Baseline Clinical Disease Activity Index Research Articles

Characteristics and 6-Month Outcomes in Patients with Rheumatoid Arthritis Initiating Infliximab Biosimilar IFX-dyyb in a Real-World Setting.

Real-world studies describing biosimilar initiation or switching in patients with rheumatoid arthritis (RA) are limited. The aim of this study was to assess treatment patterns and effectiveness of real-world patients with RA initiating infliximab biosimilar IFX-dyyb (CT-P13; Inflectra®) in the USA. This observational study evaluated patients with RA from the CorEvitas RA Registry who initiated IFX-dyyb and had Clinical Disease Activity Index (CDAI) recorded at baseline and 6months. The primary outcome was reaching low disease activity (LDA; CDAI ≤ 10) at 6months in patients with moderate or high disease activity (CDAI > 10) at baseline. Secondary outcomes were change at 6months in CDAI and certain patient-reported outcomes (PROs). Patient data were stratified by prior treatment: biologic/targeted synthetic disease-modifying antirheumatic drug (tsDMARD)-naïve, reference infliximab (IFX-REF) or IFX biosimilar, or a non-IFX biologic or tsDMARD. Of 318 patients initiating IFX-dyyb, 176 had baseline and 6-month CDAI scores; 73 (41%) switched from IFX, 61 (35%) switched from another non-IFX/biologic/tsDMARD, 32 (18%) were naïve to biologics/tsDMARDs, and 10 (6%) switched from an IFX biosimilar. Among patients with moderate or high disease activity at baseline, 32.9% (95%CI 22.9, 42.9) achieved LDA at 6months. Mean 6-month change from baseline in CDAI was - 1.8 (95%CI - 3.3, - 0.3) overall; - 4.7 (- 7.6, - 1.7) in patients who switched from a non-IFX biologic/tsDMARD, - 4.1 (- 7.8, - 0.3) in biologic/tsDMARD-naïve patients, and 1.1 (- 0.4, 2.6) in patients who switched from IFX-REF/IFX biosimilar. Other clinical outcomes/PROs improved at 6months. Of the IFX-dyyb initiators, 68% remained on IFX-dyyb at 6months. In this real-world population of patients with RA initiating IFX-dyyb, the majority switched from IFX-REF or a non-IFX biologic/tsDMARD. CDAI remained stable in patients switching from IFX-REF/IFX biosimilar and improved in patients switching from a non-IFX biologic/tsDMARD and in biologic/tsDMARD-naïve patients.

Urinary prostanoids are elevated by anti-TNF and anti-IL6 receptor disease-modifying antirheumatic drugs but are not predictive of response to treatment in early rheumatoid arthritis

BackgroundDisease-modifying antirheumatic drugs (DMARDs) are widely used for treating rheumatoid arthritis (RA). However, there are no established biomarkers to predict a patient’s response to these therapies. Prostanoids, encompassing prostaglandins, prostacyclins, and thromboxanes, are potent lipid mediators implicated in RA progression. Nevertheless, the influence of DMARDs on prostanoid biosynthesis in RA patients remains poorly understood. This study aims to assess the impact of various DMARDs on urinary prostanoids levels and to explore whether urinary prostanoid profiles correlate with disease activity or response to therapy.MethodsThis study included 152 Swedish female patients with early RA, all rheumatoid factor (RF) positive, enrolled in the NORD-STAR trial (registration number: NCT01491815). Participants were randomized into four therapeutic regimes: methotrexate (MTX) combined with (i) prednisolone (arm ACT), (ii) TNF-α blocker certolizumab pegol (arm CZP), (iii) CTLA-4Ig abatacept (arm ABA), or (iv) IL-6R blocker tocilizumab (arm TCZ). Urine samples, collected before start of treatment and at 24 weeks post-treatment, were analyzed for tetranor-prostaglandin E metabolite (tPGEM), tetranor-prostaglandin D metabolite (tPGDM), 2,3-dinor thromboxane B2 (TXBM), 2,3-dinor-6-keto prostaglandin F1a (PGIM), leukotriene E4 (LTE4) and 12-hydroxyeicosatetraenoic acid (12-HETE) using liquid chromatography–mass spectrometry (LC–MS). Generalized estimating equation (GEE) models were used to analyze the change in urinary eicosanoids and their correlations to clinical outcomes.ResultsPatients receiving MTX combined with CZP or TCZ exhibited significant elevations in urinary tPGEM and TXBM levels after 24 weeks of treatment. Other eicosanoids did not show significant alterations in response to any treatment. Baseline urinary eicosanoid levels did not correlate with baseline clinical disease activity index (CDAI) levels, nor with changes in CDAI from baseline to week 24. Their levels were also similar between patients who achieved CDAI remission and those with active disease at week 24.ConclusionsTreatment with anti-TNF or anti-IL6R agents in early RA patients leads to an increased systemic production of proinflammatory and prothrombotic prostanoids. However, urinary eicosanoid levels do not appear to be predictive of the response to DMARDs therapy.

Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study.

This multicentre, retrospective study compared the efficacy and safety of tofacitinib, baricitinib, peficitinib and upadacitinib in real-world clinical settings after minimizing selection bias and adjusting the confounding patient characteristics. The 622 patients were selected from the ANSWER cohort database and treated with tofacitinib (TOF), baricitinib (BAR), peficitinib (PEF) or upadacitinib (UPA). The patient's background was matched using propensity score-based inverse probability of treatment weighting (IPTW) among four treatment groups. The values of Clinical Disease Activity Index (CDAI), C-reactive protein (CRP), and modified Health Assessment Questionnaire (mHAQ) after drug initiation and the remission or low disease activity (LDA) rates of CDAI at 6 months after drug initiation were compared among the four groups. Further, the predictive factor for TOF and BAR efficacy was analysed. The retention and discontinuation rates until 6 months after drug initiations were not significantly different among the four JAK inhibitors treatment groups. Mean CDAI value, CDAI remission rate, and CDAI-LDA rate at 6 months after drug initiation were not significantly different among treatment groups. Baseline CDAI (TOFA: OR 1.09, P < 0.001; BARI: OR 1.07, P < 0.001), baseline CRP (TOFA: OR 1.32, P = 0.049), baseline glucocorticoid dose (BARI: OR 1.18, 95% CI 1.01-1.38, P = 0.035), a number of previous biological or targeted synthetic disease-modifying antirheumatic drugs (biological/targeted synthetic DMARDs) (BARI: OR 1.36, P = 0.004) were predictive factors for resistance to CDAI-LDA achievement to JAK inhibitor treatment. The efficacy and safety of TOF, BAR, PEF and UPA were not significantly different for the treatment of patients with rheumatoid arthritis.

Integrating PROMIS Measures in a Treat-to-Target Approach to Standardize Patient-Centered Treatment of Rheumatoid Arthritis.

To evaluate the effect of a patient-centered rheumatoid arthritis (RA) treat-to-target (T2T) disease management approach on patient outcomes and patient satisfaction with care. In this longitudinal, observational pilot study, rheumatologists implemented a modified T2T approach that integrated Patient Reported Outcomes Measurement Information System (PROMIS) measures for depression, fatigue, pain interference, physical function, and social function into RA care. Study participants selected 1 PROMIS domain to target treatment and completed quarterly follow-up assessments. Participants were classified as improved if their Clinical Disease Activity Index (CDAI) changed by > 5 points. Change in PROMIS t scores was examined for the group with improved CDAI, and then compared to those with unchanged or worsened CDAI. Satisfaction with care was assessed using multiple measures, including the Functional Assessment of Chronic Illness Therapy-Treatment Satisfaction-Patient Satisfaction Scale. The analytical sample (n = 119, median age 57 years, 90.8% female) was split between those with CDAI > 10 (n = 63) and CDAI ≤ 10 (n = 53). At 1 year, there was improvement in CDAI by > 5 points in 66% and 13% of individuals with baseline CDAI > 10 and baseline CDAI ≤ 10, respectively. Across all participants, improvement in CDAI by > 5 points correlated with improvements in the 5 PROMIS domains. Satisfaction with RA treatment also increased. The integration of PROMIS measures into the T2T approach for RA care was associated with improvements in disease activity, and improvement in disease activity was associated with improvements in PROMIS measures.

Comparative effectiveness of TNF inhibitor vs IL-6 receptor inhibitor as monotherapy or combination therapy with methotrexate in biologic-experienced patients with rheumatoid arthritis: An analysis from the CorEvitas RA Registry

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.

Patient Disease Trajectories in Rheumatoid Arthritis Patients Treated with Baricitinib 4-mg in FourPhase 3 Clinical Studies.

We sought to identify and compare treatment response groups based on individual patient responses (rather than group mean response) over time on the Clinical Disease Activity Index (CDAI) for rheumatoid arthritis (RA), in patients treated with baricitinib 4-mg in 4phase 3studies. Trajectory subgroups were identified within each study using growth mixture modeling. Following grouping, baseline characteristics and disease measures were summarized and compared. In each study, three response trajectories were identified. In the three studies of patients naïve to biological disease-modifying anti-rheumatic drugs (bDMARDs) patients had, on average, high disease activity, as measured by CDAI. In these studies, a group of rapid responders (65-71% of patients) had the lowest baseline CDAI scores and achieved mean CDAI ≤ 10 by week 16. Gradual responders (10-17%) had higher baseline CDAI, but generally achieved low disease activity (CDAI ≤ 10) by week 24. A group of partial responders (18-22%) had higher baseline CDAI and did not achieve mean CDAI ≤ 10. In bDMARD-experienced patients, the subgroups were rapid responders, who achieved mean CDAI ≤ 10 (42% of patients); partial responders, with mean CDAI decrease of ~ 15 points from baseline (42% of patients); and limited responders (15% of patients). Changes in modified total sharp score (mTSS; assessed only in biologic-naïve patients) were below the smallest detectable difference at 24/52weeks for > 90% of patients in each group, excepting partial responders in RA-BEGIN (≥ 75% no detectable change). In patients receiving baricitinib 4-mg, lower baseline CDAI was generally associated with rapid response, while higher baseline CDAI scores were generally seen for patients who either reached treatment targets more gradually, or who had a partial or limited response. Maintenance of response was observed with continued baricitinib treatment in all response groups and generally included maintenance of mTSS.

Comparison of the inhibitory effect of tocilizumab and etanercept on the progression of joint erosion in rheumatoid arthritis treatment

We compared the efficacy of tocilizumab and etanercept in inhibiting radiographic progression of joint destruction in rheumatoid arthritis. Overall, 187 patients treated with etanercept or tocilizumab were selected. To adjust for baseline patient characteristics between the tocilizumab and etanercept treatment groups, a propensity score matching was performed. Radiographic progression of joint destruction was compared between patients treated with tocilizumab or etanercept. Clinical disease activity index (CDAI) and modified health assessment questionnaire (mHAQ) scores at the administration of biologic treatment and after 12 months of tocilizumab and etanercept therapy were measured and compared to radiographical parameters between the groups. Levels of C-reactive protein (CRP), matrix metalloproteinase-3 (MMP-3), CDAI, and mHAQ scores improved after 12 months of treatment in the two groups. Proportion of patients with no Sharp erosion score progression was significantly higher with tocilizumab treatment than with etanercept treatment (p = 0.032). Multivariate analysis demonstrated that Sharp erosion score was significantly associated with baseline CDAI (odds ratio, 1.05; 95% confidence interval, 1.003–1.099, p = 0.037). Tocilizumab treatment suppressed joint erosion progression compared to etanercept, and the progression correlated with baseline CDAI.

Machine Learning Applied to Patient-Reported Outcomes to Classify Physician-Derived Measures of Rheumatoid Arthritis Disease Activity.

Patient-reported outcome (PRO) data have assumed increasing importance in the care of patients with rheumatoid arthritis (RA), yet physician-derived disease activity measures, such as Clinical Disease Activity Index (CDAI), remain the most accepted metrics to assess disease activity. The possibility that newer longitudinal PRO data might be used as a proxy for the CDAI has not been evaluated. Using data from a large pragmatic trial, we evaluated patients with RA initiating golimumab intravenous or infliximab. The classification target was low disease activity (LDA) (CDAI ≤10) at the first visit between months 3 and 12. Data were randomly partitioned into training (80%) and test (20%) data sets. Multiple machine learning (ML) methods (eg, random forests, gradient boosting, support vector machines) were used to classify CDAI disease activity category, conduct feature selection, and assess feature importance. Model performance evaluated cross-validated error, comparing different ML approaches using both training and test data. A total of 494 patients were analyzed, and 36.4% achieved LDA. The most important classification features included several Patient-Reported Outcomes Measurement Information System measures (social participation, pain interference, pain intensity, and physical function), patient global, and baseline CDAI. Among all ML methods, random forests performed best. Overall model accuracy and positive predictive values for all ML methods were approximately 80%. ML methods coupled with longitudinal PRO data appear useful and can achieve reasonable accuracy in classifying LDA among patients starting a new biologic. This approach has promise for real-world evidence generation in the common circumstance when physician-derived disease activity data are not available yet PRO measures are.

Efficacy of Abatacept Versus Tumor Necrosis Factor Inhibitors in Anti-citrullinated Protein Antibody-Positive Patients with Rheumatoid Arthritis: Results from a Korean Nationwide Biologics Registry.

Introduction To compare the efficacy of abatacept and tumor necrosis factor inhibitor (TNFi) in patients with anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) and identify those who benefit most from abatacept over TNFi.MethodsThis observational study identified RA patients who were ACPA-positive and initiated abatacept or TNFi from the Korean College of Rheumatology Biologics and Targeted therapy registry. Propensity score (PS) matching was performed to balance baseline confounding in abatacept- or TNFi-treated patients. The major endpoints were changes in Clinical Disease Activity Index (CDAI) and achievement of CDAI remission/low disease activity after 1 year of treatment. Subgroup analysis was mainly performed stratified by prior biologics use.ResultsA total of 291 PS-matched, ACPA-positive RA patients who initiated abatacept (n = 97) and TNFi (n = 194) were included. From baseline CDAI scores of 26.52 in the abatacept group and 26.38 in the TNFi group, the mean changes after 1 year were − 16.78 and − 13.61, respectively (difference − 3.17, p = 0.020). The proportion of patients achieving CDAI remission/low disease activity was 68.0% with abatacept and 52.6% with TNFi (p = 0.013). In the subgroup analysis, patients that were biologics-naïve had better improvement in CDAI after treatment with abatacept than TNFi (difference − 3.35, p = 0.021).ConclusionsThis real-world study suggests that abatacept may have better clinical response compared to TNFi in patients with established ACPA-positive RA, especially in those that were biologics-naïve.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00467-4.

Post Hoc Analysis of Predictors of Clinical Response to Repository Corticotropin Injection in Persistently Active Rheumatoid Arthritis.

IntroductionA phase IV clinical trial confirmed the safety and efficacy of repository corticotropin injection (RCI, Acthar® Gel) in patients with refractory rheumatoid arthritis (RA) that was nonresponsive to standard-of-care therapies. The objective of this post hoc analysis was to identify baseline demographics and clinical characteristics that may be predictors of response to RCI.MethodsThe phase IV trial was a two-part, randomized, placebo-controlled withdrawal study. Post hoc analysis was conducted with the open-label portion of the trial data, in which all 258 subjects received RCI (80 U) twice weekly for 12 weeks. Responders were subjects who achieved low disease activity (LDA) by a Disease Activity Score with 28-joint count and erythrocyte sedimentation rate (DAS28-ESR) of < 3.2 at week 12. Responders were compared with nonresponders by assessing the proportion of subjects in each group for demographics and clinical characteristics, including weight, disease duration, medical history including osteoarthritis and unrelated joint conditions, hemoglobin A1c, C-reactive protein, ESR, DAS28-ESR, Clinical Disease Activity Index (CDAI), depression, anxiety, tender joint count (TJC), and swollen joint count (SJC). Bivariate analysis followed by multiple logistic regression analysis were conducted to identify significant baseline predictors for the outcome of achieving LDA by week 12.ResultsBivariate analysis showed that RCI responders had significantly lower baseline TJC (p = 0.0310), SJC (p = 0.0018), ESR (p = 0.0487), and CDAI (p = 0.0112) and shorter RA disease duration (p = 0.0446). Subjects were less likely to achieve LDA if they had osteoarthritis (p < 0.0001), other joint-related conditions unrelated to RA (p < 0.0001), anemia (p = 0.0132), depression (p = 0.0006), or prior or concomitant use of targeted-synthetic or biologic disease-modifying antirheumatic drugs (p < 0.0001). Multiple logistic regression analysis revealed that, of the above, only ongoing osteoarthritis (p = 0.0272) or other joint-related conditions (p = 0.0193) were significant negative predictors of RCI response.ConclusionsThese results identify specific patient characteristics that may be considered predictors of positive or negative clinical response to RCI.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-022-00429-w.

Obesity and response to biological therapy in rheumatoid arthritis: the role of body mass index and adipose tissue cytokines.

To analyse the role of body mass index (BMI) in the clinical response to biologic dis-ease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). To per-form an in-depth analysis of the pathophysiology of obesity by assessing serum adipokine levels and their potential changes according to treatment. This study involved 105 patients with RA starting tumour necrosis factor inhibitors (TNFi) or tocilizumab (TCZ). Patients were classified ac-cording to BMI as normal-weight and overweight/obesity. The clinical response to treatment was as-sessed by Clinical Disease Activity Index (CDAI) 6 months after initiation of bDMARDs. Serum adi-pokines (leptin and adiponectin) were determined using a commercial immunoassay kit in samples ob-tained before initiation of bDMARDs and after 6 months of treatment. A correlation was observed between BMI and disease activity and between BMI and serum adipokines. Sixty percent of patients achieved low disease activity (LDA)/remission: 45 patients in TNFi group (64.2%) and 18 (51.4%) in TCZ group. In TNFi group, patients who did not attain LDA/remission had a higher BMI (kg/m2) ([28.7±5.1] vs. [24.5±4.6], p=0.001) and baseline CDAI (26.3 [17.4-33.9] vs. 19.8 [14.0-28.8], p<0.03). However, no differences in BMI or baseline CDAI were observed between patients who achieved LDA after 6 months in TCZ group. Obesity influences the extent of LDA/remission in patients treated with TNFi, but not in patients treated with TCZ, probably because of underlying pathophysiological mechanisms intrinsic to the production of proinflammatory adi-pokines. Therefore, therapeutic strategies with a mechanism of action other than TNF inhibition would be more suitable for obese patients.

Neutrophil count reduction 1month after initiating tocilizumab can predict clinical remission within 1year in rheumatoid arthritis patients.

Neutropenia is a common adverse event of tocilizumab (TCZ) in rheumatoid arthritis (RA) patients; however, the association between the decrease in neutrophil counts and the TCZ clinical efficacy remains inconclusive. This study aimed to examine whether TCZ-induced neutrophil decrease at 1month predicts clinical remission within 1year. We reviewed medical records of RA patients initiating TCZ between May 2011 and September 2019 in our hospital. The Clinical Disease Activity Index (CDAI) was evaluated at baseline (before initiating TCZ) and 1, 3, 6, and 12months after administration. Clinical remission was defined when CDAI decreased ≤ 2.8. The ratio of neutrophil counts 1month after initiating TCZ to those at baseline (neutrophil ratio) was also calculated. Among 255 TCZ-treated patients, 169 with valid CDAI and neutrophil counts were enrolled (with median age of 60years and 79% females). Rheumatoid factor and anti-cyclic citrullinated peptide antibody were positive in 75% and 83%, respectively, and 56% of the patients had concomitant methotrexate (median dose: 8mg/week). Multivariate logistic regression analysis suggested baseline CDAI (odds ratio (OR) 0.96, p = 0.045), concomitant PSL (OR 0.42, p = 0.030), and the neutrophil ratio (OR 0.19, p = 0.011) as predictors of CDAI remission. Neutrophil ratio ≤ 0.8 was associated with achieving remission (Fisher's exact test, p = 0.02) with no apparent increase of severe infection. More than 20% reduction of neutrophil count 1month after initiating TCZ predicts clinical remission within 1year at an early treatment phase.

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

Background:Rheumatoid arthritis (RA) patients who fail therapy may be switched to any of the five classes of biological disease-modifying antirheumatic drugs (DMARDs) and targeted synthetic DMARDs, to meet treatment goals. Physicians may hesitate to switch between Janus Kinase inhibitors (JAKi) and interleukin-6 receptor inhibitors (IL-6Ri) since they both impact IL-6 signalling and due to limited data on switching between the two classes.Objectives:This retrospective, observational study based on the real-world Corrona RA registry aimed to describe the response in RA patients switching between IL-6Ri and JAKi.Methods:Adult RA patients who initiated either IL-6Ri or JAKi after November 2012 and had a six-month post-initiation follow-up visit were eligible. Patients in ‘Cohort A’ initiated an IL-6Ri following discontinuation of a JAKi and those in ‘Cohort B’ initiated a JAKi following discontinuation of an IL-6Ri. Disease activity measures and patient-reported outcomes (PROs) were evaluated at baseline and at six-month follow-up. Within each group, change from baseline was assessed for Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire (HAQ), pain, fatigue, tender joint count (TJC), swollen joint count (SJC), physician global assessment (MDGA), patient global assessment (PtGA) and morning stiffness duration. Proportion of patients achieving CDAI low disease activity (LDA), CDAI remission and minimal clinically important difference (MCID) for HAQ, pain, fatigue, MDGA, PtGA were assessed. Adjusted linear and logistic regression models were performed for between-group comparisons (Cohort A vs Cohort B) excluding initiators who switched therapy prior to six-month visit.Results:Cohorts A and B included 122 and 144 initiators, respectively. Patients who switched toIL-6Ri (vs JAKi) were younger (mean [SD] age, 56.2 [11.3] vs 58.9 [12.6] years), had higher baseline CDAI (23.2 [12.9] vs 20.2 [12.8]), had higher prior use of ≥2 csDMARDs (75% vs 65%), and were less likely to initiate therapy as monotherapy (44% vs 50%).In Cohort A, significant changes from baseline were observed for all continuous outcomes except HAQ and fatigue. In Cohort B, a significant improvement was observed only for patient-reported pain (Table 1).Table 1.Unadjusted Within-Group Change from Baseline to Six Months, Mean (95% CI), nOutcomesCohort A, N = 122Cohort B, N = 144CDAI-4.7 (-7.6, -1.9), 109-2.4 (-5.2, 0.4), 116HAQ-0.0 (-0.1, 0.1), 105-0.1 (-0.1, 0.0), 118Patient-reported pain-8.2 (-13.4, -3.0), 109-5.9 (-11.5, -0.2), 120Patient-reported fatigue-4.4 (-9.0, 0.2), 109-1.7 (-6.6, 3.3), 117TJC-1.6 (-3.0, -0.1), 112-1.2 (-2.6, 0.3), 117SJC-1.5 (-2.5, -0.4), 112-0.4 (-1.3, 0.6),117MDGA-10.9 (-15.6, -6.3), 112-4.3 (-8.7, 0.2), 117PtGA-6.0 (-11.2, -0.8), 109-4.8 (-10.5, 0.8), 120Morning stiffness durationa-1.3 (-2.2, -0.5), 109-0.1 (-1.1, 0.8), 118aAmong those reporting morning stiffness at baseline.In the adjusted between-group comparison (data not shown) of change from baseline, there were no significant differences in clinical outcomes between Cohorts A and B.In both cohorts, patients achieved CDAI LDA, CDAI remission, and MCIDs across other PROs (Figure 1). In the adjusted between-group comparison (data not shown), the results were similar with the exception of achievement of CDAI LDA among patients with moderate to high disease activity at baseline.Figure 1.Rates of CDAI LDA, CDAI Remission, and MCID for PROsa at Six MonthsConclusion:In general, in both cohorts a substantial proportion of patients achieved CDAI LDA and MCID across PROs. Despite some overlap of JAKi and IL-6Ri therapies’ on the IL-6 pathway, there are some distinct mechanisms of action which may result in meaningful improvements for a subset of patients.Acknowledgements:Amy Praestgaard (Sanofi) contributed to the interpretation of the statistical analysis for this abstract. Medical writing support for this abstract was provided by Nupur Chaubey (Sanofi).Disclosure of Interests:Anisha Dua Speakers bureau: AbbVie, Consultant of: Consulting/advisory board for AbbVie, Novartis, and Chemocentryx, Employee of: Board member of Vasculitis foundation and Chicago Rheumatism Society, Kerri Ford Shareholder of: Sanofi, Employee of: Sanofi, Stefano Fiore Shareholder of: Sanofi, Employee of: Sanofi. In addition, Stefano Fiore has a patent EP 19306553.9; USPTO #s 62/799,698; 62/851,474; 62/935,395 issued, Dimitrios A Pappas Shareholder of: Corrona LLC, Consultant of: Sanofi, AbbVie, Gtech, Roche Hellas, and Novartis, Employee of: Corrona LLC. Board of directors, Corrona Research Foundation, Judson Janak: None declared, Taylor Blachley: None declared, Carla Roberts-Toler: None declared, Kelechi Emeanuru: None declared, Joel Kremer Consultant of: AbbVie, Lilly, Novartis, Pfizer, BMS, Genentech, Regeneron, Sanofi, and Corrona, Grant/research support from: AbbVie, Lilly, Novartis, and Pfizer, Alan Kivitz Shareholder of: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc., and Novartis, Speakers bureau: Celgene, Merck, Lilly, Novartis, Pfizer, Sanofi, Flexion, and AbbVie, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc. In addition, Alan Kivitz reports other from Altoona Center for Clinical Research, PC, during the conduct of the study.

Durability of Response to Tocilizumab Therapy in Rheumatoid Arthritis: Data from the US-Based Corrona Rheumatoid Arthritis Registry.

IntroductionUnderstanding the durability of response to treatment and factors associated with failure to maintain response in a real-world setting can inform treatment decisions for patients with rheumatoid arthritis (RA). The aim of this study was to analyze durability of response to tocilizumab (TCZ) and factors associated with durability among US patients with RA in routine clinical practice. MethodsTCZ initiators in the Corrona RA Registry were included. Durability of response was defined as maintaining continuous TCZ treatment and either an improvement of at least minimum clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) score or low disease activity (LDA). Secondary analyses included patients treated with intravenous (IV) TCZ and excluded those who discontinued TCZ without reporting reasons for discontinuation. Durability was calculated with Kaplan–Meier survival analysis. Cox proportional hazards modeling identified factors associated with durability.ResultsAmong 1789 TCZ initiators, 466, 272, and 162 were persistent (with or without durable response) with follow-up visits at 1, 2, and 3 years, respectively. Median MCID durability of response in CDAI was > 50% after 36 months overall, 26 months for TCZ-IV, and > 50% after 36 months for those with known reasons for discontinuation; longer durability was associated with increased duration of RA and higher baseline CDAI score and shorter durability with history of malignancy and history of diabetes. Median LDA durability of response was 13.0 months overall, for TCZ-IV, and for those with known reasons for discontinuation; shorter durability was associated with history of malignancy, history of diabetes, and higher baseline CDAI score.ConclusionsMedian durability of response to TCZ in RA was > 3 years when defined as maintenance of MCID in CDAI score and > 1 year with the more stringent criteria of maintenance of LDA.Trial RegistrationClinicalTrials.gov identifier, NCT01402661

Higher Checkpoint Inhibitor Arthritis Disease Activity may be Associated With Cancer Progression: Results From an Observational Registry.

ObjectiveTo describe clinical features associated with cancer outcomes of patients with immune checkpoint inhibitor (ICI)‐associated arthritis.MethodsObservational study of patients with ICI‐arthritis enrolled in a single‐center registry. Arthritis phenotype and activity, medications, and cancer status were recorded at every visit. We used descriptive statistic, and Kaplan‐Meier curves using two‐sided log‐rank test and Cox regression analysis were used to identify factors associated with cancer progression‐free survival (PFS).ResultsForty‐two patients with ICI‐arthritis were followed for a median (interquartile range [IQR]) of 7.4 (1.7, 14.7) months. Fifty‐seven percent were female, 33% had melanoma, and 69% received anti–programmed death ligand 1 monotherapy. Median time from ICI initiation to arthritis onset was 2.8 (0.8, 11.2) months. Sixty‐two percent had a rheumatoid arthritis (RA)‐like small‐joint presentation; 27% of all patients were rheumatoid factor and/or cyclic citrullinated peptide positive. Median (IQR) Clinical Disease Activity Index (CDAI) on presentation was 15 (8, 24); 62% required systemic glucocorticoids, 55% required disease‐modifying antirheumatic drugs (DMARDs), and 69% had ongoing arthritis at 6 months. Arthritis led to ICI discontinuation in five patients. In univariate analysis, baseline CDAI, DMARD use, earlier arthritis onset, and longer duration of follow‐up were associated with shorter PFS. In multivariable Cox regression analysis controlling for DMARD use and time to arthritis onset, CDAI was a significant predictor of cancer progression (hazard ratio 1.09, 95% confidence interval [CI] 1.00‐1.19, P = 0.05)ConclusionICI‐arthritis most commonly presents with an RA‐like phenotype. High disease activity, as measured by CDAI, may portend cancer progression.

Effect of disease duration and other characteristics on efficacy outcomes in clinical trials of tocilizumab for rheumatoid arthritis.

ObjectiveTo determine the extent to which disease duration, alone or in combination with other baseline clinical and non-clinical factors, explains variations in outcome of tocilizumab initiated in biologic-naïve patients with established RA.MethodsIn this pooled analysis of phase 3 and 4 clinical trials conducted by the sponsor, predictors of response, including demographics, disease characteristics at baseline (start of tocilizumab dosing) and study characteristics (e.g. patient inclusion criteria, tocilizumab dosing regimen) were evaluated. Response was measured as change from baseline to week 24 in Clinical Disease Activity Index (CDAI) and HAQ–Disability Index (HAQ-DI) scores and as the proportions of patients who experienced ≥50% improvement based on ACR criteria (ACR50) and CDAI remission (≤2.8) rates at week 24.ResultsImprovements in all outcomes investigated were observed in patients receiving tocilizumab. Although disease duration was statistically significant in the models, it accounted for <2% of variation in CDAI and HAQ-DI score changes from baseline to week 24; baseline CDAI and HAQ-DI values accounted for 32% and 15% of variations, respectively. Doubling of disease duration reduced the odds of achieving an ACR50 response by only 9%, and each additional 5-year period of disease duration decreased the odds of achieving CDAI remission by only 15%.ConclusionRA duration, alone or in combination with other baseline characteristics, had a statistically significant but clinically small effect on the outcomes of tocilizumab initiated in biologic-naïve patients with established RA.

Comparative effectiveness of first-line tumour necrosis factor inhibitor versus non-tumour necrosis factor inhibitor biologics and targeted synthetic agents in patients with rheumatoid arthritis: results from a large US registry study

ObjectivesThis study evaluated the comparative effectiveness of a tumour necrosis factor inhibitor (TNFi) versus a non-TNFi (biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs)) as the first-line treatment...

Patient adherence with a smartphone app for patient-reported outcomes in rheumatoid arthritis.

Electronic patient-reported outcomes (ePROs) transmitted digitally allow patients to communicate with their clinicians and track the activity of chronic diseases, such as RA. Several ePRO smartphone apps have been developed in rheumatology, yet few data have been reported regarding patient adherence. We developed a PRO app for RA and assessed adherence over 6 months. We developed an app to deliver daily assessments to participants (RA App v.1.0). The app was tested as part of a randomized controlled trial examining potential clinical benefits. The current analyses focus on the adherence to the ePRO app for patients randomized to receive the app. We recruited RA patients from an academic rheumatology practice in the USA. Patients randomized to receive the app received daily notifications regarding ePROs. We examined adherence to the PRO questionnaires over the 6-month study and examined factors related to adherence. Seventy-eight patients received the app and have data included in these analyses: 63 (80.7%) were female, mean age was 55.2 years, 71% had attended college or beyond, and the mean Clinical Disease Activity Index at baseline was 9.7 (low disease activity). Median adherence to the daily questions was 79% (interquartile range 48-90%). Significant predictors of increased adherence were age ≥65 (P = 0.03) and low baseline Clinical Disease Activity Index (P = 0.02). We developed and tested an ePRO app for RA over a 6-month study. Adherence to the app was strong. There was correlation between older age and better disease control and increased adherence. ClinicalTrials.gov, https://clinicaltrials.gov/, NCT02822521.

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

Background: Rheumatoid arthritis (RA) patients who achieve a response to therapy but fail to reach low disease activity (LDA) or remission (partial responders) may decline treatment changes for fear of clinical worsening and losing their achieved response. Little is known about the likelihood of worsening after switching therapy in partial responders, and this limits patients’ ability to make informed treatment decisions. Objectives: This post hoc analysis of the open-label extension (OLE) of MONARCH (NCT02332590) assesses the effects of switching from adalimumab to sarilumab in patients with RA who achieved a partial response to adalimumab but not remission or LDA. Methods: MONARCH was a 24-week, head-to-head monotherapy trial comparing sarilumab with adalimumab. At study end, patients randomized to adalimumab were switched to sarilumab 200 mg q2w for the OLE. Partial responders to adalimumab were defined as patients who had improved more than the minimal clinically important difference (MCID) in the Clinical Disease Activity Index (CDAI) during MONARCH, but who continued to have moderate to high disease activity (CDAI >10) at OLE baseline (BL). MCID was defined as a CDAI decrease ≥12 from a BL CDAI >22 or ≥6 from a BL CDAI >10 to ≤22. Response following treatment switch was assessed by change in CDAI and other outcomes from OLE BL to OLE Week 24. The effect of switching was analyzed descriptively and categorized: worsening = CDAI increase ≥6; improvement = CDAI decrease ≥6; stable = CDAI absolute change Results: Of 369 patients enrolled in MONARCH, 320 (87%) entered the OLE; 155 were switched from adalimumab to sarilumab, and of these, 91 were partial responders, who had a mean (SE) CDAI at OLE BL of 19.56 (0.86). Mean (SE) improvement in CDAI from OLE BL to OLE Week 24 in these patients was 7.37 (1.10). At OLE Week 24, only 6% of adalimumab partial responders had worsened after switching to sarilumab, while 57% had improved; the remaining 37% maintained stable disease activity. Analyses of other efficacy measures—patient and physician global assessments, disease activity score 28-joint erythrocyte sedimentation rate, and swollen and tender joint counts—demonstrated similar results: improvement was seen in 27–78% and worsening in 2–17%. No new safety signals emerged during the OLE. The adverse event profile among patients switching from adalimumab to sarilumab was consistent with the established safety profile of sarilumab. Conclusion: Among adalimumab CDAI partial responders who switched to sarilumab, there was a low likelihood of clinical worsening, while more than half of such patients achieved clinically meaningful improvement. Similar results were observed for other efficacy measures. This small risk of worsening coupled with the substantial likelihood of improvement after switch may help alleviate patients’ concerns around loss of response and help inform shared decision-making. Acknowledgments: Study funding and medical writing support (Gregory Bezkorovainy, Adelphi Communications, New York) were provided by Sanofi Genzyme (Cambridge, USA) and Regeneron Pharmaceuticals, Inc. (Tarrytown, USA) in accordance with Good Publication Practice (GPP3) guidelines. Amy Praestgaard (Sanofi Genzyme employee) contributed to the statistical analysis for this abstract. Disclosure of Interests: Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Lilly, Myriad, Pfizer, Regeneron, Roche, UCB, Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB, Gerd Rudiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Kerri Ford Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, Hubert van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, Henry Leher Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., Karthinathan Thangavelu Shareholder of: Sanofi Genzyme, Employee of: EMD Serono, Sanofi Genzyme, Vivian Bykerk: None declared

Methotrexate Discontinuation and Dose Decreases After Therapy With Tocilizumab: Results From the Corrona Rheumatoid Arthritis Registry.

IntroductionSimilar outcomes have been observed between patients with rheumatoid arthritis (RA) responding to tocilizumab (TCZ) with methotrexate (MTX) who discontinued vs. continued MTX and between patients receiving MTX who added TCZ vs. switched to TCZ monotherapy. This study examined MTX discontinuation and dose decreases in patients with RA initiating TCZ in a real-world setting.MethodsTCZ-naïve patients enrolled in the Corrona RA registry who initiated TCZ in combination with MTX and had a 6-month follow-up visit without TCZ discontinuation were included. Patients were grouped by MTX dose at the time of TCZ initiation (≤ 10 mg, > 10 to ≤ 15 mg, > 15 to ≤ 20 mg, > 20 mg). The primary outcome was the proportion of patients with changes in MTX use at 6 months, with a secondary analysis at 12 months. Changes in disease activity [Clinical Disease Activity Index (CDAI)] and patient-reported outcomes (PROs) at 6 and 12 months were summarized descriptively.ResultsOf 444 included patients, 82.7% were female and 83.7% white, with mean (SD) disease duration of 11.6 (9.3) years, baseline CDAI score of 24.0 (15.4), and baseline MTX dose of 17.7 (5.8) mg. At 6 months, 139 patients (31.3%) discontinued or decreased their MTX dose. All MTX dose groups and patients who discontinued, decreased, maintained, or increased their MTX dose displayed improvements in CDAI scores and PROs at 6 months. Similar patterns and results were observed at 12 months.ConclusionsA considerable proportion of patients initiating TCZ discontinued or decreased their MTX dose after TCZ initiation. Improvements in disease activity and functionality were observed in patients who decreased or stopped MTX. This real-world study confirmed prior observations that discontinuing or decreasing MTX may be a treatment strategy for patients initiating TCZ combination therapy.Trial RegistrationClinicalTrials.gov identifier, NCT01402661.