Indirect Comparison of Topiramate and Monoclonal Antibodies Against CGRP or Its Receptor for the Prophylaxis of Episodic Migraine: A Systematic Review with Meta-Analysis

Jul 17, 2021CNS drugs

Comparing Topiramate and Anti-CGRP Antibodies for Preventing Episodic Migraine: A Review and Analysis

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Abstract

The pooled mean difference in monthly migraine days was -1.55 for monoclonal antibodies compared to -1.11 for topiramate.

CGRP monoclonal antibodies reduced monthly migraine days by 1.55 compared to placebo, while topiramate reduced them by 1.11.
Adverse events related to cognitive and sensory pain occurred more frequently in patients treated with topiramate than those receiving CGRP monoclonal antibodies.
The number needed to treat () for CGRP monoclonal antibodies was 6, indicating 6 patients need treatment for one to benefit.
Topiramate had a lower NNT of 7 but a much higher number needed to harm () of 9, compared to 130 for CGRP monoclonal antibodies.
CGRP monoclonal antibodies are associated with a higher likelihood to help than to harm when compared to topiramate.

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BACKGROUND: Head-to-head comparator trials between first-line oral migraine preventatives and the new monoclonal antibodies (mAbs) blocking the calcitonin gene-related peptide () pathway have not been published to date.

OBJECTIVES: This study aimed to indirectly compare the clinical efficacy and safety of mAbs against CGRP or its receptor (CGRPR) and topiramate in episodic migraine prophylaxis using meta-analysis.

METHODS: We included controlled trials testing efficacy and safety of erenumab, galcanezumab, fremanezumab, eptinezumab, and topiramate in adults diagnosed with episodic migraine. We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from January 2000 to November 2020. We used the Risk of Bias 2 (RoB2) tool to assess the risk of bias and report pooled mean effects (mean difference and risk ratio) as estimated in a random effect model. For efficacy analysis, we determined the reduction of monthly migraine days (MMDs), reduction of days with acute medication (AMDs), and 50% responder rates (50% RR). For safety, we determined adverse events (AEs) occurring in ≥ 2% of study participants and the number of patients who discontinue treatment due to AEs (DAEs). The number needed to treat () and to harm () were estimated as well as the likelihood to help or harm (LLH).

RESULTS: We included 13 trials involving 7557 patients: three trials with erenumab, two trials with galcanezumab, two trials with fremanezumab, one trial with eptinezumab, and five trials with topiramate, for the prophylaxis of episodic migraine in adults. The placebo-subtracted reduction (pooled mean difference) of MMDs were - 1.55 (95% CI - 1.86 to - 1.24; active drug n = 3326 vs placebo n = 2219, 8 studies) for the CGRP(R) mAb and - 1.11 (95% CI - 1.62 to - 0.59; active drug n = 1032 vs placebo n = 543, 4 studies) for topiramate (p for subgroup difference = 0.15). 'Cognitive' and 'sensory & pain'-related adverse events occurred more often in patients treated with topiramate compared with those treated with a CGRP(R) mAb (p for subgroup difference 0.03 and < 0.001, respectively). Based on the 50% RR and DAE, the NNT, NNH, and LHH for the CGRP(R) mAbs were 6, 130, and 24.3:1, respectively. For topiramate, these values were 7, 9, and 1.8:1, respectively.

CONCLUSION: The efficacy of CGRP(R) mAbs to reduce migraine days does not differ from topiramate. However, the safety profile is in favor of the CGRP(R) mAbs, with a higher likelihood to help than to harm compared with topiramate. The diversity of endpoint determination and the heterogeneity between studies for some endpoints cause some limitations for this study.

Key numbers

-1.55

Reduction in Monthly Migraine Days

mAbs vs. placebo

for mAbs

Number needed to treat for benefit

24.3:1

Likelihood to Help vs. Harm Ratio

mAbs compared to topiramate

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Indirect Comparison of Topiramate and Monoclonal Antibodies Against CGRP or Its Receptor for the Prophylaxis of Episodic Migraine: A Systematic Review with Meta-Analysis

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