Atypical Post-Injection Reactions with Delayed Onset Following Glatiramer Acetate 40 mg: Need for Titration?

Chiara Zecca, G Bellavia, L Brambilla, L P Gutierrez, C Gerardi, A M Fiori, L R Bernardini, G Camera, G Disanto, L Petrini, J Perugini, C G Antozzi, V Torri Clerici, A Bellino, P A Confalonieri, C Gobbi, R E Mantegazza, S Rossi

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Glatiramer acetate (GA) 20 mg/day (GA20) is associated with immediate post-injection reactions (PIRs). For convenience of use, approved GA 40 mg three times weekly (GA40) delivers a similar weekly dose. The dose and concentration of a single GA40 injection are, however, twice as high as for GA20, and post-injection adverse events may differ. Cases of atypical PIRs to GA40 prompted us to systematically monitor such events.

OBJECTIVE: The aim was to characterize atypical PIRs in multiple sclerosis (MS) patients treated with GA40.

METHODS: Clinical practice data were prospectively collected in consecutive relapsing-remitting MS patients. Descriptive statistics for categorical and continuous variables, Mann-Whitney and Chi-squared tests for baseline comparisons, and Cox regression models for association of variables to first atypical PIRs were applied.

RESULTS: Forty-six out of 173 patients (26.6%) given GA40 experienced any PIRs. Of those, 38 (22.0%) had atypical, 14 (8.1%) had combined typical and atypical, and 26 (15.0%) had recurrent atypical PIRs, most frequently shivering (13.3%) and nausea/vomiting (8.1%). Compared to typical PIRs, onset of atypical PIRs was significantly delayed (median 30 vs 1 min, p < 0.0001), and their median duration longer (median 120 vs 6 min, p = 0.00013). Previous exposure to GA20 was associated with a lower risk of atypical PIRs [hazard ratio (HR) = 0.35, 95% confidence interval (CI) 0.17-0.72, p = 0.0039]. Patients experiencing PIRs with GA20 were at elevated risk for atypical PIRs with GA40 (HR = 5.75, 95% CI 1.66-19.94, p = 0.0059).

CONCLUSIONS: Atypical PIRs with GA40, especially gastrointestinal symptoms and/or fever/shivering, had a delayed onset and occurred in a significant proportion of our patients. Their real prevalence should be assessed in appropriately designed studies accounting for nocebo responses. Initial dose titration might reduce PIR frequency.

Original languageEnglish
Pages (from-to)653-660
Number of pages8
JournalCNS Drugs
Volume32
Issue number7
DOIs
Publication statusPublished - Jul 2018

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