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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.., (© 2024. The Author(s).)

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., Competing Interests: Declaration of Competing Interest JAS: supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers R01 AR080659, R01 AR077607, P30 AR070253, and P30 AR072577), the R. Bruce and Joan M. Mickey Research Scholar Fund, and the Llura Gund Award funded by the Gordon and Llura Gund Foundation; research support: Bristol Myers Squibb; consultant: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum, and Pfizer. LRH: employee and stakeholder: CorEvitas; consultant: AbbVie, Bristol Myers Squibb, and Roche; speakers bureau: Bristol Myers Squibb. TAS: consultant: Bristol Myers Squibb and Janssen. KW, SK, KL, and VK: employees and shareholders: Bristol Myers Squibb. KM: nothing to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Objective: To characterize patients with rheumatoid arthritis (RA) by number of poor prognostic factors (PPF: functional limitation, extraarticular disease, seropositivity, erosions) and evaluate treatment acceleration, clinical outcomes, and work status over 12 months by number of PPF., Methods: Using the Corrona RA registry (January 2005-December 2015), biologic-naive patients with diagnosed RA having 12-month (± 3 mos) followup were identified and categorized by PPF (0-1, 2, ≥ 3). Changes in medication, Clinical Disease Activity Index (CDAI), and work status (baseline-12 mos) were evaluated using linear and logistic regression models., Results: There were 3458 patients who met the selection criteria: 1489 (43.1%), 1214 (35.1%), and 755 (21.8%) had 0-1, 2, or ≥ 3 PPF, respectively. At baseline, patients with ≥ 3 PPF were older, and had longer RA duration and higher CDAI versus those with 0-1 PPF. In 0-1, 2, and ≥ 3 PPF groups, respectively, 20.9%, 23.2%, and 26.5% of patients received ≥ 1 biologic (p = 0.011). Biologic/targeted synthetic disease-modifying antirheumatic drug (tsDMARD) use was similar in patients with/without PPF (p = 0.57). After adjusting for baseline CDAI, mean (standard error) change in CDAI was -4.95 (0.24), -4.53 (0.27), and -2.52 (0.34) for 0-1, 2, and ≥ 3 PPF groups, respectively. More patients were working at baseline but not at 12-month followup in 2 (13.9%) and ≥ 3 (12.5%) versus 0-1 (7.3%) PPF group., Conclusion: Despite high disease activity and worse clinical outcomes, number of PPF did not significantly predict biologic/tsDMARD use. This may warrant reconsideration of the importance of PPF in treat-to-target approaches.

Objective: Assess whether baseline anticyclic citrullinated peptide antibodies (anti-CCP) status is associated with treatment response in patients with rheumatoid arthritis (RA) initiating abatacept (ABA) or a tumor necrosis factor-α inhibitor (TNFi)., Methods: Using the Corrona RA registry, patients were identified who initiated ABA or a TNFi (June 2004-January 2015), had a followup visit 6 months (± 3 mos) after initiation, and anti-CCP measured at or prior to initiation. Primary outcome was mean change in Clinical Disease Activity Index (CDAI) from initiation to 6 months. Treatment response was evaluated based on a typical patient profile (female, aged 57 yrs, body mass index of 30 kg/m 2 , baseline CDAI of 20, 1 prior biologic, and no comorbidities other than RA). Secondary outcomes included remission and low disease activity., Results: There were 566 ABA initiators [anti-CCP+ (≥ 20 units/ml): n = 362; anti-CCP- (< 20 units/ml): n = 204] and 1715 TNFi initiators (anti-CCP+: n = 1113; anti-CCP-: n = 602). Differences between treatment groups included baseline disease duration, CDAI, and prior biologic use. At 6 months, anti-CCP+ ABA initiators were associated with significantly greater CDAI response versus anti-CCP- ABA initiators; no significant difference was observed for TNFi initiators. When considering a typical RA patient profile, CDAI response was greater in anti-CCP+ versus anti-CCP- ABA initiators; anti-CCP+ versus anti-CCP- TNFi initiators were similar. Secondary outcome responses were also greater in anti-CCP+ versus anti-CCP- ABA initiators; TNFi initiators did not differ by anti-CCP status., Conclusion: In a US-based clinical practice setting, anti-CCP status was associated with a differential treatment response to ABA, but not TNFi.

The objective of the study was to examine whether disease duration independently predicts treatment response among biologic-naïve patients with rheumatoid arthritis (RA) initiating abatacept in clinical practice. Using the Corrona RA registry (February 2006-January 2015), biologic-naïve patients with RA initiating abatacept with 12-month (±3 months) follow-up and assessment of disease activity (Clinical Disease Activity Index [CDAI]) at initiation and at 12 months were identified. The primary outcome was mean change in CDAI (ΔCDAI) from baseline to 12 months. Secondary outcomes at 12 months included achievement of low disease activity (LDA; CDAI ≤10 in patients with moderate/high disease activity at initiation) and remission (CDAI ≤2.8 in patients with low, moderate or high disease activity at initiation). Linear and logistic regression analyses were performed to examine the relationship between disease duration and response to abatacept. There were 281 biologic-naïve patients with RA initiating abatacept (disease duration 0-2 years, n = 107; 3-5 years, n = 45; 6-10 years, n = 50; >10 years, n = 79). Increased disease duration was associated with older age (p = 0.047), and the median number of prior conventional disease-modifying antirheumatic drugs used was lowest in the 0- to 2-year duration group (p < 0.001). Mean ΔCDAI (SE) ranged from -10.22 (1.19) for 0-2 years to -4.63 (1.38) for >10 years. In adjusted analyses, shorter disease duration was significantly associated with greater mean ΔCDAI (p = 0.015) and greater likelihood of achieving LDA (p = 0.048). In biologic-naïve patients with RA initiating abatacept, earlier disease (shorter disease duration) was associated with greater ΔCDAI and likelihood of achieving LDA.

Background: Patients with rheumatoid arthritis (RA), including those treated with biologics, are at increased risk of some vaccine-preventable infections. We evaluated the antibody response to standard 23-valent pneumococcal polysaccharide vaccine (PPSV23) and the 2011-2012 trivalent seasonal influenza vaccine in adults with RA receiving subcutaneous (SC) abatacept and background disease-modifying anti-rheumatic drugs (DMARDs)., Methods: Two multicenter, open-label sub-studies enrolled patients from the ACQUIRE (pneumococcal and influenza) and ATTUNE (pneumococcal) studies at any point during their SC abatacept treatment cycle following completion of ≥3 months' SC abatacept. All patients received fixed-dose abatacept 125 mg/week with background DMARDs. A pre-vaccination blood sample was taken, and after 28 ± 3 days a final post-vaccination sample was collected. The primary endpoint was the proportion of patients achieving an immunologic response to the vaccine at Day 28 among patients without a protective antibody level to the vaccine antigens at baseline (pneumococcal: defined as ≥2-fold increase in post-vaccination titers to ≥3 of 5 antigens and protective antibody level of ≥1.6 μg/mL to ≥3 of 5 antigens; influenza: defined as ≥4-fold increase in post-vaccination titers to ≥2 of 3 antigens and protective antibody level of ≥1:40 to ≥2 of 3 antigens). Safety and tolerability were evaluated throughout the sub-studies., Results: Pre- and post-vaccination titers were available for 113/125 and 186/191 enrolled patients receiving the PPSV23 and influenza vaccine, respectively. Among vaccinated patients, 47/113 pneumococcal and 121/186 influenza patients were without protective antibody levels at baseline. Among patients with available data, 73.9 % (34/46) and 61.3 % (73/119) met the primary endpoint and achieved an immunologic response to PPSV23 or influenza vaccine, respectively. In patients with pre- and post-vaccination data available, 83.9 % in the pneumococcal study demonstrated protective antibody levels with PPSV23 (titer ≥1.6 μg/mL to ≥3 of 5 antigens), and 81.2 % in the influenza study achieved protective antibody levels (titer ≥1:40 to ≥2 of 3 antigens) at Day 28 post-vaccination. Vaccines were well tolerated with SC abatacept with background DMARDs., Conclusions: In these sub-studies, patients with RA receiving SC abatacept and background DMARDs were able to mount an appropriate immune response to pneumococcal and influenza vaccines., Trial Registration: NCT00559585 (registered 15 November 2007) and NCT00663702 (registered 18 April 2008).

Objective: To assess the overall safety, including rare events, of intravenous (IV) abatacept treatment in rheumatoid arthritis (RA)., Methods: Data from 8 clinical trials of IV abatacept in RA were pooled. Safety events were assessed during the short-term (duration ≤ 12 months) and cumulative (short-term plus longterm extensions) abatacept treatment periods. Incidence rates per 100 patient-years were calculated. Standardized incidence ratios (SIR) for hospitalized infections and malignancies were compared with external RA cohorts and, for malignancies, with the US general population., Results: There were 3173 IV abatacept-treated patients with 2331 patient-years of exposure in the short-term periods, and 4149 IV abatacept-treated patients with 12,132 patient-years of exposure in the cumulative period. Incidence rates for serious infections were low and consistent over time (3.68 for abatacept vs 2.60 for placebo during the short-term, and 2.87 for abatacept during the cumulative period). Hospitalized infections were generally similar to external RA patient cohorts and were consistent over time. Incidence rates of malignancies were similar for abatacept- and placebo-treated patients during the short-term period (0.73 vs 0.59) and remained low during the abatacept cumulative period (0.73). SIR of some tissue-specific malignancies (e.g., colorectal and breast) in the cumulative period tended to be lower, while others (lymphoma and lung) tended to be higher, compared with the general population; however, incidence rates were comparable with RA cohorts. Autoimmune events were rare and infusion reactions uncommon., Conclusion: Longterm safety of IV abatacept was consistent with the short-term, with no unexpected events and low incidence rates of serious infections, malignancies, and autoimmune events.