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.
Subject(s)
Glatiramer Acetate/drug effects , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Adult , Dose-Response Relationship, Drug , Drug Delivery Systems , Female , Humans , Male , Middle Aged , Severity of Illness Index , Statistics, Nonparametric , Treatment OutcomeABSTRACT
BACKGROUND: Delayed-release dimethyl fumarate (DMF) treatment can be associated with reduced lymphocyte and leucocyte counts, which might persist after DMF discontinuation. CASE PRESENTATION: We report the case of a patient with severe disease reactivation despite prolonged lymphopenia after DMF discontinuation. We describe the frequency and impact of prolonged lymphopenia after DMF discontinuation at two tertiary MS centres. A 36-year-old female patient with multiple sclerosis was switched to DMF after 14 years of treatment with interferon beta-1a. DMF was suspended after 4 months because of persistent lymphopenia for 3 months. Six months later, the patient had a severe relapse with multiple enhancing brain lesions at MRI although lymphopenia was still persistent. Haematological assessment excluded other causes of lymphopenia, which was evaluated as a probable iatrogenic complication of DMF. The patient was treated with i.v. methylprednisolone 1 gr daily for 3 days with clinical recovery. CONCLUSIONS: Prolonged lymphopenia after DMT discontinuation does not protect against disease reactivation. Starting a new immune therapy should be balanced against the option of a "wait and see." A different immunotherapeutic strategy such as an anti-B therapeutic approach could be considered.
