Acupuncture vs fremanezumab 2023

…in the preventative treatment of episodic migraine

Stimulated by Zheng et al 2023.[1]

Photo by Anh Nguyen on Unsplash.

NMA – network meta-analysis
MAIC – matching adjusted indirect comparison analysis
SR – systematic review
TSA – trial sequential analysis

key to acronyms

This paper was published online at the end of January 2023, but it took me a while to be able to access the full text. It was clearly of interest to me following a comment by an editorialist in the BMJ incorrectly suggesting that the benefits of acupuncture were less than those associated with GCRP receptor monoclonals.[2,3] See my previous blog from March 2020: Manual acupuncture for migraine.

Direct comparisons of acupuncture with drugs, or other treatments, are inherently prone to bias by being open trials. The double dummy approach allows blinding of participants, but it is technically difficult and expensive to perform. Secondary research, in particular NMA, can perform indirect comparisons without introducing excessive bias. But here we see a different form of indirect comparison – an MAIC. It is one that I have not seen before in the acupuncture literature.

This paper selected two suitable trials of patients with episodic migraine – one RCT on manual acupuncture,[4] and one large RCT on fremanezumab.[5] Interestingly, both RCTs were published in the same journal – JAMA – but some 13 years apart.

Patient level data was obtained for the acupuncture RCT so that baseline data could be matched to the fremanezumab trial population, for which there was only summary data. The results of a matched population (a subgroup of the acupuncture trial) could then be compared to the whole group of patients in the fremanezumab trial.

There was no difference in the reduction of monthly migraine days or responder rate between acupuncture and fremanezumab; however, the rate of reported adverse events was 25% in the acupuncture group and 66% in the fremanezumab group.

The acupuncture data used in this analysis came from one of the first large 3-armed RCTs conducted as part of the Modellvorhaben Akupunktur,[6] and the first author was Klaus Linde. Klaus was also responsible for the first SR to demonstrate an effect of acupuncture over sham in migraine prophylaxis.[7] The same review demonstrated a marginal benefit of acupuncture over drug prophylaxis. Subsequently, a more recent SR with TSA has confirmed superiority of acupuncture over the drugs in terms of responder rates,[8] but not yet in terms of migraine episodes. I’ll explain on the blog webinar – it is easier to understand when looking at the TSA graphical results.


1          Zheng H, Fan S-Q, Shi Y-Z, et al. Matching adjusted indirect comparison of acupuncture versus fremanezumab in the preventive treatment of episodic migraine. Curr Med Res Opin 2023;:1–26. doi:10.1080/03007995.2023.2174746

2          Angus-Leppan H. Manual acupuncture for migraine. BMJ 2020;1096:m1096. doi:10.1136/bmj.m1096

3          Cummings M. Re: Manual acupuncture for migraine. BMJ 2020;1096:m1096/rr.

4          Linde K, Streng A, Jürgens S, et al. Acupuncture for patients with migraine: a randomized controlled trial. JAMA 2005;293:2118–25. doi:10.1001/jama.293.17.2118

5          Dodick DW, Silberstein SD, Bigal ME, et al. Effect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial. JAMA 2018;319:1999–2008. doi:10.1001/jama.2018.4853

6          Cummings M. Modellvorhaben Akupunktur–a summary of the ART, ARC and GERAC trials. Acupunct Med 2009;27:26–30. doi:10.1136/aim.2008.000281

7          Linde K, Allais G, Brinkhaus B, et al. Acupuncture for the prevention of episodic migraine. Cochrane Database Syst Rev Published Online First: 28 June 2016. doi:10.1002/14651858.CD001218.pub3

8          Fan S-Q, Jin S, Tang T-C, et al. Efficacy of acupuncture for migraine prophylaxis: a trial sequential meta-analysis. J Neurol 2021;268:4128–37. doi:10.1007/s00415-020-10178-x

Declaration of interests MC