Clinical Disease Activity Index Low Disease Activity Research Articles

Real-world experience with filgotinib for rheumatoid arthritis in Germany : Aretrospective chart review.

Real-world data for filgotinib, aJanus kinase (JAK)1 inhibitor, are limited in patients with rheumatoid arthritis (RA). To explore real-world filgotinib use in patients with RA in Germany. This retrospective chart review included patients aged ≥ 18years with confirmed moderate to severe RA who initiated filgotinib before December1, 2021, with ≥ 6months of medical records available prior to filgotinib initiation or after initial diagnosis. Patient characteristics, prior treatments, reasons for initiating/discontinuing filgotinib, disease activity, dose adjustments and concomitant treatments were recorded. In total, 301 patients from 20 German rheumatology outpatient units were included. One-third were aged ≥ 65years and almost half had ≥ 1 cardiovascular (CV) risk factor. Most patients initiated filgotinib as monotherapy (83.7%; 12.7% of whom with glucocorticoids) and at the 200 mg dose (84.7%); higher proportions of those initiating the 100 versus 200 mg dose were aged ≥ 65years and had renal impairment or ≥ 1 CV risk factor. Oral administration (78.4%), fast onset of action (66.8%) and administration as monotherapy (65.4%) were the most common reasons for initiating filgotinib. At 12months, 41 (18.4%) patients had discontinued filgotinib, most commonly due to lack of effectiveness. After 6‑months of follow-up, 36.8% of patients had achieved Clinical Disease Activity Index (CDAI) remission and 45.6% had achieved CDAI low disease activity. In clinical practice in Germany, reasons for initiating filgotinib in patients with RA were related to dosing flexibility and general JAK inhibitor attributes. Filgotinib was used predominantly as monotherapy and was effective and generally well tolerated; however, longer-term data in larger, prospective cohorts are needed.

Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept

BackgroundTo compare a treat-to-target (T2T) approach and routine care (RC) in adults with active to severely active rheumatoid arthritis (RA) initiating subcutaneous abatacept.MethodsA 12-month cluster-randomized trial in active RA patients treated with abatacept was conducted. Physicians were randomized to RC or T2T with a primary endpoint of achieving sustained Clinical Disease Activity Index (CDAI) low disease activity (LDA) at two consecutive assessments approximately 3 months apart. Additional outcomes included Simple Disease Activity Index (SDAI), Disease Activity Score 28-CRP (DAS28-CRP), Routine Assessment of Patient Index Data 3 (RAPID3), and the Health Assessment Questionnaire-Disability Index (HAQ-DI). Time to achieve therapeutic endpoints was assessed with survival analysis.ResultsAmong the 284 enrolled patients, 130 were in the T2T group and 154 in RC. Primary endpoint was achieved by 36.9% and 40.3% of patients in T2T and RC groups, respectively. No significant between-group differences were observed in the odds of achieving secondary outcomes, except for a higher likelihood of CDAI LDA in the T2T group vs. RC (odds ratio [95% confidence interval]: 1.33 [1.03–1.71], p = 0.0263). Compared with RC, patients in the T2T group achieved SDAI remission significantly faster (Kaplan–Meier-estimated mean [standard error]: 14.0 [0.6] vs. 19.3 [0.8] months, p = 0.0428) with a trend toward faster achievement of CDAI LDA/remission, DAS28-CRP remission, and HAQ-DI minimum clinically important difference.ConclusionsPatients managed per T2T and those under RC experienced significant improvements in RA disease activity at 12 months of abatacept treatment. T2T was associated with higher odds of CDAI LDA and a shorter time to achieving therapeutic endpoints.Trial registrationName of the registry: ClinicalTrials.gov.Trial registrations: NCT03274141.Date of registration: September 6, 2017.

Systematic Literature Review of Real-World Evidence on Baricitinib for the Treatment of Rheumatoid Arthritis.

Baricitinib, an orally available small-molecule inhibitor of Janus kinase (JAK)1 and JAK2, is indicated to treat active moderate-to-severe rheumatoid arthritis (RA). This systematic review described the real-world clinical characteristics of baricitinib-treated patients with RA, prescription patterns, effectiveness, drug persistence, patient-reported outcomes (PROs; physical function, pain, health-related quality of life [HRQoL]), patient global assessment (PGA), and safety of baricitinib. A PRISMA systematic review of real-world studies was conducted to identify relevant literature published between January 2016 and September 2022 using MEDLINE®, EMBASE®, and evidence-based medicine review databases. Websites or online repositories of the American College of Rheumatology and the European Alliance of Associations for Rheumatology were searched manually to include relevant abstracts from conferences held between January 2016 and November 2022. A total of 11,472 records were identified by searching online databases. Seventy studies were included in the study, of which 40 were abstracts. Most patients were older (51-71 years), female, and with mean RA duration of 4-19 years. Baricitinib was mostly used after the failure of one or more bDMARDs, and 4 mg dosing was prevalent in patients with RA (range 22-100%). Clinical effectiveness of baricitinib was reported in real-world settings regardless of prior biologic/targeted synthetic disease-modifying antirheumatic drug (DMARD) use and concomitant conventional synthetic DMARD use. Achievement of Clinical Disease Activity Index (CDAI) remission was reported in 8.7-60% of patients at week 12 and CDAI low disease activity (LDA) in 20.2-81.6% at week 24. The proportion of patients attaining Simple Disease Activity Index (SDAI) remission was reported in 12% at week 4 to 45.4% at 24 weeks. Drug persistence was high, similar, or equal to anti-tumor necrosis factor drugs. No new safety signals were identified. Baricitinib demonstrated effectiveness in the real-world setting with a consistent safety profile observed in clinical studies. Better persistence rates for baricitinib compared to bDMARDs with improvement in PROs were reported, although baricitinib-treated patients had RA with poor prognostic characteristics.

Anti-GM-CSF otilimab versus tofacitinib or placebo in patients with active rheumatoid arthritis and an inadequate response to conventional or biologic DMARDs: two phase 3 randomised trials (contRAst 1 and contRAst 2)

ObjectivesTo investigate the efficacy and safety of otilimab, an antigranulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis.MethodsTwo phase 3, double-blind randomised controlled trials including patients with inadequate responses...

Real-World Sarilumab Use and Rule Testing to Predict Treatment Response in Patients with Rheumatoid Arthritis: Findings from the RISE Registry.

Clinical trial findings may not be generalizable to routine practice. This study evaluated sarilumab effectiveness in patients with rheumatoid arthritis (RA) and tested the real-world applicability of a response prediction rule, derived from trial data using machine learning (based on C-reactive protein [CRP] > 12.3mg/l and seropositivity [anticyclic citrullinated peptide antibodies, ACPA +]). Sarilumab initiators from the ACR-RISE Registry, with ≥ 1 prescription on/after its FDA approval (2017-2020), were divided into three cohorts based on progressively restrictive criteria: Cohort A (had active disease), Cohort B (met eligibility criteria of a phase3 trial in RA patients with inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi]), and CohortC (characteristics matched to the phase3 trial baseline). Mean changes in Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) were evaluated at 6 and 12months. In a separate cohort, predictive rule was tested based on CRP levels and seropositive status (ACPA and/or rheumatoid factor); patients were categorized into rule-positive (seropositive with CRP > 12.3mg/l) and rule-negative groups to compare the odds of achieving CDAI low disease activity (LDA)/remission and minimal clinically important difference (MCID) over 24weeks. Among sarilumab initiators (N = 2949), treatment effectiveness was noted across cohorts, with greater improvement noted for Cohort C at 6 and 12months. Among the predictive rule cohort (N = 205), rule-positive (vs. rule-negative) patients were more likely to reach LDA (odds ratio: 1.5 [0.7, 3.2]) and MCID (1.1 [0.5, 2.4]). Sensitivity analyses (CRP > 5mg/l) showed better response to sarilumab in rule-positive patients. In real-world setting, sarilumab demonstrated treatment effectiveness, with greater improvements in the most selective population, mirroring phase 3 TNFi-refractory and rule-positive RA patients. Seropositivity appeared a stronger driver for treatment response than CRP, although optimization of the rule in routine practice requires further data.

P128 Long-term safety and efficacy of upadacitinib in patients with rheumatoid arthritis: final results from the BALANCE-EXTEND open-label extension study

Abstract Background/Aims Upadacitinib (UPA) was previously evaluated in two Phase 2, randomized, controlled trials (RCTs) in patients (pts) with rheumatoid arthritis (RA) and inadequate response to tumor necrosis factor inhibitors (BALANCE-1) or methotrexate (BALANCE-2). Objectives: To assess the final safety and efficacy of UPA in BALANCE-EXTEND, a 312-week open-label extension (OLE) enrolling pts who completed either BALANCE1 or BALANCE-2. Methods All pts initially received UPA 6 mg twice daily (BID). Increase to 12 mg BID was required for pts with <20% improvement in swollen or tender joint counts (S/TJC) at Week 6 or 12, and permitted for those not achieving Clinical Disease Activity Index (CDAI) low disease activity (LDA). Pts with <20% improvement in SJC or TJC 6 weeks after escalation, or at any two consecutive visits, discontinued. Return to 6 mg BID was permitted for safety or tolerability reasons. After January 2017, the 6 and 12 mg BID doses were replaced by 15 and 30 mg once-daily (QD) extended-release equivalents. As-observed efficacy data are shown at Week 312 for three subgroups: pts who received 6 mg BID/15 mg QD throughout (“Never titrated”), those titrated up to 12 mg BID/30 mg QD for efficacy (“Titrated up”), and those titrated up to 12 BID/30 mg QD and then back to 6 mg BID/15 mg QD due to safety concerns (“Titrated up and down”). Exposure-adjusted adverse events (EAERs) per 100 patient-years (PY) of exposure were summarized from OLE Day 1 in all pts who received UPA (Any UPA). Results Overall, 493 pts entered the OLE, receiving UPA for ≤6.2 years (Never titrated, n = 306; Titrated up, n = 149; Titrated up and down, n = 38), and 270 pts (54.8%) discontinued, mostly due to withdrawal of consent (16.8%; n = 83) or AEs (14.6%; n = 72). Mean (standard deviation) duration of UPA exposure was 3.8 (2.4) years (range <1-6.2 years); cumulative exposure was 1863 PY. The AE profile in pts receiving UPA 15 mg was generally similar to the Any UPA population, and to that observed in the Phase 3 UPA 15 mg clinical trial population. Efficacy was maintained to Week 312, with 84.5% and 86.6% of pts in the Never titrated group achieving DAS28-CRP ≤3.2 and CDAI LDA, respectively. Conclusion In this OLE, UPA treatment over ∼312 weeks showed sustained long-term efficacy in pts with RA who had completed Phase 2 RCTs. Overall safety results showed that UPA was well tolerated over time; the types and frequencies of AEs were consistent with those in pts with similar populations of moderately to severely active RA receiving Janus kinase inhibitors. Disclosure A. Kivitz: Consultancies; A Kivitz has received consulting fees and/or honoraria from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly and Company, Flexion, Genzyme, Gilead, Horizon, Janssen, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sanofi Aventis, SUN Pharma Advanced Research, and UCB. Shareholder/stock ownership; A Kivitz owns stocks or options in Amgen, Gilead, GlaxoSmithKline, Novartis, Pfizer, and Sanofi. Honoraria; A Kivitz has received honoraria from AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly and Company, Flexion, Genzyme, Gilead, Horizon, Janssen, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sanofi Aventis, SUN Pharma Advanced Research, and UCB. Grants/research support; A Kivitz's institution received fees from AbbVie for his role as a Principal Investigator in the study. A.F. Wells: Consultancies; AF Wells has received consulting fees from AbbVie. J.I. Vargas: Honoraria; JI Vargas has received honoraria from AbbVie. Grants/research support; JI Vargas has received fees from AbbVie as Principal Investigator in the study. H.S.B. Baraf: Consultancies; HSB Baraf has acted as a consultant for Gilead and Janssen. Grants/research support; HSB Baraf has received grant/research support from AbbVie, Eli Lilly, Genentech, Gilead, and Janssen. M. Rischmueller: Consultancies; M Rischmueller has acted as a consultant for AbbVie, Bristol-Myers Squibb, CSL Behring, Eli Lilly, Gilead Sciences, Janssen Global Services, Pfizer, Sanofi US Services, and UCB Biosciences. Grants/research support; M Rischmueller has received grant/research support from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen Global Services, Novartis, Pfizer, Sanofi Pasteur Biologics, and UCB Biosciences. J. Klaff: Shareholder/stock ownership; J Klaff is employee of AbbVie and may own stocks or options. N. Khan: Shareholder/stock ownership; N Khan is an employee of AbbVie and may own stocks or options. Y. Li: Shareholder/stock ownership; Yihan Li is an employee of AbbVie and may own stocks and options. K. Carter: Shareholder/stock ownership; K Carter is an employee of AbbVie and may own stocks and options. A. Friedman: Shareholder/stock ownership; A Friedman is an employee of AbbVie and may own stocks and options. P. Durez: Corporate appointments; P Durez has received speaker fees from Eli Lilly and Galapagos.

Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate.

The objective of this analysis was to assess disease activity metrics using a variety of disease outcome measures following methotrexate (MTX) withdrawal in ORAL Shift, a phase 3b/4 study of tofacitinib with/without MTX, in patients with rheumatoid arthritis (RA) achieving Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA). Patients aged ≥ 18years with active RA and an inadequate response to MTX received open-label tofacitinib modified-release 11mg once daily plus MTX for 24weeks. In the double-blind MTX withdrawal phase, those who had achieved CDAI LDA (≤ 10) at week 24 were randomised 1:1 to receive tofacitinib monotherapy or continued tofacitinib plus MTX. Efficacy analyses were performed in subgroups defined by whether remission and/or LDA had been achieved at week 24 with: Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)], Routine Assessment of Patient Index Data 3 (RAPID3), CDAI and Simplified Disease Activity Index (SDAI); or DAS28-4[C-reactive protein(CRP)] < 2.4/ < 2.6/ < 2.9/ ≤ 3.2. Five hundred and thirty patients received treatment in the double-blind MTX withdrawal phase. Proportions of patients achieving each disease activity criterion at week 24 varied by metric. Across disease activity metrics [excluding DAS28-4(ESR) remission], 58-89% of patients per group, and numerically more patients receiving tofacitinib plus MTX, achieved the same criterion at week 48 as at week 24. Differences between groups in least squares mean change from baseline (Δ) DAS28-4(ESR) from week 24-48 favoured tofacitinib plus MTX (nominal pvalues < 0.05). RAPID3 and DAS28-4(CRP) estimated a higher proportion of patients with acceptable disease state versus DAS28-4(ESR), CDAI remission and SDAI remission. Response rates at the beginning of the double-blind phase varied across metrics. A consistent trend towards higher response rates with tofacitinib plus MTX was observed across metrics after randomisation, with nominal differences in DAS28-4(ESR) responses. Compared with continued combination therapy, MTX withdrawal did not lead to a clinically meaningful reduction in the response to tofacitinib. DAS28-4(CRP) and RAPID3 were the least stringent metrics. ClinicalTrials.gov identifier: NCT02831855.

POS0677 CONSISTENCY IN TIME TO RESPONSE WITH UPADACITINIB AS MONOTHERAPY OR COMBINATION THERAPY AND ACROSS PATIENT POPULATIONS WITH RHEUMATOID ARTHRITIS

BackgroundUpadacitinib (UPA) has demonstrated efficacy in patients with moderate-to-severe rheumatoid arthritis (RA) across various patient populations.1–4ObjectivesThis post hoc analysis aimed to evaluate the consistency in time to achieving meaningful clinical response with UPA 15 mg + conventional synthetic (cs) DMARDs in biologic (b) DMARD-inadequate responder (IR) versus csDMARD-IR patients with RA as well as with UPA 15 mg monotherapy versus UPA 15 mg + csDMARDs in csDMARD-IR patients.MethodsPatients originally randomized to UPA 15 mg once daily from four Phase 3 trials were included in this analysis: SELECT-BEYOND1 and SELECT-CHOICE2 (UPA 15 mg + csDMARDs in bDMARD-IR patients), SELECT-NEXT3 (UPA 15 mg + csDMARDs in csDMARD-IR patients), and SELECT-MONOTHERAPY4 (UPA 15 mg monotherapy in methotrexate-IR patients). Time to response was estimated using the Kaplan–Meier method for clinical outcomes over 24 weeks (26 weeks in SELECT-MONOTHERAPY). Clinical outcomes included achievement of 28-joint Disease Activity Score with C-reactive protein (DAS28[CRP]) ≤3.2; low disease activity (LDA) defined as Clinical Disease Activity Index (CDAI) ≤10 and Simple Disease Activity Index (SDAI) ≤11; and 50% improvement in American College of Rheumatology (ACR) core components and morning stiffness (MS) duration/severity. Data presented were as observed.ResultsOverall, 905 patients were included (SELECT-BEYOND: n=164; SELECT-CHOICE: n=303; SELECT-NEXT: n=221; SELECT-MONOTHERAPY: n=217). csDMARD-IR patients had a mean disease duration of 7.3 (SELECT-NEXT) or 7.5 years (SELECT-MONOTHERAPY); bDMARD-IR patients had a mean disease duration of 12.4 years, with a more refractory population (≥3 prior bDMARDs) in SELECT-BEYOND (23%) than SELECT-CHOICE (10%). In general, the median time to DAS28(CRP) ≤3.2, CDAI LDA, 50% improvement in ACR core components, and 50% improvement in MS duration/severity were consistent across the studies in bDMARD-IR and csDMARD-IR patients. For SELECT-BEYOND, SELECT-CHOICE, SELECT-NEXT, and SELECT-MONOTHERAPY, the median (95% CI) time to achieve DAS28(CRP) ≤3.2 was 12 (12, 16), 12 (8, 12), 12 (8, 12), and 14 (8, 14) weeks, respectively (Figure 1), and the median time to achieve CDAI LDA was 20 (12, 24), 16 (12, 16), 16 (12, 16), and 20 (14, 20) weeks, respectively (Figure 2). A longer median (95% CI) time to achieve SDAI LDA was observed with UPA monotherapy (20 [14, 20] weeks) versus UPA + csDMARDs (12 [12, 16] weeks) in csDMARD-IR patients. Among bDMARD-IR patients, the median (95% CI) time to 50% improvement in pain was longer in SELECT-BEYOND versus SELECT-CHOICE (16 [12, 20] versus 8 [8, 12] weeks).ConclusionIn diverse patient populations with RA, patients treated with UPA 15 mg, as monotherapy or with csDMARDs, generally demonstrated consistent time to achieving DAS28(CRP) ≤3.2, CDAI LDA, and 50% improvement in clinical outcomes.

Impact of multimorbidity on disease modifying antirheumatic drug therapy in early rheumatoid arthritis: Data from the ESPOIR cohort.

Multimorbidity is frequent in rheumatoid arthritis (RA) and could interfere with the therapeutic response. The aim of this study was to evaluate multimorbidity in the French cohort of early arthritis, the ESPOIR cohort, and its possible impact on the therapeutic response. We included patients fulfilling 2010 ACR/EULAR criteria for RA. An adapted MultiMorbidity Index (aMMI) was developed. Each patient was assigned scores of binary aMMI (0=no comorbidity, 1=at least 1 comorbidity) and counted and weighted aMMI. The primary endpoint was achievement of Clinical Disease Activity Index (CDAI) low disease activity after initiation of a first disease-modifying antirheumatic drug (DMARD) according to the aMMI. We collected data from the visit preceding the first DMARD initiation and the visit after at least 3 months of treatment. The impact of aMMI on therapeutic maintenance at 1, 3, 5 and 10 years was evaluated. Analyses involved 472 patients: 302 (64%) had at least 1 comorbidity. Overall, 45.3% and 44.7% with binary aMMI=0 or 1, respectively (non-significant), achieved CDAI low disease activity. Similar results were found with counted and weighted aMMI. Therapeutic maintenance was significantly better with binary aMMI=1 than binary aMMI=0 (OR at 10 years=14.0 [CI 95% 3.3-59.4]). Increased counted aMMI was associated with increased probability of still being on the first initiated DMARD at each time point. In the ESPOIR cohort, therapeutic response to a first DMARD was not affected by multimorbidity but therapeutic maintenance was better in multimorbid patients.

Physician- and Patient-reported Effectiveness Are Similar for Tofacitinib and TNFi in Rheumatoid Arthritis: Data From a Rheumatoid Arthritis Registry.

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.

The Aftermath of Tapering Tocilizumab After Achieving Treatment Target in Patients With Rheumatoid Arthritis: A Nationwide Cohort Study.

BackgroundAlthough recent guidelines recommend that tapering of biologic disease-modifying anti-rheumatic drugs (bDMARDs) can be considered in patients with rheumatoid arthritis (RA), there has been little evidence supporting the strategy during the non-tumor necrosis factor inhibitor treatment. This study aims to investigate the effectiveness and safety of tapering tocilizumab (TCZ) dose in patients with RA who attain low disease activity (LDA) after TCZ therapy in a nationwide cohort.MethodsData were collected from a nationwide cohort of patients with RA receiving biologic disease-modifying anti-rheumatic drugs in South Korea (KOBIO-RA). This study included 350 patients who were treated with TCZ and achieved Clinical Disease Activity Index-low disease activity (CDAI)-LDA (CDAI ≤ 10) after 1 year of treatment. We performed longitudinal analysis considering clinical data measured at all 1-year intervals for the included patients using the generalized estimating equation. A total of 575 intervals were classified into two groups according to their dose quotient (DQ) of TCZ (tapering group vs. standard-dose group). The main outcome was maintaining CDAI-LDA in the following 1-year interval.ResultsTapering TCZ dose strategy was used in 282 (49.0%) intervals with a mean (SD) DQ of 66.0 (15.5) %. Loss of CDAI-LDA occurred in 91 (15.1%) intervals. Multivariable GEE showed that the tapering group was associated with more frequent failure to sustain CDAI-LDA (adjusted OR [95% CI]: 0.57 [0.33–0.99]), which subsequently led to impaired functional status. The likelihood of achieving DAS28-deep remission (DAS28-ESR <1.98) was also significantly lower in the tapering group (adjusted OR 0.68 [0.46–0.99]). CDAI remission was achieved in only 69 (12.0%) of the total intervals, with no significant difference in the proportion of intervals achieving the target between the two groups. Incidence of adverse events was comparable in both groups except for hypercholesterolemia, which was lower in the tapering group.ConclusionsTapering TCZ dose after achieving LDA increases the risk of losing LDA without a significant merit in safety.

Differential influence of Clinical Disease Activity Index components based on disease state in rheumatoid arthritis patients: real-world results from the Ontario Best Practices Research Initiative.

The Clinical Disease Activity Index (CDAI) is routinely used in clinical care when treating-to-target RA patients. Previous validation studies have looked at CDAI's overall performance; this analysis aimed at evaluating its properties by disease state and identifying drivers of variance. RA patients enrolled in the OBRI registry, with available follow-up of ≥6 months were included. Construct validity of CDAI was assessed with principal component analysis; internal consistency with Cronbach's alpha (α); correlational validity with Spearman's rho (ρ); agreement in disease state classification with the kappa statistic. Stratification by disease states was performed. CDAI correlation with DAS28 was strong when CDAI>10 (ρ=0.79), moderate when CDAI≤10 (ρ=0.56) or 2.8<CDAI≤10 (ρ=0.44), and very weak when CDAI≤2.8 (ρ=0.02). Classification agreement of low disease activity (LDA)/remission between CDAI (≤10) and DAS28 (≤3.2) or HAQ-DI (≤2) was fair-to-moderate, while poor-to-fair for remission. For CDAI>10, CDAI was able to be reduced to a single component with patient global assessment (PtGA) having the lowest loading. When CDAI≤10, two distinct components were identified: (1) PtGA and physician global assessment; (2) SJC28 and TJC28. Moderate levels (α=0.71) of internal consistency were observed when CDAI>10 but low when CDAI≤10 (α=0.23), 2.8<CDAI≤10 (α=-0.42) or CDAI≤2.8 (α=-0.35). PtGA showed lowest correlation with remaining CDAI components. CDAI and DAS28 correlated well in moderate/high disease activity and poorly in LDA/remission. PtGA correlated weakly with other CDAI components and had a stronger influence on CDAI in LDA/remission. Thus, careful interpretation of PtGA is necessary when making treatment decisions, particularly in patients in CDAI LDA who are non-remitters.

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.

POS0666 TREATMENT EFFECTIVENESS OF UPADACITINIB AT 3 MONTHS IN US PATIENTS WITH RHEUMATOID ARTHRITIS FROM THE UNITED RHEUMATOLOGY NORMALIZED INTEGRATED COMMUNITY EVIDENCE (NICE[TM]) REAL-WORLD DATA

Background:Upadacitinib (UPA), an oral Janus kinase inhibitor (JAKi), has demonstrated efficacy in the phase 3 SELECT clinical program, conducted across a range of patients (pts) with rheumatoid arthritis (RA).1–6 Real-world data for UPA, including in pts previously treated with a JAKi, have not yet been reported since global approvals beginning in 2019.Objectives:To assess the characteristics of US-based pts receiving UPA and its effectiveness in clinical practice at 3 months.Methods:This observational study included US-based pts from the United Rheumatology Normalized Integrated Community Evidence (UR-NICE) database who initiated UPA 15 mg once daily from FDA approval (August 2019) to July 31, 2020 and had ≥6-month pre-baseline data available. Effectiveness was assessed in pts with a reported Clinical Disease Activity Index (CDAI) score at 3 months after UPA initiation and included proportions of pts achieving CDAI remission (≤2.8), CDAI low disease activity (≤10), other disease activity measures, and pt-reported outcomes. A subgroup analysis assessed UPA effectiveness in pts with or without prior tofacitinib (TOFA) treatment.Results:This analysis included 252 pts treated with UPA 15 mg, of whom 98 (38.9%) received UPA monotherapy and 154 (61.1%) received UPA combined with conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs). 64.3% of pts were from the Southern region of the USA. 86.1%, 72.2%, and 47.6% of pts had been previously treated with csDMARDs, biologic DMARDs, and JAKis, respectively. Baseline characteristics were largely similar between UPA monotherapy and combination therapy groups and those with or without prior TOFA treatment (Table 1). Pts with prior TOFA treatment had a longer duration of RA since diagnosis and higher steroid use versus those without. UPA 15 mg improved disease activity scores (including CDAI) and pt-reported outcomes (including physical function and pain) after 3 months of treatment (Figure 1). Similar effectiveness was observed with UPA 15 mg in pts with or without prior TOFA treatment.Conclusion:In the UR-NICE real-world database of US-based pts, improvements in clinical and pt-reported outcomes were observed at 3 months in UPA-treated pts with RA, including those with or without prior TOFA treatment, despite the treatment-refractory population included in this dataset.

Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis

ObjectivesTo evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy.MethodsSELECT-COMPARE randomised patients...

Body Mass Index and Clinical Response to Tocilizumab in Patients With Rheumatoid Arthritis.

This study aims to determine whether baseline body mass index (BMI) affects clinical response to tocilizumab (TCZ) after six months of treatment in rheumatoid arthritis (RA) patients. In this prospective study, a total of 52 RA patients (10 males, 42 females; mean age 50.6±12.2 years; range, 23 to 73 years) receiving intravenous TCZ were consecutively recruited and followed-up for six months. BMI was calculated before initiation of TCZ treatment. The primary clinical response criterion was clinical disease activity index (CDAI) low disease activity (LDA) and the secondary clinical response criteria included CDAI remission, disease activity score based on 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) LDA, DAS28-ESR remission, European League Against Rheumatism (EULAR) good response, and decreased DAS28-ESR (ΔDAS28-ESR)≥1.2. The number of RA patients classified as normal weight, overweight, and obese according to baseline BMI was 38 (73.1%), eight (15.4%), and six (11.5%), respectively. Similar baseline BMI median levels were found between RA patients reaching CDAI LDA and non-LDA: 21.11 (18.94-23.72) versus 20.78 (20.03-22.29) (p=0.98), and non-significant difference in the proportion of responders between normal weight and overweight/obese RA patients was found (p=0.47). No significant difference was found when the secondary clinical response criteria were applied. Our study demonstrates that BMI is not associated with clinical response to TCZ among RA patients and TCZ may be used to treat RA patients regardless of BMI levels.

Toward Defining Primary and Secondary Nonresponse in Rheumatoid Arthritis Patients Treated with Anti-TNF: Results from the BioTRAC and OBRI Registries

Although most patients with rheumatoid arthritis (RA) respond to anti-tumor necrosis factor (anti-TNF) treatment, some present with initial nonresponse (1ry nonresponse) or lose initial responsiveness (2ry nonresponse). We compared the rate of real-world "nonresponse" to first anti-TNF as reported by treating physicians to the nonresponse rate per accepted definitions and recommended treat-to-target strategies. Patients were included from the Biologic Treatment Registry Across Canada (BioTRAC) and Ontario Best Practices Research Initiative (OBRI) registries who were taking their first anti-TNF, with ≥ 1 followup visit. Posthoc reclassification of physician-reported nonresponse was based on prior achievement of 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) low disease activity (LDA), Clinical Disease Activity Index (CDAI) LDA, or good/moderate European League Against Rheumatism (EULAR) response, and actual time of physician-reported nonresponse. Among 736 BioTRAC and 640 OBRI patients, 13.7% and 18%, respectively, discontinued their anti-TNF because of physician-reported nonresponse. Based on reclassification using disease activity, 65.6% (BioTRAC) and 87.2% (OBRI) of 1ry nonresponders did not achieve DAS28-ESR LDA, 65.6%/90.7% CDAI LDA, and 46.9%/61.5% good/moderate EULAR response. Among 2ry nonresponders, 50.7%/47.8% did not achieve DAS28-ESR LDA, 37.7%/52.9% CDAI LDA, and 15.9%/19.6% good/moderate EULAR response before treatment discontinuation. Regarding actual time of nonresponse, 18.8% of BioTRAC and 60.8% of OBRI 1ry nonresponders discontinued at ≤ 6 months. In both registries, a high proportion of 2ry nonresponders discontinued their anti-TNF after 12 months (87.0% BioTRAC, 60.9% OBRI). Physician-reported 1ry nonresponse was more correlated with non-achievement of DAS28-ESR LDA or CDAI LDA, whereas 2ry nonresponse with actual time of discontinuation. Further work is needed to confirm the importance of response and type of response to the initial anti-TNF in identifying patients most likely to benefit from a second biologic agent treatment.

Comparative effectiveness of subcutaneous tocilizumab versus intravenous tocilizumab in a pan-European collaboration of registries

ObjectiveTo compare the real-word effectiveness of subcutaneous tocilizumab (TCZ-SC) and intravenous tocilizumab (TCZ-IV) in rheumatoid arthritis (RA).MethodsPatients with RA with TCZ from eight European registries were included. Drug retention was...

Comparative effectiveness of tocilizumab versus TNF inhibitors as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis after the use of at least one biologic disease-modifying antirheumatic drug: analyses from the pan-European TOCERRA register collaboration

ObjectiveTo compare the effectiveness of tocilizumab (TCZ) and tumour necrosis factor (TNF) inhibitors (TNFi) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid...

Safety and maintenance of response for tofacitinib monotherapy and combination therapy in rheumatoid arthritis: an analysis of pooled data from open-label long-term extension studies

ObjectiveTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. This post hoc analysis evaluated patients receiving tofacitinib monotherapy or combination therapy, as well as those who...