Rheumatoid arthritis is a chronic inflammatory disease, and interstitial lung disease is one of the important extra-articular manifestations. There is limited evidence comparing abatacept (ABA) and tumor necrosis factor inhibitors (TNFi) regarding the risk of mortality among patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD). The aim of this study is to investigate the risk of mortality in patients with RA-ILD treated with ABA compared to TNFi. This retrospective cohort study utilized TriNetX electronic health record database. We enrolled patients who were diagnosed with RA-ILD and had received a new prescription for either ABA or TNFi. Patients were categorized into two cohorts based on their initial prescription. The primary outcome was all-cause mortality, and secondary outcomes were healthcare utilizations, including hospitalization, critical care services, and mechanical ventilation. Subgroup analyses were performed on age, presence of anti-citrullinated peptide antibodies (ACPA), and cardiovascular risk. Among 34,388 RA-ILD patients, 895 were selected for each group (ABA and TNFi) following propensity score matching. The ABA group exhibited a higher all-cause mortality risk. (HR 1.296, 95% CI 1.006-1.671). Subgroup analysis showed a heightened risk of receiving mechanical ventilation in ABA-treated patients aged 18-64 years old (HR 1.853, 95% CI 1.002-3.426), and those with cardiovascular risk factors (HR 2.015, 95% CI 1.118-3.630). Another subgroup analysis indicated a higher risk of mortality among ABA-treated patients with positive-ACPA. (HR 4.138 95% CI 1.343-12.75). This real-world data research demonstrated a higher risk of all-cause mortality in RA-ILD patients treated with ABA compared to TNFi, particularly those aged 18-64 years, lacking cardiovascular risk factors, and positive-ACPA. ABA was associated with an increased risk of mechanical ventilation in patients aged 18-64 years and those with cardiovascular risk factors.

UNASSIGNED: Tapering biologic agents can be considered for patients with stable disease activity in rheumatoid arthritis (RA). However, the specific strategy for abatacept is uncertain. This study aimed to examine the impact of tapering abatacept on disease activity in RA patients and assess the potential influence of concomitant methotrexate (MTX) treatment.
UNASSIGNED: Using data from the KOBIO registry, we included 505 1 year intervals from 176 patients with RA that initiated abatacept with concomitant MTX at baseline. The intervals were divided into two groups based on the dose quotient (DQ) of abatacept during each period (i.e., the tapering group (DQ < 1) and control group (DQ = 1)). The primary outcome was achieving DAS28-remission at 1 year intervals. Marginal structural models (MSM) were used to minimize confounding caused by an imbalance in time-varying variables.
UNASSIGNED: Abatacept was tapered at 146 (28.9%) intervals, and the mean DQ was 0.68. DAS28-remission was achieved in 207 (41.8%) intervals. Tapering abatacept did not affect the odds of achieving DAS28-remission compared with the control group (OR 1.04 [0.67-1.62]). The odds remained unaffected in the subgroup that continued MTX (OR 1.42 [0.88-2.30]) but not in the subgroup that discontinued MTX (OR 0.26 [0.10-0.57]). The effects of interaction between tapering abatacept and concomitant MTX use on DAS28 and patient\'s functional status showed consistent results. The incidence of adverse events within a 1 year interval was comparable between the two groups.
UNASSIGNED: Withdrawal of MTX while tapering abatacept may compromise meeting the treatment goal for patients with RA.

Seven of the 11 newer medications recently or soon to be approved to treat rheumatologic diseases discussed in this article are biologic agents and reflect the current ability of science to target specific components of the immune system. The other agents are molecules that are directed against specific immune pathway targets as well. All have shown superiority to placebo and in some cases have been compared to currently accepted therapies. Safety issues are generally centered around infections due to the immune-interrupting nature of these therapies.

OBJECTIVE: To investigate whether rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPAs) and shared epitope (SE) allele-related genetic markers associate with treatment response to abatacept, certolizumab pegol or tocilizumab versus active conventional treatment (ACT).
METHODS: Patients with treatment-naïve early rheumatoid arthritis were randomised in the NORD-STAR trial to ACT, certolizumab pegol, abatacept or tocilizumab, all with methotrexate. Centralised laboratory analyses for ACPA, RF and SE were performed. Clinical Disease Activity Index remission was analysed longitudinally with logistic generalised estimating equations. Differences in treatment effect across RF, ACPA and SE subgroups were assessed with interaction terms at 24 and 48 weeks, adjusted for sex, country, age, body mass index, Disease Activity Score of 28 joints based on C-reactive protein and smoking.
RESULTS: In total, 778 patients were included. At 24 weeks, abatacept treatment showed a better response than ACT in the RF and/or ACPA-positive subgroups, but this effect was not significantly different from the negative subgroups. By 48 weeks, abatacept treatment showed better response regardless of RF/ACPA status. No differences were found across RF, ACPA, SE allele, valine at amino acid position 11 or valine-arginine-alanine haplotype subgroups for any biological treatment at 48 weeks.
CONCLUSIONS: Based on this randomised controlled trial, abatacept treatment was associated with a better response than ACT in the RF and/or ACPA-positive subgroup at 24 weeks, but this was no longer seen at 48 weeks; adding SE allele-related genetic markers did not strengthen the association. Moreover, ACPA, RF and SE allele-related genotypes were not, alone or in combination, associated with clinical responses of importance sufficiently strongly to warrant implementation in clinical practice.
BACKGROUND: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.

Post-allogeneic hematopoietic cell transplant (HCT) immunosuppression regimens are given as graft-versus-host disease (GVHD) prophylaxis. Most GVHD prophylaxis regimens are based on calcineurin inhibitors (CNIs). Unfortunately, CNIs are associated with significant associated morbidity, frequently cannot be tolerated, and often need to be discontinued. There is no consensus as to which alternative immunosuppression should be used in cases where CNIs have to be permanently discontinued. Cytotoxic T-lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocking agents are well tolerated and have been used extensively in patients with autoimmune disease and as post-transplant immunosuppression. There are two CTLA4-Ig agents: belatacept and abatacept. Belatacept is routinely used in adult kidney transplantation to prevent rejection and abatacept has been approved by the Food and Drug Administration (FDA) for GVHD prophylaxis in patients undergoing a matched or one allele-mismatched unrelated allogenic HCT. Herein, we describe a case in which abatacept was given off-label to replace tacrolimus GVHD prophylaxis in a patient with neurotoxicity undergoing haploidentical HCT. This case suggests that CTLA4-Ig blockade may be a good alternative to a CNI in cases where the CNI needs to be discontinued and warrants further investigation.

BACKGROUND: Evidence on abatacept (ABA) utility for rheumatoid arthritis (RA) - associated interstitial lung disease (ILD) is growing. Clinical trials have shown equivalence in subcutaneous (SC) and intravenous (IV) administration of ABA for articular manifestations. However, this has not been studied in respiratory outcomes.
OBJECTIVE: To compare the effectiveness of ABA in RA-ILD patients according to the route of administration.
METHODS: National retrospective multicentre study of RA-ILD patients on treatment with ABA. They were divided into 2 groups: a) IV, and b) SC. The following outcomes were analysed from baseline to final follow-up using linear mixed models: a) forced vital capacity (FVC), b) diffusing capacity of the lungs for carbon monoxide (DLCO), c) chest high resolution computed tomography (HRCT), d) dyspnoea, e) RA activity, and f) sparing corticosteroids effect.
RESULTS: A total of 397 patients were included (94 IV-ABA and 303 SC-ABA), median follow-up of 24 [10-48] months. After adjustment for possible confounders, FVC and DLCO remained stable during the first 24 months without differences between IV-ABA and SC-ABA (p = 0.6304 and 0.5337). Improvement/ stability of lung lesions in HRCT was observed in 67 % of patients (75 % IV-ABA, 64 % SC-ABA; p = 0.07). Dyspnoea stabilized/ improved in 84 % of patients (90 % IV-ABA, 82 % SC-ABA; p = 0.09). RA - disease activity improved in both groups. No statistically significant differences regarding any of the variables studied between the two groups were found. ABA was withdrawn in 87 patients (21.9 %), 45 % IV-ABA and 37 % SC-ABA (p = 0.29). ILD worsening and articular inefficacy were the most common reasons for ABA discontinuation.
CONCLUSIONS: In patients with RA-ILD, ABA seems to be equally effective regardless of the route of administration.

BACKGROUND: The safety and efficacy of upadacitinib 15 mg (UPA15) through week 216 was evaluated in patients with rheumatoid arthritis (RA) from the long-term extension (LTE) of the phase 3 SELECT-CHOICE study.
METHODS: Patients with RA refractory to biologic disease-modifying antirheumatic drugs (bDMARDs) were randomized to UPA15 or abatacept (ABA) for 24 weeks. During the open-label LTE, patients on ABA switched to UPA15 at week 24, and those on UPA15 continued treatment. The safety and efficacy of continuous UPA15, and ABA to UPA15, are summarized through week 216.
RESULTS: The LTE was comprised of 91.4% (n = 277/303) of patients that initially received UPA15, and 89.6% (n = 277/309) that initially received ABA. Of patients on UPA15 in the LTE (n = 547), 28.3% (n = 155/547) discontinued the study drug by week 216. Relative to other adverse events of special interest, and largely consistent with previous findings at week 24, higher rates of serious infection, COVID-19, herpes zoster, and elevated creatine phosphokinase were reported, while rates of malignancy excluding nonmelanoma skin cancer (NMSC), NMSC, major adverse cardiovascular event (MACE), and venous thromboembolism (VTE) were low. Long-term safety data with UPA through week 216 aligned with previous observations and no new safety risks were identified, including in patients who switched from ABA to UPA15. Proportions of patients achieving 28-joint disease activity score based on C-reactive protein (DAS28[CRP]) < 2.6/ ≤ 3.2, clinical disease activity index (CDAI) and simple disease activity index (SDAI) low disease activity/remission, ≥ 20%/50%/70% improvement in the American College of Rheumatology (ACR20/50/70) response criteria, and Boolean remission were maintained or improved with UPA15 through week 216. Improvements in the Health Assessment Questionnaire-Disability Index (HAQ-DI), patient\'s assessment of pain, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were also maintained or improved with UPA15 through week 216. Across all efficacy endpoints, similar results were observed in patients who switched from ABA to UPA15 versus continuous UPA15. Patients with an inadequate response to ≥ 1 prior tumor necrosis factor (TNF) inhibitor (UPA15: n = 263/303, 86.8%; ABA to UPA15: n = 273/309, 88.3%) showed similar responses to the total population.
CONCLUSIONS: The long-term safety profile of UPA was consistent with previous findings and the broader RA clinical program. Compared to the primary analyses at week 24, efficacy responses were maintained or further improved with UPA15 through week 216 in patients with RA. Trial registration, ClinicalTrials.gov identifier: NCT03086343.
A long-term study looked at a drug named upadacitinib to treat people with rheumatoid arthritis (RA), a disease that causes joint pain and damage. The study included patients whose RA was not improved by other injectable medicines. The study compared upadacitinib with another drug called abatacept. After 24 weeks, patients who were taking abatacept switched to upadacitinib, and patients taking upadacitinib continued on upadacitinib treatment for over 4 years. The researchers looked at how well the treatments worked over the long-term and if there were any side effects. The side effects with upadacitinib treatment in this long-term study were similar to side effects reported in previous studies with upadacitinib. The researchers also found that upadacitinib helped to lessen the symptoms of RA over time and helped patients complete their daily activities and reduced their pain and tiredness. This was true for patients who switched from abatacept to upadacitinib after 24 weeks and for patients who took upadacitinib from the start of the study. Patients who had not responded to other medicines also had similar improvements with upadacitinib. In conclusion, upadacitinib can help people with RA over the long term and no new safety risks were found.

UNASSIGNED: Since adalimumab approval in childhood chronic non-infectious uveitis (cNIU), the prognosis has been dramatically changed, but the 25 % failed to achieve inactivity. There is not accordance if it is better to switch to another anti-TNF or to swap to another category of biologic. Thus, we aim to summarize evidence regarding the best treatment of cNIU refractory to the first anti-TNF.
UNASSIGNED: A systematic literature review and meta-analysis, according to PRISMA Guidelines, was performed(Jan2000-Aug2023). Studies investigating the efficacy of treatment in cNIU refractory to the first anti-TNF were considered for inclusion. The primary outcome was the improvement of intraocular inflammation according to SUN. A combined estimation of the proportion of children responding to switch or swap and for each drug was performed.
UNASSIGNED: 23 articles were eligible, reporting 150 children of whom 109 switched anti-TNF (45 adalimumab, 49 infliximab, 9 golimumab) and 41 swapped to another biologics (31 abatacept, 8 tocilizumab and 1 rituximab). The proportion of responding children was 46 %(95 % CI 23-70) for switch and 38 %(95 % CI 8-73) for swap (χ20.02, p = 0.86). Instead analysing for each drug, the proportion of responding children was the 24 %(95 % CI 2-55) for adalimumab, 43 %(95 % CI 2-80) for abatacept, 79 %(95 % CI 61-93) for infliximab, 56 %(95 % CI 14-95) for golimumab and 96 %(95 % CI 58-100) for tocilizumab. We evaluated a superiority of tocilizumab and infliximab compared to the other drugs(χ2 27.5 p < 0.0001).
UNASSIGNED: Although non-conclusive, this meta-analysis suggests that, after the first anti-TNF failure, tocilizumab and infliximab are the best available treatment for the management of cNIU.

OBJECTIVE: To evaluate real-world abatacept retention and clinical outcomes in patients with rheumatoid arthritis in Taiwan.
METHODS: This prospective, observational study enrolled patients with rheumatoid arthritis aged ≥20 years who received abatacept in real-world practice. The primary endpoint was the abatacept retention rate at 24 months. Patients were categorized into subgroups based on abatacept treatment status and previous biological disease-modifying antirheumatic drug (bDMARD) therapy. Risk factors affecting abatacept retention were determined by regression analysis.
RESULTS: A total of 212 patients were enrolled. The overall abatacept retention rate at 24 months among all patients was 59.9% (95% confidence interval 53.0%-66.6%). Patients who were ongoing users of abatacept and bDMARD-naïve had the highest retention rate (76.3%); of these, 31.6% achieved low disease activity or remission after 2 years. Previous treatment with bDMARDs was associated with an increased risk of abatacept discontinuation (hazard ratio 1.99; p = .002). The most common reasons for abatacept discontinuation were drug switch (11.3%) and loss to follow-up (6.1%). Abatacept was well-tolerated with no new safety signals.
CONCLUSIONS: The 24-month retention rate of abatacept was 59.9%; abatacept was associated with improved clinical outcomes and was well-tolerated in the real-world setting in Taiwan.

OBJECTIVE: To evaluate the survival of different biologic or targeted-synthetic disease-modifying antirheumatic drugs (b/tsDMARD) administered after fulfilling difficult-to-treat rheumatoid arthritis (D2TRA) criteria, and to assess factors related to treatment discontinuation.
METHODS: Retrospective study including D2TRA patients. Drug retention of the b/tsDMARD administered after fulfilling D2TRA was assessed by Kaplan-Meier plots and the log-rank test. Cox hazard models were used to identify factors affecting treatment discontinuation.
RESULTS: Of the 122 patients included, 75 maintained active treatment (61.5%) with a subsequent line after D2T compared to 47 (38.5%) who discontinued and required more successive lines of b/tsDMARDs. The median survival of the treatments was 78.3(7.6) months and the treatment after D2T with the better rate of survival was rituximab, followed by JAKi and IL6Ri, while worse survival rates were associated with abatacept and TNFi. Significant differences were noted among b/tsDMARDs (log-rank p < 0.01) and to evaluate these differences, a Cox regression was performed, taking each b/tsDMARD as a reference and comparing it with the others. DAS28 values 6-months after initiation of treatment were higher in those patients who discontinued treatment [4.4(1.2) vs 3.5(1.3), p = 0.01]. The multivariate cox regression model revealed that treatment choice after D2T [HR = 1.26(95%CI 1.06-1.05)] and lower DAS28 values at 6 months [HR = 1.49(95%CI 1.16-1.52)] were independent risk factors associated with treatment discontinuation.
CONCLUSIONS: Once patients met the D2TRA criteria, the subsequent line of b/tsDMARDs with the best survival rates were rituximab, JAKi and IL6Ri. Moreover, DAS28 at 6-months of treatment after D2T was an independent risk factor for drug discontinuation. Key Points • Rituximab, IL6Ri and JAKi have better retention rates in patients after fulfilling D2TRA criteria • Clinical disease activity in the first six months after fulfillment of D2TRA criteria is an independent risk factor of subsequent treatment survival.