New Canadian guidelines for managing rheumatoid arthritis with DMARDs

The Canadian Rheumatology Association (CRA) has begun the development of “living” guidelines for the management of rheumatoid arthritis with disease-modifying antirheumatic drugs (DMARDs). The living guidelines will allow new recommendations to be added over time, while existing recommendations may be modified, based on new evidence.1 The living guidelines initially focus on whether biologic or targeted synthetic DMARDs should be tapered in adults who are in sustained remission or low disease activity.1 Biologic DMARDs include tumor necrosis factor (TNF) inhibitors (etanercept, adalimumab, infliximab, certolizumab pegol, golimumab) and biologics that target other molecules (abatacept, rituximab, tocilizumab, sarilumab, anakinra); all are administered by injection. Targeted synthetic DMARDs (e.g., tofacitinib, baricitinib, upadacitinib) are orally administered Janus kinase (JAK) inhibitors, are produced by traditional drug-manufacturing techniques.2,3 Read: QUIZ: Test your knowledge of preventing fractures in postmenopausal patients Recommendation In adults with RA who have been in sustained low disease activity or remission for at least six months, the CRA suggests offering a stepwise reduction in the dose of biologic or targeted synthetic DMARD without discontinuation. This should be done in the context of shared decision-making and with the proviso that patients are able to rapidly access rheumatology care and re-establish their medications in case of a flare. (conditional recommendation; moderate certainty of evidence). This recommendation applies to both biologic originator and biosimilar DMARDs. Where rapid access to care or re-establishing access to medications is challenging, the CRA conditionally recommends against tapering. (conditional recommendation; moderate certainty of evidence).1 In making this recommendation, the CRA panel judged that if therapy is tapered, most patients who flare can regain disease control promptly once medications are re-established. Therefore, a trial of treatment reduction (without complete discontinuation) would be appropriate for many patients to reduce medication burden and possible side effects. Given the increase in flares seen over relatively short follow-up in the trials of discontinuation of treatment, the CRA panel made a conditional recommendation against complete discontinuation of advanced therapies.1 Rapid access to care and ability to re-establish medications is a particularly important consideration when deciding whether to taper. In situations where access to care is difficult, tapering should typically not be recommended. However, tapering may still be appropriate for some patients in the context of a shared decision.1 The majority of the evidence on tapering relates to anti-tumour necrosis factor (TNF) therapy, although results for drugs with other mechanisms of action that have been studied (rituximab, abatacept, tocilizumab, baricitinib) appear similar.1 Read: Helping patients with rheumatoid arthritis transition from biologics to other drugs Although six months of adequate disease control was felt to be the minimum duration before tapering, sustained disease control for 12 months would be ideal prior to tapering.1 Dose reduction may include extending the interval between doses or reducing the amount with each dose. A typical initial reduction would be 25% of the original effective dose (e.g., increasing the interval for adalimumab from every 2 weeks to every 3 weeks). Further reductions (e.g., extending the interval to every 4 weeks) may also be possible. Complete discontinuation of the biologic or targeted synthetic DMARD is not routinely recommended, although it may be possible in some patients; in these situations, a conventional synthetic DMARD (e.g., methotrexate, sulfasalazine, leflunomide, hydroxychloroquine) should be continued.1 In people taking conventional synthetic DMARD(s) in combination with a biologic or targeted synthetic DMARD, the doses of conventional synthetic DMARD(s) should be kept stable during dose reduction of the biologic or targeted synthetic DMARD. Before reducing biologic or targeted synthetic DMARDs, glucocorticoids should be discontinued, if possible.1 While tapering, patients should be reassessed (usually at three months). In the case of flare, a typical approach would be to increase the dose to the previous effective dose. A flare management plan should be discussed with patients prior to tapering.1 Shared decision-making features prominently in this CRA recommendation. For some patients, the risk of flaring will outweigh the potential benefits. A decision aid tool to support shared decision-making regarding biologic or targeted synthetic DMARDs tapering is available on the CRA website.1 References 1. Hazlewood GS, Pardo JP, Barnabe C, et al. Canadian Rheumatology Association living guidelines for the pharmacological management of rheumatoid arthritis with disease-modifying anti-rheumatic drugs. J Rheumatol 2022, jrheum.220209; DOI. 2. UoToDate. Patient education: Disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (Beyond the Basics). July 27, 2022. (accessed August 18, 2022). 3. Hall J. Rheumatoid arthritis update. Pharmacy Practice + Business 2021;8(8):17-20.(accessed August 18, 2022)

New Canadian guidelines for managing rheumatoid arthritis with DMARDs

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