Calcitonin gene-related peptide monoclonal antibody treatment for new daily persistent headache.

Background: New daily persistent headache (NDPH) is a rare headache disorder that often resembles chronic migraine (CM) phenotypically, but unlike CM is daily from onset. Several calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) have been proven to be effective in CM. It is not known whether CGRP mAbs are effective in NDPH. We sought to assess the efficacy, tolerability, and safety of CGRP mAbs in NDPH and compare their effect in NDPH to CM.

Methods: We performed an observational study using prospectively collected data in consecutive patients treated with CGRP mAbs in three groups: Group 1 included patients with NDPH with migraine features; Group 2 included patients with CM with daily headache; and Group 3 patients with non-daily CM. Given the observational nature of the study, propensity score matching was used in an attempt to balance the three groups on baseline factors to make them comparable. The majority of patients were treated with erenumab while the remainder received galcanezumab. Patients completed a headache diary and disability questionnaires at baseline and 12-week follow-up, with the primary endpoint being the proportion who achieved a reduction of at least 30% in monthly moderate-to-severe headache days (MSHD) compared between the three groups.

Results: A total of 48 patients with NDPH, 101 with daily-CM, and 68 with non-daily-CM were included. From baseline to week 12, 11/47 (23%) of patients with NDPH had a ≥ 30% improvement in MSHD, compared to 46/99 (46%) in daily CM (OR 2.02, 95% CI 0.82-4.97, p = 0.125), and 51/61 (84%) in non-daily-CM (OR 4.41, 95% CI 1.17-16.6, p = 0.028). Only 5/47 (11%) of patients with NDPH had a ≥ 30% improvement in monthly headache days, and 24/44 (54%) reported an overall subjective improvement of ≥ 30%. Almost 50% of patients experienced at least one side effect, which were mild in almost all cases, and similar between groups.

Conclusions: CGRP mAbs were effective in approximately 1/4 patients with treatment-refractory NDPH,but less likely to be effective in NDPH than CM. This suggests that NDPH cannot be seen as equivalent to CM and that new treatment options are required for this highly disabling disorder.