We included 210 patients from 22 Spanish hospitals between February 2019-to-June 2020 who has finished at least 12 weeks of erenumab treatment. The included centres had a homogeneous geographic distribution around the country. The mean age was 46.4 years-old [18-65], and 86.7% of patients were women.
The mean migraine duration as disease in their lives was 26.5 years [3-to-25 years]. Most patients (89.5%) had CM with an evolution average for 8.6 years [3 months – to - 25 years] and the remain presented HFEM (10.5%). The 70% of patients presented MOH, and 17.1% fulfilled migraine with aura. The average of MMD was 17.1 days [4-30], and MHD was 23.5 days. The mean MIDAS score was 101.9 points, and the mean HIT-6 score was 68.8 points.
The average number preventive drugs that had previously failed was 7.8 [2-20] including BoNT/A. The later had been used by 95.2% of patients. The most frequently used oral preventive drugs were topiramate (98.2%), amitriptyline (98.2%), flunarizine (94.7%), and beta-blockers (92.9%).
The initial dose of erenumab was 70 mg in 67.6% of patients and 140 mg in the remain 32.4%.
Regarding simultaneous preventive treatments, only 39.5% patients received exclusively erenumab as preventive treatment, and in the remaining patients (60.5%) erenumab was added to another preventive drug: BoNT/A – 27.6%, topiramate - 12,2%, and miscellaneous drugs - 49.1%.
Regarding efficacy (Table 1), the responder rate was 37.1%, and the mean reduction of MMD was 6.5 days (from 17.1 to 11 days). MHD was also reduced in 8.6 days (from 23.5 to 14.9 days).
After the 12-week period of treatment (Figure 1), 28 patients (13.3%) discontinued the treatment. The reasons were: 1. Conversion into a low frequency episodic migraine (20 patients - 9.5%), 2. Lack of efficacy (4 patients – 1.9%), and 3. adverse events (4 patients - 1.9%).
The remaining 182 patients (86.7%) continued with erenumab treatment: with the same dose (44.7%), while 41,9% increased the dose thereafter (Figure 1). After three months of follow-up, 14.8% continued to receive simultaneously BoNT/A and 50% were still under treatment with oral preventive drugs.
Regarding PROs (Table 1): MIDAS score was reduced 35 points (from 101.9 – to - 66.9), HIT-6 reduced 11.6 points (from 68.8 to 57.2) and the mean PIGC assessment was 4.7 points.
The number of prior preventives was a predictor factors of good response (p=0.026) (Table 2). Specifically, 90% of responder patients had taken previously a mean of 5.9 preventive drugs, and patients who had taken nine or more preventive drugs account only 16% of the sample of responder patients. Furthermore, ineffectiveness prior to BoNT/A treatment does not predicted erenumab response (p=0.867). Other predictor factors were MIDAS score inferior to 100 points (p=0.006), less than 80 points in HIT-6 score (p=0.01), and absence of MOH (p=0.039). All the responder patients showed a HIT-6 score inferior to 80 points making this index in a strong predictor factor of response at this cut point.
None of both erenumab doses, 70 or 140 mg, showed a better statistical power as predictor of good response than the other (p=0.647). However, the simultaneous BoNT/A treatment showed the strongest predictor factor of a good response (p<0.001). On the contrary, simultaneous oral preventives did not predict a positive or negative response (p=0.213).
In addition, the presence of aura showed a non-significant tendency as a predictor factor of good response (p=0.088). However, age (p=0.557), gender (p=0.294), HFEM/CM (p=0.727), and evolution of CM (p=0.514) did not show any association to response.
The percentage of adverse events was 20%, but only four patients (1.9%), suffered severe adverse events provoking a treatment discontinuation. Two patients had a skin rash attributed to the first erenumab injection; the other two patients presented adverse events not related to erenumab: one patient, under paroxetine treatment, presented a serotoninergic syndrome while overusing zolmitriptan; and the other one was diagnosed of cutaneous melanoma, but the skin lesion existed previously to the erenumab treatment onset.
Specifically, forty-two patients presented 57 side-effects: being constipation the most frequent (7.6%). No patients needed treatment nor consultation by this adverse effect. Table 3 details adverse events reported by patients after 12 weeks of treatment with erenumab.
Finally, we did not find any predictive factor of adverse events. Only the dose of 140 mg showed a non-significant tendency to present more adverse events than the dose of 70 mg (p=0.069).