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.

Cardiovascular Risk Factors and the Risk of Discontinuation of Advanced Therapies Due to Treatment Failure in Rheumatoid Arthritis: Results From the Ontario Best Practices Research Initiative.

OBJECTIVES: Our goal was to investigate whether cardiovascular disease (CVD) risk factors are associated with the retention of biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted-synthetic DMARDs (tsDMARDs) in patients with rheumatoid arthritis (RA). METHODS: We included participants in the Ontario Best Practices Initiative RA registry who initiated their first bDMARD or tsDMARD. Participants were grouped by the number of baseline CVD risk factors (0, 1, or ≥2). The primary outcome was time-to-discontinuation of therapy for any reason. Secondary outcomes included discontinuation for primary failure, secondary failure, or due to adverse events. Competing risks hazards model, adjusted for clinically important confounders, estimated the association between CVD risk factors and treatment retention. RESULTS: The sample included 872 patients, of which 58% (n = 508) discontinued their b/tsDMARD after a median of 13 months from the time of initiation. The most common causes for treatment discontinuation were primary failure (n = 72), secondary failure (n = 126), or adverse events (n = 133). Patients with no CVD risk factors experienced significantly longer treatment survival compared to patients with 1 or ≥2 CVD risk factors. In multivariable-adjusted analysis, there was no association between all-cause discontinuation and CVD risk factors. However, there was a significant association between the presence of >1 CVD risk factor and treatment discontinuation, notably due to secondary treatment failure, but not due to adverse events. CONCLUSION: Multiple CVD risk factors increase the risk of treatment failure in RA, particularly for secondary treatment failure. To improve patient outcomes, future research should focus on developing strategies to identify early treatment nonresponse and investigate the potential modifiability of this association.

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.

Post-switch Effectiveness of Etanercept Biosimilar Versus Continued Etanercept in Rheumatoid Arthritis Patients with Stable Disease: A Prospective Multinational Observational Study.

INTRODUCTION: To better inform clinicians about the use of etanercept biosimilar (SB4) in patients with rheumatoid arthritis (RA), COMPANION-B, a prospective real-world observational study, evaluated the effectiveness of the voluntary switch from originator (etanercept, ETN) to SB4 in patients with stable RA (low-disease activity/remission). METHODS: The study recruited adult patients (18 years or older) with RA (2010 American College of Rheumatology criteria) prescribed ETN as their first or second biologic for at least 6 months across 14 sites in Canada and five in Australia. Patients had stable disease (Disease Activity Score-28 using erythrocyte sedimentation rate [DAS28-ESR] less than 3.2) at enrollment with no evidence of flare within the previous 3 months. Concomitant disease-modifying antirheumatic drugs (DMARDs) were permitted. Patients could elect to continue ETN or voluntarily switch to SB4 in consultation with their doctors. The primary effectiveness measure was the proportion of patients with disease worsening (defined as a DAS28-ESR increase of at least 1.2 from baseline and minimum score of at least 3.2 or a defined modification in RA treatment) during 12 months of follow-up. The secondary effectiveness measure was the proportion of patients with disease worsening at month 6. Serious adverse events (SAEs) and non-serious adverse reactions (NSARs) were recorded. RESULTS: Of 163 patients enrolled, 109 elected to continue on ETN and 54 switched to SB4; 65.8% of patients received non-biologic DMARD(s), 52.6% methotrexate, and 10.5% oral corticosteroid(s). At month 12, the proportion of patients with disease worsening was comparable in the ETN group (22.8% [95% CI 15.0-32.2]) and SB4 group (17.6% [95% CI 8.4-30.9]). Similarly, the proportions of patients with disease worsening were also comparable at month 6 (ETN: 7.9% [95% CI 3.5-15.0]; SB4: 7.8% [95% CI 2.2-18.9]). SAEs were low and similar across both groups (ETN: 8.7%; SB4: 5.7%). NSARs were slightly higher in the SB4 vs. ETN group (13.2% vs. 2.9%). CONCLUSIONS: SB4 demonstrated comparable effectiveness to ETN over 12 months in patients with stable RA who voluntarily switched to the biosimilar in a real-world setting.

Canadian Rheumatology Association Living Guidelines for the Pharmacological Management of Rheumatoid Arthritis With Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: To provide the initial installment of a living guideline that will provide up-to-date guidance on the pharmacological management of patients with rheumatoid arthritis (RA) in Canada. METHODS: The Canadian Rheumatology Association (CRA) formed a multidisciplinary panel composed of rheumatologists, researchers, methodologists, and patients. In this first installment of our living guideline, the panel developed a recommendation for the tapering of biologic and targeted synthetic disease-modifying antirheumatic drug (b/ts DMARD) therapy in patients in sustained remission using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, including a health equity framework developed for the Canadian RA population. The recommendation was adapted from a living guideline of the Australia & New Zealand Musculoskeletal Clinical Trials Network. RESULTS: In people with RA who are in sustained low disease activity or remission for at least 6 months, we suggest offering stepwise reduction in the dose of b/tsDMARD without discontinuation, in the context of a shared decision, provided patients are able to rapidly access rheumatology care and reestablish their medications if needed. In patients where rapid access to care or reestablishing access to medications is challenging, we conditionally recommend against tapering. A patient decision aid was developed to complement the recommendation. CONCLUSION: This living guideline will provide contemporary RA management recommendations for Canadian practice. New recommendations will be added over time and updated, with the latest recommendation, evidence summaries, and Evidence to Decision summaries available through the CRA website (www.rheum.ca).

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.

Heterogeneity in Patient Characteristics and Differences in Treatment Across 4 Canadian Rheumatoid Arthritis Cohorts.

OBJECTIVE: To compare clinical characteristics and treatment of patients with rheumatoid arthritis (RA) across 4 Canadian cohorts. METHODS: The 4 longitudinal cohorts included the following: the Canadian Early Arthritis Cohort (CATCH; n = 2878), Ontario Best Practices Research Initiative (OBRI; n = 3734), RHUMADATA (Quebec, n = 2890), and the Rheum4U Precision Health Registry (Calgary, Alberta, n = 709). Data were from cohort inception (range 1998-2016) to 2020. Clinical characteristics and drug treatments were summarized descriptively. RESULTS: In total, 10,211 patients with RA were included. The percentage of patients who entered the cohort with early RA (2 yrs of disease at enrollment) ranged from 29% (Rheum4U) to 100% (CATCH). Mean age (55 yrs), sex (74% female), and seropositivity (69%) were similar between cohorts. At the time of initial disease-modifying antirheumatic drug (DMARD) use, median Disease Activity Score in 28 joints (DAS28) varied, ranging from 2.99 (Rheum4U) to 5.19 (CATCH), but were more similar at the time of the first DMARD switch (range 3.57-5.03), first biologic (bDMARD) or targeted synthetic DMARD (tsDMARD) use (range 4.01-4.67), and second bDMARD or tsDMARD (range 3.71-4.39). The initial DMARD was most commonly methotrexate, either in monotherapy (32%, range 18-40%) or dual therapy (34%, range 29-42%). The first DMARD switch was to another DMARD monotherapy in 20% (range 10-32%), dual therapy in 49% (range 39-56%), and bDMARD or tsDMARD in 24% (range 15-28%). The first bDMARD was an anti-tumor necrosis factor in 79% (range 78-82%). CONCLUSION: Canadian RA cohorts demonstrate some heterogeneity in treatment, which could reflect differences in inclusion criteria, calendar year, or regional differences. This project is a first step toward conducting harmonized analyses across Canadian RA cohorts.

Bridging the Gap Between Symptom Onset and Diagnosis in Axial Spondyloarthritis.

OBJECTIVE: To evaluate a stratified screening process for the early identification of axial spondyloarthritis (SpA) with consideration of the following: 1) wait times from primary care to rheumatology screen, 2) incremental precision and accuracy from primary care to rheumatology screening, and 3) diagnostic delay. METHODS: Adults with low back pain attending primary care at low back pain clinics prospectively underwent a primary standardized clinical screening. Patients with low back pain of >3 months who experienced symptom onset at age <50 years were referred for a comprehensive secondary screening by a physical therapist with advanced rheumatology training. At secondary screening, patients with features of inflammation were classified as being at a low, medium, or high risk for axial SpA versus no risk for axial SpA. Precision and accuracy of this screening strata were measured against a rheumatologist with expertise in axial SpA. RESULTS: Overall, 405 patients underwent primary and secondary screening in the present study. The study cohort had a mean ± SD age of 36.9 ± 9.9 years, and 55% were women. HLA-B27 was present in 14.4% of patients. Median wait time from primary screening to secondary screening was 15 days. Axial SpA risk assignment by rheumatologist was 64.9% for no risk or low risk for axial SpA and 35.1% for medium risk or high risk for axial SpA. The best combination of sensitivity (68%), specificity (90%), positive predictive values (80%), and negative predictive values (84%) was evident in the secondary screening. In this cohort, 15.6% of patients received a final diagnosis of axial SpA. Median low back pain duration from symptom onset to diagnosis was 2 years for nonradiographic axial SpA and 7 years for ankylosing spondylitis. CONCLUSION: A stratified interprofessional screening process can facilitate rapid diagnosis of persistent low back pain with high precision and accuracy in patients who have axial SpA.

Interventions for tophi in gout.

BACKGROUND: Tophi develop in untreated or uncontrolled gout. This is an update of a Cochrane Review first published in 2014.  OBJECTIVES: To assess the benefits and harms of non-surgical and surgical treatments for the management of tophi in gout. SEARCH METHODS: We updated the search of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase databases to 28 August 2020. SELECTION CRITERIA: We included all published randomised controlled trials (RCTs) or controlled clinical trials examining interventions for tophi in gout in adults. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included one trial in our original review. We added four more trials (1796 participants) in this update. One had three arms; pegloticase infusion every two weeks (biweekly), monthly pegloticase infusion (pegloticase infusion alternating with placebo infusion every two weeks) and placebo. Two studies looked at lesinurad 200 mg or 400 mg in combination with allopurinol. One trial studied lesinurad 200 mg or 400 mg in combination with febuxostat. One trial compared febuxostat 80 mg and 120 mg to allopurinol. Two trials were at unclear risk of performance and detection bias due to lack of information on blinding of participants and personnel. All other trials were at low risk of bias. Moderate-certainty evidence (downgraded for imprecision; one study; 79 participants) showed that biweekly pegloticase resolved tophi in 21/52 participants compared with 2/27 on placebo (risk ratio (RR) 5.45, 95% confidence interval (CI) 1.38 to 21.54; number needed to treat for a benefit (NNTB) 3, 95% CI 2 to 6). Similar proportions of participants receiving biweekly pegloticase (80/85) had an adverse event compared to placebo (41/43) (RR 0.99, 95% CI 0.91 to 1.07). However, more participants on biweekly pegloticase (15/85) withdrew due to an adverse event compared to placebo (1/43) (RR 7.59, 95% CI 1.04 to 55.55; number needed to treat for a harm (NNTH) 7, 95% CI 4 to 16). More participants on monthly pegloticase (11/52) showed complete resolution of tophi compared with placebo (2/27) (RR 2.86, 95% CI 0.68 to 11.97; NNTB 8, 95% CI 4 to 91). Similar numbers of participants on monthly pegloticase (84/84) had an adverse event compared to placebo (41/43) (RR 1.05, 95% CI 0.98 to 1.14). More participants on monthly pegloticase (16/84) withdrew due to adverse events compared to placebo (1/43) (RR 8.19, 95% CI 1.12 to 59.71; NNTH 6, 95% CI 4 to 14). Infusion reaction was the most common reason for withdrawal. Moderate-certainty evidence (2 studies; 103 participants; downgraded for imprecision) showed no clinically significant difference for complete resolution of target tophus in the lesinurad 200 mg plus allopurinol arm (11/53) compared to the placebo plus allopurinol arm (16/50) (RR 0.40, 95% CI 0.04 to 4.57), or in the lesinurad 400 mg plus allopurinol arm (12/48) compared to the placebo plus allopurinol arm (16/50) (RR 0.79, 95% CI 0.42 to 1.49). An extension study examined lesinurad 200 mg or 400 mg in combination with febuxostat, or placebo (low-certainty evidence, downgraded for indirectness and imprecision). Participants on lesinurad in the original study continued (CONT) on the same dose. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution; 43/65 in the lesinurad 400 mg CONT arm compared to 38/64 in the lesinurad 200 mg CONT arm had tophi resolution (RR 1.11, 95% CI 0.85 to 1.46). Lesinurad 400 mg plus febuxostat may result in no difference in adverse events; 57/65 in the lesinurad 400 mg CONT arm had an adverse event compared to 50/64 in lesinurad 200 mg CONT arm (RR 1.12, 95% CI 0.96 to 1.32). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events; 10/65 participants in the lesinurad 400 mg CONT arm withdrew due to an adverse event compared to 10/64 participants in the lesinurad 200 mg CONT arm (RR 0.98, 95% CI 0.44 to 2.20). Lesinurad 400 mg plus febuxostat may result in no difference in mean serum uric acid (sUA), which was 3 mg/dl in the lesinurad 400 mg CONT group compared to 3.9 mg/dl in the lesinurad 200 mg CONT group (mean difference -0.90, 95% CI -1.51 to -0.29). Participants who were not on lesinurad in the original study were randomised (CROSS) to lesinurad 200 mg or 400 mg, both in combination with febuxostat. Low-certainty evidence downgraded for indirectness and imprecision showed that lesinurad 400 mg (CROSS) may result in tophi resolution (17/34) compared to lesinurad 200 mg (CROSS) (14/33) (RR 1.18, 95% CI 0.70 to 1.98). Lesinurad 400 mg in combination with febuxostat may result in no difference in adverse events (33/34 in the lesinurad 400 mg CROSS arm compared to 27/33 in the lesinurad 200 mg (CROSS); RR 1.19, 95% CI 1.00 to 1.41). Lesinurad 400 mg plus febuxostat may result in no difference in withdrawals due to adverse events, 5/34 in the lesinurad 400 mg CROSS arm withdrew compared to 2/33 in the lesinurad 200 mg CROSS arm (RR 2.43, 95% CI 0.51 to 11.64). Lesinurad 400 mg plus febuxostat results in no difference in sUA (4.2 mg/dl in lesinurad 400 mg CROSS) compared to lesinurad 200 mg (3.8 mg/dl in lesinurad 200 mg CROSS), mean difference 0.40 mg/dl, 95% CI -0.75 to 1.55. AUTHORS' CONCLUSIONS: Moderate-certainty evidence showed that pegloticase is probably beneficial for resolution of tophi in gout. Although there was little difference in adverse events when compared to placebo, participants on pegloticase had more withdrawals due to adverse events. Lesinurad 400 mg plus febuxostat may be beneficial for tophi resolution compared with lesinurad 200 mg plus febuxostat; there was no difference in adverse events between these groups. We were unable to determine whether lesinurad plus febuxostat is more effective than placebo. Lesinurad (400 mg or 200 mg) plus allopurinol is probably not beneficial for tophi resolution, and there was no difference in adverse events between these groups. RCTs on interventions for managing tophi in gout are needed, and the lack of trial data is surprising given that allopurinol is a well-established treatment for gout.

Health care costs of rheumatoid arthritis: A longitudinal population study.

Quantifying the contribution of rheumatoid arthritis to the acquisition of subsequent health care costs is an emerging focus of the rheumatologic community and payers of health care. Our objective was to determine the healthcare costs before and after diagnosis of rheumatoid arthritis (RA) from the public payer's perspective. The study design was a longitudinal observational administrative data-based cohort with RA cases from Ontario Canada (n = 104,933) and two control groups, matched 1:1 on year of cohort entry from 2001 to 2016. The first control group was matched on age, sex and calendar year of cohort entry (diagnosis year for those with RA); the second group added medical history to the match before RA diagnosis year. The main exposure was new onset RA. The secondary exposure was calendar year of RA diagnosis to compare attributable costs over the study observation window. Main outcomes were health care costs in 2015 Canadian dollars, overall and by cost category. We used attribution methods to classify costs into those associated with RA, those associated with comorbidities, and age/sex-related underlying costs. Health care costs associated with RA increased up to the year of diagnosis, where they reached $8,591: $4,142 in RA associated costs; $1,242 in RA comorbidity associated costs; and $3,207 in underlying costs. In the eighth-year post diagnosis, the RA costs declined to $2,567 while the RA comorbidity associated costs remained relatively constant at $1,142, and the underlying age/sex related cost increased to $4,426. RA patients had lower costs when diagnosed in later calendar years. Our results suggest a large proportion of disease related health care costs are a result of costs associated with RA comorbidities, which may appear many years before diagnosis.

Cardiovascular risk factors are negatively associated with rheumatoid arthritis disease outcomes.

AIMS: Rheumatoid arthritis (RA) is associated with cardiovascular disease (CVD), but the influence of CVD risk factors on RA outcomes is limited. We examined if CVD risk factors alone are associated with RA disease activity and disability. METHODS: We performed a cross-sectional analysis of participants in the Ontario Best Practices Research Initiative, RA registry. Patients were categorized into mutually exclusive CVD categories: (1) No established CVD and no CVD risk factors; (2) CVD risk factors only including ⩾1 of hypertension, dyslipidemia, diabetes, or smoking; or (3) history of established CVD event. Multivariable regression analyses examined the effect of CVD status on Disease Activity Score 28 (DAS28-ESR), Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire Disability Index (HAQ-DI) scores at baseline. RESULTS: Of 2033 patients, 50% had at least 1 CVD risk factor, even in the absence of established CVD. The presence of ⩾1 CVD risk factor was independently associated with higher CDAI [ß coefficient 1.59, 95% confidence interval (CI) 0.29-2.90, p = 0.02], DAS28-ESR (ß coefficient 0.20, 95% CI 0.06-0.34, p = 0.01) and HAQ-DI scores (ß coefficient 0.15, 95% CI 0.08-0.22, p < 0.0001). The total number of CVD risk factors displayed a dose response, as >1 CVD risk factor was associated with higher disease activity and disability, compared with having one or no CVD risk factors. CONCLUSION: CVD risk factors alone, or in combination, are associated with higher disease activity and disability in RA. This emphasizes the importance of risk factor recognition and management, not only to prevent CVD, but also to improve potential RA outcomes.

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.