The clinical outcome of patients starting monoclonal antibodies anti-CGRP with concomitant migraine preventive treatments

Background: The management and role of standard preventive treatments (SPTs) in patients co-treated with monoclonal antibodies (mAbs) directed towards calcitonin gene-related peptide (CGRP) has been poorly investigated. The present study aimed to prospectively compare the clinical profile of patients co-treated with SPTs and anti-CGRP mAbs with patients with anti-CGRP mAb monotherapy and to assess the possible SPT influence on their outcome. The SPT withdrawal or a new SPT prescription during the 12-month treatment period with anti-CGRP mAbs and their possible relation with comorbidities were also evaluated. Methods: Our Italian multicentric, prospective observational cohort study enrolled patients with migraine receiving the first prescription of subcutaneous anti-CGRP mAbs. Only patients who completed the annual cycle of therapy were included in the analyses. At baseline, the population was divided into two groups: with (SPT+ patients) or without concomitant SPTs (SPT– patients). At baseline (T0), T6 (after six months of therapy) and T12 (at the end of the one-year treatment period), we collected migraine clinical data (monthly migraine days (MMDs) and/or the pain intensity, by a numerical rating scale (NRS)); disability (Migraine Disability Assessment (MIDAS) score); and the type and the presence of SPTs at baseline, the beginning of a new SPT or its withdrawal. The primary endpoint was to compare the clinical outcome (variation of MMDs at T6) of baseline SPT+ patients with that of baseline SPT– patients. Secondary endpoints were: (i) to describe the percentage of concomitant SPTs from T0 to T12 in the SPT+ group; (ii) to investigate the factors (i.e. comorbidities, demographics, migraine burden), if any, influencing the persistence of concomitant SPTs from T0 to T12; (iii) to evaluate whether baseline SPT presence influences pain intensity (NRS) and disability (MIDAS) at T0, T6 and T12. Results: We enrolled 599 patients who started a new treatment with anti-CGRP mAbs. The analysis was conducted on 555 patients who started galcanezumab (260; 46.8%), erenumab 140 mg (167; 30.0%) or fremanezumab (128; 23.1%). Patients with baseline concomitant SPTs presented lower T0 MMDs than SPT+ patients (18.6 ± 7.8 vs. 20.3 ± 7.2; p = 0.007) and a lower MMD reduction from T0 to T6 (−10.4 ± 7.2 vs −12.4 ± 7.4, p = 0.007), reaching similar MMD numbers at T6 (p = 0.984). Baseline SPTs were not associated with MMD 50% response rate at T6 (odds ratio = 0.779, 95% confidence interval = 0.534–1.138; p = 0.205). Moreover, the changes in MIDAS score (p = 0.919) and NRS (p = 0.664) from T0 to T6 and T6 to T12 did not differ according to baseline concomitant SPTs. During the 12-month treatment period, anti-CGRP mAbs SPT+ patients progressively decreased from 35.0% at baseline to 28.8% at T6 and to 19.6% at T12. A comorbid condition, although neither MMD 50% response rate nor T12 MMDs, influenced the use of concomitant SPTs at T12 (odds ratio = 3.132, 95% confidence interval = 1.981–4.954; p < 0.001). The introduction of a new SPT during 12-month mAb therapy occurred only in seven subjects. Overall, 13% of patients reported at least one adverse event. Conclusions: Our study confirms that concomitant SPTs at baseline do not influence the clinical outcome of CGRP mAbs after six months of treatment. A progressive withdrawal of SPTs during 12-month anti-CGRP therapy was observed, dissimilar among preventive classes, with persistence of SPTs at T12, mainly in patients with comorbid conditions.