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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.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 of3 months who experienced symptom onset at age50 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.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.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.

ObjectiveTofacitinib (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).MethodsPatients 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.ResultsFour 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).ConclusionIn patients with RA, physician- and patient-reported effectiveness are similar in the TNFi and TOF groups 6 months after treatment.

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.

ObjectiveTo compare clinical characteristics and treatment of patients with rheumatoid arthritis (RA) across 4 Canadian cohorts.MethodsThe 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.ResultsIn 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%).ConclusionCanadian 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.

ObjectiveTo 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.MethodsThe 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.ResultsIn 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.ConclusionThis 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).

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).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.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%).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.

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 naive 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.

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.

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.

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.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.CDAI correlation with DAS28 was strong when CDAI10 (ρ=0.79), moderate when CDAI≤10 (ρ=0.56) or 2.8CDAI≤10 (ρ=0.44), and very weak when CDAI≤2.8 (ρ=0.02). Classification agreement of low disease activity (LDA)/remission between CDAI (≤10) and DAS28 (≤3.2) or HAQ-DI (≤2) was fair-to-moderate, while poor-to-fair for remission. For CDAI10, 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 CDAI10 but low when CDAI≤10 (α=0.23), 2.8CDAI≤10 (α=-0.42) or CDAI≤2.8 (α=-0.35). PtGA showed lowest correlation with remaining CDAI components.CDAI and DAS28 correlated well in moderate/high disease activity and poorly in LDA/remission. PtGA correlated weakly with other CDAI components and had a stronger influence on CDAI in LDA/remission. Thus, careful interpretation of PtGA is necessary when making treatment decisions, particularly in patients in CDAI LDA who are non-remitters.

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.

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.

BACKGROUND CONTEXT Lumbar spinal stenosis (LSS) can impair blood flow to the spinal nerves giving rise to neurogenic claudication and limited walking ability. Reducing lumbar lordosis can increases the volume of the spinal canal and reduce neuroischemia. We developed a prototype LSS belt aimed at reducing lumbar lordosis while walking. PURPOSE The aim of this study was to assess the short-term effectiveness of a prototype LSS belt compared to a lumbar support in improving walking ability in patients with degenerative LSS. STUDY DESIGN This was a two-arm, double-blinded (participant and assessor) randomized controlled trial. PATIENT SAMPLE We recruited 104 participants aged 50 years or older with neurogenic claudication, imaging confirmed degenerative LSS, and limited walking ability. OUTCOME MEASURES The primary measure was walking distance measured by the self-paced walking test (SPWT) and the primary outcome was the difference in proportions among participants in both groups who achieved at least a 30% improvement in walking distance from baseline using relative risk with 95% confidence intervals. METHODS Within 1 week of a baseline SPWT, participants randomized to the prototype LSS belt group (n=52) and those randomized to the lumbar support group (n=52) performed a SPWT that was conducted by a blinded assessor. The Arthritis Society funded this study ($365,000 CAN) with salary support for principal investigator funded by the Canadian Chiropractic Research Foundation ($500,000 CAN for 5 years). RESULTS Both groups showed significant improvement in walking distance, but there was no significant difference between groups. The mean group difference in walking distance was −74 m (95% CI: −282.8 to 134.8, p=.49). In total, 62% of participants wearing the prototype LSS belt and 82% of participants wearing the lumbar support achieved at least 30% improvement in walking distance (relative risk, 0.7; 95% CI: 0.5–1.3, p=.43). CONCLUSIONS A prototype LSS belt demonstrated significant improvement in walking ability in degenerative LSS but was no better than a lumbar support.

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.

ObjectivesRA 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).MethodsRA 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.ResultsA 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.ConclusionTime 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.

Objective To quantify patient preferences for maintenance therapy of Crohn’s disease and understand the impact on treatment selection. Methods We conducted a discrete-choice experiment in patients with Crohn’s disease (n = 155) to measure the importance of attributes relevant to choosing between different medical therapies for maintenance of Crohn’s disease. The attributes included efficacy and withdrawals due to adverse events, as well as dosing and other rare risks of treatment. From the discrete-choice experiment we estimated the part-worth (importance) of each attribute level, and explored preference heterogeneity through latent class analysis. We then used the part-worths to apply weights across each outcome from a prior network meta-analysis to estimate patients’ preferred treatment in pairwise comparisons and for the overall group of treatments. Results The discrete-choice experiment revealed that maintaining remission was the most important attribute. Patients would accept a rare risk of infection or cancer for a 14% absolute increased chance of remission. Latent class analysis demonstrated that 45% of the cohort was risk averse, either to adverse events or requiring a course of prednisone. When these preferences were used in modelling studies to compare pairs of treatments, there was a ≥ 78% probability that all biologic treatments were preferred to azathioprine and methotrexate, based on the balance of benefits and harms. When comparing all treatments, adalimumab was preferred by 53% of patients, who were motivated by efficacy, and vedolizumab was preferred by 30% who were driven by the preference to avoid risks. However, amongst biologic treatment options, there was considerable uncertainty regarding the preferred treatment at the individual patient level. Conclusion Patients with Crohn’s disease from our population were, on average, focused on the benefits of treatment, supporting intensive treatment approaches aimed at maintaining remission. Important preference heterogeneity was identified, however, highlighting the importance of shared decision making when selecting treatments.

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.

Despite the availability of treatment guidelines and effective treatments, real-world effectiveness remains suboptimal partly due to poor patient medication adherence. We evaluated a comprehensive set of sociodemographic, health insurance, and disease-related factors for association with patient decision to discontinue anti-rheumatic medications (ARMs) in a large observational RA cohort in Ontario, Canada. Patients from the Ontario Best Practices Research Initiative registry were included. The following predictors of ARM discontinuation were evaluated with cox-regression: patient age, gender, education, income, smoking, health insurance type/coverage, RA duration, erosion presence, RF positivity, DAS28-ESR, physician global, HAQ-DI, comorbidity number, ARM types, and physician characteristics (gender, academic position, urban vs. rural, distance from patient's residence). Patients (1762) were included with a mean (SD) age of 57.4 years (13.0). Approximately 80% were female, 29% had early (≤ 1 year) RA, and 70% were RF-positive. Mean (SD) baseline DAS28-ESR and HAQ-DI were 4.5 (1.5) and 1.2 (0.76), respectively. In multivariate analysis, married status (HR [95%CI] 0.73 [0.56-0.96]), RF positivity (0.73 [0.56-0.96]), and higher comorbidity number (0.92 [0.85-0.99]) were significant predictors of ARMs continuation while higher physician global (1.10 [1.04-1.15]), NSAID use (1.75 [1.29-2.38]), and number of ARMs (1.23 [1.07-1.40]) were associated with ARMs discontinuation. In a subset analysis assessing conventional or biologic DMARD discontinuation, higher HAQ-DI and biologic use over time were associated with lower hazard for discontinuation. Several sociodemographic, disease, and treatment parameters were identified as independent predictors of patient discontinuation of ARMs. These results should be considered when developing patient adherence support programs and in the choice of treatment regimens.

Background context Lumbar spinal stenosis (LSS) leads to diminished blood flow to the spinal nerves causing neurogenic claudication and impaired walking ability. Animal studies have demonstrated increased blood flow to the spinal nerves and spinal cord with superficial para-spinal electrical stimulation of the skin. Purpose The aim of this study was to assess the effectiveness of active para-spinal transcutaneous electrical nerve stimulation (TENS) compared to de-tuned TENS applied while walking, on improving walking ability in LSS. Study design This was a two-arm double-blinded (participant and assessor) randomized controlled trial. Patient sample We recruited 104 participants 50 years of age or older with neurogenic claudication, imaging confirmed LSS and limited walking ability. Outcome measures The primary measure was walking distance measured by the self-paced walking test (SPWT) and the primary outcome was the difference in proportions among participants in both groups who achieved at least a 30% improvement in walking distance from baseline using relative risk with 95% confidence intervals. Methods The active TENS group (n = 49) received para-spinal TENS from L3-S1 at a frequency of 65–100 Hz modulated over 3-s intervals with a pulse width of 100–200 usec, and turned on 2 min before the start and maintained during the SPWT. The de-tuned TENS group (n = 51) received similarly applied TENS for 30 s followed by ramping down to zero stimulus and turned off before the start and during the SPWT. Study funded by The Arthritis Society ($365,000 CAN) and salary support for Carlo Ammendolia funded by the Canadian Chiropractic Research Foundation ($500,000 CAN over 5 years). Results From August 2014 to January 2016 a total of 640 potential participants were screened for eligibility; 106 were eligible and 104 were randomly allocated to active TENS or de-tuned TENS. Both groups showed significant improvement in walking distance but there was no significant difference between groups. The mean difference between active and de-tuned TENS groups was 46.9 m; 95% CI (− 118.4 to 212.1); P = 0.57. A total of 71% (35/49) of active TENS and 74% (38/51) of de-tuned TENS participants achieved at least 30% improvement in walking distance; relative risk (RR), 0.96; 95% CI, (0.7 to 1.2) P = 0.77. Conclusions Active TENS applied while walking is no better than de-tuned TENS for improving walking ability in patients with degenerative LSS and therefore should not be a recommended treatment in clinical practice. Registration ClinicalTrials.gov ID: NCT02592642. Registration October 30, 2015.

Supplemental Digital Content is available in the text, 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

Objective.We evaluated the influence of triage assessments by extended role practitioners (ERP) on improving timeliness of rheumatology consultations for patients with suspected inflammatory arthritis (IA) or systemic autoimmune rheumatic diseases (SARD).Methods.Rheumatologists reviewed primary care providers’ referrals and identified patients with inadequate referral information, so that a decision about priority could not be made. Patients were assessed by an ERP to identify those with IA/SARD requiring an expedited rheumatologist consult. The time from referral to the first consultation was determined comparing patients who were expedited to those who were not, and to similar patients in a usual care control group identified through retrospective chart review.Results.Seven rheumatologists from 5 communities participated in the study. Among 177 patients who received an ERP triage assessment, 75 patients were expedited and 102 were not. Expedited patients had a significantly shorter median (interquartile range) wait time to rheumatologist consult: 37.0 (24.5–55.5) days compared to non-expedited patients [105 (71.0–135.0) days] and controls [58.0 (24.0–104.0) days]. Accuracy comparing the ERP identification of IA/SARD to that of the rheumatologists was fair (κ 0.39, 95% CI 0.25–0.53).Conclusion.Patients triaged and expedited by ERP experienced shorter wait times compared to usual care; however, some patients with IA/SARD were missed and waited longer. Our findings suggest that ERP working in a triage role can improve access to care for those patients correctly identified with IA/SARD. Further research needs to identify an ongoing ERP educational process to ensure the success of the model.

Prescribing the first biologic treatment for rheumatoid arthritis (RA) is an important decision for patients, their physicians, and payers, with considerable costs and clinical implications. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) have known effectiveness and safety profiles and are less expensive; therefore, determining the variables contributing to csDMARD treatment duration is an essential question for patients, physicians, and payers.To describe access to the first biologic DMARD prescription in a population of patients with RA and identical comprehensive health insurance coverage in Ontario, Canada, and to explore the associations of patient, prescriber, and geographic region with differences in time to first biologic prescription.This cohort study of incident patients with RA used administrative data with surveillance and patient-level data collected at yearly intervals. A total of 17 672 patients were included in the study; they were residents of Ontario, Canada, had an incident RA diagnosis at age 67 or older between 2002 and 2015, and received at least 1 csDMARD. Data were analyzed in November 2017.Patient variables were age, sex, disease duration, socioeconomic status, distance to care, and supply of care in the patient's area of residence. Prescriber covariates were year of graduation, specialty of practice, and supply of rheumatologic care in the patient's geographic region.Time from first csDMARD prescription to receipt of first biologic medication.Of 17 672 patients, 11 598 (65.6%) were women, and the mean (SD) age was 75.2 (5.8) years. Characteristics associated with longer time to receipt of a biologic prescription were older age (HR for every 5-year increase, 0.66; 95% CI, 0.62-0.71; P .001), male sex (HR, 0.76; 95% CI, 0.66-0.89; P .001), and distance to the nearest rheumatologist (HR per 10-km increase, 0.99; 95% CI, 0.98-0.99; P .001). Prescribers were primarily rheumatologists (151 of 214 [70.6%]) and primary care physicians (26 of 214 [12.1%]). After adjusting for the number of patients eligible to receive biologic DMARDs, rheumatologists' preferences (ie, yearly prescription rates) for using biologic DMARDs increased over time, from 1.7% in 2001 to 4.9% in 2015. After adjusting for calendar year and patient-, prescriber-, and region-level characteristics, substantial variation between prescribers in rates of prescribing a first biologic DMARD were found (65% variance).This study found variation in time to receipt of first biologic DMARD after prescription of first csDMARD in a population with RA after adjustment for individual-level patient, prescriber, and geographic area covariates, despite identical universal health insurance coverage.

Objective.We sought to determine if initial high disease activity or changes in disease activity contribute to persistent depression in early rheumatoid arthritis (ERA). We also determined if disease activity and depression is modified by sex.Methods.Depression was ascertained by self-report among patients enrolled in the Ontario Best Practices Research Initiative. The association between baseline disease activity, measured by the Clinical Disease Activity Index (CDAI), and persistent depression was evaluated with multivariate regression models, and effect modification by sex was tested. A general estimating equation assessed the association between change in CDAI over time and risk of depression.Results.The sample of 469 ERA subjects was predominantly female (73%). At baseline, the prevalence of depression was 26%, and 23% reported persistent depression. After adjusting for potential confounders, higher baseline CDAI was associated with both baseline and persistent depression (OR 1.03, 95% CI 1.01–1.05). Female sex was an effect modifier of this relationship (OR 1.04, 95% CI 1.01–1.06). Maintaining a moderate or high CDAI score over 2 years also increased the risk of future depression.Conclusion.Depression in ERA is common and initial high disease activity is associated with the probability of depression and its persistence. This risk seems particularly modified in women with active disease and represents an area for targeted focus and screening. Future studies in ERA are needed to determine if intervening during the “window of opportunity” to control disease activity has the potential to mitigate the development and maintenance of adverse mental health outcomes, including depression.

This study aims to compare characteristics between late-onset rheumatoid arthritis (RA) and young-onset RA and determine the association between age at disease onset and disease severity. We cross-sectionally studied 971 patients at the time of entry into the Ontario Best Practices Research Initiative, a registry of RA patients followed up in routine care. We restricted patients to ≤5 years of disease duration. Late-onset RA was defined as an onset ≥60 years of age and young-onset RA

Objectives To assess how well treatment recommendations for rheumatoid arthritis (RA) address Grading of Recommendations Assessment, Development and Evaluation (GRADE) steps and determine whether these steps can be adequately appraised using Appraisal of Guidelines Research & Evaluation II (AGREE-II). Study Design and Setting We systematically reviewed English-language treatment recommendations for the pharmacologic management of RA since 2000, assessed how well GRADE steps were addressed, rated AGREE-II quality, and compared the findings. Results GRADE steps were poorly addressed by the 44 included guidelines. Few guidelines discussed study limitations and/or risk of bias (23%), inconsistency (50%), indirectness (39%), imprecision (23%), or potential for publication bias (0%). Observational evidence was cited in 96% but rarely evaluated systematically. Only one guideline considered evidence on patients' preferences for health outcomes, and few provided an explicit justification for the strength of evidence or recommendation. The five GRADE steps that overlapped with AGREE-II questions were addressed more frequently (by 54–100% of guidelines) than the 13 GRADE steps not directly assessed by AGREE-II (0–50%). Among the nine guidelines rated as “Recommended for use” by AGREE-II, 8 of 13 GRADE steps were not addressed consistently by any guideline. Conclusion GRADE's steps are poorly addressed by RA recommendations. AGREE-II provides a broad assessment of quality but lacks sufficient granularity to assess how well a guideline addresses GRADE's steps.

Objective.To develop a Canadian Rheumatoid Arthritis Core Clinical Dataset (CAN-RACCD) to standardize documentation encouraging high-quality care.Methods.A set of candidate elements was drafted through meetings with 27 rheumatologists, researchers, and patients, and supplemented with focused literature reviews. A 3-round online-modified Delphi consensus process was held with rheumatologists (n = 26), allied health professionals (n = 7), and patients (n = 4); for the remainder there was no demographic information. Participants rated both the importance and feasibility of documenting candidate elements on a Likert scale of 1–9, contributed to an online moderated discussion, and re-rated the elements for inclusion in the CAN-RACCD. Elements were included in the final set if importance and feasibility ratings had a median score of ≥ 6.5 and there was no disagreement among participants.Results.Fifty-five individual elements in 10 subgroups were proposed to the Delphi participants: measures of RA disease activity; dates to calculate waiting times, disease duration, and disease-modifying antirheumatic drug start; comorbidities; smoking status; patient-reported pain and fatigue; physical function; laboratory and radiographic investigations; medications; clinical characteristics; and vaccines. All groups were included in the final set, with the exception of vaccination status. Additionally, 3 individual elements from the smoking subgroup were eliminated with a recommendation to record smoking status as never/ever/current, and 2 elements relating to coping and effect of fatigue were eliminated due to low feasibility and importance ratings.Conclusion.The CAN-RACCD stands as a national recommendation on which data elements should be routinely collected in clinical practice to monitor and support high-quality RA care.

In active rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX), guidelines support adding or switching to another conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) and/or a biologic DMARD (bDMARD). The purpose of this analysis was to describe treatment practices in routine care and to evaluate determinants of regimen selection after MTX discontinuation.Biologic-naïve patients in the Ontario Best Practice Research Initiatives registry discontinuing MTX due to primary/secondary failure, adverse events, or patient/physician decision were included.Of 313 patients discontinuing MTX, 102 (32.6%) were on MTX monotherapy, 156 (49.8%) on double, and 55 (17.6%) on multiple csDMARDs. Patients on MTX monotherapy were older than patients on double or multiple csDMARDs (p=0.013), less likely to have joint erosions (p=0.009) and had lower patient global assessment (p=0.046) at MTX discontinuation. Post-MTX discontinuation, 169 (54.0%) transitioned to, or added new DMARD(s) (new csDMARD(s): 139 [44.4%]; bDMARD: 30 [9.6%]), and 144 (46.0%) opted for no new DMARD treatment. Patients on MTX monotherapy transitioning monotherapy, whereas patients on combination csDMARDs switched more to new csDMARDs and bDMARD combination therapy. Early RA (adjOR [95%CI]: 3.07 [1.40-6.72]) and treatment with multiple csDMARDs vs. MTX monotherapy (4.15 [1.35-12.8]) at MTX discontinuation were significant predictors of transitioning to or adding new csDMARD(s)/bDMARD treatment versus opting for no new DMARD treatment.Differences in subsequent treatment patterns exist between patients discontinuing MTX when used as monotherapy versus in combination with other csDMARDs where the former are more likely to use a subsequent monotherapy treatment.

Objective. To systematically review the evidence on treatment available to prevent an acute attack of gout when initiating a urate-lowering therapy (ULT) and for how long this treatment should be continued. To also evaluate the evidence on the optimal time to start a ULT after an acute attack of gout. Methods. A systematic review as part of the 3e (Evidence, Expertise, Exchange) Initiative on Diagnosis and Management of Gout was performed using Medline, Embase, Cochrane Central Register of Controlled Trials (from 1950 to October 2011), and the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) 2010/2011 meeting abstracts. Two reviewers independently screened titles and abstracts for selection criteria. Included articles were reviewed in detail, and a risk of bias assessment (using the Cochrane tool) was performed. Results. The search identified 8168 articles and 197 abstracts, from which 4 randomized controlled trials were included in the review. Two of these studies compared placebo with colchicine, 1 compared differing durations of colchicine, and 1 compared colchicine with canakinumab. Conclusion. Two randomized controlled trials have shown that colchicine prophylaxis for at least 6 months, when starting a ULT, reduces the risk of acute attacks. Canakinumab, although not currently licensed for gout, has been shown to provide prophylaxis superior to colchicine, when starting a ULT. There is no evidence on the optimum time to start a ULT after an acute gout attack.

OBJECTIVE Patients with rheumatoid arthritis (RA) are at increased risk of TB. Little is known about the risk of nontuberculous mycobacteria (NTM) disease in these patients. We sought to ascertain the rate of NTM infection and TB in all residents of Ontario, Canada, with and without RA. METHODS In a cohort study, all Ontarians aged ≥ 15 years in January 2001 were followed until December 2010. Individuals with RA were identified using a validated algorithm to search hospitalization and physician billing claims. We linked Public Health Ontario Laboratory data to identify all cases of laboratory-confirmed TB and NTM disease. Analysis was performed using Cox proportional hazards regression. RESULTS We identified 113,558 Ontarians with RA and 9,760,075 Ontarians without RA. Relative to the non-RA group, adjusted hazard ratios (HRs) and 95% CIs for TB (1.92, [1.50-2.47]) and NTM disease (2.07, [1.84-2.32]) demonstrated increased risks in the RA group. Among those with RA, per 100,000 person-years, NTM disease (HR, 41.6; 95% CI, 37.1-46.5) was more common than TB (HR, 8.5; 95% CI, 6.5-10.8). After full adjustment, people with RA who developed NTM disease were 1.81 times as likely to die than uninfected people with RA. CONCLUSIONS Mycobacterial infections are more common in Ontarians with RA, with NTM disease more likely than TB. NTM disease is associated with an increased risk of death in patients with RA. Given the rising rates of NTM disease worldwide, determining whether this risk is due to the use of immunosuppressive medications vs RA itself is an important objective for future research.

Objective. To determine the efficacy and safety of glucocorticoids (GC), colchicine, nonsteroidal antiinflammatory drugs (NSAID), interleukin-1 (IL-1) inhibitors, and paracetamol to treat acute gout. Methods. We searched MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to September 2011. Randomized controlled trials (RCT) or quasi-RCT in adults with acute gout that compared GC, colchicine, NSAID, IL-1 inhibitors, and paracetamol to no treatment, placebo, another intervention, or combination therapy were included. Two authors independently extracted data and assessed risk of bias. Primary endpoints were pain and adverse events. Data were pooled where appropriate. Results. Twenty-six trials evaluating GC (N = 5), NSAID (N = 21), colchicine (N = 2), and canakinumab (N = 1) were included. No RCT assessed paracetamol or intraarticular (IA) GC. No RCT compared systemic GC with placebo. Moderate quality evidence (3 trials) concluded that systemic GC were as effective as NSAID but safer. Low quality evidence (1 trial) showed that both high- and low-dose colchicine were more effective than placebo, and low-dose colchicine was no different to placebo with respect to safety but safer than high-dose colchicine. Low quality evidence (1 trial) showed no difference between NSAID and placebo with regard to pain or inflammation. No NSAID was superior to another. Moderate quality evidence (1 trial) found that 150 mg canakinumab was more effective than a single dose of intramuscular GC (40 mg triamcinolone) and equally safe. Conclusion. GC, NSAID, low-dose colchicine, and canakinumab all effectively treat acute gout. There was insufficient evidence to rank them. Systemic GC appeared safer than NSAID and lower-dose colchicine was safer than higher-dose colchicine.

The objective of the Outcome Measures in Rheumatology (OMERACT) Worker Productivity working group is to identify worker productivity outcome measures that meet the requirements of the OMERACT filter. At the OMERACT 11 Workshop, we focused on the at-work limitations/productivity component of worker productivity (i.e., presenteeism) — an area with diverse conceptualization and instrumentation approaches. Various approaches to quantify at-work limitations/productivity (e.g., single-item global and multi-item measures) were examined, and available evidence pertaining to OMERACT truth, discrimination, and feasibility were presented to conference participants. Four candidate global measures of presenteeism were put forth for a plenary vote to determine whether current evidence meets the OMERACT filter requirements. Presenteeism globals from the Work Productivity and Activity Impairment Questionnaire (72% support) and Rheumatoid Arthritis-specific Work Productivity Survey (71% support) were endorsed by conference participants; however, neither the presenteeism global item from the Health and Work Performance Questionnaire nor the Quantity and Quality method achieved the level of support required for endorsement at the present time. The plenary was also asked whether the central item from the Work Ability Index should also be considered as a candidate measure for potential endorsement in the future. Of participants at the plenary, 70% supported this presenteeism global measure. Progress was also made in other areas through discussions at individual breakout sessions. Topics examined include the merits of various multi-item measures of at-work limitations/productivity, methodological issues related to interpretability of outcome scores, and approaches to appraise and classify contextual factors of worker productivity. Feedback gathered from conference participants will inform the future research agenda of the working group.

Objectives To compare the effectiveness of a comprehensive nonsurgical training program to a self-directed approach in improving walking ability in lumbar spinal stenosis (LSS). Design Randomized controlled trial. Setting Academic hospital outpatient clinic. Participants Participants (N=104) with neurogenic claudication and imaging confirmed LSS were randomized. The mean age was 70.6 years, 57% were women, 84% had leg symptoms for >12 months, and the mean maximum walking capacity was 328.7 m. Interventions A 6-week structured comprehensive training program or a 6-week self-directed program. Main Outcome Measures Continuous walking distance in meters measured by the Self-Paced Walk Test (SPWT) and proportion of participants achieving at least 30% improvement (minimally clinically important difference [MCID]) in the SPWT at 6 months. Secondary outcomes included the Zurich Claudication Questionnaire (ZCQ), Oswestry Disability Index (ODI), ODI walk score, and the Short-Form General Health Survey subscales. Results A total of 48 versus 51 participants who were randomized to comprehensive (n=51) or self-directed (n=53) treatment, respectively, received the intervention and 89% of the total study sample completed the study. At 6 months, the adjusted mean difference in walking distance from baseline was 421.0 m (95% confidence interval [95% CI], 181.4-660.6), favoring the comprehensive program and 82% of participants in the comprehensive group and 63% in the self-directed group achieved the MCID (adjusted relative risk, 1.3; 95% CI, 1.0-1.7; P=.03). Both primary treatment effects persisted at 12 months favoring the comprehensive program. At 6 months, the ODI walk score and at 12 months the ZCQ, Medical Outcomes Study 36-Item Short-Form Health Survey-physical function and -bodily pain scores showed greater improvements favoring the comprehensive program. Conclusions A comprehensive conservative program demonstrated superior, large, and sustained improvements in walking ability and can be a safe nonsurgical treatment option for patients with neurogenic claudication due to LSS.

This year marks the 20th anniversary of the Cochrane Collaboration. This means that for 2 decades, members of the Collaboration have searched, reviewed, and synthesized clinical trials, with the goal of facilitating a timely and efficient transfer of research evidence into practice. Members of the C

Objective.To establish cutoffs for the minimum clinically important improvement (MCII) and the patient-acceptable symptom state (PASS) for the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) in patients with ankylosing spondylitis (AS).Methods.Patients with AS who started nonsteroidal antiinflammatory drugs were included. After 4 weeks, the PASS and the MCII were defined using external anchor questions (for the PASS, patients considering their condition of AS over the prior 48 h as “acceptable” forever; and for the MCII, those reporting moderate or slightly important improvement). Consistency of the MCII and PASS were tested according to HLA-B27 status, presence/absence of SpA extraarticular manifestations, age, sex, disease duration, and baseline BASDAI/BASFI score. The 75th percentile of the cumulative distribution was used to determine the MCII and PASS.Results.In total, 283 patients from a multinational cohort were included. Overall cutoffs for the PASS were 4.1 in the BASDAI and 3.8 in the BASFI. Cutoffs for the MCII were 0.7 and 0.4 for the BASDAI and BASFI, respectively. Subgroup analyses revealed that disease duration and baseline BASDAI/BASFI were significantly associated with the PASS and MCII. In a subanalysis limited to patients with active disease (baseline BASDAI ≥ 4), the MCII was 1.1 for the BASDAI and 0.6 for the BASFI.Conclusion.The conceptual viability of the PASS for the BASDAI is questionable because levels approach those required for the start of biological therapy. Because the MCII is less variable than the PASS, we propose its exclusive use, with cutoffs of 1.1/0.6 for the BASDAI/BASFI in patients with active disease. Because these values are based on a subset of the study population, we recommend confirmation in larger studies focused on patients with baseline BASDAI ≥ 4.

Quality measurement for rheumatoid arthritis (RA) patients has largely focused on care provided by rheumatologists. Our aim was to develop and assess quality measures related to the screening and management of comorbidity in RA patients in primary care.We used the primary care Electronic Medical Record Administrative data Linked Database in Ontario, Canada. We harmonized Canadian general population and RA clinical recommendations to develop and assess screening, process, and outcome measures. For each RA patient, 10 non-RA patients were matched by age and sex. Stratified analyses were performed, comparing patients with RA to those without RA, to assess the performance of quality measures.We compared 1,405 RA patients to 14,050 matched non-RA patients (72.8% female; mean age 62.5 years). Compared to non-RA patients, RA patients more frequently had influenza (44.9% versus 40.0%) and pneumococcal (40.4% versus 34.1%) vaccinations and bone mineral density testing (67.4% versus 58.1%). Herpes zoster vaccinations were less frequent among RA patients (13.8% versus 19.5%), as was screening for cervical cancer (58.6% versus 64.0%). No significant differences were observed between RA and non-RA patients in screenings for breast (70.7% versus 73.8%) or colorectal (31.7% versus 34.5%) cancers. Only a quarter of RA patients had a comprehensive cardiovascular risk assessment. No definitive differences were detected in the management of patients who had co-occurring cardiovascular disease or diabetes mellitus.For both RA and non-RA patients, compliance with Canadian recommendations for preventive medical services and screening for comorbid conditions in primary care was less than optimal. This indicates key targets for improvement.

Objectives The objective of the study was to estimate the preferred treatment for early rheumatoid arthritis using a novel Bayesian approach that jointly considers patients’ preferences and comparative effectiveness research. Study Design and Setting We estimated the preferred treatment using patients' preferences measured in a discrete-choice experiment to apply weights to benefit and harm outcomes from a network meta-analysis and other considerations (dosing, rare adverse events). Using Bayesian analyses, we considered the variability in patients' preferences and the imprecision in both patients’ preferences and the treatment effects; all key considerations in the Grading of Recommendations Assessment, Development, and Evaluation approach. Results We estimated that most patients in our population would prefer triple therapy as initial treatment (78%) or after an inadequate response to methotrexate (62%). The probability of choosing triple therapy as initial treatment was further from 50% (the point of indifference) for more patients, making our prediction more confident, and suggesting a stronger recommendation could be made. After an inadequate response to methotrexate, the choice was more split, suggesting a decision aid may be helpful. Conclusion Using a novel approach, we estimated that many patients with early rheumatoid arthritis may prefer triple therapy to other treatment options, in contrast to existing guidelines. This offers an approach that may help inform Grading of Recommendations Assessment, Development, and Evaluation treatment recommendations.

© Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved. Objectives: To determine the extent to which knowledge from clinical trial protocols is transferred to nonparticipating patients. Design: Retrospective review of prospectively collected data from a large clinical trial. Setting: Six level-1 international trauma centers. Methods: We compared rates and timing of reoperation in a subset of patients enrolled in the Study to Prospectively evaluate Reamed Intramedullary Nails in Patients with Tibial Fractures (SPRINT) to concurrent patients who were eligible but not enrolled. This was a retrospective review of prospectively collected trial data. The records of 6 of the original SPRINT centers were searched for non-SPRINT patients who underwent intramedullary nailing of a closed tibial fracture. The rate and timing of reoperation were compared. A P < 0.05 was considered significant. Results: One hundred fourteen non-SPRINT patients were compared with 328 patients enrolled in SPRINT from those same sites. There were 7 reoperations (6.1%) in non-SPRINT patients versus 18 (5.2%) in SPRINT patients [odds ratio (OR) 1.19, 95% confidence interval (CI) 0.41 to 3.13; P 0.811]. There was no difference in the time to reoperation between the SPRINT and non-SPRINT patients (6.2 vs. 6.8 months, 95% CI of the difference -3.8 to 2.6; P 0.685) or in the proportion of patients who underwent reoperation before 6 months (29% vs. 43%; OR 1.75; 95% CI 0.18 to 15.41; P 0.647). Conclusions: Patients not enrolled in SPRINT had similarly low rates of reoperation for nonunion, and the average time to reoperation for both groups was longer than 6 months. A 6-month waiting period may have allowed slow-to-heal fractures adequate time to heal, thereby reducing the rate of diagnosis of nonunion. As such, this waiting period could contribute to lower-than-expected reoperation rates for nonunion. It is possible that clinical trials may beneficially influence the care of nonenrolled patients.

Objective.Disease-modifying antirheumatic drugs (DMARD) have the greatest effect when initiated early. We evaluated the influence of early exposure to DMARD on time to joint replacement surgery among patients with incident rheumatoid arthritis (RA).Method.Using a common protocol, we undertook 2 independent population-based cohort studies of patients with incident RA aged 66 years or older in Ontario (ON) and Quebec (QC) covering the period 2000–2013. We used Cox proportional hazards regression with time-dependent variables measuring duration of drug use in the first year, separately for methotrexate (MTX) and other DMARD, adjusting for baseline demographics, clinical factors, and other potentially confounding drug exposures. Our outcome measure was any joint replacement derived from standardized procedure codes. Adjusted HR and 95% CI were estimated.Results.Among 20,918 ON and 6754 QC patients with RA followed for a median of 4.5 years, 2201 and 494 patients underwent joint replacement surgery for crude event rates of 2.0 and 1.4 per 100 person-years, respectively. Greater cumulative exposure to MTX (HR 0.97, 95% CI 0.95–0.98) and other DMARD (HR 0.98, 95% CI 0.97–0.99) in the first year after diagnosis was associated with longer times to joint replacement in ON, corresponding to a 2–3% decrease in the hazard of surgery with each additional month of early use. Similar results were observed in QC.Conclusion.Greater duration of exposure to DMARD soon after RA diagnosis was associated with delays to joint replacement surgery in both provinces. Early intensive treatment of RA may ultimately reduce demand for joint replacement surgery.

Rheumatoid arthritis (RA) is the most common chronic inflammatory joint disease. Using the Ontario administrative health data housed at the Institute for Clinical Evaluative Sciences, researchers have quantified the population-level burden and epidemiology of RA, mapped its geographic distribution in relation to rheumatologist supply, studied trends in access to rheumatology care and treatment and evaluated patient outcomes. The findings highlight the excess morbidity and mortality associated with the growing burden of RA in the face of a strained rheumatology supply, and raise urgent questions about how best to meet the needs of Ontarians with RA.

Systematic review of randomized controlled trials (RCTs).To determine the effectiveness of herbal medicine for nonspecific low back pain (LBP).Many people with chronic LBP use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in treating people with LBP. This is an update of a Cochrane Review first published in 2006.We searched numerous electronic databases up to September 2014; checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this area. We included RCTs examining adults (over 18 years of age) suffering from acute, sub-acute, or chronic nonspecific LBP. The interventions were herbal medicines that we defined as plants used for medicinal purposes in any form. Primary outcome measures were pain and function. Two review authors assessed risk of bias, GRADE criteria (GRADE 2004), and CONSORT compliance and a random subset were compared with assessments by a third individual. Two review authors assessed clinical relevance and resolved any disagreements by consensus.Fourteen RCTs (2050 participants) were included. Capsicum frutescens (cayenne) reduces pain more than placebo. Although Harpagophytum procumbens (devil's claw), Salix alba (white willow bark), Symphytum officinale L. (comfrey), Solidago chilensis (Brazilian arnica), and lavender essential oil also seem to reduce pain more than placebo, evidence for these substances was of moderate quality at best. No significant adverse events were noted within the included trials.Additional well-designed large trials are needed to test these herbal medicines against standard treatments. In general, the completeness of reporting in these trials was poor. Trialists should refer to the CONSORT statement extension for reporting trials of herbal medicine interventions.N/A.

Objective.To determine the proportion of patients with rheumatoid arthritis (RA) under rheumatologic care treated with disease-modifying antirheumatic drugs (DMARD) within 6 months from symptom onset and the components of time to treatment and its predictors.Methods.A historical inception cohort of 339 patients with RA randomly selected from 18 rheumatology practices was audited. The proportion that initiated DMARD treatment within 6 months from symptom onset was estimated using Kaplan-Meier analysis. Time to each component of the care pathway was estimated. Multivariable modeling was used to determine predictors of early treatment using 12 preselected variables available in the clinical charts. Bootstrapping was used to validate the model.Results.Within 6 months from symptom onset, 41% (95% CI 36%−46%) of patients were treated with DMARD. The median time to treatment was 8.4 (interquartile range 3.8−24) months. Events preceding rheumatology referral accounted for 78.1% of the time to treatment. The most prominent predictor of increased time to treatment was a concomitant musculoskeletal condition, such as osteoarthritis or fibromyalgia. The significance of other variables was less consistent across the models investigated. Included variables accounted for 0.69 ± 0.03 of the variability in the model.Conclusion.Fewer than 50% of patients with RA are treated with DMARD within 6 months from symptom onset. Time to referral to rheumatology represents the greatest component delay to treatment. Concomitant musculoskeletal condition was the most prominent predictor of delayed initiation of DMARD. Implications of these and other findings warrant further investigation.

Objective. To develop evidence-based recommendations for pain management by pharmacotherapy in patients with inflammatory arthritis (IA). Methods. A total of 453 rheumatologists from 17 countries participated in the 2010 3e (Evidence, Expertise, Exchange) Initiative. Using a formal voting process, 89 rheumatologists representing all 17 countries selected 10 clinical questions regarding the use of pain medications in IA. Bibliographic fellows undertook a systematic literature review for each question, using MEDLINE, EMBASE, Cochrane CENTRAL and 2008–09 European League Against Rheumatism (EULAR)/ACR abstracts. Relevant studies were retrieved for data extraction and quality assessment. Rheumatologists from each country used this evidence to develop a set of national recommendations. Multinational recommendations were then formulated and assessed for agreement and the potential impact on clinical practice. Results. A total of 49 242 references were identified, from which 167 studies were included in the systematic reviews. One clinical question regarding different comorbidities was divided into two separate reviews, resulting in 11 recommendations in total. Oxford levels of evidence were applied to each recommendation. The recommendations related to the efficacy and safety of various analgesic medications, pain measurement scales and pain management in the pre-conception period, pregnancy and lactation. Finally, an algorithm for the pharmacological management of pain in IA was developed. Twenty per cent of rheumatologists reported that the algorithm would change their practice, and 75% felt the algorithm was in accordance with their current practice. Conclusions. Eleven evidence-based recommendations on the management of pain by pharmacotherapy in IA were developed. They are supported by a large panel of rheumatologists from 17 countries, thus enhancing their utility in clinical practice.

OBJECTIVE To quantify the preferences of patients with early RA (ERA) with the benefits and harms of DMARDs. METHODS We assessed patients' preferences using a discrete-choice experiment, an experimentally designed survey to measure trade-offs. Consecutive adult patients with ERA (

Our aim was to characterize referrals to rheumatologists, the early care management of patients with rheumatic diseases, and timeliness of care and treatment.We conducted a retrospective observational study involving patients with first-time rheumatology referrals between 2000 and 2013 in the primary care Electronic Medical Record Administrative data Linked Database (EMRALD) in Ontario, Canada. Referrals were characterized in terms of diagnoses, patient demographics, diagnostic tests, treatment initiated by family physicians and rheumatologists, and other specialists seen prior to rheumatology consultation. Timeliness of referrals, rheumatologist consultations, and treatment were determined overall and for each diagnostic category.Among 2,430 patients referred to a rheumatologist, 69% were female, with an average age of 53 years. The principal diagnosis associated with the referral included osteoarthritis (32%), systemic inflammatory rheumatic diseases (31%), regional musculoskeletal conditions (16%), chronic pain conditions (14%), osteoporosis (2%), and other/miscellaneous (5%). Family physicians most frequently prescribed nonsteroidal antiinflammatory drugs/cyclooxygenase 2 inhibitors (38%), and their pre-referral diagnostic testing practice varied considerably. The duration of time from symptom onset to rheumatology consultation varied by diagnoses, with the shortest being for patients with systemic rheumatic diseases; for rheumatoid arthritis (RA), the median time to consultation was 327 days. Most of the delay occurred prior to referral; 36% of RA patients initiated a disease-modifying antirheumatic drug within 6 months of symptom onset.Approximately 1 in 3 referrals to rheumatologists were for a systemic inflammatory rheumatic disease. We observed substantial delays to rheumatology consultations and variations in patterns of care that could be amenable to quality improvement interventions.

Objective To examine the quality of reporting and predictors of reporting in randomized clinical trials (RCTs) of herbal medicine interventions. Study Design and Setting We searched Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, and Academy of Microscope Enhanced Dentistry up to December 2007 for any English language RCT of 11 commonly used herbal medicine interventions. Two individuals separately and independently assessed all trials using the Consolidated Standards of Reporting Trials (CONSORT) checklist for herbal medicines interventions. We randomly selected 100 of these trials, extracted a set of potential predictor variables identified through a literature search and consultation with experts, and performed a conceptually driven stepwise elimination regression analyses for predictor variables. Results The 406 trials reported on average 38% of the information suggested in the checklist. Regression analyses revealed better overall reporting in trials with a participant flow diagram ( P =0.008), those of Panax quinquefolius ( P =0.018), and those published in more recent years ( P =0.02). Conclusion Our results indicate that RCTs of herbal medicine interventions frequently do not report important characteristics of the intervention. Trialists should refer to the CONSORT for herbal medicines when reporting their trials.

Objective.To determine the proportion of patients with rheumatoid arthritis (RA) seen by rheumatologists and treated with disease-modifying antirheumatic drugs (DMARD) within 3 months of symptom onset, to determine where treatment delays occur, and to identify contributing factors.Methods.A retrospective cohort study in which adult patients with RA, diagnosed between January 1, 2003, and May 31, 2006, were recruited from rheumatologists’ offices to participate in a telephone survey and chart review. The percentage treated with DMARD within 3 months of symptom onset was determined, along with median times for delay. Factors contributing to the delay were explored using multivariable logistic regression.Results.Our study included 204 patients. Within 3 months of symptoms, 22.6% (95% CI 16.8%, 28.3%) received DMARD and within 6 months, 47.6% (95% CI 40.7%, 54.4%). The median time from symptom onset to DMARD was 6.4 months [interquartile range (IQR) 3.3, 12.0] with a median time from RA diagnosis by a rheumatologist to DMARD of 0.0 months (IQR 0.0, 1.0). Higher baseline swollen joint counts resulted in earlier treatment. Age, sex, education, comorbidity, rheumatologist practice type, and years since the physician’s graduation did not affect time to treatment.Conclusion.Fewer than 25% of patients referred to rheumatologists were treated within 3 months of symptom onset. Identification of inflammatory arthritis and referral to rheumatologists are the key factors in timely care, because once patients are seen there is no delay to treatment. Future resources should be focused on development and evaluation of interventions to facilitate rapid triage, referral, and assessment by a rheumatologist.

Objective. To systematically review the differential diagnosis and minimal clinical investigation used prior to making a diagnosis of undifferentiated peripheral inflammatory arthritis (UPIA). Methods. A systematic literature search was performed for articles published between January 1950 and December 2008 in Medline and Embase, and for abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR). Studies including defined cohorts of patients with UPIA were retrieved according to predefined inclusion/exclusion criteria. Selected studies were systematically reviewed and relevant data extracted. Baseline characteristics were also recorded to obtain a clinical picture of patients classified as UPIA. Results. Seventy-four articles were included. Of those, 52 reported baseline characteristics. Tremendous variation existed among studies, reflecting the different inclusion/exclusion criteria used. Rheumatoid arthritis, spondyloarthropathies, osteoarthritis, crystal arthritis, connective tissue diseases, and infections were the most common diagnoses of exclusion for UPIA and made up the other subsets of patients in cohorts with mixed populations. The baseline investigation undertaken prior to diagnosis of UPIA was reported in 7 articles. History, physical examination, tender and swollen joint count, rheumatoid factor, HLA-B27, erythrocyte sedimentation rate, C-reactive protein, and radiographs of hands and feet were the only items mentioned in at least 50% of the reports. Conclusion. Studies of UPIA are heterogeneous. Few studies reported on the minimal clinical investigation necessary to arrive at a diagnosis of UPIA. Differential diagnosis usually consisted of the most common rheumatologic conditions but could be vast.

Objective. To critically appraise the validity of activity indices used in the followup of patients with undifferentiated peripheral inflammatory arthritis (UPIA). Methods. A systematic review was performed in Medline, Embase, the Cochrane Library, and abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology and European League Against Rheumatism. Selection criteria were: patients with UPIA, the assessment of instruments to evaluate disease activity, and assessment of validity of the instruments. Two reviewers screened titles and abstracts independently and collected data using ad hoc standard forms. Results. The search yielded 179 articles and 834 abstracts, of which 4 articles and 1 abstract were included. We found no study that validated Disease Activity Score (DAS), Clinical Disease Activity Index (CDAI), or Simplified Disease Activity Index (SDAI). Included studies addressed validation of 4 questionnaires: WHO Disability Assessment Schedule (WHODAS), London Handicap Scale (LHS), Disease Repercussion Profile (DRP), and the Health Assessment Questionnaire (HAQ); and 3 indexes: RA Disease Activity Index (RADAI), McGill Range of Motion Index (McROMI), and NOAR Damaged Joint Count (NOAR-DJC). Questionnaires were self-administered and feasible; RADAI was the most feasible index. Internal consistency was studied in the questionnaires (Cronbach’s α > 0.83). Responsiveness was tested in the DRP, LHS, and HAQ, but the approach to study sensitivity to change was poorly explained, with no clear intervention. Construct validity, examined by means of convergence with other instruments, was generally moderate, and slightly higher for the RADAI. Conclusion. No instrument of disease activity has been fully validated for use in UPIA. We found no direct evidence of what is the most useful index to follow up patients with UPIA.