BackgroundA treat-to-target (T2T) approach to the care of patients with rheumatoid arthritis (RA) has been advocated, which involves regular assessment of disease activity using validated metrics, frequent follow-up visits for patients with moderate to high disease activity, and escalation of therapy when patients have inadequate therapeutic response as assessed by standard disease activity scores.ObjectivesThe goal of this abstract is to examine whether cluster randomization will result in comparable patients for a behavioral intervention trial designed to assess the impact of implementing a structured T2T approach vs routine care.MethodsThis trial cluster-randomized 31 rheumatology practices based on practice size from the Corrona network of private and academic rheumatology sites to either the T2T intervention (n=16) or usual care (n=15) between July 29, 2011, and July 30, 2013. RA patients with moderate or high disease activity, defined as Clinical Disease Activity Index (CDAI) >10, and no contraindication to T2T were enrolled by the practices and followed for 12 months. In the T2T group, medications were to be accelerated based on disease activity levels with visits occurring as frequently as monthly in those with active disease. Treatment acceleration was defined as a new initiation or increase to the dose or frequency of a prescribed biologic or non-biologic DMARD, or changing route of methotrexate from oral to subcutaneous. In contrast, the usual care subjects were seen at least every 3 months with medication changes per the treating provider. The co-primary endpoints were achievement of low disease activity, defined as CDAI of ≤10, and an assessment of feasibility of implementing T2T in rheumatology practices (e.g., rates of treatment acceleration, frequency of visits, time to next visit conditional on disease activity, and probability of acceleration conditional on disease activity).ResultsThere were 249 patients enrolled from the T2T practices and 289 from usual care practices. The two groups were similar in terms of mean age, gender, and race but not for ethnicity (Table). Patients were also similar in terms of education level, employment status, insurance type and clinical features (disease duration, rheumatoid factor seropositivity, tender joint count, swollen joint count, disease activity, and patient pain); however, functional status was different. Both groups had similar proportions of subjects receiving prednisone and methotrexate as well as similar dosing for those taking these medications. Study retention at 12 months (time window is 9 to 15 months after enrollment) was 83% of the usual care subjects and 79% of the T2T subjects.ConclusionsThis cluster-randomized approach to implementing a behavioral intervention successfully identified similar patients for the two treatment arms for a study of T2T.AcknowledgementsThe Corrona T2T study is sponsored by Corrona, LLC, with support from a development and subscription agreement/contract with Genentech and additional support from AbbVie.Disclosure of ...

Background Depression is a common comorbid condition in rheumatoid arthritis (RA) patients that may influence the evolution of disease progression, and consequently, affect response to therapeutic treatments. Objectives The aim of this study was to determine if depression is a moderator of clinical response to biologic disease modifying anti-rheumatic drug (DMARD) therapy. Methods RA patients initiating a biologic DMARD with a 6 or 12 months (±2 months) follow-up visit were identified from a national RA registry sample (Consortium of Rheumatology Researchers of North America; CORRONA). Patients with self-reported depression at treatment initiation or a clinical visit within 6-months prior were classified as depressed. They were compared to controls with no self-reported history of depression with respect to achieving remission or low disease activity (LDA) based on the clinical disease activity index (CDAI). To account for confounders, particularly differences in baseline disease severity, inverse probability weighting was used due to the high correlation between disease activity measures and their strong association with the outcomes. Predicted probabilities for depression at treatment initiation were used to derive inverse probability weights from propensity score models incorporating baseline values for variables selected a priori that were associated with depression. Logistic regression was then used to estimate unadjusted odd ratios (ORs) and 95% confidence intervals (CIs) for the likelihood of response, and adjusted associations were assessed with weighted models. Results Response rates were significantly different between patients with and without reports of depression receiving biologic treatment at 6 and 12 months follow-up: 15.51% vs. 6.59, 16.71% vs. 9.52%, 36.99% vs. 27.15%, 35.84% vs. 25.24 for remission and LDA, respectively. The corresponding ORs for remission and LDA in the depressed were 0.38 [0.25-0.58] and 0.64 [0.49-0.83] at 6 months and 0.53 [0.36-0.77] and 0.60 [0.45-0.81] at 12 months, respectively. The remission ORs from propensity score weighted models displayed similar patterns: 0.48 [0.30-0.77] at 6 months and 0.67 [0.44-1.04] at 12 months. Although, adjusted LDA effect estimates indicated only a slightly lower likelihood of response: 0.90 [0.66-1.22] at 6 months and 0.88 [0.63-1.23] at 12 months. Conclusions The findings indicate that depression is associated with a lower likelihood of response, particularly CDAI remission, but not LDA. However, it is unclear whether this association with achieving clinical remission is related to depression having a substantive impact on disease expression or is due to the effect on patient's experience of their symptoms. Nonethelss, these data suggest that rheumatologists should consider the presence of affective symptoms when treating their patients to provide the best care possible and address any challenges due to depression Acknowledgements This study is sponsored by CORRONA. In the last 2 years, AbbVie, Amgen, AstraZeneca, Genentec...

BackgroundClinical studies have shown that the efficacy of TCZ monotherapy (TCZ mono) is superior to that of TNFi monotherapy and comparable to that of TCZ in combination with MTX.ObjectivesTo compare the effectiveness of TCZ mono vs TNFi plus varying doses of MTX in patients with rheumatoid arthritis (RA) and prior exposure to TNFi in routine clinical practice.MethodsEligible participants were TCZ-naïve patients from the Corrona RA registry who had prior exposure to ≥1 TNFi, initiated TCZ mono or a TNFi + MTX between 2010 and 2016 and had a 6-month follow-up visit. The primary outcome was mean change from baseline in Clinical Disease Activity Index (CDAI) at 6 months. Secondary outcomes included achievement of low disease activity (LDA; CDAI ≤10) at 6 months. Patients initiating a TNFi + MTX were grouped by MTX dose (≤10 mg; >10 to ≤15 mg; >15 to ≤20 mg; >20 mg); outcomes in each group were compared with those initiating TCZ mono using trimmed populations, excluding patients outside the propensity score (PS) distribution overlap (not on common support). The PS included age, sex, race, body mass index, smoking status, work status, disease duration, concomitant prednisone use/dose, prior biologic use, American College of Rheumatology functional class and baseline modified Health Assessment Questionnaire, CDAI and patient pain scores. As a sensitivity analysis, stratified-matched populations were created (stratified by 1 vs ≥2 prior biologics, then matched on PS). Linear and logistic regression models were estimated in the trimmed populations, adjusting for the same covariates as in the PS.ResultsBaseline demographics were generally comparable between the TNFi + MTX groups and their matched TCZ mono groups. Overall, the mean age was 54 to 59 years, and the mean disease duration was 10.5 to 15 years. A higher proportion of patients initiating TCZ mono had received ≥3 prior biologics compared with those initiating TNFi + MTX. Patients initiating TCZ mono had significantly longer mean disease duration than those initiating TNFi + MTX >15 to ≤20 mg (13.0 vs 10.5 years) or TNFi + MTX >20 mg (12.3 vs 9.3 years) and a higher mean baseline CDAI than those initiating TNFi + MTX ≤10 mg (28.1 vs 25.4). Patients in all groups had improvement in CDAI scores at 6 months. In adjusted models, improvement in CDAI and the likelihood of achieving LDA were similar between the TCZ mono group and all TNFi + MTX groups (Table). Similar results were observed in the PS-matched cohorts.ConclusionsTCZ mono was as effective as TNFi + MTX, regardless of MTX dose, for improving disease activity in patients with prior TNFi exposure. These data suggest that TCZ mono is an effective treatment option for patients with RA who cannot tolerate or prefer not to use MTX.AcknowledgementsThis study is sponsored by Corrona, LLC. Corrona, LLC, has been supported through contracted subscriptions in the past 2 years by AbbVie, Amgen, BMS, Crescendo, Eli Lilly and Company, Genentech, GSK, Horizon Pharma USA, Janssen, Momenta Pharmaceuticals, Novartis, Pfizer, R...

Background:RA is more responsive to treatment in the early stages of disease, and early treatment may lead to better long-term outcomes.1,2 Data on the effectiveness of specific drugs as first or later lines of therapy will help inform treatment sequencing.Objectives:Data from patients enrolled in the Corrona RA Registry were used to compare the effectiveness of abatacept across lines of therapy overall (primary cohort) and in a subset of patients who were anti-citrullinated protein antibody positive (ACPA+).Methods:Patients with RA who initiated abatacept (January 2006 to October 2020), had 6 months’ follow-up (within 4−9 months of starting abatacept), had baseline (BL) and follow-up CDAI scores available, and had BL CDAI >2.8 were included. Outcomes were compared for first-, second- and third or higher-line therapy: 0, 1 or ≥2 prior biologic DMARDs or Janus kinase inhibitors, respectively. Continuous outcomes included change from BL to 6 months in mean CDAI and patient-reported pain, fatigue, and HAQ. Binary outcomes included rate of achieving minimal clinically important difference (MCID) in CDAI or modified ACR20/50/70 at 6 months. Continuous and binary outcomes were analysed using multiple linear and logistic regression, respectively. The models included line of therapy, age, sex, disease duration, work status, SC nodules, history of hypertension and depression, BL CDAI, BL patient-reported pain and BL fatigue. Additional subgroup analyses were carried out in patients with moderate/high disease activity (CDAI >10) at BL.Results:In total, 2876 patients (2327 with BL CDAI >10; 890 ACPA+) were included; 442, 911, and 1523 patients initiated first-, second- or third/higher-line abatacept, respectively. Compared with patients on second/third/higher-line abatacept therapy, those on first-line abatacept were significantly older, had shorter disease duration, and had lower BL CDAI, pain and fatigue (all p<0.001). In adjusted analyses, patients receiving abatacept as earlier lines of therapy had significantly greater improvement from BL in mean CDAI and in patient-reported fatigue and HAQ (Table 1). There was no significant difference between lines of therapy in change in patient-reported pain. Patients receiving first-line abatacept had significantly higher odds of achieving a MCID in CDAI or modified ACR20/50/70 response (Figure 1). Similar patterns were seen when the sample was limited to patients with moderate/high disease activity or in patients who were ACPA+.Conclusion:There were significant differences in improvement in clinical disease activity and patient-reported outcomes across lines of therapy. Better treatment responses were observed with earlier lines of abatacept therapy in the overall population, in patients who were ACPA+ and in those with moderate/high BL disease activity.References:[1]Harrold LR, et al. Clin Rheumatol 2017;36:1215−1220.[2]Monti S, et al. RMD Open 2015;1(Suppl 1):e000057.Table 1.Adjusted mean change in CDAI and patient-reported outcomes from BL to 6 months after initiation of abatacept by line of therapy (primary cohort)Adjusted outcome, mean change (SE)First-line (n=440)Second-line (n=898)Third/higher-line (n=1515)p valueaCDAI−7.96 (0.33)−7.49 (0.27)−5.74 (0.19)<0.001Patient-reported pain (VAS 0–100)−9.43 (0.69)−7.98 (0.47)−7.70 (0.35)0.074Patient-reported fatigue (VAS 0–100)−7.49 (0.71)−5.87 (0.51)−4.81 (0.36)0.002Patient-reported HAQ−0.16 (0.01)−0.12 (0.01)−0.08 (0.01)<0.001aEstimated by multiple linear regression model adjusted for age, sex, disease duration, work status, SC nodules, history of hypertension and depression, BL CDAI, BL patient-reported pain and BL fatigue (factors that were identified a priori based on clinical experience or that differed significantly by line of therapy); p values reflect ANOVA overall test of differences across lines of therapy.VAS=visual analogue scale.Acknowledgements:Professional medical writing and editorial assistance was provided by Claire Line, PhD, at Caudex and was funded by Bristol Myers Squibb. The poster was a collaborative effort between Corrona and Bristol Myers Squibb, with financial support provided by Bristol Myers Squibb. This study was sponsored by Corrona, LLC. Corrona is supported through contracted subscriptions with multiple pharmaceutical companies.Disclosure of Interests:Leslie Harrold Consultant of: AbbVie, Bristol Myers Squibb, Genentech/Roche, Grant/research support from: Pfizer, Keith Wittstock Employee of: Bristol Myers Squibb, Sheila Kelly Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Sang Hee Park Employee of: Bristol Myers Squibb, Xue Han Employee of: Bristol Myers Squibb, Ying Shan: None declared, Carla Roberts-Toler: None declared, Nicole Middaugh: None declared, Vadim Khaychuk Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb

BackgroundRheumatoid arthritis (RA) is a systemic, inflammatory disease and its burden extends beyond joint disease. In recent years, there has been significant advances in treating joint disease but we need a greater understanding of physical and especially psychosocial comorbities to improve quality of life in RA patients. In particular, patients often report “brain fog” meaning a diminished ability to think, learn, remember and perform other mental tasks. Doctors have long recognized that patients with certain physical conditions can experience cognitive dysfunction. Limited information is available in the literature with regard to the prevalence of cognitive dysfunction and factors associated with the condtion in RA.ObjectivesTo characterize the association of disease activity with patient reported cognitive dysfunction in patients with RA overall and stratified by age.MethodsWe identified patients with RA aged ≥18 years who were enrolled in the Corrona registry who were biologic naïve at their last follow-up visit (October 2010–June 2016). We compared those who reported cognitive dysfunction (responded “yes” to the question asking if they had “problems with thinking”) to those who did not with respect to disease activity based on the Clinical Disease Activity Index (CDAI). Unadjusted and adjusted logistic regression models controlling for demographic (age, gender, race, education), comorbidity/lifestyle (diabetes, fibromyalgia, body mass index, smoking) and RA disease characteristics (disease duration, disability and prednisone dose) were conducted. We further examined whether the relationship between disease activity and cognitive dysfunction varied based on patients age (<55 vs. >55 years) testing the moderating effect using a likelihood ratio test.ResultsThere were 10,401 patients who met inclusion criteria of whom 863 (8%) reported cognitive dysfunction. Those who reported cognitive dysfunction were more likely to be women (83% vs. 73%, p<0.001), younger (62 vs. 64 years, p<0.001), disabled (24% vs. 8%, p<0.001), with moderate/high disease activity based on the CDAI (51% vs. 31%, p<0.001). In adjusted models, the likelihood of cognitive dysfunction increased with higher levels of disease activity in the total population (Table). The impact was more pronounced in those age <55 (p=0.007; Table).Total population*Age <55**Age ≥55** Disease activity OR (95% CI)* Remission111 Low2.70 (2.11–3.45)3.97 (2.34–6.75)2.42 (1.84–3.20) Moderate3.56 (2.75–4.61)5.93 (3.45–10.19)3.01 (2.24–4.05) High3.90 (2.92–5.21)7.92 (4.49–13.98)2.90 (2.04–4.12)*Adjusted for age, gender, race, disability, education, smoking status, body mass index, diabetes, fibromyalgia, disease duration and prednisone dose. **Adjusted for gender, race, disability, education, smoking status, body mass index, diabetes, fibromyalgia, disease duration and prednisone dose.ConclusionsIncreasing disease activity is associated with a higher likelihood of reporting cognitive disfunction. The effect was more pronounced in younger as opposed to older RA patient...