Therapeutic patterns and migraine disease burden in switchers of CGRP-targeted monoclonal antibodies - insights from the German NeuroTransData registry.

BACKGROUND: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have shown good efficacy in migraine prophylaxis. However, a subset of patients does not respond to the first mAb treatment and switches among the available mAbs. The goal of this study is to characterize the switching pattern of migraine patients treated with anti-CGRP(-receptor, -R) mAbs, and to describe the headache burden of those who did not switch, switched once, and switched twice. METHODS: This study used real world data from the NeuroTransData Cohort, a registry of migraine patients treated at outpatient neurology clinics across Germany. Patients who had received at least one anti-CGRP(-R) mAb were included. Headache diaries were collected at baseline and during treatment, along with quality of life measures every three months. Results were summarized for the subgroups of patients who did not switch and those with one and two switches. RESULTS: Of the 655 eligible patients, 479 did not switch, 135 switched once, 35 twice, and 6 three or more times. The ≥ 50% response rates for monthly migraine days were 64.7%, 50.7%, and 25.0% for the no switch, one switch, and two switches groups in their last treatment cycles, respectively. Quality of life measures improved for the no switch and one switch groups, but not for the two switches group. CONCLUSION: Patients who switched among anti-CGRP(-R) mAbs during the course of their treatment still benefited overall but to a lesser extent than those who did not switch. Treatment response in patients who switched twice was markedly lower compared to the no switch and one switch subgroup.

Effect of antibody switch in non-responders to a CGRP receptor antibody treatment in migraine: A multi-center retrospective cohort study.

BACKGROUND: Switching between antibody classes might be a treatment option in migraine patients who have not responded to one class of a CGRP-(receptor) monoclonal antibody (mAb), but there are no efficacy data so far. In this real-world analysis, we assessed the treatment response to a CGRP-mAb in patients that have previously failed the CGRP-receptor-mAb erenumab. METHODS: We analyzed retrospective headache diary data of 78 patients with migraine who switched between CGRP-mAbs classes at four German headache centers either due to lack of efficacy or intolerable side effects. Among these, we identified 25 patients who did not respond to erenumab after three treatment cycles (defined as <30% reduction of monthly headache days) and had complete headache documentation at least one month before and during both treatments. We assessed the ≥30% responder rate at month three after switching from erenumab to a CGRP-mAb (galcanezumab or fremanezumab) (primary endpoint). Secondary endpoints included ≥50% responder rate, monthly headache days, and monthly days with acute medication use. In an exploratory subgroup analysis patients were stratified for daily and non-daily headache. RESULTS: The switch from erenumab to a CGRP-mAb led to a ≥30% response in one-third (32%) of the patients after three treatment cycles. A ≥50% response was achieved in 12% of the patients. Monthly headache days were reduced in month three compared to baseline (20.8 ± 7.1 to 17.8 ± 9.1; p = 0.009). Stratified analysis revealed that no patient with daily headache (n = 9) responded to the treatment switch, while a 30% response was achieved by 50% of patients with non-daily headache (n = 16). CONCLUSION: Our findings demonstrate that a relevant proportion of erenumab non-responders might benefit from a treatment switch to a CGRP-mAb. Switching seems to be a promising treatment option especially in migraine patients with non-daily headache.

Effect of calcitonin gene-related peptide (-receptor) antibodies in chronic cluster headache: Results from a retrospective case series support individual treatment attempts.

OBJECTIVE: To assess the efficacy of monoclonal antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor in chronic cluster headache (CCH) treatment under real world conditions. BACKGROUND: Calcitonin gene-related peptide has an important pathophysiological role in cluster headache. Although the randomised controlled trial with the calcitonin gene-related peptide antibody galcanezumab was negative, chronic cluster headache patients with insufficient response to other preventive treatments have been receiving individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies. METHODS: Data from 22 chronic cluster headache patients who received at least one dose of a calcitonin gene-related peptide(-receptor) antibody and recorded attack frequency in a headache diary were retrospectively collected at eight headache centres. RESULTS: The number of previous preventive therapies was 6.5 ± 2.4 (mean ± standard deviation, range: 2-11). The average number of attacks per week was 23.3 ± 16.4 at baseline and significantly decreased by -9.2 ± 9.7 in the first month of treatment with a calcitonin gene-related peptide(-receptor) antibody (p < 0.001). Fifty-five percent of the patients were 50% responders and 36% were 75% responders with respect to attack frequency. Significant reduction of attack frequency started at week 1 (-6.8 ± 2.8 attacks, p < 0.01). Results were corroborated by significant decreases in weekly uses of acute headache medication (-9.8 ± 7.6, p < 0.001) and pain intensity during attacks (-1.2 ± 2.0, numerical rating scale (NRS) [0-10], p < 0.01) in the first month. In months 2 (n = 14) and 3 (n = 10), reduction of attack frequency from baseline was -8.0 ± 8.4 (p = 0.004) and -9.1 ± 10.0 (p = 0.024), respectively. CONCLUSION: Under real-world conditions, individual treatment with calcitonin gene-related peptide(-receptor) antibodies was effective in 55% of our chronic cluster headache patients. This finding supports individual off-label treatment attempts with calcitonin gene-related peptide-(receptor) antibodies in chronic cluster headache patients insufficiently responding to other therapies.

Triptan efficacy does not predict onabotulinumtoxinA efficacy but improves with onabotulinumtoxinA response in chronic migraine patients.

Chronic migraine (CM) is a highly disabling primary headache. Botulinum toxin (onabotulinumtoxinA) is effective for treatment of CM, with ~ 50% of patients responding after 24 weeks. A response predictor would prevent unnecessary treatments. Inhibiting calcitonin gene related peptide (CGRP) release from trigeminal nociceptive fibres is one of the modes of acting discussed for onabotulinumtoxinA in CM. Therefore, we hypothesized that the response to triptans might predict response to onabotulinumtoxinA. Contrariwise, onabotulinumtoxinA treatment might affect triptan efficacy. 49 CM patients scheduled for their first onabotulinumtoxinA treatment were included. Before (T0) and three months after (T1) onabotulinumtoxinA treatment, patients rated triptan efficacy and indicated number of headache days/month. At T1, patients additionally rated onabotulinumtoxinA efficacy. Headache days/month were on average reduced by 7.1 ± 7.0 days from T0 to T1 (p < 0.001). Triptan efficacy ratings at T0 did not predict onabotulinumtoxinA efficacy ratings at T1 (p = 0.19) or reduction of headache days (p = 0.37). However, triptan efficacy significantly improved from T0 to T1 in onabotulinumtoxinA responders (p < 0.001) but not in non-responders (p = 1.00). Triptan efficacy did not predict response to onabotulinumtoxinA in CM. However, triptan efficacy increased after successful onabotulinumtoxinA treatment. This supports the hypothesis that efficacy of acute migraine treatment with triptans improves with effective migraine prophylaxis.

The efficacy of lymphatic drainage and traditional massage in the prophylaxis of migraine: a randomized, controlled parallel group study.

This study aimed at examining the efficacy of lymphatic drainage (LD) and traditional massage (TM) in the prophylactic treatment of migraine using controlled prospective randomized clinical trial of 64 patients (57 women, 45 ± 10 years) with migraine with and without aura. Patients were randomized into three groups: LD (n = 21); TM (n = 21); waiting group (WG, n = 22). After a 4-week-baseline, a treatment period of 8 weeks was applied followed by a 4-week observation period. The patients filled in a headache diary continuously; every 4 weeks they filled in the German version of the CES-D and the German version of the Headache Disability Inventory. The main outcome measure was migraine frequency per month. At the end of the observation period, the number of migraine attacks and days decreased in the LD group by 1.8 and 3.1, respectively, in the TM group by 1.3 and 2.4, and in the WG by 0.4 and 0.2, respectively. The differences between LD and WG were significant (p = 0.006 and p = 0.015, respectively) as well as the differences between TM und WG (p = 0.042 and p = 0.016, respectively). There was a significant decrease in the amount of analgesic intake in the LD group compared to the two other groups (p = 0.004). TM and LD resulted in a reduction of migraine attack frequency. The analgesic intake only decreased significantly during LD intervention. Useful effects were identified for LD and TM as compared to WG for the prophylaxis of migraine. LD was more efficacious in some parameters than TM.

Sexual headache in young adolescence: a case report.

We present the case of a boy who first experienced typical primary headache associated with sexual activity, orgasmic type, at age 12. Neurological examination and brain imaging were normal. A family history of migraine existed. The case shows the broad age spectrum of this primary headache disorder.