RA. Methods. Using the American College of Rheumatology’s Rheumatology Informatics System for Effectiveness (RISE) electronic health record–based registry, we identified patients with RA who had ≥ 1 rheumatologist visit with a HAQ measured in 2016 (index visit), ≥ 1 previous visit, and a subsequent outcome visit with the same HAQ measured at 12 months (± 3 months). We identified DM by diagnosis codes, medications, or laboratory values. Outpatient infection was defined by diagnosis codes or antiinfective medications. We calculated mean HAQ change and incidence rate (IR) of outpatient infections among patients with and without DM. Generalized linear models and Cox regression were used to calculate the adjusted mean HAQ change and HRs. Results. We identified 3853 RA patients with DM and 18,487 without DM. The mean HAQ change between index and outcome visit among patients with DM was 0.03 and without DM was 0.002 (P < 0.01). We identified 761 outpatient infections for patients with DM with an IR of 22.6 (95% CI 21.0–24.2) per 100 person-years and 3239 among patients without DM with an IR of 19.8 (95% CI 19.1–20.5). The adjusted HR of outpatient infections among patients with DM was 0.99 (95% CI 0.91–1.07), compared to patients without DM. Conclusion. Patients with RA with concomitant DM had greater worsening, or less improvement, in their functional status, suggesting additional interventions may be needed for RA patients with DM to optimize treatment and management of other comorbidities.

The objectives of this analysis were to assess the prevalence of Sjögren’s syndrome (SS) associated with rheumatoid arthritis (RA) and to compare baseline characteristics of patients with RA with and without SS. Adult patients with RA from a large observational US registry (Corrona RA), with ≥ 1 visit for assessment of SS status between 22 April 2010 and 28 February 2018, were considered. Patients with RA with versus without SS were compared. SS status was determined from a yes/no variable and reported at enrollment into the Corrona RA registry and follow-up visits. Outcomes were unadjusted prevalence of SS in patients with RA, prevalence of SS by RA disease duration, and baseline characteristics in patients with RA by SS status. Of 24,528 eligible patients, 7870 (32.1%) had a diagnosis of RA and SS. The unadjusted overall rate for SS prevalence in patients with RA was 0.30 (95% confidence interval 0.29, 0.31). SS prevalence increased with increasing RA duration. Patients with RA with versus without SS were more likely to be older, female, and seropositive; had a longer RA duration; higher disease activity; and a higher incidence of comorbidities (hypertension, cardiovascular disease, malignancies, and serious infections), erosive disease, and subcutaneous nodules at index date. Patients with RA and SS had a higher disease burden than those with RA only. The prevalence of SS increased as duration of RA increased. RA with SS was associated with seropositivity, more severe RA, extra-articular manifestations, and comorbidities. Key Points • The overall prevalence of SS among patients with RA was 30%. • The prevalence of SS increased with increasing RA disease duration. • Identifying specific clinical characteristics of patients with RA with SS, such as a greater incidence of extra-articular manifestations and comorbidities, may help clinicians to better characterize this patient population.

ObjectiveExaminations of Patient‐Reported Outcomes Measurement Information System (PROMIS) measures in adult systemic lupus erythematosus (SLE) have provided support for their cross‐sectional validity in SLE. We estimated responsiveness to change, meaningful changes (minimally important differences [MIDs]), and the patient acceptable symptom state (PASS) for five PROMIS short forms to facilitate longitudinal use and interpretation of PROMIS scales in SLE.MethodsData from five administrations of PROMIS short forms in the FORWARD SLE cohorts were used. Pearson correlation coefficients were used to assess associations between changes in PROMIS measures and changes in anchor measures for responsiveness analyses. Worse, same, or better groups were defined for each anchor. Differences in PROMIS scores were calculated for each consecutive PROMIS administration; mean changes in PROMIS scores of individuals in the worse, same, and better groups were calculated. Both anchor‐based and distribution‐based methods were used to estimate MIDs. PASS was defined as the 75th‐percentile positive score among those who considered their health to be acceptable or who were somewhat or very satisfied with their health.ResultsAll PROMIS short forms showed adequate responsiveness to changes in related patient‐reported outcomes. However, only the fatigue and pain interference scales were responsive to self‐reported SLE activity. Taking into account all methods, we estimated MIDs for each scale to be approximately two points. All PASS values were better than the population mean T‐score of 50.ConclusionThese results support use and further study of PROMIS short forms in SLE and should facilitate interpretation of PROMIS scores and changes.

Background Sjögren's syndrome (SS) is considered an extra-articular manifestation of RA and is an autoantibody-mediated condition similar to RA. In an open-label, prospective, observational multicentre study, abatacept (ABA) was found to be effective for both RA and SS-related manifestations.1 However, there are limited data on the healthcare resource utilisation (HCRU) and cost in patients (pts) with RA with SS managed with ABA compared with those managed with anti-TNFs. Objectives To evaluate the HCRU and cost for pts with SS associated with RA treated with ABA or anti-TNF DMARDs. Methods Pts (≥18 years) from the Truven MarketScan™ administrative claims database with incident RA (≥2 claims for RA using International Classification of Diseases [ICD]-9 or ICD-10 codes and ≥1 claim for a conventional DMARD), incident SS (≥1 claim for SS using ICD-9 or ICD-10 codes) and with a prescription for ABA or an anti-TNF on or after the first diagnosis of SS from Jan 2011 to Sep 2017 were included. Pts were divided into two mutually exclusive cohorts. Pts with prescriptions for both ABA and an anti-TNF were excluded. The index date was the date of ABA or anti-TNF prescription. All-cause HCRU (healthcare visits) and costs were captured during the 2-year enrolled period prior to the index date (baseline) and in the 2-year enrolled follow-up period or until the pt was taken off the index drug, whichever occurred earlier. The baseline and follow-up periods were divided into intervals of 6 months each. Total healthcare visits (inpatient, outpatient, emergency care, urgent care and pharmacy) and total healthcare costs associated with these visits were calculated for each interval. A fixed-effects model was used to compare the HCRU and costs for pts taking ABA vs anti-TNFs after controlling for baseline Charlson Comorbidity Index and other comorbidities of interest. Results Overall, 1367 pts met inclusion criteria, of which 148 (10.8%) and 1219 (89.2%) were treated with ABA and anti-TNFs, respectively. ABA (vs anti-TNF) pts were older and had a higher comorbidity index (Table 1). Overall HCRU decreased in both the ABA and anti-TNF groups (relative to pts not being treated with biologic DMARDs). The HCRU was lower in ABA pts vs anti-TNF pts (average visits 20.0 vs 20.8, Figure 1) in the adjusted analysis. The average adjusted total healthcare cost for ABA (vs anti-TNF) pts was lower in the four 6-month cycles evaluated (average cost $17,050 vs $27,469; Figure 1). The overall healthcare costs were primarily driven by all-cause pharmacy cost (data not shown). Conclusion Pts with RA with SS managed with abatacept had lower HCRU and costs relative to pts managed with anti-TNFs. Further analysis is warranted to understand the drivers of the differential economic burden among pts with RA with SS. References: [1] Tsuboi H, et al. Mod Rheumatol 2016;26:891–9. Disclosure of Interests Evo Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Aarti Rao Consultant for: Bristol-Myers Squibb, Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Chidananda Samal Consultant for: Bristol-Myers Squibb, Robert Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Paul Allison: None declared