Association of oral disease-modifying agents and their adherence trajectories with annual relapses in multiple sclerosis

Mult Scler Relat Disord. 2024 May:85:105539. doi: 10.1016/j.msard.2024.105539. Epub 2024 Mar 12.

Abstract

Background: Real-world effectiveness can vary across oral disease-modifying agents (DMAs) and their adherence trajectories in patients with multiple sclerosis (MS). However, previous studies have not considered longitudinal adherence patterns while evaluating oral DMAs.

Objectives: This study aimed to evaluate the association of oral DMAs and their adherence trajectories with annualized relapse rate (ARR) in patients with MS.

Methods: This retrospective observational cohort study based on the 2015-2019 MarketScan Commercial Claims and Encounters Database involved continuous enrolled adults (18-64 years) with ≥1 MS diagnosis (ICD-9/10-CM:340/G35) and ≥ 1 oral DMA prescription. Patients were grouped into incident fingolimod (FIN), teriflunomide (TER), and dimethyl fumarate (DMF) users based on the index DMA with a one-year washout period. Annual DMA adherence trajectories based on the monthly Proportion of Days Covered (PDC) one year after treatment initiation were identified using Group-Based Trajectory Modeling (GBTM). The validated claims-based ARR was evaluated during the one-year follow-up period using generalized boosted model-based inverse probability treatment weights with negative binomial regression model.

Results: The study cohort consisted of 994 MS patients who initiated with FIN (23.0%), TER (22.3%), and DMF (54.7%) during the study period. GBTM grouped eligible patients into three adherence trajectories: complete adherers (59.2%), slow decliners (23.8%), and rapid decliners (17.0%). The proportion of complete adherers varied across the oral DMAs (FIN: 67.1%, TER: 55.4%, and DMF: 57.4%). The negative binomial regression modeling revealed that, while there was no difference in ARR across the three DMAs, rapid decliners (adjusted incidence rate ratio[aIRR]: 1.6, 95% CI: 1.1-2.4) had a higher rate of relapses compared to completely adherent patients. The type of oral DMAs did not moderate the relationship between ARR and the adherence trajectory groups.

Conclusions: Adherence trajectories classified as rapid decliners were associated with a higher ARR than complete adherers after adjusting for their type of oral DMAs. Longitudinal medication adherence patterns are critical in reducing relapse rates in MS.

Keywords: Comparative effectiveness; Multiple sclerosis; Real-world evidence; Treatment adherence.

Publication types

  • Observational Study

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Crotonates* / administration & dosage
  • Crotonates* / therapeutic use
  • Dimethyl Fumarate* / administration & dosage
  • Dimethyl Fumarate* / therapeutic use
  • Female
  • Fingolimod Hydrochloride* / administration & dosage
  • Fingolimod Hydrochloride* / therapeutic use
  • Humans
  • Hydroxybutyrates*
  • Immunologic Factors / administration & dosage
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Medication Adherence* / statistics & numerical data
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Nitriles*
  • Recurrence*
  • Retrospective Studies
  • Toluidines* / administration & dosage
  • Toluidines* / therapeutic use
  • Young Adult

Substances

  • teriflunomide
  • Crotonates
  • Toluidines
  • Hydroxybutyrates
  • Dimethyl Fumarate
  • Nitriles
  • Fingolimod Hydrochloride
  • Immunosuppressive Agents
  • Immunologic Factors