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Research Article
12 August 2024

A matching-adjusted indirect comparison of centanafadine versus lisdexamfetamine, methylphenidate and atomoxetine in adults with attention-deficit/hyperactivity disorder: long-term safety and efficacy

Authors: Jeff Schein, Martin Cloutier https://orcid.org/0000-0002-4867-4739, Marjolaine Gauthier-Loiselle https://orcid.org/0000-0002-9439-595X, Maryaline Catillon https://orcid.org/0000-0002-1360-8133 [email protected], Chunyi Xu, Alice Qu, Francesca Lee, and Ann ChildressAuthor Info & Affiliations
Volume 13, Number 9
https://doi.org/10.57264/cer-2024-0089
PDFFormats

Abstract

Aim: To compare long-term safety and efficacy outcomes of centanafadine versus lisdexamfetamine dimesylate (lisdexamfetamine), methylphenidate hydrochloride (methylphenidate) and atomoxetine hydrochloride (atomoxetine), respectively, in adults with attention-deficit/hyperactivity disorder (ADHD) using matching-adjusted indirect comparisons (MAICs). Patients & methods: Patient-level data from a centanafadine trial (NCT03605849) and published aggregate data from a lisdexamfetamine trial (NCT00337285), a methylphenidate trial (NCT00326300) and an atomoxetine trial (NCT00190736) were used. Patient characteristics were matched in each comparison using propensity score weighting. Study outcomes were assessed up to 52 weeks and included safety (rates of adverse events [AEs]) and efficacy (mean change from baseline in the Adult ADHD Investigator Symptom Rating Scale [AISRS] or ADHD Rating Scale [ADHD-RS] score). Results: In all comparisons of matched populations, risks of AEs were statistically significantly lower with centanafadine or non-different between centanafadine and comparator; the largest differences in AE rates included upper respiratory tract infection (risk difference in percentage points: 18.75), insomnia (12.47) and dry mouth (12.33) versus lisdexamfetamine; decreased appetite (20.25), headache (18.53) and insomnia (12.65) versus methylphenidate; and nausea (26.18), dry mouth (25.07) and fatigue (13.95) versus atomoxetine (all p < 0.05). Centanafadine had a smaller reduction in the AISRS/ADHD-RS score versus lisdexamfetamine (6.15-point difference; p < 0.05) and no statistically significant difference in the change in AISRS score versus methylphenidate (1.75-point difference; p = 0.13) and versus atomoxetine (1.60-point difference; p = 0.21). Conclusion: At up to 52 weeks, centanafadine showed significantly lower incidence of several AEs than lisdexamfetamine, methylphenidate and atomoxetine; efficacy was lower than lisdexamfetamine and non-different from methylphenidate and atomoxetine.

Plain language summary

What is this article about?

Attention-deficit/hyperactivity disorder (ADHD) is a long-term condition that disrupts a person's ability to stay focused, sit still and control their behavior. Adults with ADHD may be treated with traditional stimulants or non-stimulants. Stimulants are typically more efficacious but are associated with side effects that are not tolerated by all patients. Centanafadine sustained-release is an investigational medication for adults with ADHD that has a different mechanism of action than stimulants. No clinical trials have been conducted to compare the long-term safety and efficacy of centanafadine versus other common ADHD medications. In this study, we used clinical trial data to indirectly compare the long-term safety and efficacy of centanafadine versus lisdexamfetamine dimesylate (lisdexamfetamine; Vyvanse®), methylphenidate hydrochloride (methylphenidate; Concerta®) and atomoxetine hydrochloride (atomoxetine; Strattera®), respectively, across balanced patient populations.

What were the results?

At up to a year of treatment, centanafadine was associated with fewer cases of upper respiratory tract infection, dry mouth, headache, decreased appetite and irritability than all of its comparators. Efficacy of centanafadine, as measured by reduction in ADHD symptoms, was statistically lower than lisdexamfetamine and non-different from methylphenidate and atomoxetine.

What do the results of the study mean?

Our indirect comparisons show that centanafadine has fewer cases of some side effects and lower or non-different efficacy than common ADHD treatments over time. These findings can help doctors and patients understand the long-term safety and efficacy profiles of different ADHD medications and select a suitable option based on their need.

Supplementary Material

File (supplementary materials.docx)

References

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