Steroids + Galcanezumab for MOH
(2025)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
• 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.
Inclusion Criteria
Adults ≥18 years with medication overuse headache per ICHD-3 criteria, history of ≥3 failed migraine preventives at standard doses for ≥2 months.
Study Design
Arms: Prednisone alone (n=25) vs Galcanezumab alone (n=25) vs Galcanezumab + Prednisone (n=25)
Patients per Arm: 25 per arm (75 total)
Outcome
• Combination vs prednisone: P = 0.001; combination vs galcanezumab: not statistically significant
• MIDAS at 3 months: combination 20, prednisone 42 (P = 0.001)
• Adverse events: 36% combination, 28% prednisone, 0% galcanezumab (P = 0.002)
• Most common AEs: gastro-esophageal reflux, anxiety, edema (all mild, none required discontinuation)
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.
Study Design
- Study Type
- Prospective three-arm observational cohort study
- Randomization
- No
- Blinding
- Open-label
- Sample Size
- 75
- Follow-up
- 3 months
- Centers
- 1
- Countries
- Italy
Primary Outcome
Definition: Reduction in mean monthly days with headache after 3 months of treatment
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 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 | - | <0.001 within-group; combination vs prednisone P = 0.001; combination vs galcanezumab not statistically significant |
Limitations & 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
Citation
Revue Neurologique. 2025;181(1-2):106-113