Erenumab in the Prevention of High-frequency Episodic and Chronic Migraine

Erenumab in Real Life in Italy (EARLY), The First Italian Multicenter, Prospective Real-life Study

Piero Barbanti MD, PhD; Cinzia Aurilia MD; Gabriella Egeo MD, PhD; Luisa Fofi MD; Sabina Cevoli MD, PhD; Bruno Colombo MD; Massimo Filippi MD; Fabio Frediani MD; Francesco Bono MD; Licia Grazzi MD; Antonio Salerno MD; Bruno Mercuri MD, PhD; Antonio Carnevale MD; Claudia Altamura MD, PhD; Fabrizio Vernieri MD

Disclosures

Headache. 2021;61(2):363-372. 

In This Article

Results

In total, 372 patients with migraine were treated with at least one monthly dose of erenumab 70 mg (HFEM n = 103; CM n = 269). All patients enrolled had failed ≥3 classes of migraine preventive medications. Their characteristics are summarized in Table 1. Migraine patients were included in the study and started erenumab treatment at different times, depending on their prescheduled visit at each headache center (Figure 1). The analysis was performed on the 364 patients treated with erenumab for at least 12 weeks (HFEM n = 101; CM n = 263). Overall, seven patients discontinued erenumab before the week 12 follow-up visit due to adverse events (n = 5 pts: 2 at week 4, 1 at week 8, and 2 at week 12), ineffectiveness (n = 2 pts: 1 at week 8, 1 at week 12), or lost to follow-up (n = 1 pt, at week 12). Consequently, no imputation of missing values for lost to follow-up patients was performed.

Figure 1.

Number of eligible patients; adverse events, effectiveness and safety analysis

Erenumab was effective in both HFEM and CM. In the HFEM group, at weeks 4, 8, and 12 erenumab rapidly and progressively decreased MMDs (−3.3 ± 3.9, −4.0 ± 4.4, and −4.5 ± 4.1, respectively), median monthly analgesic intake [baseline 12.0 (IQR 10.0–14.0) to 7.0 (IQR 3.0–10.0), 5.0 (IQR 3.0–8.0), and 5.0 (IQR 3.0–7.0)], VAS score (−1.3 ± 1.6, −1.8 ± 2.2, and −1.9 ± 1.9), and HIT-6 score (−7.5 ± 8.5, −9.0 ± 9.2, and −10.7 ± 8.8) compared to the baseline. In patients with CM at weeks 4, 8, and 12 erenumab reduced MMDs (−7.7 ± 8.5, −9.1 ± 9.0, and −9.3 ± 9.1, respectively), median monthly analgesic intake [baseline 20.0 (IQR 15.0–30.0) to 10.0 (IQR 5.0–20.0), 8.0 (IQR 4.0–16.0), and 8.0 (IQR 5.0–15.0)], VAS score (−1.7 ± 1.6, −1.7 ± 1.8, and −1.7 ± 2.0), and HIT-6 score (−7.7 ± 9.3, −9.9 ± 9–7, and −9.7 ± 10.4) compared to the baseline (Table 2).

Among patients with HFEM the proportion of ≥50% responders at weeks 4, 8, and 12 was 40/103 (38.8%), 46/102 (45.1%), and 60/101 (59.4%), respectively. At the same time points, ≥75% responders were 17/103 (16.5%), 20/102 (19.6%), and 17/101 (16.8%). At week 8 and 12, 3/102 (2.9%) and 1/101 (1.0%) of patients became migraine free (Figure 2). Patients with CM showed at weeks 4, 8, and 12 a ≥ 50% response rate of 125/269 (46.5%), 146/266 (54.9%), and 146/263 (55.5%) and a ≥ 75% response of 48/269 (17.8%), 58/266 (21.8%), and 59/263 (22.4%). A 100% response at week 8 and 12 was achieved by 2/266 (0.8%) and 3/263 (1.1%) of the subjects (Figure 3).

Figure 2.

Response rates at weeks 4, 8 and 12 in patients with HFEM

Figure 3.

Response rates at weeks 4, 8 and 12 in patients with CM

The adverse events reported during the 3 months of erenumab treatment are detailed in Table 3. The most common was constipation (8.8% at week 12), usually rated as mild but severe in one case and classified as a serious adverse event.

The erenumab dose was increased to 140 mg in 40 out of 364 patients (11%; CM: 38 pts, HFEM: 2 pts) at week 8, due to ineffectiveness (28 pts) or loss of previous effectiveness (12 pts), resulting in a clinical benefit in two patients with CM. Conversely, no improvement was observed in two patients, one with HFEM, and one with CM of this subpopulation.

Univariate Analyses

The results of the univariate analyses are presented in Table 4. In the HFEM group, we found a significant association between unilateral pain localization and ≥50% response rate (p = 0.031), while in the CM group, a positive association emerged between the ≥50% response rate and MHDs at baseline (p = 0.004), dopaminergic symptoms (p = 0.003), and psychiatric comorbidities (p = 0.020).

Exploratory Multivariable Analyses

The stepwise logistic regression analysis revealed that erenumab responsiveness (≥50% reduction in MMDs compared to baseline) in patients with HFEM was independently positively associated with unilateral pain localization (OR: 3.03, 95% CI: 1.24–7.40; p = 0.015) (Table 5), whereas in patients with CM, responsiveness (≥50% reduction in MHDs compared to baseline) was independently positively associated with MHDs at baseline (OR: 1.06, 95% CI: 1.02–1.11; p = 0.031) and dopaminergic symptoms (OR: 2.01, 95% CI: 1.14–3.52), and negatively associated with the presence of psychiatric comorbidities (OR: 0.43, 95% CI: 0.20–0.93; p = 0.003) (Table 6).

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....