Disparities in burden of disease in patients with rheumatoid arthritis across racial and ethnic groups.

To examine racial/ethnic differences in rheumatoid arthritis (RA) disease burden and change in clinical outcomes over time. We included CorEvitas Rheumatoid Arthritis Registry patients from two time periods (2013-2015 and 2018-2020). Clinical Disease Activity Index (CDAI) (as a continuous measure and as a dichotomous measure) and the Health Assessment Questionnaire-Disability Index (HAQ-DI) were assessed at each visit. Marginal means and their corresponding 95% confidence interval (CI) by race/ethnicity were estimated for each outcome using adjusted mixed effects linear and logistic regression models. Overall and pairwise tests were conducted to detect differences between race/ethnicity groups. Of 9,363 eligible patients (8,142 White, 527 Black, 545 Hispanic, 149 Asian), most (76%-85%) were female. At Visit 1, the mean disease duration ranged from 9.8-11.8 years. Estimated CDAI was significantly higher for Hispanics compared to Whites at Visit 1 (11.1 vs. 9.9; pairwise P = 0.033) and Visit 2 (9.2 vs. 8.0, pairwise P = 0.005). Disease activity improved over the 5-year study period among all race/ethnicity groups, though Hispanics improved less than Whites. Disease activity improved over the 5-year period across all racial/ethnicity groups, and disparities between racial/ethnicity groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies to close this race/ethnicity gap. Key Points • Disease activity improved over the 5-year period across all racial and ethnic groups. • Disparities between racial and ethnic groups in disease activity and functional status did persist over time, suggesting that further effort is needed to understand the drivers of these discrepancies and close this racial gap.

Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive.

BACKGROUND: The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. METHODS: Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. RESULTS: In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). CONCLUSION: In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort..

Effectiveness of bDMARDs in ankylosing spondylitis patients by biologic use: experience from the CorEvitas PsA/SpA Registry.

OBJECTIVE: To describe bDMARD initiators by biologic experience among ankylosing spondylitis (AS) patients and change in disease activity and patient-reported outcomes (PROs) in real-world US patients. METHODS: We included patients ≥18 years with AS based on physician diagnosis enrolled between 3/2013 and 11/2019 in the CorEvitas Psoriatic Arthritis (PSA)/Spondyloarthritis Registry (NCT02530268). Patients concurrently diagnosed with PSA were excluded. Baseline (bDMARD initiation) demographics, comorbidities, disease characteristics, treatment, and PROs were collected. Response rates and changes in disease activity and PROs between baseline and 6- and 12- month follow-up visits were calculated. RESULTS: Of the 489 AS patients in the PsA/SpA Registry, 254 AS (52.0%) patients initiated a bDMARD at enrollment or during follow-up (total initiations: AS = 313). Of the 313 AS initiations, 179 (57.2%) had a 6-month follow-up, 122 (39.0%) had a 12-month follow-up, and 94 (30.0%) had a 6- and 12-month follow-up visit. For those AS initiators with a 6-month follow-up, the mean age was 49.1 years, 44.4% were female, and 70.4%, 47.5%, 96.1%, and 46.9% had never used cDMARDs, TNFis, non-TNFis, and bDMARDs, respectively. Of these 179 AS initiators, 20.1% and 14.0% achieved ASAS20/40, respectively. Further, only 34% achieved low disease activity (ASDAS <2.1). When stratified by biologic-naivete and biologic-experience, the ASAS 20/40 achievement rates were 26.2% and 14.7%, and 21.4% and 7.4%, respectively, for this cohort. CONCLUSION: Although AS patients initiate bDMARDs, many do not achieve optimal treatment responses. Future research is needed to investigate the aspects associated with inadequate improvement and treatment response to bDMARDs.

Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive

Abstract Background The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. Methods Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. Results In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). Conclusion In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort. .

A Real-World Effectiveness Study Using a Mobile Application to Evaluate Early Outcomes with Upadacitinib in Rheumatoid Arthritis.

INTRODUCTION: The impact of upadacitinib on rheumatoid arthritis (RA) symptoms was evaluated during the first 12 weeks of treatment via patient-reported outcomes (PROs) using a mobile health application (app). METHODS: Participating rheumatologists from the CorEvitas RA Registry (prospective, observational cohort) recruited patients with RA initiating upadacitinib treatment. A modified version of the ArthritisPower® app was used to collect PROs, including the Routine Assessment of Patient Index Data 3 (RAPID3), duration of morning joint stiffness, and the Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue 7a Short Form at baseline and weeks 1-4, 8, and 12. RAPID3 responses over time were assessed using Kaplan-Meier estimation to determine the proportion of patients achieving disease activity improvement and minimal clinically important difference (MCID). Results were analyzed for all patients initiating upadacitinib and a subsample of TNF inhibitor (TNFi)-experienced patients with moderate to severe disease at baseline. RESULTS: A total of 103 patients with RA initiating upadacitinib (62.1% TNFi-experienced) were included. At week 12, 53 patients (51.4%) completed the study and provided PRO data via the app. Among all patients, improvements in RAPID3, pain, morning stiffness, and fatigue were observed at week 1 and were maintained or further improved through week 12. At week 12, 37.5% of patients achieved RAPID3 low disease activity. Starting at week 1, improvements in RAPID3 disease activity category (19.4% of patients) and achievement of MCID (16.3%) were reported, with nearly 50% of patients achieving these outcomes by week 4 (RAPID3 category: 48.8%; MCID: 49.2%) and 60% by week 12 (RAPID3 category: 59.6%; MCID: 59.8%). TNFi-experienced patients generally reported similar outcomes. Patient-reported medication convenience and compliance were generally high. CONCLUSIONS: In this real-world cohort of patients with RA, treatment with upadacitinib was associated with early and significant improvement in RAPID3, pain, morning stiffness, and fatigue regardless of prior TNFi experience. Clinically meaningful improvement in RAPID3 patient-reported disease activity was observed as early as week 1, with continued improvement reported through week 12.

Understanding Heterogeneity in Patients' Conceptualisation of Treatment for Rheumatoid Arthritis: A Cluster Analysis.

OBJECTIVE: Uptake of treat-to-target (TTT) strategies for rheumatoid arthritis (RA) management is low. Our objective was to understand the heterogeneity in patients' conceptualisation of RA treatment to inform interventions improving TTT uptake. DESIGN: Eligible participants recruited from an online research registry rated 56 items (on 5-point scales) reflecting concepts raised from patient interviews. Using items describing adhering to physician recommendations to create a binary criterion variable for medication adherence, we conducted a principal components analysis on the remaining items using Varimax rotation, describing how these factors predict adherence over and above demographic characteristics. We further use optimal sets in regression to identify the individual concepts that are most predictive of medication adherence. RESULTS: We found significant heterogeneity in patients' conceptualisation of RA treatment among 621 persons with RA. A scree plot revealed a four-factor solution explained 38.4% of the variance. The four factors expected to facilitate TTT uptake were (% variance explained): (1) Access to high quality care and support (11.3%); (2) low decisional conflict related to changing disease-modifying antirheumatic drugs (DMARDs) (10.1%); (3) endorsement of a favourable DMARD risk/benefit ratio (9.9%); and (4) confidence that testing reflects disease activity (7.2%). These factors account for 13.8% of the variance in full medication adherence, fully explaining the only significant demographic predictor, age of the patient. The individual items most predictive of poor adherence centre on the lack of effective patient-physician communication, specifically insufficient access to information from rheumatologists, along with the need to seek information elsewhere. CONCLUSION: Patients' conceptualisation of RA treatment varies; however, almost all patients have difficulty escalating DMARDs, even with access to quality information and an understanding of the benefits of TTT. Tailored interventions are needed to address patient hesitancy to escalate DMARDs.

Comparative effectiveness of treatments for rheumatoid arthritis in clinical practice: A systematic review.

OBJECTIVE: To assess real-world comparative effectiveness studies of biologic (b) and targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) in adults with rheumatoid arthritis (RA) through a systematic review. METHODS: We searched Medline for journal articles (2001-2021) and Embase® for abstracts presented at the European Alliance of Associations for Rheumatology and American College of Rheumatology (ACR) 2020 and 2021 annual meetings on non-randomized studies comparing the effectiveness of b/tsDMARDs using ACR-recommended disease activity measures, measures of functional status, and patient-reported outcomes (HAQ, PROMIS PF, patient pain, Patient and Physician Global Assessment of disease activity). Methodological heterogeneity between studies precluded meta-analyses. Risk of bias was assessed using the Cochrane Risk Of Bias In Non-randomized Studies of Interventions-I tool. RESULTS: Of 1283 records screened, 68 were selected for data extraction, of which 1 was excluded due to critical risk of bias. Most studies were multicenter observational cohort/registry studies (n = 60) and were published between 2011 and 2021 (n = 60). Mean or median reported RA duration was between 6 and 15 years. Disease Activity Score in 28 joints (46 studies), Clinical Disease Activity Index (37 studies), and Health Assessment Questionnaire-Disability Index (32 studies) were the most common outcomes used in clinical practice, with regional differences identified. The most common comparison was between tumor necrosis factor inhibitors (TNFis) and non-TNFi bDMARDs (35 studies). There were no evident differences between b/tsDMARDs in clinical effectiveness. CONCLUSION: This systematic review summarizing real-world evidence from a very large number of global studies found there are many effective options for the treatment of RA, but relatively less evidence to support the use of any one b/tsDMARD or drug class over another. Treatment for patients with RA should be tailored to suit individual clinical profiles. Further research is needed to identify whether specific patient subgroups may benefit from specific drug classes.

Accuracy of administrative claims prescription fill data to estimate glucocorticoid use and dose in patients with rheumatoid arthritis.

PURPOSE: To assess accuracy of administrative claims prescription fill-based estimates of glucocorticoid use and dose, and approximate bias from glucocorticoid exposure misclassification. METHODS: We identified adults with rheumatoid arthritis with linked Medicare and CorEvitas registry data. An algorithm identifying glucocorticoid use and average dose over 90 days from Medicare prescription fills was compared to physician-reported measures from a CorEvitas visit during the same period, using weighted kappa to compare doses (none, ≤5 mg, 5-10 mg, >10 mg/day). A deterministic sensitivity analysis examined the effect of exposure misclassification on estimated glucocorticoid-associated infection risk from a prior study. RESULTS: We identified 621 observations among 494 patients. Prescription fills identified glucocorticoid use in 41.9% of observations versus 31.1% identified by CorEvitas physician-report. For glucocorticoid use (yes/no), prescription fills had sensitivity 88.1% (95% CI 82.7-92.3), specificity 79.0% (74.8-82.7), PPV 65.4% (59.3-71.2), NPV 93.6% (90.6-95.9), and 81.8% agreement with CorEvitas, with kappa 0.61 (moderate to substantial agreement). There was 89.5% agreement between prescription fills and physician-reported doses, with weighted kappa 0.56 (moderate agreement). Applying these results to a prior Medicare study evaluating glucocorticoid-associated infection risk [risk ratio 1.44 (95% CI 1.41-1.48)] led to an externally adjusted risk ratio of 1.74 when accounting for exposure misclassification, representing -17% bias in infection risk estimate. CONCLUSIONS: This study supports the use of claims data to estimate glucocorticoid use and dose, but investigators should account for exposure misclassification, which may lead to underestimates of glucocorticoid risks. Our results could be applied to adjust risk estimates in other studies that use prescription fills to estimate glucocorticoid use.

Comparative Effectiveness of Abatacept vs. Tofacitinib in Rheumatoid Arthritis Patients who are CCP.

INTRODUCTION: Currently there is limited data to drive clinical decision making regarding  the choice of biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARD); thus, head-to-head comparisons are needed to help guide prescribing. In recent years, significant advancements have helped clarify the mechanistic basis of the clinical associations of autoantibodies in rheumatoid arthritis (RA). This study evaluated the effectiveness of abatacept versus tofacitinib in anti-cyclic citrullinated peptide (CCP+) patients with rheumatoid arthritis (RA). METHODS: CorEvitas (formerly known as CORRONA) Registry patients aged ≥ 18 years, who were CCP+ before initiating abatacept or tofacitinib (December 2012 onwards through October 2019), had 6-month follow-up data (baseline and 6-month Clinical Disease Activity Index [CDAI]), and were not in remission at index were included. Patients were frequency matched 1:1 by prior biologic use before propensity score matching (PSM). Primary (mean change [D] in CDAI) and secondary outcomes 6 months after index were compared using mixed-effects models adjusted for variables that remained unbalanced after PSM. RESULTS: Following PSM, most baseline characteristics for 291 patient pairs were well balanced between treatments, although fewer patients initiating abatacept versus tofacitinib received prior non-TNFi biologic DMARDs, and patients initiating abatacept versus tofacitinib had a higher physician global assessment score, patient-reported fatigue, and modified Health Assessment Questionnaire (mHAQ). In adjusted analyses, there were no significant differences in mean [D] from baseline in CDAI at 6 months with abatacept versus tofacitinib (P = 0.936). Patients naïve for b/tsDMARDs initiating abatacept had a numerically greater mean [D] in CDAI at 6 months versus tofacitinib, although this difference was not statistically significant (P = 0.662). There were no significant differences for any secondary outcomes. CONCLUSIONS: In adjusted analyses, CCP+ patients with RA initiating treatment with abatacept versus tofacitinib did not show a statistically significant difference in reducing disease activity or improving patient-reported outcomes.

Rheumatoid Arthritis Disease Activity and Hospitalized Infection in a Large US Registry.

OBJECTIVES: The association between disease activity and infection risk among patients with rheumatoid arthritis (RA) is not clear, and it is challenging to determine because of confounding due to the effects of RA treatments and comorbidities. METHODS: Using patients with RA in the CorEvitas registry with Medicare coverage in 2006-2019, we identified eligible patients who had at least 1 visit with moderate disease activity based on the Clinical Disease Activity Index (CDAI; CDAI >10 and ≤22). Follow-up started at the subsequent CorEvitas visit. Hospitalized infection during follow-up was assessed in linked Medicare data. We calculated the incidence rate of hospitalized infection for patients in remission, and low and moderate disease activity, and estimated the effect of time-varying CDAI on hospitalized infection by controlling for baseline and time-dependent confounders using marginal structural models (MSMs). RESULTS: A total of 3,254 patients with RA were eligible for analysis, among which 529 hospitalized infections were identified during follow-up. The crude incidence of hospitalized infection was 3.8 per 100 person-years for patients in remission, 6.6 for low disease activity, and 8.0 for moderate disease activity. Using MSMs and compared with being in remission, the hazard ratio of hospitalized infection associated with low disease activity was 1.60 (95% confidence interval [95% CI] 1.13-2.28) and with moderate disease activity was 1.83 (95% CI 1.30-2.64). CONCLUSION: The risk of hospitalized infection was higher for patients with RA in low or moderate disease activity than for those in remission after accounting for the interplay of disease activity, RA treatments, treatment switching, and other potential confounders.

Examining the potential direct cardiovascular benefit of tumor-necrosis factor inhibitor in rheumatoid arthritis: Natural and controlled direct effect analyses.

BACKGROUND/PURPOSE: Tumor necrosis factor inhibitors (TNFi) may have a direct benefit on cardiovascular (CV) disease beyond reducing rheumatoid arthritis (RA) disease activity measured by the Clinical Disease Activity Index (CDAI). METHODS: We compared TNFi initiators and methotrexate (MTX) monotherapy initiators from the CorEvitas RA registry. Two approaches to the "direct effect" of TNFi beyond CDAI were used. In the natural direct effect (NDE) analysis, the potential CV benefit of TNFi was partitioned into NDE and the natural indirect effect (NIE) mediated by CDAI during the first 6 months. We also estimated the controlled direct effects (CDE), corresponding to the direct benefit of TNFi when CDAI trajectories were hypothetically equalized between the initiators of TNFi and MTX monotherapy at a constant value. Estimates were given on the hazard ratio scale. RESULTS: We identified 5764 initiators of TNFi and 3588 initiators of MTX monotherapy. TNFi initiators were younger (58 vs. 64 years) with a shorter disease duration. Our total effect estimates (TNFi vs. MTX [reference]) were protective in direction (0.76-0.91). The NDE estimate was 0.76 [95% confidence interval (CI) 0.59, 0.98], whereas the NIE estimate was 1.00 [95%CI 1.00, 1.00]. In the CDE analyses accounting for longitudinal CDAI, the CDE estimates was 1.27 [95%CI 0.60, 2.69]. CONCLUSIONS: We could not convincingly demonstrate a direct benefit of TNFi outside its impact on CDAI. At present, the emphasis should be on the stringent control of RA disease activity, a known important CV risk factor, regardless of medication choice.

Rheumatologist and Patient Mental Models for Treatment of Rheumatoid Arthritis Help Explain Low Treat-to-Target Rates.

OBJECTIVE: Despite proven benefits, less than half of patients with rheumatoid arthritis (RA) are treated using a treat-to-target (TTT) strategy. Our objective was to identify critical discrepancies between rheumatologist and patient mental models related to the treatment of RA to inform interventions designed to increase implementation of TTT. METHODS: We developed rheumatologist and patient mental models using the Mental Models Approach to Risk Communication. We conducted semistructured interviews to elicit views related to RA treatment decisions with 14 rheumatologists and 30 patients with RA. We also included responses (n = 284) to an open-ended question on a survey fielded to augment qualitative descriptions from the interviews. Interviews were transcribed and coded independently by two members of the research team. RESULTS: Rheumatologist and patient mental models for RA treatment are significantly more complex than the TTT model. Both consider domains (system factors and patient readiness) outside of disease activity measurement, target setting, and risk versus benefit assessment in their decision-making. Furthermore, specific factors were found to be unique to each model. For example, the physician model stresses the importance of evaluating disease activity over time and patient adherence. In contrast, patients discussed the impact of chronic disease weariness, medication-related fatigue, the importance of feeling adequately informed, and stress associated with changing medications. CONCLUSION: We found several discrepancies primarily related to information gaps and differences in how patients and physicians value trade-offs that can serve as specific targets to improve patient-physician communication and ultimately inform interventions to improve uptake of TTT.

Time-Varying Association of Rheumatoid Arthritis Disease Activity to Subsequent Cardiovascular Risk.

OBJECTIVE: It is unknown how the relationship between disease activity in rheumatoid arthritis (RA) and cardiovascular (CV) events may change over time. We examined the potentially time-varying association of RA disease activity to CV events. METHODS: We used the CorEvitas prevalent RA registry. The Clinical Disease Activity Index (CDAI) score category, averaged within each 6-month window since enrollment, was the exposure, and the outcome was major adverse CV events (MACEs). We used marginal structural models to estimate the hazard ratio (HR), comparing each CDAI score category with remission, allowing for differential association over time. We predicted MACE-free survival under several CDAI score scenarios. RESULTS: We found 44,816 eligible patients (77% female; mean age 58 years) with a crude event rate of 5.3/1000 person-years (median follow-up 3.4 years). The strongest association between higher CDAI score and MACEs was observed during the first 6 months of enrollment (HR for CDAI score low 2.29 [95% CI: 1.21-4.36], moderate 2.81 [95% CI: 1.46-5.43], and high 2.99 [95% CI: 1.48-6.02]). These estimates gradually diminished; by year 5, the HRs were 1.00 (95% CI: 0.49-2.05) for low, 1.18 (95% CI: 0.51-2.71) for moderate, and 1.04 (95% CI: 0.45-2.40) for high CDAI score. Predicted MACE-free survival suggested a potential decrease in MACEs with a hypothetical earlier transition to remission. CONCLUSION: The association of higher disease activity with CV events may be stronger earlier in the disease course of RA. Interventional studies may be warranted to precisely determine the effect of disease activity suppression on CV events in RA.

Obesity and Response to Advanced Therapies in Rheumatoid Arthritis.

OBJECTIVE: We performed a study of tumor necrosis factor inhibitors (TNFi) compared to non-TNFi biologic therapies in rheumatoid arthritis to test whether body mass index (BMI) modified the effect of each therapy. METHODS: We utilized data from CorEvitas. We studied 3 clinical outcomes based on the Clinical Disease Activity Index (CDAI) at 6 months from therapy initiation: 1) achievement of low disease activity (LDA); 2) a change as large as the minimum clinically important difference (MCID); and 3) the absolute change. We categorized BMI and utilized restricted cubic splines to consider nonlinear associations. We used linear and logistic regression to evaluate associations with response, adjusting for confounders. To determine if comparative effectiveness of therapy varied by BMI, we tested for interactions between BMI and class of therapy. RESULTS: The sample included 2,891 TNFi and 3,010 non-TNFi initiators. Among all initiators, those with severe obesity experienced lower odds of achieving LDA or MCID and less improvement in CDAI score, although associations were attenuated with adjustment. Low BMI was associated with reduced response rates in adjusted models including lower odds of LDA (odds ratio 0.32 [95% confidence interval (95% CI) 0.15, 0.71], P = 0.005). Analyses stratified by TNFi and non-TNFi therapies demonstrated no differences in clinical response rates for TNFi versus non-TNFi across BMI categories (all P for interaction >0.05). Estimates for non-TNFi biologics fit within the 95% CI for TNFi. CONCLUSION: This study observed lower response rates among obese and underweight patients and no evidence of a superior effect of non-TNFi therapy over TNFi therapy in particular BMI categories.

Baseline Anti-Citrullinated Protein Antibody Status and Response to Abatacept or Non-TNFi Biologic/Targeted-Synthetic DMARDs: US Observational Study of Patients with RA.

INTRODUCTION: Patients with rheumatoid arthritis (RA) may respond to treatments differently based on their underlying serology and biomarker status, but real-world data comparing treatment responses to abatacept versus other non-TNFi biologic or targeted-synthetic DMARDs by anti-citrullinated protein antibody (ACPA) status remain limited. We assessed the association between ACPA status and response to treatment in patients with RA. METHODS: Adults from CorEvitas' RA Registry were identified who initiated abatacept, rituximab, tocilizumab, or tofacitinib, and had ACPA measured at/prior to treatment initiation and at the 6-month follow-up visit. Three cohorts were included: abatacept/rituximab (2006-2019), abatacept/tocilizumab (2010-2019), and abatacept/tofacitinib (2012-2019). Patient characteristics at initiation were compared by ACPA status (positive [+], anti-cyclic citrullinated peptide-2 [anti-CCP2] ≥ 20 U/ml; negative [-], anti-CCP2 < 20 U/ml). Outcomes over 6 months: changes in Clinical Disease Activity Index (CDAI), modified Health Assessment Questionnaire (mHAQ), patient global assessment (PGA) scores, and proportion of patients achieving a clinical response. Adjusted mean differences and odds ratios were estimated using mixed-effects linear regression models. RESULTS: Overall, 982 abatacept, 246 rituximab, 404 tocilizumab, and 429 tofacitinib initiators were identified. ACPA+ (vs. ACPA-) patients had longer disease duration and more erosive disease. During most time periods adjusted mean changes in CDAI, mHAQ, and PGA scores and the proportion of patients achieving a clinical response were significantly higher for ACPA+ versus ACPA- patients initiating abatacept. Adjusted mean change in PGA score and patient fatigue were significantly higher for ACPA+ versus ACPA- patients initiating rituximab. No significant differences were seen by ACPA status for patients initiating tocilizumab or tofacitinib. CONCLUSIONS: Patients who initiated abatacept or rituximab and were ACPA+ had a greater clinical response at 6-month follow-up post index compared to patients who were ACPA- treated with the same biologic.

Evaluation of an Intervention to Support Patient-Rheumatologist Conversations About Escalating Treatment in Patients with Rheumatoid Arthritis: A Proof-of-Principle Study.

OBJECTIVE: This study's objective was to test whether an online video intervention discussing appropriate treatment escalation improves willingness to change treatment in people living with rheumatoid arthritis (RA). METHODS: We conducted a controlled, randomized trial among patients with RA enrolled in ArthritisPower, a United States patient registry. We recruited participants by email and surveyed their assessment of disease activity (patient global), satisfaction with disease control (patient acceptable symptom state), attitudes about RA medications, decisional conflict (decisional conflict scale), and willingness to modify RA treatment (choice predisposition scale, higher scores are better) if or when recommended by their rheumatologist. Intervention groups watched educational videos relevant to a treat-to-target (T2T) strategy, whereas control groups viewed vaccination-related videos as an "attention control." We compared the between-group difference in patients' willingness to modify RA treatment (primary outcome) and difference in decisional conflict about changing RA treatment (secondary outcome) after watching the videos using t tests. RESULTS: Participants with self-reported RA (n = 208) were 90% White and 90% women, with a mean (standard deviation) age of 50 (11) years, and 52% reported familiarity with the RA T2T strategy. We found a significant improvement in between-group difference in willingness to change RA treatment among intervention versus control participants (0.49 [95% confidence interval 0.09-0.88], P = 0.02). The effect size (Glass's delta) for the intervention was 0.48. Decisional conflict about treatment change decreased, but the between-group difference was not significant. CONCLUSION: This novel educational patient-directed intervention discussing appropriate treatment escalation was associated with improved willingness to change RA treatment if or when recommended by a rheumatologist. Further studies should evaluate whether this change in patients' predisposition translates into actual treatment escalation.

Association Between Baseline Anti-cyclic Citrullinated Peptide Antibodies and 6-Month Clinical Response Following Abatacept or TNF Inhibitor Treatment: A Real-World Analysis of Biologic-Experienced Patients with RA.

INTRODUCTION: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with poor prognosis in patients with rheumatoid arthritis (RA). Previous data from randomized controlled trials and clinical practice have shown anti-CCP-positive (+) patients had a better response to treatment with abatacept or tumor necrosis factor inhibitor (TNFi) treatment than those who were anti-CCP negative. This study assessed the association between baseline anti-CCP2 [a surrogate for anti-citrullinated protein antibody (ACPA)] concentration and 6-month treatment responses to abatacept or TNFi in patients with RA. METHODS: This real-world analysis included biologic-experienced patients from CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory CoNditions) who initiated abatacept or TNFi, had prior biologic disease-modifying drug exposure and baseline anti-CCP2 concentration/serostatus and serum samples (baseline and 6 months). Baseline demographics and disease characteristics were compared. Change from baseline at 6 months in Clinical Disease Activity Index (CDAI) score and patient-reported outcomes [PROs: pain, fatigue, patient global assessment (PtGA), modified Health Assessment Questionnaire (mHAQ) score], by baseline anti-CCP2 quartile and binary cut-off (> 10-250 and > 250 U/ml), were evaluated separately in the abatacept and TNFi groups using a linear regression model adjusted for age, sex, CDAI/PROs, comorbidity index, and methotrexate use. RESULTS: Included were 138 abatacept and 137 TNFi initiators who were anti-CCP2+. At baseline, there were significant differences between anti-CCP2 quartiles and mean CDAI, swollen joint count 28, C-reactive protein (CRP), Disease Activity Score 28 (CRP), rheumatoid factor (RF), mHAQ and physician global assessment among abatacept initiators, and in mean RF, mHAQ, and PtGA among TNFi initiators. Among abatacept (but not TNFi) initiators, CDAI numerically improved (p = 0.208) and PROs significantly improved (p < 0.05) with increasing baseline anti-CCP2. CONCLUSIONS: In patients treated with abatacept, not TNFi, higher anti-CCP2 concentrations at baseline were associated with numerically greater improvements in CDAI and significant improvements in PROs after 6 months. CLINICAL TRIAL NUMBER: NCT01625650.

Rheumatoid arthritis (RA) is an autoimmune disease ­ a disease that causes the immune system to attack an individual's own body. A key feature of RA is the presence of proteins called autoantibodies in the blood. While antibodies help protect against external threats such as viruses, autoantibodies mistakenly target an individual's own tissues and organs. One type of autoantibody often found in patients with RA is called anti-cyclic citrullinated peptide (anti-CCP). Studies have shown that patients with RA with anti-CCP antibodies may experience worse physical symptoms, function, disease activity, and outcomes than patients with RA without anti-CCP antibodies. Clinical trials suggest that some drugs may be more effective than others at managing symptoms of RA in patients who have anti-CCP in their blood. It is important to study this further to give doctors a sense of how patients respond to drug therapy in the 'real world', without clinical trial constraints. This study examined real-world patient data to see whether the presence of anti-CCP in patients' blood impacted how their RA symptoms responded to treatment with two different drugs: abatacept or a tumor necrosis factor inhibitor (TNFi). This study found that patients with higher levels of anti-CCP at the start of the study, compared with patients with lower levels of anti-CCP, experienced less disease activity and greater improvement in physical function after 6 months of treatment with abatacept. The study found no relationship between anti-CCP and treatment response after 6 months of treatment with a TNFi.

Unmet Medical Needs in the Treatment and Management of Generalized Pustular Psoriasis Flares: Evidence from a Survey of Corrona Registry Dermatologists.

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening systemic and chronic autoinflammatory disease characterized by sterile, neutrophilic pustules. The standard of care for GPP varies by region, with limited information and experience of flares and their treatment. Our aim was to establish current unmet needs in GPP by better understanding the natural history of GPP, examining how dermatologists diagnose GPP and GPP flares, and establishing the range and adequacy of GPP treatment options currently prescribed by dermatologists. METHODS: Eligible dermatologists (N = 29) completed a 28-question structured survey, covering ten themes, ranging from GPP diagnostic criteria to GPP symptoms and treatment. RESULTS: All dermatologists stated that pustules were necessary to diagnose a GPP flare. The most frequently reported triggering factors for GPP were steroid withdrawal (64%), infection (58%), and stress (50%). Most dermatologists indicated that available treatment options for GPP flares were adequate "most" (79%) or "all" (14%) of the time. Despite this reported adequacy, 38% of dermatologists reported that it was at least "somewhat common" for a flare to require hospitalization. Furthermore, 72% of dermatologists indicated that treatments were too slow to control flares, and 66% indicated that treatments did not adequately prevent new flares at least "sometimes". CONCLUSION: This survey suggests that there are key features of GPP flares, and could initiate discussion around forming consensus guidelines for diagnosis and management. While the results suggest that moderately effective therapies may exist, the need for GPP-specific treatments remains.

Characterization of insufficient responders to ustekinumab in patients with moderate-to-severe psoriasis in the US Corrona Psoriasis Registry.

OBJECTIVE: Biologic therapies have revolutionized the management of moderate-to-severe psoriasis; however, there are a limited number of US real-world studies characterizing patients based on response to these treatments. This study examined characteristics at enrollment and change in outcomes of US patients with moderate-to-severe psoriasis who achieved insufficient responses with ustekinumab. METHODS: This study included patients enrolled in the Corrona Psoriasis Registry from April 2015 to June 2018 who initiated ustekinumab at enrollment and who were stratified based on achievement of psoriasis body surface area improving to <3% or by 75% from enrollment to the 6-month follow-up visit (response vs insufficient response). Patient demographics and disease characteristics were described at enrollment, and changes in outcomes were assessed at 6-month follow-up for ustekinumab responders and insufficient responders. RESULTS: Of the 178 patients who initiated ustekinumab in the Corrona Psoriasis Registry and had ≥1 follow-up visit, 99 (55.6%) were classified as responders at the 6-month follow-up visit. Logistic regression modeling showed that increasing age was significantly associated with a decreased likelihood of achieving a response (OR, 0.981 [95%CI, 0.962-0.999]; p = .049). CONCLUSIONS: These findings may help dermatologists characterize patients with moderate-to-severe psoriasis who have inadequate responses to biologic treatments.