A Canadian Retrospective Chart Review Evaluating Concomitant Methotrexate De-escalation Patterns in Patients with Rheumatoid Arthritis Treated with Biologic or Targeted Synthetic DMARDs.

INTRODUCTION: Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX)-anchored therapy with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); however, tolerability issues often lead to non-adherence. Canadian data on MTX tapering and/or withdrawal following b/tsDMARD initiation are minimal. This chart review assessed frequency of MTX tapering or withdrawal following b/tsDMARD initiation and the impact on disease status in Canadian adults with RA. METHODS: Eligible patients had received MTX for ≥ 3 months before b/tsDMARD initiation. The b/tsDMARD was prescribed continuously for ≥ 18 months. Patients taking > 10 mg/day oral prednisone or equivalent were excluded. RESULTS: Eight hundred eighty-nine patients (mean baseline MTX dose 19.0 mg/week) prescribed b/tsDMARDs (tumor necrosis factor inhibitor 52.1%, Janus kinase inhibitor 18.3%, interleukin-6 inhibitor [IL-6i] 11.9%, other 17.7%) were evaluated at 22 Canadian centers. Within 2 years of b/tsDMARD initiation, MTX was tapered in 123 (13.8%) patients and discontinued in 147 (16.5%), most commonly due to planned tapering (36.6%) and patient decision (27.2%), respectively, and most commonly with IL-6i use (34.9%). The MTX dose was unchanged for 582 (65.5%) patients and increased for 37 (4.2%). Missing data limit interpretations of MTX dose effects on some secondary endpoints and challenge the assertion that a disease activity measure-based treat-to-target approach is routinely used in Canadian rheumatology practice. CONCLUSIONS: Methotrexate tapering or withdrawal occurred in 30.4% of Canadians with RA within 2 years following b/tsDMARD initiation. Baseline disease activity measures were missing from many medical records. However, for patients with baseline assessments, MTX tapering or discontinuation did not worsen disease activity.

The incidence of giant cell arteritis in Ontario, Canada.

OBJECTIVE: The incidence of giant cell arteritis (GCA) is insufficiently documented for Canada, but important to ascertain for public health planning. We estimate the incidence of biopsy-proven GCA (BPGCA) in Kingston, Ontario, and for the province of Ontario. METHOD: The number of cases of BPGCA was tabulated from retrospective chart review of all temporal artery biopsies (TABx) in Kingston, Ontario from 2011-15. The relevant population denominator was determined from the Canada census federal electoral district and the patient's postal code. The province-wide estimate for the incidence of BPGCA was calculated from provincial billing data of TABx from 2015-17, the Canada census for Ontario, and the expected positive yield of TABx. RESULTS: There were 35 subjects with BPGCA in the Kingston area over the 4-year period, from a population of 179 503 individuals 50 years of age or older (≥50 years). Ontario billing data identified 2404 patients who underwent TABx for suspected GCA over a 2-year period, from a population of 5 143 610 persons ≥50 years. Meta-analysis of 5 provincial TABx series suggested a 21% positive yield from TABx procedures (95% CI 0.18-0.24). The minimum cumulative incidence of BPGCA was 4.9 per 100 000 persons ≥50 years in Kingston, and 4.9 (95% CI 4.2-5.6) per 100 000 persons ≥50 years for Ontario as a whole. CONCLUSION: The estimated incidence of BPGCA in Ontario using 2 different estimation techniques was comparable, but low compared with other countries. The actual incidence of GCA in Ontario may be higher.

Patterns and predictors of long-term retention of inflammatory bowel or rheumatoid disease patients on innovator infliximab: an analysis of a Canadian prescriptions claims database.

BACKGROUND: Long-term effectiveness is an important factor when considering treatment decisions. OBJECTIVE: To determine the long-term retention patterns of Canadian inflammatory bowel disease (IBD) and rheumatologic disease (RD) patients, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with innovator infliximab (IFX) and to assess the impact of year-over-year cumulative IFX exposure on retention in both patient populations. PATIENTS AND METHODS: This analysis used a Canadian longitudinal prescription claims database to measure retention on IFX over a period of 5 years. Twelve-month unadjusted odds ratios of retention by time on IFX were calculated for the overall cohort, and within-group comparisons evaluated differences according to age, sex, region, insurance coverage, use of concomitant immunosuppressant therapy, indication (RD cohort only), and previous biologic experience. Between-group analyses compared unadjusted 5-year retention among the same variables. Variables that were independently associated with longer retention on IFX were identified using multivariable regression. RESULTS: Seven thousand eight hundred and six IBD patients and 2,935 RD patients on stable treatment with IFX were included in the analysis. Sixty-nine percent of IBD patients and 66% of RD patients were retained on IFX after 1 year and 33% and 29%, respectively, were retained after 5 years. Moreover, the probability of being retained on IFX significantly increased with cumulative time on IFX. Independent predictors of 5-year retention included sex, region, and type of insurance coverage among IBD patients and region, type of insurance, prior biologic therapy, and specific indication among RD patients. Patients with IBD were 17% more likely to be retained on IFX over 5 years compared to patients with RD. CONCLUSION: Real-world Canadian IBD and RD patients on IFX have good overall long-term treatment retention. Previous duration of IFX treatment predicts better future retention, and this knowledge could help inform treatment decisions when patients have been stable on IFX treatment for varying periods of time.

Treatment of osteoarthritis of the knee with a topical diclofenac solution: a randomised controlled, 6-week trial [ISRCTN53366886].

BACKGROUND: Topical NSAIDs have been proven to relieve the symptoms of osteoarthritis (OA) in short-term studies (2 weeks). To justify its chronic use, efficacy of a topical NSAID over a longer term of study should be demonstrated. The efficacy and safety of a topical diclofenac solution over a 6-week treatment course in symptomatic primary OA of the knee was investigated. METHODS: 216 men and women, age 40-85 years, with radiologically confirmed primary OA of the knee and a flare of pain at baseline following discontinuation of prior therapy were enrolled into this double-blind study. Participants applied either a topical diclofenac solution (Pennsaid) or vehicle control solution (carrier with no diclofenac); 40 drops 4 times daily directly to the painful knee(s), without massage, for 6 weeks. Pre-planned primary efficacy outcome measures included the core continuous variables pain relief and improved physical function measured by the Western Ontario and McMaster Universities (WOMAC) LK3.1 OA Index, and improved patient global assessment (PGA). Secondary efficacy measure was reduced stiffness. Safety assessments included adverse events and vital signs. RESULTS: The topical diclofenac group had a significantly greater mean change in score (final minus baseline) compared to the vehicle control group for pain (-5.2 vs. -3.3, p = 0.003), physical function (-13.4 vs. -6.9, p = 0.001), PGA (-1.3 vs. -0.7, p = 0.0001) and stiffness (-1.8 vs. -0.9, p = 0.002). The mean difference between treatment arms (95% confidence interval [CI]) was 1.9 (0.7 to 3.2), 6.5 (2.5 to 10.5), 0.6 (0.2 to 0.9), and 0.9 (0.3 to 1.4), respectively. Safety analyses showed that topical diclofenac caused skin irritation, mostly minor local skin dryness, in 42/107 (39%), leading to discontinuation of treatment in 5/107 (5%) participants. CONCLUSION: This topical diclofenac solution demonstrated relief at 6 weeks of the symptoms of primary osteoarthritis of the knee.