A new study has found that calcitonin gene-related peptide (CGRP) monoclonal antibodies, a newer class of drugs, are not significantly more effective in treating chronic migraine compared to topiramate or Botox. The research, led by Hema Mistry, PhD, from the Warwick Clinical Trials Unit at Warwick Medical School, UK, suggests that the high cost of CGRP monoclonal antibodies may not be justified by superior clinical outcomes.
The systematic review and economic modeling aimed to compare the clinical and cost-effectiveness of prophylactic drug treatments for individuals with chronic migraine. The analysis included 11 randomized controlled trials involving 7352 participants, evaluating six drugs: topiramate, Botox, eptinezumab, erenumab, fremanezumab, and galcanezumab. The primary focus was on headache days, migraine days, headache-related quality of life, and the incidence of adverse events.
Efficacy Comparison
The study revealed that CGRP monoclonal antibodies reduced headache or migraine days by 2.0 to 2.5 days per month. In comparison, topiramate and Botox reduced headaches by less than 1.5 days per month. Specifically, eptinezumab 300 mg was found to be the most effective in reducing monthly headaches, with a reduction of 2.46 days (95% credible interval [CrI], -3.24 to -1.67). Fremanezumab monthly was the most effective in reducing monthly migraine days, reducing them by 2.76 days (95% CrI -3.36 to -2.15).
Cost-Effectiveness Analysis
The economic model, based on a 2-year time horizon and using data from a National Health Service perspective, indicated that topiramate was the least expensive option but also provided the fewest quality-adjusted life-year gains. Eptinezumab 300 mg, while more expensive, resulted in the most quality-adjusted life-year gains. The analysis concluded that topiramate remains the most cost-effective medication if the patient is willing to pay ≥ £50,000 per quality-adjusted life-year.
Adverse Events
The review of adverse events, which included 40 randomized controlled trials with 25,891 participants, found that adverse events were common across all treatments. Participants on CGRP monoclonal antibodies reported injection site issues, while those on topiramate or amitriptyline experienced nervous system or gastrointestinal issues. No serious adverse events were directly linked to any of the medications.
Implications for Clinical Practice
"Within the current care pathway, it is unlikely that CGRP [monoclonal antibodies] will be recommended ahead of topiramate without a very substantial reduction on price," the investigators wrote. The findings suggest that clinicians should carefully consider the cost-effectiveness of CGRP monoclonal antibodies in relation to other available treatments, particularly in healthcare systems with budget constraints.
Future Research Directions
The study authors identified three key areas for future research: comparing CGRP monoclonal antibodies and Botox with CGRP monoclonal antibodies alone; candesartan versus placebo; and flunarizine versus placebo. The lack of sufficient data on commonly used drugs like amitriptyline, candesartan, flunarizine, and propranolol was noted as a limitation, highlighting the need for further trials in these areas.
