Persistent effectiveness of CGRP antibody therapy in migraine and comorbid medication overuse or medication overuse headache - a retrospective real-world analysis

Abstract

Background: Management of patients with migraine who have concomitant medication overuse (MO) or medication overuse headache (MOH) is a major problem in clinical practice. Detoxification of acute analgesics before or during initiation of prophylactic therapy has long been recommended although this concept has recently been questioned. Additionally, relapse after detoxification is a common problem. This real-world study analyses the initial and sustained effectiveness of prophylactic migraine therapy with CGRP (receptor) antibodies without prior detoxification in patients with comorbid MO or MOH for up to one year.

Methods: A retrospective real-world analysis was performed on 291 patients (episodic migraine (EM) with MO (EM-MO; n = 35), EM without MO (EM-noMO; n = 77), chronic migraine (CM) with MOH (CM-MOH; n = 109), CM without MOH (CM-noMOH; n = 70). All patients began treatment with either erenumab (n = 173), fremanezumab (n = 70) or galcanezumab (n = 48) without prior detoxification. Data were available for up to 12 months of treatment. Responder rates for monthly headache days (MHD), monthly migraine days (MMD) and monthly acute medication intake (AMD) were analysed.

Results: All groups showed a significant reduction in MHD, MMD and AMD at the last observed time point compared to baseline. In patients with CM and MOH, 60.6% (66/109) no longer fulfilled the definition of MO or MOH and a further 13.8% (15/109) had only EM-MO. In the EM cohort, 89% (31/35) of MO patients lost their MO during therapy. MHD and AMD 30% responder rates were comparable for CM-MOH and CM-noMOH (MHD: CM-MOH: 56.0% vs. CM-noMOH: 41.4%, p = 0.058, AMD: CM-MOH: 66.1% vs. CM-noMOH: 52.9%, p = 0.077). MMD responder rate did not differ significantly (after Bonferroni adjustment) (CM-MOH: 62.4% vs. CM-noMOH: 47.1%, p = 0.045, α = 0.017). After successful initiation of therapy, 15.4% of the initial CM-MOH patients relapsed and met the criterion for CM-MOH at the end of follow-up. There were no antibody specific differences in response to therapy.

Conclusions: Our data confirms the effectiveness of CGRP antibody treatment in migraine patients with additional MOH or MO in a real-world setting. Low relapse rates after initial successful therapy support an early start of CGRP antibody treatment in patients with MOH or MO.

Trial registration: No registration, retrospective analysis.

Keywords: Chronic migraine; Detoxification; Erenumab; Fremanezumab; Galcanezumab; MO; MOH.

Fig. 1

Patients included in study. (AMD: monthly acute drug intake, MHD: monthly headache days, MMD: monthly migraine days, MO: medication overuse, MOH: medication overuse headache)

Fig. 2

Treatment response up to 12 months. Development of MHD, MMD and AMD before and during treatment for EM with and without MO (a) and CM with and without MOH (b) up to 12 months. The number below shows the analysed patients at the respective time point. (AMD: monthly acute drug intake, MHD: monthly headache days, MMD: monthly migraine days, MO: medication overuse, MOH: medication overuse headache)

Fig. 3

Equivalence analysis of 30% responder rates of CM patients with and without MOH. Equivalence bounds was set to 20%. Mean differences (black squares) and 90% confidence intervals (CIs; thick horizontal lines) and 95% CIs (thin horizontal lines) with equivalence limits ΔL = -.2 and ΔU = .2 showing whether the difference in responder rates between the two groups CM-noMOH and CM-MOH is statistically equivalent or not (TOST: two one-sided tests) and statistically different from zero or not (NHST: null hypothesis significance tests)

Fig. 4

Changes of migraine type and MO/MOH during CGRP (receptor) antibody therapy. Migraine type and MO/MOH at baseline and at the LOTP (CM-MOH: chronic migraine with medication overuse headache, CM-noMOH: chronic migraine without medication overuse headache, EM-MO: Episodic migraine with medication overuse, EM-noMO: Episodic migraine without medication overuse, LOTP: last observation time point)

Fig. 5

Changes of migraine type and MO/MOH after initial response to CGRP (receptor) antibody therapy. Migraine type and MO/MOH after three months of therapy and at the LOTP (CM-MOH: chronic migraine with medication overuse headache, CM-noMOH: chronic migraine without medication overuse headache, EM-MO: Episodic migraine with medication overuse, EM-noMO: Episodic migraine without medication overuse, LOTP: last observation time point)