A. Shewade

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.

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

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

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).

FRI0307 Persistency and Its Predictors of Biologic Monotherapy in Patients with RA: Analyses from the Corrona RA Registry

Background International task forces recommend conventional disease-modifying antirheumatic drugs (DMARDs) as first-line therapy in patients (pts) with rheumatoid arthritis (RA).1,2 In some pts, treatment with a biologic DMARD as monotherapy (MT) may provide clinical benefit without the potential undesirable side effects associated with conventional DMARDs; however, research on the persistency of biologic initiations as MT is limited. Objectives To estimate the persistency of biologic use as MT using combination therapy (CMB) as a reference and to examine predictors of MT persistency in pts with RA participating in the Consortium of Rheumatology Researchers of North America (CORRONA) registry. Methods Pts in CORRONA who initiated their first use of a particular biologic as on-label MT or in combination with methotrexate (MTX) between 2007 and 2013 were eligible for inclusion in this analysis. Unadjusted Kaplan-Meier analyses were performed to estimate the rates of persistency and failure (end of therapy) for all MT and CMB initiations. Failure of persistency was defined as any modification to a particular biologic initiation as MT or CMB, including switch/discontinuation of the biologic or addition/switch/discontinuation of conventional DMARD. Cox regression models were used to examine predictors of MT persistency. Factors from the unadjusted analysis significantly associated with persistency (P<0.2) and with <3% missing data were included in the full adjusted model. Results There were 4422 eligible initiations, including 1518 MT and 2904 CMB initiations. At baseline, mean ± SD age was similar between pts initiating MT vs CMB (56.0±12.7 vs 56.1±13.4 years); however, MT initiators had longer mean ± SD duration of RA (10.3±9.4 vs 9.4±9.5 years; P<0.01) and higher mean ± SD clinical disease activity index (CDAI; 21.9±15.1 vs 20.7±14.2; P<0.05). Of MT initiators who previously discontinued MTX, reasons included toxicity (51.6%), loss of efficacy (17.4%) and other (e.g. insurance, pt preference etc; 45.3%). Unadjusted comparison of rates of persistency at 12, 24 and 36 months were in favor of CMB initiations (Figure). Factors associated with failure of MT persistency included shorter disease duration (HR 0.93; [95% CI 0.86, 0.99] per 10 years), previous smoking status (HR 1.23; 95% CI 1.05, 1.43), prednisone dose ≥10 mg (HR 1.31; 95% CI 1.06, 1.61), increased pt assessment of pain (HR 1.05; [95% CI 1.02, 1.07] per 10 units) and higher CDAI (HR 1.06; [95% CI 1.01, 1.11] per 10 units). The treatment modifications resulting in end of MT persistency were addition of a conventional DMARD (31.6%), switch of the biologic (32.9%), discontinuation of the biologic (22.4%) and switch to a conventional DMARD (13.0%). Conclusions The proportion of pts remaining on their initiated biologic treatment decreased over time in both groups. Several clinical characteristics were associated with increased persistency of MT. Further analyses will investigate differences across individual biologics. References Singh JA, et al. Arthritis Care Res (Hoboken). 2012;64:625-39. Smolen JS, et al. Ann Rheum Dis. 2013 Oct 25. [Epub ahead of print]. 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 D. Pappas Employee of: CORRONA, Inc., Paid instructor for: Novartis., A. John Employee of: Genentech, Inc., G. Reed Employee of: CORRONA, Inc., C. Karki Employee of: CORRONA, Inc., J. Greenberg Shareholder of: CORRONA, Inc., Consultant for: AstraZeneca and Pfizer., A. Shewade Employee of: Genentech, Inc., J. Kremer Shareholder of: CORRONA, Inc., Employee of: CORRONA, Inc. DOI 10.1136/annrheumdis-2014-eular.1550

FRI0222 Prevalence of low immunoglobulin levels and associations with rheumatoid arthritis factors

Background Little is known about the prevalence and the clinically associated factors of low IgG and IgM levels in patients (pts) with RA. Objectives To estimate the prevalence of low IgG and IgM levels in pts with RA and to investigate factors associated with low Ig Methods This cross-sectional analysis evaluated Ig levels measured centrally at the time of enrollment in CERTAIN, a prospective comparative effectiveness study of biologics nested within CORRONA. Multivariate models (MV) evaluated factors associated with low Ig levels. Results Characteristics for the 1151 enrollments were analyzed: 76% women, 86% Caucasian, 67% seropositive. The mean (±SD) age was 56.1 (±13.5) years, RA duration was 8.5 (±9.1) years and CDAI was 29.1 (±13.0). At the time of evaluation 35.7% of pts were biologic-naïve and 39.6% received prednisone in the last 6 months (34.8% of them ≤10mg/day). Low IgG (<700mg/dl) was noted in 76 (6.6%) pts and low IgM (<40mg/dl) in 63 (5.5%) pts. MV (Table 1) showed that pts with high disease activity were more likely to have low IgG. Prior exposure to biologics was not associated with low IgG or IgM. Instead, an opposite trend was suggested for prior exposure to TNF-α inhibitors. MV suggested that higher doses of prednisone are likely to be associated with low IgG levels and that seropositive pts are more likely to have normal Ig levels. Image/graph Conclusions High disease activity was associated with increased odds of low IgG. Effect of biologic agents, steroids and other factors on Ig levels, and clinical outcomes will be evaluated in a longitudinal analysis when CORRONA-CERTAIN is completed. Disclosure of Interest: D. Pappas Employee of: Columbia University, Paid instructor for: Novartis, A. John Employee of: Genentech, Inc., J. Curtis Grant/research support from: Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, Abb Vie, Consultant for: Roche/Genentech, UCB, Janssen, CORRONA, Amgen, Pfizer, BMS, Crescendo, Abb Vie, J. Kremer Shareholder of: CORRONA, Employee of: CORRONA, W. Reiss Employee of: Genentech, Inc., A. Shewade Employee of: Genentech, Inc., G. Silverman Grant/research support from: NIH, ACR, RRF, Consultant for: Lilly, Genentech, Roche, Pfizer, Employee of: New York University, J. Greenberg Shareholder of: CORRONA, Consultant for: AstraZeneca, CORRONA, Novartis, Pfizer