PMID- 34272688 OWN - NLM STAT- MEDLINE DCOM- 20220203 LR - 20220203 IS - 1179-1934 (Electronic) IS - 1172-7047 (Print) IS - 1172-7047 (Linking) VI - 35 IP - 8 DP - 2021 Aug TI - Indirect Comparison of Topiramate and Monoclonal Antibodies Against CGRP or Its Receptor for the Prophylaxis of Episodic Migraine: A Systematic Review with Meta-Analysis. PG - 805-820 LID - 10.1007/s40263-021-00834-9 [doi] AB - BACKGROUND: Head-to-head comparator trials between first-line oral migraine preventatives and the new monoclonal antibodies (mAbs) blocking the calcitonin gene-related peptide (CGRP) 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 (NNT) and to harm (NNH) 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. CI - (c) 2021. The Author(s). FAU - Overeem, Lucas Hendrik AU - Overeem LH AD - Department of Neurology and Experimental Neurology, Charite-Universitatsmedizin Berlin, Chariteplatz 1 (Bonhoeffer-Weg 3), 10117, Berlin, Germany. FAU - Raffaelli, Bianca AU - Raffaelli B AUID- ORCID: 0000-0001-9758-1494 AD - Department of Neurology and Experimental Neurology, Charite-Universitatsmedizin Berlin, Chariteplatz 1 (Bonhoeffer-Weg 3), 10117, Berlin, Germany. FAU - Mecklenburg, Jasper AU - Mecklenburg J AUID- ORCID: 0000-0002-0777-0038 AD - Department of Neurology and Experimental Neurology, Charite-Universitatsmedizin Berlin, Chariteplatz 1 (Bonhoeffer-Weg 3), 10117, Berlin, Germany. FAU - Kelderman, Tim AU - Kelderman T AUID- ORCID: 0000-0003-4380-0721 AD - Department of Neurology, Sint Vincentius Hospital, Sint-Vincentiusstraat 20, 2018, Antwerp, Belgium. FAU - Neeb, Lars AU - Neeb L AUID- ORCID: 0000-0002-1940-6399 AD - Department of Neurology and Experimental Neurology, Charite-Universitatsmedizin Berlin, Chariteplatz 1 (Bonhoeffer-Weg 3), 10117, Berlin, Germany. FAU - Reuter, Uwe AU - Reuter U AUID- ORCID: 0000-0002-8527-0725 AD - Department of Neurology and Experimental Neurology, Charite-Universitatsmedizin Berlin, Chariteplatz 1 (Bonhoeffer-Weg 3), 10117, Berlin, Germany. uwe.reuter@charite.de. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20210716 PL - New Zealand TA - CNS Drugs JT - CNS drugs JID - 9431220 RN - 0 (Antibodies, Monoclonal) RN - 0 (Calcitonin Gene-Related Peptide Receptor Antagonists) RN - 0H73WJJ391 (Topiramate) RN - JHB2QIZ69Z (Calcitonin Gene-Related Peptide) SB - IM MH - Administration, Oral MH - Adult MH - Antibodies, Monoclonal/administration & dosage/adverse effects/pharmacology MH - Calcitonin Gene-Related Peptide/antagonists & inhibitors MH - Calcitonin Gene-Related Peptide Receptor Antagonists/*administration & dosage/adverse effects/pharmacology MH - Humans MH - Migraine Disorders/*drug therapy/physiopathology MH - Topiramate/*administration & dosage/adverse effects/pharmacology MH - Treatment Outcome PMC - PMC8354912 COIS- LHO has nothing to disclose. BR has nothing to disclose related to the submitted work. BR reports grants from Novartis; personal fees from Novartis, TEVA, and Allergan. JM reports personal fees from Novartis, outside the submitted work. TH has nothing to disclose. LN has nothing to disclose related to the submitted work. LN reports personal fees from Novartis, Allergan, TEVA, and BIAL; personal fees from Hormosan, and Eli Lilly. UR has nothing to disclose related to the submitted work. UR reports personal fees from AbbVie, Allergan, Medscape, and StreaMedUp; personal fees and institutional fees from Amgen, Eli Lilly, and TEVA; grants, personal fees, and institutional fees from Novartis; institutional fees from Alder. EDAT- 2021/07/18 06:00 MHDA- 2022/02/04 06:00 PMCR- 2021/07/16 CRDT- 2021/07/17 06:30 PHST- 2021/06/05 00:00 [accepted] PHST- 2021/07/18 06:00 [pubmed] PHST- 2022/02/04 06:00 [medline] PHST- 2021/07/17 06:30 [entrez] PHST- 2021/07/16 00:00 [pmc-release] AID - 10.1007/s40263-021-00834-9 [pii] AID - 834 [pii] AID - 10.1007/s40263-021-00834-9 [doi] PST - ppublish SO - CNS Drugs. 2021 Aug;35(8):805-820. doi: 10.1007/s40263-021-00834-9. Epub 2021 Jul 16.