Use of a Molecular Signature Response Classifier to Inform Treatment Selection Improves Clinical Disease Activity Among Patients with Rheumatoid Arthritis Initiating a Biologic or Targeted Synthetic Disease-Modifying Antirheumatic Drug.

SAT0118 COMPARATIVE EFFECTIVENESS OF TOCILIZUMAB IN COMBINATION WITH METHOTREXATE VERSUS TUMOR NECROSIS FACTOR INHIBITORS (TNFIS) IN COMBINATION WITH METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS WITH PRIOR EXPOSURE TO TNFIS

Tofacitinib (TOF) is an oral, small-molecule drug used for rheumatoid arthritis (RA) treatment and is one of several alternative treatments to tumor necrosis factor inhibitors (TNFi). We evaluated physician- and patient-reported effectiveness of TNFi compared to TOF, using real-world data from the Ontario Best Practices Research Initiative (OBRI). Patients enrolled in the OBRI initiating TOF or TNFi between 2014 and 2019 were included. Patients were required to have physician- and patient-reported effectiveness outcome data, including Clinical Disease Activity Index (CDAI) and RA Disease Activity Index (RADAI), available at treatment initiation and 6 (± 2) months later. To deal with confounding by indication, we estimated propensity scores (PS) for covariates. Four hundred nineteen patients were included. Of those, 226 initiated a TNFi and 193 TOF, and had a mean (SD) disease duration of 8.0 (8.7) and 12.6 (9.6) years, respectively. In addition, the TNFi group was less likely to have prior biologic use (21.7%) compared to the TOF group (67.9%). The proportion of patients in CDAI low disease activity (LDA)/remission (REM) at 6 months was 36.7% and 33.2% in the TNFi and TOF groups, respectively. The generalized linear mixed models adjusting for PS quantile showed that there was no significant difference in CDAI LDA/REM (odds ratio [OR] 0.85, 95% CI 0.51-1.43) and RADAI coefficient (OR 0.48, 95% CI -0.18 to 1.14) between the 2 groups (ref: TOF). In patients with RA, physician- and patient-reported effectiveness are similar in the TNFi and TOF groups 6 months after treatment.

IntroductionThis study aimed to evaluate a subsequent treatment response among patients with rheumatoid arthritis (RA) who initiated and remained on a first-line tumor necrosis factor inhibitor (TNFi) after achieving or not achieving an initial response.MethodsThis real-world, retrospective cohort study included patients with RA in moderate/high disease activity (MDA/HDA), defined by Clinical Disease Activity Index (CDAI) score > 10, who initiated a first-line TNFi and remained on therapy for ≥ 12 months. Data were analyzed according to the time of initial evaluation: 3 months (N = 1215) or 6 months (N = 1318). Primary outcome: proportion of patients achieving low disease activity (LDA)/remission in CDAI (≤ 10) at the initial evaluation; secondary outcome: proportion of patients achieving minimal clinically important difference (MCID) in CDAI. Patients were categorized as responders or nonresponders according to outcome achievement, then analyzed for subsequent response at 12 months and maintenance of initial response through 12 months.ResultsAfter 3 months, 65.9% of patients were in MDA/HDA. Among these nonresponders, 73.5% remained in MDA/HDA at 12 months and 64.2% failed to improve through 12 months. Of patients in LDA/remission at 3 months, 27.0% lost their response at 12 months. Among the 59.2% of nonresponders at 6 months, 80.1% were in MDA/HDA at 12 months and 74.5% never improved through 12 months. For patients in LDA/remission at 6 months (40.8%), 23.4% subsequently lost their response at 12 months. Similar trends were observed for achievement of MCID in CDAI.ConclusionsIn patients with RA treated with a first-line TNFi, most patients who did not achieve a treatment target at an initial evaluation also failed to achieve the treatment target at 12 months. Therefore, evaluating treatment as early as 3 months after initiation may help indicate future clinical improvements and could serve as a reasonable timepoint to consider changing therapy for patients with an inadequate response.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-025-00808-z.

ObjectiveRandomized controlled trials (RCTs) in biologic-naïve rheumatoid arthritis (RA) patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 (IL-6) receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy. This observational study aimed to compare the effectiveness of TNFi vs IL-6Ri as mono- or combination therapy in biologic/targeted synthetic (b/ts) -experienced RA patients with moderate/high disease activity.MethodsEligible b/ts-experienced patients from the CorEvitas RA registry were categorized as TNFi and IL-6Ri initiators, with subgroups initiating as mono- or combination therapy. Mixed-effects regression models evaluated the impact of treatment on Clinical Disease Activity Index (CDAI), patient-reported outcomes, and disproportionate pain (DP). Unadjusted and covariate-adjusted effects were reported.ResultsPatients initiating IL-6Ri (n = 286) vs TNFi monotherapy (n = 737) were older, had a longer RA history and higher baseline CDAI, and were more likely to initiate as third-line therapy; IL-6Ri (n = 401) vs TNFi (n = 1315) combination therapy initiators had higher baseline CDAI and were more likely to initiate as third-line therapy. No significant differences were noted in the outcomes between TNFi and IL-6Ri initiators (as mono- or combination therapy).ConclusionThis observational study showed no significant differences in outcomes among b/ts-experienced TNFi vs IL-6Ri initiators, as either mono- or combination therapy. These findings were in contrast with the previous RCTs in biologic-naïve patients and could be explained by the differences in the patient characteristics included in this study. Further studies are needed to help understand the reasons for this discrepancy in the real-world b/ts-experienced population.Key Points• Patients with rheumatoid arthritis (RA) often require switching between biologics or targeted synthetic (b/ts) disease-modifying anti-rheumatic drugs (DMARDs) to achieve their treatment target.• Head-to-head randomized controlled trials (RCTs) in biologic-naïve RA patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy; however, there are no RCTs comparing these therapies in a population previously treated with b/tsDMARDs (i.e., b/ts-experienced patients).• This observational study compared the effectiveness of TNFi vs IL-6Ri (as mono- or combination therapy) in b/ts-experienced RA patients with moderate or high disease activity and found no significant differences in clinical outcomes for the two treatments.• A discrepancy is noted between our study and RCTs, which have shown superiority of IL-6Ri therapy (albeit in biologic-naïve patients). Further analyses may help elucidate the reason for this discrepancy in the real-world b/ts-experienced population.

Simplified measures to quantify rheumatoid arthritis (RA) disease activity are increasingly used. The minimum clinically important differences (MCID) for some measures, such as the Clinical Disease Activity Index (CDAI), have not been well-defined in real-world clinic settings, especially for early RA patients with low/moderate disease activity. Data from Canadian Early Arthritis Cohort patients were used to examine absolute change in CDAI in the first year after enrollment, stratified by disease activity. MCID cut points were derived to optimize the sum of sensitivity and specificity versus the gold standard of patient self-reported improvement or worsening. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated against patient self-reported improvement (gold standard) and for change in pain, Health Assessment Questionnaire (HAQ), and Disease Activity Score in 28 joints (DAS28) improvement. Discrimination was examined using the area under receiver operator curves. Similar methods were used to evaluate MCIDs for worsening for patients who achieved low disease activity. A total of 578 patients (mean ± SD age 54.1 ± 15.3 years, 75% women, median [interquartile range] disease duration 5.3 [3.3, 8.0] months) contributed 1,169 visit pairs to the improvement analysis. The MCID cut points for improvement were 12 (patients starting in high disease activity: CDAI >22), 6 (moderate: CDAI 10-22), and 1 (low disease activity: CDAI <10). Performance characteristics were acceptable using these cut points for pain, HAQ, and DAS28. The MCID for CDAI worsening among patients who achieved low disease activity was 2 units. These minimum important absolute differences in CDAI can be used to evaluate improvement and worsening and increase the utility of CDAI in clinical practice.

THU0162 LIKELIHOOD OF CLINICAL WORSENING AMONG RHEUMATOID ARTHRITIS PATIENTS WHO ACHIEVED A PARTIAL RESPONSE TO ADALIMUMAB AND WERE SUBSEQUENTLY SWITCHED TO SARILUMAB

THU0266 Determining the Absolute Change in the Clinical Disease Activity Index (CDAI) to Define A Minimally Important Difference

POS0606 DISEASE ACTIVITY AND PATIENTS-REPORTED OUTCOMES AFTER SWITCHING BETWEEN IL-6 RECEPTOR INHIBITORS AND JAK INHIBITORS: AN ANALYSIS FROM THE CORRONA REGISTRY

Objective To compare disease activity score 28 joints DAS28, simplified disease activity index(SDAI) and clinical disease activity index(CDAI) for assessing disease activity in patients with rheumatoid arthritis (RA). Method Total of 423 patients with RA hospiltalized in the department of the first Affiliated Hospital of Anhui Medical University between January 2006 and December 2014 were enrolled in this study.DAS28, CDAI and SDAI were used to evaluate disease activity.According to the classification criteria of RA, patients were divided into three groups: group of remission or low-disease activity, group of moderate-disease activity and high-disease activity. Results ①According to classification criteria of DAS28, the patients in the above three groups were respectivelly accounted for 4.14%(17/423), 38.2%(157/423) and 57.66%(237/423). For CDAI, the ratios were 6.86%(29/423), 29.79%(126/423) and 63.36%(268/423). For SDAI, to ratio were 5.26%(22/423), 32.78%(137/423) and 61.96%(259/423). There were good correlations among CDAI, SDAI and DAS28 (Spearman correlation=0.812, 0.796; both P<0.05), and both CDAI and SDAI had well consistency with DAS28 (Kappa=0.719, 0.740, both P<0.05). ② Correlation analyses showed that CDAI and SDAI were positively correlated with DAS28(r=0.913, 0.912, both P<0.05), and there was a higher positive linear correlation between CDAI and SDAI(r=0.973, P<0.05). ③There was significant difference regarding swollen joint count, tender joint count, healthy assessment questionnaive(HAQ) score, blood platelet count, erythrocyte sedimentation Rate(ESR), C-reaction protein(CRP), rheumatoid factor(RF) among patients with different disease activity(P<0.05). All of the above indexes increased along with the rising disease activity.Serum hemoglobin(HB) levels(P<0.05) decreased along with the rising disease activity.④DAS28, CDAI and SDAI positively correlated with swollen joint count, tender joint count, HAQ score, blood platelet count, ESR, CRP and RF(P<0.05). DAS28, CDAI and SDAI negatively correlated with HB levels(P<0.05). Conclusion CDAI, SDAI and DAS28 have good association and consistency.SDAI and CDAI have better correlations with disease activity in RA. Key words: Rheumatoid arthritis; Disease activity index; Disease activity score 28 joint; Clinical disease activity idex; Simplified disease activity index

ObjectivesTo evaluate if baricitinib, a Janus kinase inhibitor, further enhances disease-modifying effects by uncoupling the link between disease activity and structural damage progression in patients with rheumatoid arthritis (RA) using...

AB1070 Comparison of Ultrasound Disease Activity Score in Assessing Joint Inflammation in RA: Comparison with CDAI

SAT0106 LONG-TERM SAFETY AND EFFICACY OF SARILUMAB OVER 5 YEARS IN PATIENTS WITH RHEUMATOID ARTHRITIS WITH 1 OR >1 PRIOR TUMOR NECROSIS FACTOR INHIBITOR FAILURES

AB0296 The Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) Scores as Alternatives to the Current DAS28 Score

FRI0133 Understanding Anemia in Rheumatoid Arthritis: The Association of Hemoglobin and Hepcidin Levels with Clinical Disease Activity and Acute Phase Response

BackgroundStringent remission criteria are crucial in rheumatoid arthritis (RA) assessment. Disease activity score in 28 joints (DAS28)-remission has not been included among American College of Rheumatology/European League Against Rheumatism definitions, because of its association with significant residual disease activity, partly due to high weighting of acute-phase reactants (APR). New, more stringent cut-points for DAS28-remission have recently been proposed that are suggested to reflect remission by clinical and simplified disease activity indices (clinical disease activity index (CDAI), simple disease activity index (SDAI)). However, their stringency in therapies directly influencing APR, like IL-6-blockers, has not been tested. We tested the new cut-points in patients with RA receiving tocilizumab.MethodsWe used data from randomised controlled trials of tocilizumab and evaluated patients in remission according to new DAS28-C-reactive protein (DAS-CRP) and DAS-erythrocyte sedimentation rate (DAS-ESR) cut-points (1.9 and 2.2). We assessed their disease activity state using the CDAI, SDAI and Boolean criteria and analysed their individual residual core set variables, like swollen joint counts (SJC28).ResultsAbout 50% of patients in DAS28-CRP-remission (<1.9) fell into higher disease activity states when assessed with CDAI, SDAI or Boolean criteria. Also, 15% had three or more (up to eight) SJC. Even higher disease activity was seen in patients classified as being in DAS28-ESR-remission (<2.2).ConclusionsEven with new, more stringent cut-points, DAS28-remission is frequently associated with considerable residual clinical disease activity, indicating that this limitation of the DAS28 is related to score construction rather than the choice of cut-points.