Ani John

Factors associated with gastrointestinal perforation in a cohort of patients with rheumatoid arthritis

To estimate the incidence and risk factors for gastrointestinal (GI) perforation among patients with rheumatoid arthritis (RA).

Dyslipidemia and changes in lipid profiles associated with rheumatoid arthritis and initiation of anti–tumor necrosis factor therapy

To investigate the frequency of lipid testing in clinical practice and to explore the relationship between rheumatoid arthritis (RA), dyslipidemia, and other cardiovascular (CV) risk factors with RA treatment.

Effectiveness of Rituximab for the Treatment of Rheumatoid Arthritis in Patients with Prior Exposure to Anti-TNF: Results from the CORRONA Registry

Objective. To characterize the real-world effectiveness of rituximab (RTX) in patients with rheumatoid arthritis. Methods. Clinical effectiveness at 12 months was assessed in patients who were prescribed RTX based on the Clinical Disease Activity Index (CDAI). Change in CDAI was calculated (CDAI at 12 mos minus at initiation). Achievement of remission or low disease activity (LDA; CDAI ≤ 10) among those with moderate/high disease activity at the time of RTX initiation was compared based on prior anti-tumor necrosis factor agent (anti-TNF) use (1 vs ≥ 2) using logistic regression models. Results. Patients (n = 265) were followed for 12 months with a mean change in CDAI of −8.1 (95% CI −9.8 – −6.4). Of the 218 patients with moderate/high disease activity at baseline, patients with 1 prior anti-TNF (baseline CDAI 25.0) demonstrated a mean change in CDAI of −10.1 (95% CI −13.2 – −7.0); patients with ≥ 2 prior anti-TNF (baseline CDAI 30.0) demonstrated a mean change of −10.5 (95% CI −12.9 – −8.0). The unadjusted OR for achieving LDA/remission in patients with moderate/high disease activity at baseline exposed to ≥ 2 versus 1 prior anti-TNF was 0.40 (95% CI 0.22–0.73), which was robust to 4 different adjusted models (OR range 0.38–0.44). Conclusion. A good clinical response was observed in all patients; however, patients previously treated with 1 anti-TNF, who had lower baseline CDAI and a greater opportunity for clinical improvement compared with patients previously treated with ≥ 2 anti-TNF, were more likely to achieve LDA/remission.

Validation of ICD‐9‐CM codes to identify gastrointestinal perforation events in administrative claims data among hospitalized rheumatoid arthritis patients

To validate, using physician review of abstracted medical chart data as a gold standard, a claims‐based algorithm developed to identify gastrointestinal (GI) perforation cases among rheumatoid arthritis (RA) patients.

AB0286 A Cluster-Randomized Trial of a Behavioral Intervention to Incorporate a Treat-To-Target Approach in the Clinical Care of Rheumatoid Arthritis Patients

Background A 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. Objectives The 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. Methods This 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). Results There 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. Conclusions This cluster-randomized approach to implementing a behavioral intervention successfully identified similar patients for the two treatment arms for a study of T2T. Acknowledgements The 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 Interest L. Harrold Employee of: University of Massachusetts Medical School, G. Reed Employee of: Corrona, LLC, J. T. Harrington Shareholder of: AbbVie, Amgen, BMS, GlaxoSmithKline, Johnson & Johnson, Pfizer and Roche, Consultant for: AbbVie, Amgen, Antares, AstraZeneca, Celgene, Horizon, Iroko, Pfizer, Roche and UCB, Speakers bureau: AbbVie, Amgen, Pfizer, Roche and UCB, C. Barr Employee of: Corrona, LLC, K. Saunders Employee of: Corrona, LLC, A. Gibofsky: None declared, J. Greenberg Shareholder of: Corrona, LLC, Consultant for: AstraZeneca, Celgene, Novartis and Pfizer, Employee of: Corrona, LLC, A. John Employee of: Genentech, Inc, J. Devenport Employee of: Genentech, Inc, J. Kremer Shareholder of: Corrona, LLC, Grant/research support from: Genentech, Inc, Consultant for: Genentech, Inc, Employee of: Corrona, LLC

FRI0254 Comparative effectiveness of rituximab versus anti-tumor necrosis factor switching for rheumatoid arthritis patients

Background In patients who have failed 1 or more TNF-α inhibitors (TNFi), there is little data to guide clinical decision making in terms of changing mechanism of action or prescribing another TNFi. Objectives To compare the effectiveness of rituximab (RTX) versus a subsequent TNFi among RA patients with prior TNFi exposure using data from a multi-center observational registry within the United States (the Consortium of Rheumatology Researchers of North America: CORRONA). Methods We identified RA patients from 3/1/06 to present who had discontinued at least 1 TNFi and initiated either RTX or a subsequent TNFi, had moderate or high disease activity based on the Clinical Disease Activity Index (CDAI) at the time of initiation and had follow-up at 12 months (3 month window). A propensity score (PS) for TNFi vs. RTX was estimated using patient demographic information, disease characteristics (severity, duration, activity), comorbidities, past medication history and concurrent medications. We trimmed the PS distributions, excluding patients who fell outside the region of common support (n=2). Our primary outcome was achievement of low disease activity (CDAI ≤10). Multivariable logistic regression models with adjustment for fixed and random effects (patient and provider) were performed. Covariates with a standardized difference of <0.1 as well as 4 factors chosen a priori (baseline CDAI, steroid use, background methotrexate use, and number of prior TNFi’s) were included in the models. As a sensitivity analysis, we reran the analyses using PS matched TNFi and RTX initiators. Results 266 RTX users and 744 TNFi users who met inclusion criteria were included in the analyses. Baseline characteristics are described in Table 1. As compared to the TNFi users, RTX users were older, had a greater duration of RA, had prior exposure to a greater number of prior biologics and were more likely to be receiving prednisone. Achievement of low disease activity occurred in 35% of the RTX users and 28% of the TNFi users. RTX was associated with a greater likelihood of achievement of low disease activity (1.74, 95% CI 1.22-2.47) after adjustment for age, race, insurance status, comorbidity, and RA characteristics (baseline disease activity, severity and medication use [current and prior]). Results from PS matched multivariable analyses were similar. Overall reported rates in RTX users were 0.02 events per person-year (PPY) (95% CI 0.01-0.04) for cardiovascular events, 0.02 PPY (95% CI 0.01-0.05) for serious infections and 0.02 PPY (95% CI 0.01-0.04) for malignancies. The rates in TNFi users were 0.02 PPY (95% CI 0.01-0.03), 0.03 PPY (95% 0.02-0.05) and 0.02 PPY (95% 0.01-0.03), respectively. Image/graph Conclusions In RA patients who failed 1 or more TNFi agents, use of RTX was associated with a higher likelihood of achieving CDAI low disease activity than use of a subsequent TNFi. Disclosure of Interest: L. Harrold Grant/research support from: National Institute of Health - K23AR053856, Consultant for: CORRONA, G. Reed Consultant for: University of Massachusetts Medical School, Employee of: CORRONA, R. Magner Employee of: University of Massachusetts Medical School, A. Shewade Employee of: Genentech, Inc., A. John Employee of: Genentech, Inc., W. Reiss Employee of: Genentech, Inc., J. Greenberg Shareholder of: CORRONA, Consultant for: AstraZeneca, CORRONA, Novartis and Pfizer, J. Kremer Shareholder of: CORRONA, Employee of: CORRONA

Cluster-Randomized Trial of a Behavioral Intervention to Incorporate a Treat-to-Target Approach to Care of US Patients With Rheumatoid Arthritis

To assess the feasibility and efficacy of implementing a treat‐to‐target approach versus usual care in a US‐based cohort of rheumatoid arthritis patients.

FRI0334 Comparative Effectiveness of Rituximab versus Subsequent Anti-Tumor Necrosis Factor in Cumulative Prednisone Exposure in Patients with Rheumatoid Arthritis with Prior Exposure to Tnfi

Background In a US cohort of RA patients (pts) with prior exposure to 1 or more TNF inhibitors (TNFi), use of rituximab (RTX) was associated with a higher likelihood of low disease activity or remission (based on Clinical Disease Activity Index [CDAI] ≤10) as compared with a subsequent TNFi.1,2 However, it is not known whether the increased efficacy was due to greater use of prednisone. Objectives To examine the comparative effectiveness of RTX vs a subsequent TNFi in terms of cumulative prednisone exposure in RA pts with prior TNFi exposure using data from the Consortium of Rheumatology Researchers of North America (CORRONA), a multi-center observational registry within the US. Methods Using CORRONA data spanning from 2/28/2006 through 10/31/2012, we identified RTX-naïve RA pts with prior TNFi use who were initiating RTX or a subsequent TNFi, had a 1-year follow-up visit and had CDAI measurements at baseline and 1-year follow-up. Pts from the stratified-matched cohort of the previously described comparative effectiveness analysis were assessed in the current analysis.1,2 A propensity score for TNFi vs RTX was estimated using baseline clinical characteristics with matching of pts stratified based on 1 vs ≥2 prior TNFi use. The primary outcome was area under the curve (AUC) for cumulative prednisone dose divided by time. The percentage of time spent at 10mg or higher of prednisone was examined as a secondary outcome. Multivariable linear mixed models were performed adjusting for age, gender, 1 vs ≥2 prior TNFi, baseline CDAI, baseline prednisone use and baseline methotrexate use. Results There were 205 RTX pts and 205 TNFi matched pts who met the inclusion criteria. Patients were mostly female (81-83%), with a mean age of 58, mean disease duration of 15 years, and mean CDAI of 26-27. Baseline prednisone was used in 55.6% of RTX users and 51.5% of TNFi users. Overall there was a significant decrease in cumulative prednisone use over time (P=0.04). The mean AUC for RTX was 3.7 vs 3.2 for TNFi (P=0.22). In adjusted models, the mean difference in AUC over time for RTX as compared with TNFi was 0.26 (95% CI: -0.29, 0.82). The mean percentage of time at prednisone dose ≥10mg was 15.0% in RTX users vs 11.3% in TNFi users (P=0.21). With adjustment for confounders, the mean difference in the percentage of time at prednisone dose ≥10mg for RTX compared with TNFi was 2.79 (95% CI: -2.45, 8.03). Approximately 14.0% and 22.9% of RTX and TNFi baseline prednisone users, respectively, discontinued prednisone during follow-up. Conclusions In this population of RA pts with prior exposure to TNFi, treatment with RTX was associated with a higher likelihood of achieving low disease activity and remission (OR 1.54, 95% CI 1.01-2.35) compared with subsequent TNFi users1,2 and it was not related to greater prednisone use. Both RTX and TNFi users had a reduction in cumulative prednisone use. References Harrold LH, et al. Arthritis Rheum. 2013;65(suppl 10) [abstract 1438]. Harrold LH, et al. Ann Rheum Dis. 2013;72(suppl 3) [abstract 460]. Acknowledgements This study is sponsored by CORRONA. In the last 2 years, AbbVie, Amgen, AstraZeneca, Genentech, Horizon Pharma, Eli Lilly, Novartis, Pfizer, Vertex, and UCB have supported CORRONA through contracted subscriptions. Disclosure of Interest L. Harrold Grant/research support: CORRONA., G. Reed Employee of: CORRONA, Inc., R. Magner Employee of: University of Massachusetts., A. Shewade Employee of: Genentech, Inc., A. John Employee of: Genentech, Inc., J. Greenberg Shareholder of: CORRONA., Consultant for: AstraZeneca, Pfizer., Employee of: CORRONA., J. Kremer Shareholder of: CORRONA., Employee of: CORRONA. DOI 10.1136/annrheumdis-2014-eular.1534

Long-Term Safety of Rituximab in Rheumatoid Arthritis: Analysis From the SUNSTONE Registry

OBJECTIVE To evaluate the long-term safety of rituximab in an observational cohort of patients with rheumatoid arthritis (RA) who had an inadequate response to ≥ 1 antitumor necrosis factor therapies in the United States (SUNSTONE Registry). METHODS In this prospective, observational cohort study, patients received rituximab according to their physicians standard practice and were evaluated at standard-of-care follow-up visits at least every 6 months. The primary outcome was the incidence of protocol-defined significant infections. Secondary outcomes included serious adverse events potentially associated with rituximab, cardiovascular or thrombotic (CVT) events, seizures, deaths and pregnancies. Posthoc analyses assessed outcomes by concomitant medication use. RESULTS Overall, 989 patients (safety-evaluable population) received ≥ 1 dose of rituximab, with a total follow-up of 3844 patient-years (PYs; mean duration, 3.9 years). In total, 341 significant infections occurred in 197 patients (19.9%). The incidence rates (95% CI) for significant infections, CVT events, and seizures were 8.87 (7.98, 9.86), 1.95 (1.56, 2.45), and 0.18 (0.09, 0.38) per 100 PYs, respectively. The incidence of significant infections did not increase with time or with cumulative rituximab exposure. During the study, 64 patients died (crude mortality [95% CI]: 1.66 per 100 PYs [1.30, 2.13]). The most common causes of death were infections (19 patients), malignancy (14), and cardiovascular events (13). Eight pregnancies were reported in 7 patients. CONCLUSION In patients with RA treated with rituximab for up to 5 years, the rates of significant infections were stable over time and higher in patients who received long-term systemic steroid treatment. This article is protected by copyright. All rights reserved.To evaluate the long‐term safety of rituximab in an observational cohort of patients with rheumatoid arthritis (RA) who had an inadequate response to ≥1 anti–tumor necrosis factor therapy in the US (SUNSTONE [Study of the Safety of Rituxan in Patients With Rheumatoid Arthritis After an Inadequate Response to Previous Anti‐TNF Therapy] registry).

Risk of Infection Associated With Subsequent Biologic Agent Use After Rituximab: Results From a National Rheumatoid Arthritis Patient Registry

To assess whether the time between the last rituximab infusion and initiation of a different biologic agent influenced infection risk in patients with rheumatoid arthritis (RA).