Steroids + Galcanezumab for MOH
Adding corticosteroids to galcanezumab in medication overuse headache: A three-arm head-to-head prospective observational cohort study
Clinical Question
Does adding a 28-day prednisone taper to galcanezumab improve outcomes in medication overuse headache compared with either treatment alone?
Study Overview
Objective
To compare the effectiveness and safety of galcanezumab alone, galcanezumab plus prednisone, and prednisone alone for the treatment of medication overuse headache (MOH).
Study Summary
- All three treatments significantly reduced monthly headache days at 3 months (P < 0.001)
- Galcanezumab + prednisone achieved the greatest reduction: 25 → 7 days (IQR 5–10), vs galcanezumab alone 25 → 10 days (IQR 5–14), vs prednisone alone 25 → 15 days (IQR 8–22)
- Combination therapy was significantly superior to prednisone alone (P = 0.001) but not to galcanezumab alone
- MIDAS score reduction followed the same pattern, with combination (median 20) significantly better than prednisone alone (median 42, P = 0.001)
- Adverse events occurred in 36% of combination, 28% of prednisone-only, and 0% of galcanezumab-only patients (P = 0.002)
Intervention
Galcanezumab 240 mg loading dose then 120 mg monthly, with or without prednisone tapered from 50 mg to 12.5 mg daily over 28 days, alongside outpatient analgesic withdrawal.
Patients per Arm
25 per arm (75 total)
Bottom Line
Both galcanezumab and a 28-day prednisone taper effectively reduce headache frequency in MOH, with combination therapy producing the greatest reduction in monthly headache days. However, prednisone (alone or combined) caused significant adverse events, while galcanezumab alone was free of side effects — supporting galcanezumab as preferred monotherapy and reserving combination therapy for non-responders.
Major Points
- All three treatments (prednisone alone, galcanezumab alone, galcanezumab + prednisone) significantly reduced monthly headache days at 3 months (P < 0.001).
- Combination therapy showed greatest reduction (median 25 → 7 days) vs galcanezumab alone (25 → 10) vs prednisone alone (25 → 15).
- Combination was statistically superior to prednisone alone (P = 0.001) but not to galcanezumab alone.
- Galcanezumab alone produced zero adverse events vs 28% with prednisone alone and 36% with combination (P = 0.002).
- A novel 28-day prednisone taper (longer than typical short courses) appeared effective, possibly via prolonged reduction in acute medication intake.
- Authors recommend galcanezumab as preferred monotherapy; combination reserved for non-responders without comorbidities.
Design
Study Type: Prospective three-arm observational cohort study
Randomization:
Blinding: Open-label
Allocation: Sequential fixed-order assignment (prednisone, then galcanezumab, then prednisone + galcanezumab) via mandatory prescribing platform
Enrollment Period: October 2022 to June 2023
Follow-up Duration: 3 months
Centers: 1
Countries: Italy
Sample Size: 75
Analyzed: 75
Analysis: Kruskal–Wallis with Dunn's procedure for between-group comparisons; Wilcoxon matched-pairs signed-rank for within-group; Fisher's exact test for qualitative variables; mixed models for sex/medication-type effects; Bonferroni-corrected significance threshold P < 0.02 (0.05/3 = 0.0167)
Inclusion Criteria
- Diagnosis of medication overuse headache fulfilling ICHD-3 criteria
- Age ≥18 years
- History of ≥3 failed treatments with validated migraine preventives at standard dose for ≥2 months
Exclusion Criteria
- Contraindications to galcanezumab or prednisone
- Severe arterial hypertension
- History of cardiovascular or cerebrovascular disease
- Osteoporosis
- Glaucoma
Arms
| Field | Control | Galcanezumab alone | Galcanezumab + Prednisone |
|---|---|---|---|
| N | 25 | 25 | 25 |
| Intervention | Prednisone tapered: 50 mg/day week 1, 37.5 mg/day week 2, 25 mg/day week 3, 12.5 mg/day week 4, with outpatient analgesic withdrawal | Galcanezumab 240 mg loading dose, then 120 mg monthly, with outpatient analgesic withdrawal | Galcanezumab 240 mg loading then 120 mg monthly + prednisone 50→37.5→25→12.5 mg/day taper over 28 days, with outpatient analgesic withdrawal |
| Duration | 28 days of prednisone; 3 months follow-up | 3 months | 3 months |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Reduction in mean monthly days with headache after 3 months of treatment | Primary | Prednisone: 25 (IQR 20–28) → 15 (IQR 8–22) days | Galcanezumab + Prednisone: 25 (IQR 20–30) → 7 (IQR 5–10) days; Galcanezumab alone: 25 (IQR 20–30) → 10 (IQR 5–14) days | Combination achieved ~8 fewer headache days/month vs prednisone alone | <0.001 within-group; combination vs prednisone P = 0.001; combination vs galcanezumab not statistically significant |
| MIDAS score at 3 months | Secondary | Combination vs prednisone P = 0.001; combination vs galcanezumab not statistically significant | |||
| Monthly acute medication intake at 3 months | Secondary | No statistically significant differences between groups | |||
| Overall incidence of adverse events at 3 months | Safety | 0.002 | |||
| Total with side effects | Adverse | 16/75 (overall) | |||
| Prednisone alone (n=25) | Adverse | Any AE: 7 (28.0%) · Anxiety: 3 (42.9% of AEs) · Edema: 1 (14.3%) · Gastro-esophageal reflux: 2 (28.6%) · Tachycardia: 1 (14.3%) | |||
| Galcanezumab alone (n=25) | Adverse | Any AE: 0 (0.0%) | |||
| Galcanezumab + Prednisone (n=25) | Adverse | Any AE: 9 (36.0%) · Alopecia: 1 (11.1%) · Anxiety: 1 (11.1%) · Edema: 3 (33.3%) · Insomnia: 1 (11.1%) · Gastro-esophageal reflux: 3 (33.3%) | |||
| Discontinuations due to AE | Adverse | None — all AEs were mild | |||
Subgroup Analysis
Mixed models assessed effects of sex and medication type (NSAIDs vs triptans) on outcomes; Spearman correlations evaluated relationships with disease duration and age. Specific subgroup results not detailed in available text.
Criticisms
- Observational, non-randomized, single-center design with sequential fixed-order treatment assignment introduces selection and temporal bias
- Small sample size (n=25 per arm) limits power to detect differences between active treatments
- Open-label design with no blinding or placebo control
- Short follow-up (3 months) does not capture durability or rebound effects after prednisone taper completion
- Single Italian Headache Center limits generalizability
- All patients had chronic migraine — findings may not apply to MOH from other primary headaches
- Adverse event collection methodology not detailed; longer-term steroid-related risks (adrenal insufficiency, bone density) not assessed
Based on: Steroids + Galcanezumab for MOH (Revue Neurologique, 2025)
Authors: Braca S, De Simone R, Stornaiuolo A, ..., Russo CV
Citation: Revue Neurologique. 2025;181(1-2):106-113
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