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Tapering Biologics After Prolonged Inactive Disease may Benefit Pediatric Patients

Although effective therapies are crucial, adverse events, financial burden, and other factors make a "taper-to-target" approach appealing to both pediatric patients and their caregivers.

Although the guidance for optimal tapering strategies and/or discontinuation is limited, new research suggests that reducing biological treatment after a period of inactive disease should be considered in patients with autoinflammatory diseases (AID). Future studies should focus on a personalized “taper-to-target” approach, which can combine therapeutic drug monitoring and pharmacometrics modelling, according to a study published in Pediatric Rheumatology.1

“Early diagnosis and rapid start of effective therapies are crucial,” investigators explained. “Long-term treatment results in sustained remission on medication and prevention of organ damage… However, this comes at a price: children and youth particularly dislike daily, weekly, or monthly injections/infusions. Dreaded complications mainly include increased risk of infections, injection-site reactions, and gastrointestinal adverse events. Furthermore, the costs of biological treatments constitute a significant financial burden.”

A comprehensive, systemic literature search was performed using the OVID platform that included Embase, MEDLINE, Cochrane Database of Systematic Reviews, and Cochrane Central register of Controlled Trials, as well as a bibliographic search of reviews. Eligible studies and case series (n ≥ 5) included pediatric patients with AID treated with biologics that provided information on tapering and treatment discontinuation. Tapering strategies were also evaluated.

Inactive disease was defined as no fever, joints with active arthritis, active uveitis, rash, splenomegaly, serositis, or generalized lymphadenopathy attributed to juvenile idiopathic arthritis (JIA). Patients also needed a normal erythrocyte sedimentation rate or C-reactive protein (CRP) as well as a physician’s global assessment (PGA) that indicated no disease activity.

Of the 6035 records identified, 4 papers, all of which focused on systemic juvenile idiopathic arthritis (sJIA), were deemed high quality (2 prospective studies, 1 open-label randomized trial, and 1 retrospective observational study). The biological treatments included were the interleukin-1 (IL-1) inhibitor, anakinra (n = 2), IL-6 inhibitor, tocilizumab (n = 1), and IL-1 inhibitor, canakinumab (n = 1). Of these treatments, tapering of canakinumab was randomized for dose reduction or through interval prolongation, tocilizumab utilized interval prolongation, and anakinra was tapered using an alternate-day regimen. Factors acknowledged in tapering included early start of biological treatment as well as sustained inactive disease.

In the first anakinra study, a total of 11/15 patients with sJIA (73%) were able to discontinue treatment while maintaining disease inactivity. In the second study, nearly all (n = 31/33, 94%) of patients were able to discontinue the drug and over half (n = 18/31, 58%) remained in remission for years. Seven of 37 patients receiving tocilizumab were able to successfully discontinue the medication, although they were allowed the add-on option of methotrexate (MTX). Lastly, a total of 75/182 patients (41%) in the canakinumab cohort were able to initially achieve clinical remission for 6 or more months. After tapering, approximately one third (n = 25/75, 33%) of patients were able to discontinue the drug and sustain inactive disease.

A risk of reporting bias may be a limiting factor of the study as currently unpublished trials were not included. Additionally, research that had evaluated a mix of adult and pediatric patients were excluded. Although strict inclusion criteria resulted in high quality data, information on tapering biologics in AID are limited. Therefore, only patients with sJIA were identified.

“The question arises as to whether a paradigm shift from standardized tapering to personalized ‘taper-to-target’ strategies is necessary, addressing patient related factors, disease aspects, and treatment-related factors,” investigators concluded. “Therefore, for the next decade the attention of the rheumatology community should also include clinical trials of safely and effectively tapering and discontinuation of biological treatment. This research will help to develop personalized ‘taper-to-target’ strategies based on PK-PD modelling and/or TDM to assist clinicians in daily patients’ care.”

Reference:

Welzel T, Oefelein L, Twilt M, Pfister M, Kuemmerle-Deschner JB, Benseler SM. Tapering of biological treatment in autoinflammatory diseases: a scoping review. Pediatr Rheumatol Online J. 2022;20(1):67. Published 2022 Aug 13. doi:10.1186/s12969-022-00725-3