Retention of triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine compared to combination methotrexate and leflunomide in rheumatoid arthritis.

OBJECTIVE: There are various combination conventional synthetic disease-modifying-antirheumatic drug (csDMARD) treatment strategies used in rheumatoid arthritis (RA). A commonly used csDMARD combination is triple therapy with methotrexate (MTX), sulfasalazine (SSZ) and hydroxychloroquine (HCQ). Another approach is double therapy with MTX and leflunomide (LEF). We compared the real-world retention of these two treatment combinations. METHODS: Patients with RA from the Ontario Best Practices Research Initiative (OBRI) who received triple or double therapy on or after OBRI enrolment were included. Retention rates were compared between these two groups. We also analyzed which medication in the combination was discontinued and the reasons for treatment discontinuation. Disease activity was assessed at baseline, 6 and 12 months after treatment initiation as well as at time of discontinuation. Risk factors for treatment discontinuation were also examined. RESULTS: Six hundred and ninety-two patients were included (258 triple and 434 double therapy). There were 175 (67.8%) discontinuations in the triple therapy group and 287 (66.1%) discontinuations in patients on double therapy. The median survival for triple therapy was longer (15.1 months; 95% CI: 11.2-21.2) compared to double therapy (9.6 months; 95%CI: 7.03-12.2). However, this was not statistically significant. Disease activity at 6 and 12 months, measured by 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) was lower with triple therapy (mean DAS28 at 6 months 3.4 vs. 3.9, P<0.0001 and at 12 months 3.2 vs. 3.5, P=0.0005). CONCLUSION: Patients on triple therapy remained on treatment longer than patients on double therapy. However, this difference was not statistically significant.

Biologics initiation in moderate versus severe rheumatoid arthritis: real-world experience from a Canadian registry.

OBJECTIVES: To evaluate the treat-to-target experience, and quality of life measures of moderate and severe rheumatoid arthritis (RA) patients initiating a biologic in a real-world setting of a publicly funded payer system. METHODS: Biologic naive RA patients who had initiated their first biologic while enrolled in the Ontario Best Practices Research Initiative registry from 2008 to 2020 were selected if they had moderate (DAS28 >3.2 to ≤5.1) or severe (DAS28 >5.1) RA. Remission, LDA, DAS28, HAQ-DI, fatigue, sleep, drug persistence and characteristics associated with remission were assessed at 12 months post biologic initiation. RESULTS: Overall, 838 patients initiated their first biologic, 264 had moderate RA and 219 had severe RA. After 12 months, 44% moderate RA vs. 21% severe RA achieved remission (p<0.0001), and 59% moderate RA vs. 35% severe RA reached LDA (p<0.0001). Mean change (SD) from baseline in DAS28 was 2.2 (1.5) in severe RA vs. 1.4 (1.3) in moderate RA (p<0.0001), in fatigue score was 1.11 (3.2) in severe RA vs. 0.98 (3.2) in moderate RA (p<0.0001). Moderate disease at a biologic initiation was positively associated with remission (p=0.0016). Female gender (p=0.0170), and a higher HAQ-DI score at baseline (p=0.0042) were negatively associated with remission. Biologic persistence was 77% for moderate, and 73% for severe (p=0.2444). CONCLUSIONS: Severe RA patients had higher mean score improvements in DAS28, sleep and fatigue. Moderate RA was more likely to reach remission or LDA. Both groups had similar biologic persistence at 12 months. These findings highlight the importance of the treat-to-target approach and its potential underutilisation in the real-world setting.

Factors affecting the discrepancy between patient and physician global assessment in early rheumatoid arthritis: The Ontario Best Practices Research Initiative.

OBJECTIVES: We aimed to assess the prevalence and factors affecting the discrepancy between patient global assessment (PtGA) and physician global assessment of disease activity (PhGA) in patients with early rheumatoid arthritis (RA) at enrolment and after one year. METHODS: Patients from the Ontario Best Practices Research Initiative (OBRI) were included. The discrepancy between PtGA and PhGA was calculated by simple subtraction (PtGA-PhGA). An absolute value ≥30 was considered discordant. Linear regression analysis was used to assess factors affecting PtGA, PhGA, and PtGA-PhGA discrepancy at enrolment and 1-year follow-up. RESULTS: A total of 531 patients with mean disease duration of 0.3 years were analysed. The discordance prevalence was 22.4% at enrolment and 20.3% after one year. PtGA was higher in the majority of the discordant cases. Multivariable regression analysis showed higher PtGA was significantly associated with higher pain score, tender joint counts (TJC28), ESR, and fatigue at enrolment and 1-year follow-up while PtGA was associated with higher swollen joint counts (SJC28) only at enrolment. Similar associations were found for PhGA, with the exception of fatigue, which was not a significant factor at one year. Multivariable analysis showed that higher discrepancy between PtGA-PhGA was associated with lower SJC28 and higher pain score at enrolment and lower SJC28 and higher pain and fatigue score at 1-year follow-up. CONCLUSIONS: Significant PtGA-PhGA discrepancy was found in approximately one-quarter of early RA patients. In the majority of these patients, PtGA was higher than PhGA. The main predictors of PtGA and PhGA remained the same after one year.

Impact of the COVID-19 pandemic on patients with rheumatoid arthritis: data from the Ontario Best Practices Research Initiative (OBRI).

Objective: The coronavirus disease 2019 (COVID-19) pandemic created challenges for patients with RA. We examined the potential impact of the pandemic on patient-reported outcomes (PROs), disease activity and medication profiles, comparing the periods pre-pandemic and during the pandemic. Methods: Patients enrolled in the Ontario Best Practices Research Initiative were included if they had at least one visit to a physician or study interviewer within 12 months before and after the start of pandemic-related closures in Ontario (15 March 2020). Baseline characteristics, disease activity, PROs [i.e. health assessment questionnaire disability index, RA disease activity index (RADAI), European quality of life five-dimension questionnaire], medication use and changes were included. Student's paired two-sample t-tests and McNamar's tests were performed for continuous and categorical variables between time periods. Results: The sample for analysis consisted of 1508 patients, with a mean (s.d.) age of 62.7 (12.5) years, and 79% were female. Despite decreases in the number of in-person visits during the pandemic, there was no significant negative impact on disease activity or PRO scores. The DASs in both periods remained low, with either no clinically significant differences or slight improvement. Scores for mental, social and physical health were either stable or improved. There were statistically significant decreases in conventional synthetic DMARD use (P < 0.0001) and increased Janus kinase inhibitor usage (P = 0.0002). Biologic DMARD use remained stable throughout the pandemic. Conclusion: In this cohort, disease activity and PROs of RA patients remained stable during the COVID-19 pandemic. The longer-term outcomes of the pandemic warrant investigation.

Discontinuation of tofacitinib and TNF inhibitors in patients with rheumatoid arthritis: analysis of pooled data from two registries in Canada.

OBJECTIVES: The similarity in retention of tumour necrosis factor inhibitors (TNFi) and tofacitinib (TOFA) was previously reported separately by the Ontario Best Practices Research Initiative and the Quebec cohort Rhumadata. However, because of small sample sizes in each registry, we aimed to confirm the findings by repeating the analysis of discontinuation of TNFi compared with TOFA, using pooled data from both these registries. DESIGN: Retrospective cohort study. SETTING: Pooled data from two rheumatoid arthritis (RA) registries in Canada. PARTICIPANTS: Patients with RA starting TOFA or TNFi between June 2014 and December 2019 were included. A total of 1318 patients were included TNFi (n=825) or TOFA (n=493). OUTCOME MEASURES: Time to discontinuation was assessed using Kaplan-Meier survival and Cox proportional hazards regression analysis. Propensity score (PS) stratification (deciles) and PS weighting were used to estimate treatment effects. RESULTS: The mean disease duration in the TNFi group was shorter (8.9 years vs 13 years, p<0.001). Prior biological use (33.9% vs 66.9%, p<0.001) and clinical disease activity index (20.0 vs 22.1, p=0.02) were lower in the TNFi group.Discontinuation was reported in 309 (37.5%) and 181 (36.7%) TNFi and TOFA patients, respectively. After covariate adjustment using PS, there was no statistically significant difference between the two groups in discontinuation due to any reason HR=0.96 (95% CI 0.78 to 1.19, p=0.74)) as well as discontinuation due to ineffectiveness only HR=1.08 (95% CI 0.81 to 1.43, p=0.61)).TNFi users were less likely to discontinue due to adverse events (AEs) (adjusted HRs: 0.46, 95% CI 0.29 to 0.74; p=0.001). Results remained consistent for firstline users. CONCLUSIONS: In this pooled real-world data study, the discontinuation rates overall were similar. However, discontinuation due to AEs was higher in TOFA compared with TNFi users.

Medical cannabis use by rheumatology patients in routine clinical care: results from The Ontario Best Practices Research Initiative.

OBJECTIVES: Medical cannabis is often used to alleviate common symptoms in patients with chronic conditions. With cannabis legalisation in Canada and easier access, it is important that rheumatologists understand its potential impact on their practice. Among patients attending rheumatology clinics in Ontario we assessed: the prevalence of medical cannabis use; symptoms treated; rheumatologists' perceptions. METHODS: Eight rheumatology clinics recruited consecutive adult patients in a 3-part medical cannabis survey: the first completed by rheumatologists; the second by all patients; the third by medical cannabis users. Student's t-test and Chi-square test were used to compare medical cannabis users to never users. RESULTS: 799 patients participated, 163 (20.4%) currently using medical cannabis or within <2 years and 636 never users; most had rheumatoid arthritis (37.8%) or osteoarthritis (34.0%). Compared to never users, current/past-users were younger; more likely to be taking opioids/anti-depressants, have psychiatric/gastrointestinal disorders, and have used recreational cannabis (p<0.05); had higher physician (2.9 vs. 2.1) and patient (6.0 vs. 4.2) global scores, and pain (6.2 vs. 4.7) (p<0.0001). Pain (95.5%), sleeping (82.3%) and anxiety (58.9%) were the most commonly treated symptoms; 78.2% of current/past-users reported medical cannabis was at least somewhat effective. Most rheumatologists reported being uncomfortable to authorise medical cannabis, primarily due to lack of evidence, knowledge, and product standardisation. CONCLUSIONS: Medical cannabis use among rheumatology patients in Ontario was two-fold higher than that reported for the general population of similar age. Use was associated with more severe disease, pain, and prior recreational use. Reported lack of research, knowledge, and product standardisation were barriers for rheumatologist use authorisation.

Late-onset rheumatoid arthritis has a similar time to remission as younger-onset rheumatoid arthritis: results from the Ontario Best Practices Research Initiative.

BACKGROUND: The prevalence of rheumatoid arthritis (RA) in persons 60 years or older is estimated to be 2%. Late-onset rheumatoid arthritis (LORA) is traditionally defined as the onset of RA after the age of 60 years. Compared to younger-onset rheumatoid arthritis (YORA) which occurs before the age of 60 years, LORA has unique characteristics and disease manifestations. To date, few reports have addressed LORA and the prognosis of LORA patients remains unclear. We compared the clinical characteristics, time to remission and treatment regimen at remission between LORA and YORA patients. METHODS: This prospective cohort study used a registry database in Ontario, Canada from 2008 to 2020. Patients were included if they had active rheumatoid arthritis (RA) disease (≥1 swollen joint) and were enrolled within 1 year of diagnosis. LORA was defined as a diagnosis of RA in persons 60 years and older and YORA as a diagnosis of RA in persons under the age of 60. Remission was defined by Disease Activity Score 28 (DAS28) ≤2.6. A multivariable Cox proportional hazards model was used to estimate time to remission. RESULTS: The study included 354 LORA patients and 518 YORA patients. The mean (standard deviation) baseline DAS28 score was 5.0 (1.3) and 4.8 (1.2) in LORA and YORA patients, respectively (p=0.0946). Compared to YORA patients, the hazard ratio for remission in LORA patients was 1.10 (95% confidence interval 0.90 to 1.34 p=0.36) after adjusting for other prognostic factors. For patients who reached remission, LORA patients were less likely to be on a biologic or Janus kinase (JAK) inhibitor (16% vs. 27%) and more likely to be on a single conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) (34% vs. 27%) than YORA patients (p=0.0039). CONCLUSION: LORA and YORA patients had similar prognosis in terms of time to remission. At remission, LORA patients were more likely to be on a single csDMARD without a biologic or JAK inhibitor.

Disease activity trajectories for early and established rheumatoid arthritis: Real-world data from a rheumatoid arthritis cohort.

OBJECTIVES: Disease activity status described at fixed time points does not accurately reflect disease course in chronic and relapsing diseases such as rheumatoid arthritis (RA). We described longitudinal disease activity trajectories in early and established RA. METHODS: Patients with available 28-Joint Disease Activity Score-erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI) over two years were included. Using latent growth curve modelling (LCGM), subgroups of patients following distinct patterns were identified. RESULTS: 1920 patients were included with 34.4% in early RA (< 2 years' disease duration). Three subgroups were identified using DAS28-ESR in early RA: 1) low disease activity to remission (LDA-REM: 19.1%); 2) moderate disease to remission (MD-REM: 54%); 3) high to moderate disease (HD-MD: 26.9%). The HD-MD group had a significantly higher number of comorbidities, biologic and steroid use and lower post-secondary education. Using CDAI, we identified seven subgroups with only 1.9% remission in early RA. In established RA, seven subgroups were identified using either DAS28-ESR or CDAI. Using DAS28-ESR 27.8% with HD showed improvement in disease status (14.2% HD-REM, 10.3% HD-LDA and 3.3% HD-MD) while using CDAI 17.9% showed improvement. CONCLUSION: Disease course was different in early and established RA. Only 14.2% of established RA reached DAS28-ESR remission compared to 73.1% of early RA. Using CDAI only 1.9% of early RA and none of the established RA achieved remission, likely reflecting the impact of the patient global assessment on this score. Findings also illustrate the impact of sociodemographic characteristics and early treatment on disease course.

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.

OBJECTIVES: 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. METHODS: 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. RESULTS: CDAI correlation with DAS28 was strong when CDAI>10 (ρ=0.79), moderate when CDAI≤10 (ρ=0.56) or 2.810, 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

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

OBJECTIVE: 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). METHODS: 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. RESULTS: 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). CONCLUSION: In patients with RA, physician- and patient-reported effectiveness are similar in the TNFi and TOF groups 6 months after treatment.

Changes in Market Share of Biologic and Targeted Synthetic Disease-Modifying Anti-Rheumatic Drugs for Treatment of Rheumatoid Arthritis: Results from the Ontario Best-Practice Research Initiative Database.

OBJECTIVE: For patients with Rheumatoid Arthritis (RA) who do not achieve adequate clinical response with combined conventional synthetic disease-modifying anti-rheumatic drugs (cs- DMARDs), initiation of advanced therapies such as biologic DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) is recommended. Tumour necrosis factor inhibitors (TNFi) are the oldest and most commonly used subgroup of advanced therapies. In the last decade, new non-TNFi advanced therapy options have become available. We described the relative use of TNFi vs. non-TNFi in Ontario-based practices from 2008-2017. METHODS: Adult patients with RA enrolled in the Ontario Best Practices Research Initiative (OBRI) database who started bDMARDs or tsDMARDs anytime during or within 30 days prior to enrollment were included. The proportion of patients treated with TNFi vs. non-TNFi agents between 2008 and 2017 was described for all patients and those initiating their first bDMARD/tsDMARD. All TNFi therapies were included. Non-TNFi included Abatacept, Rituximab, Tocilizumab, and Tofacitinib. RESULTS: A total of 1,057 patients were included, of whom 72.0% were bDMARD/tsDMARD naïve. In 2008, the relative non-TNFi use was 5.4% in all patients while it was 0% in bDMARD/ts- DMARD-naïve patients. In 2017, the proportion of patients using non-TNFi increased to 33.8% among all patients and 33.3% in bDMARD/tsDMARD-naïve patients. CONCLUSION: This descriptive analysis of data from the OBRI cohort reveals that TNFi are still used in the majority of cases; however, there has been an increase in the use of non-TNFi therapies both overall and as first-line advanced therapy. This trend towards non-TNFi therapies as first-line advanced therapy may be partially explained by the shift in guideline recommendations from TNFi as first-line to any of the advanced therapeutics.

Time to remission in swollen joints is far faster than patient reported outcomes in rheumatoid arthritis: results from the Ontario Best Practices Research Initiative (OBRI).

OBJECTIVES: RA patients are often not in remission due to patient global assessment of disease activity (PtGA) included in disease activity indices. The aim was to assess the lag of patient-reported outcomes (PROs) after remission measured by clinical disease activity index (CDAI) or swollen joint count (SJC28). METHODS: RA patients enrolled in the Ontario Best Practices Research Initiative registry not in low disease state at baseline with at ≥6 months of follow-up, were included. Low disease state was defined as CDAI ≤ 10, SJC28 ≤ 2, PtGA ≤ 2cm, pain score ≤ 2cm, or fatigue ≤ 2cm. Remission included CDAI ≤ 2.8, SJC28 ≤ 1, PtGA ≤ 1cm, pain score ≤ 1cm, or fatigue ≤ 1cm. Time to first low disease state/remission based on each definition was calculated overall and stratified by early vs established RA. RESULTS: A total of 986 patients were included (age 57.4 (12.9), disease duration 8.3 (9.9) years, 80% women). The median (95% CI) time in months to CDAI ≤ 10 was 12.4 (11.4, 13.6), SJC28 ≤ 2 was 9 (8.2, 10), PtGA ≤ 2cm was 18.9 (16.1, 22), pain ≤ 2cm was 24.5 (19.4, 30.5), and fatigue ≤ 2cm was 30.4 (24.8, 31.7). For remission, the median (95% CI) time in months to CDAI ≤ 2.8 was 46.5 (42, 54.1), SJC28 ≤ 1 was 12.5 (11.4, 13.4), PtGA ≤ 1cm was 39.6 (34.6, 44.8), pain ≤ 1cm was 54.7 (43.6, 57.5) and fatigue ≤ 1cm was 42.6 (36.8, 48). Time to achieving low disease state and remission was generally significantly shorter in early RA compared with established RA with the exception of fatigue. CONCLUSION: Time to achieving low disease state or remission based on PROs was considerably longer compared with swollen joint count. Treating to a composite target in RA could lead to inappropriate changes in DMARDs.

Discontinuation of biologic therapy due to lack/loss of response and adverse events is similar between TNFi and non-TNFi class: Results from a real-world rheumatoid arthritis cohort.

OBJECTIVES: Time to discontinuation of biologic therapy may be related to mechanism of action. We aimed to compare discontinuation of tumor necrosis factor inhibitors (TNFi) versus non-TNFi in an observational rheumatoid arthritis cohort. METHODS: Patients enrolled in the Ontario Best Practices Research Initiative (OBRI) starting biologic agents on or after 1st January 2010 were included. Time to discontinuation due to (1) any reason, (2) any of lack/loss of response, adverse events (AEs), physician, or patient decision, (3) lack/loss of response, and (4) AEs were assessed using Kaplan-Meier survival and Cox proportional hazards regression analysis. RESULTS: A total of 932 patients were included of whom 174 (18.7%) received non-TNFi and 758 (81.3%) received TNFi. Over a median follow-up of 1.7 years, discontinuation was reported for 416 (44.6%) due to any reason, 367 (39.4%) due to any of lack/loss of response, AEs, physician, or patient decision, 192 (20.6%) due to lack/loss of response, and 102 (10.9%) due to AEs. After adjusting for propensity score, there was no significant difference in discontinuation between the two classes due to any reason [HR 1.14 (0.90-1.46), p = 0.28], lack/loss of response [HR: 1.01 (0.70-1.47), p = 0.95], and AEs [HR: 1.06 (0.64-1.73), p = 0.83]. Similar results were found in biologic naïve patients. CONCLUSIONS: This analysis demonstrates that discontinuation of therapy is similar in patients started on TNFi and non-TNFi therapies. There was also no significant difference in stopping due to lack/loss of response or AEs, suggesting that these reasons should not drive the selection of one treatment over another.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Collection of antirheumatic medication data from both patients and rheumatologists shows strong agreement in a real-world clinical cohort: the Ontario Best Practices Research Initiative-a rheumatoid arthritis cohort.

OBJECTIVES: The objective of the study was to examine the agreement between patient- and rheumatologist-reported antirheumatic medication (ARM) use in the Ontario Best Practices Research Initiative. STUDY DESIGN AND SETTING: We included adult patients who enrolled on or after September 1st 2010 and compared ARM use where rheumatologist visits and interviews occurred within 60 days of each other. Kappa statistic was used to measure agreement. We calculated sensitivity, specificity, and positive and negative predictive value, considering patient-reported data as the gold standard. To examine factors associated with agreement, a hierarchical generalized linear model was used. A subset analysis was also completed to compare start and stop dates of ARM. RESULTS: Overall agreement for ARM was good with higher sensitivity and lower specificity for conventional synthetic disease-modifying antirheumatic drugs compared with biologic disease-modifying antirheumatic drugs. Increased Health Assessment Questionnaire pain index and 28 disease activity score-erythrocyte sedimentation rate (DAS28-ESR) were significantly associated with lower agreement. Reporting stop dates was higher (19.4%) for patient-reported data compared with rheumatologist-reported data (13.1%). CONCLUSION: ARM reports had strong agreement particularly for patients who have low disease activity and pain. ARM discontinuation was reported more frequently by patients, which may indicate that patients may be discontinuing use of their rheumatoid arthritis medications before consulting their rheumatologist.

Frailty and risk of osteoporotic fractures in patients with rheumatoid arthritis: Data from the Ontario Best Practices Research Initiative.

The evidence assessing the relationship between frailty and risk of adverse health outcomes in patients with rheumatoid arthritis (RA) remains limited and sparse in the literature. Data from the Ontario Best Practices Research Initiative (OBRI), a clinical registry of patients with RA, were used to explore the relationship between frailty and fracture risk in patients with RA. Patients were referred to OBRI by their participating rheumatologist, and contacted by OBRI trained interviewers. Primary outcome was time to first incident osteoporotic fractures during follow-up that led to a hospitalization or emergency room visit. Frailty was measured by a Rockwood-type frailty index (FI) of deficit accumulation that consisted of 32 health-related deficits. To quantify the relationship between frailty and risk of fracture, we used Cox proportional hazards models with hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) reported. We included 2923 patients (mean age 57.7 standard deviation [SD]: 12.7; 78% female,) for analyses. During a mean follow-up of 3.7 years, there were 125 (4.3%) incident fractures reported. The FI was significantly higher in patients with a fracture compared to controls (0.24 vs. 0.20, p = 0.02). The FI was found to be significantly related to increased risk of fracture in the fully-adjusted models, with a HR of 1.04 (95% CI: 1.02-1.06, p < 0.001) and 1.58 (95% CI: 1.32-1.89, p < 0.001) for per-0.01 and per-SD increase in the FI respectively. In summary, our study demonstrates that higher frailty status is significantly related to increased risk of osteoporotic fractures in patients with RA. Quantifying the frailty status as a research tool may aid in fracture risk assessment, management and decision-making in RA.

Impact of residential area on the management of rheumatoid arthritis patients initiating their first biologic DMARD: Results from the Ontario Best Practices Research Initiative (OBRI).

Access to care and management of Rheumatoid Arthritis (RA) patients may differ based on residential area. We described differences in the profile of patients initiating their first biologic disease modifying antirheumatic drug (bDMARD) based on their residential area type.Cross-sectional analysis of 793 adult RA patients in the longitudinal Ontario Best Practices Research Initiative (OBRI) registry initiating their first bDMARD <30 days prior to or anytime post-enrolment. Patient residential and clinic areas (rural vs. urban) were classified using 2 methods: postal codes and Statistics Canada population centres. Sociodemographics, disease characteristics, and RA medications (tumor necrosis factor inhibitor [TNFi] vs. non-TNFi, concurrent use of conventional synthetic DMARDs [csDMARDs], and intravenous [IV] vs. subcutaneous [SC] bDMARD) at initiation of first bDMARD were contrasted between residential area types.Other than marital status, first language, and race (higher proportion of married, English speaking, Caucasian patients in rural areas), no significant differences were observed in the demographic and disease characteristics of patients living in rural and urban areas. In multivariate analysis, there was no association between residential area type and type of bDMARD use, concurrent csDMARD(s) use or route of bDMARD. However, patients living farther from their treating clinic were significantly less likely to initiate IV bDMARD. Female rheumatologist and rural clinic location were independently associated with lower odds of IV bDMARD use.The use of SC vs. IV bDMARD was associated with being seen in a clinic located in a rural area, being treated by a female rheumatologist, and living farther from treating clinic. These results suggest possible prescription bias in bDMARD selection and/or patient preferences due to convenience.

Effect of Concomitant Disease-modifying Antirheumatic Drugs and Methotrexate Administration Route on Biologic Treatment Durability in Rheumatoid Arthritis: OBRI Cohort Results.

OBJECTIVE: Prior studies have suggested that concurrent conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy enhances the efficacy of biologic DMARD (bDMARD). Here, we assessed the effect of concomitant csDMARD use and methotrexate (MTX) route of administration on time to bDMARD discontinuation in a large Canadian (Ontario), observational, rheumatoid arthritis (RA) cohort. METHODS: Patients from the Ontario Best Practices Research Initiative (OBRI) who initiated bDMARD therapy and had ≥ 1 followup assessment were included. The effect of concomitant csDMARD use (primary analysis) and MTX route of administration (secondary analysis) on bDMARD discontinuation owing to (1) any reason, (2) ineffectiveness, (3) adverse events (AE), and (4) both (2) and (3), were assessed with multivariate Cox regression. RESULTS: Among the 814 patients included, 153 (18.8%) received bDMARD monotherapy and 661 (81.2%) combination csDMARD/bDMARD therapy. Over a mean followup of 1.9 years, bDMARD were discontinued in 38.7% of patients. In multivariate analysis, there was a nonsignificant trend toward lower discontinuation for the csDMARD/bDMARD group compared to bDMARD monotherapy for any reason (HR 0.76, 95% CI 0.55-1.05) and owing to ineffectiveness/AE (HR 0.73, 95% CI 0.50-1.06). Further, patients taking combination therapy had significantly lower risk of bDMARD discontinuation due to AE (HR 0.43, 95% CI 0.24-0.76). In the secondary analysis, no statistical association between MTX dose or route of administration and bDMARD durability was observed. CONCLUSION: Concomitant csDMARD use was associated with a significantly lower hazard for bDMARD discontinuation due to AE among patients with RA followed in routine clinical practice in Ontario, Canada. Neither MTX route of administration nor dose were significant predictors of bDMARD durability.

ACPA and RF as predictors of sustained clinical remission in patients with rheumatoid arthritis: data from the Ontario Best practices Research Initiative (OBRI).

OBJECTIVES: This study evaluated the interaction of anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF) in predicting sustained clinical response in an observational registry of patients with rheumatoid arthritis (RA) followed in routine practice. METHODS: Patients with RA enrolled in the Ontario Best Practices Research Initiative registry, with ≥1 swollen joint, autoantibody information and ≥1 follow-up assessment were included. Sustained clinical remission was defined as Clinical Disease Activity Index (CDAI) ≤2.8 in at least two sequential visits separated by 3-12 months. Time to sustained remission was assessed using cumulative incidence curves and multivariate cox regression. RESULTS: Among 3251 patients in the registry, 970 were included, of whom 262 (27%) were ACPAneg/RFneg, 60 (6.2%) ACPApos /RFneg, 117 (12.1%) ACPAneg/RFpos and 531 (54.7%) ACPApos /RFpos at baseline. Significant between group differences were observed in age (p=0.02), CDAI (p=0.03), tender joint count (p=0.02) and Health Assessment Questionnaire (p=0.002), with ACPApos patients being youngest with lowest disease activity and disability. No difference in biologic use was found between groups (20.2% of patients).Over a mean follow-up of 3 years, sustained remission was achieved by 43.5% of ACPApos/RFpos patients, 43.3% of ACPApos /RFneg patients, 31.6 % of ACPAneg/RFpos patients and 32.4% of ACPAneg/RFneg patients (p=0.01). Significant differences were observed in CDAI improvement based on ACPA and RF status where ACPApos/RFpos had a shorter time to achieving sustained remission (HR 1.30; 95% CI 1.01 to 1.67) and experienced significantly higher improvements compared with ACPAneg/RFneg patients. CONCLUSIONS: Combined ACPA and RF positivity were associated with improved and faster response to antirheumatic medications in patients with RA.