Number needed to treat
“The study was large, appears to have been well conducted, is clearly reported, and used appropriate outcome measures,” said Elizabeth Loder, MD, commenting on the trial.
Dr. Elizabeth Loder
A year ago, Dr. Loder, chief of the division of headache at Brigham and Women’s Hospital and professor of neurology at Harvard Medical School in Boston, coauthored a paper with Peer Tfelt-Hansen, MD, DMSc, of the University of Copenhagen, that said the phase 3 trials of gepants so far have found the drugs to have small effect sizes and low efficacy (Headache. 2019 Jan;59[1]:113-7. doi: 10.1111/head.13444).
Their publication included preliminary figures from ACHIEVE II, which are consistent with those published in JAMA. “The effect size for both doses of ubrogepant is small and of debatable clinical significance,” Dr. Loder said. “The therapeutic gain over placebo is 7.5% for the 50-mg dose and 6.4% for the 25-mg dose for the outcome of pain freedom at 2 hours. That corresponds to a number needed to treat of 13 and 15.6 people, respectively, in order to have one person achieve pain freedom at 2 hours that is attributable to the active treatment.”
For a secondary outcome of pain relief at 2 hours, defined as reduction of headache pain severity from moderate or severe to mild or none, the therapeutic gain versus placebo is 14.5% for the 50-mg dose and 12.3% for the 25-mg dose. “That corresponds to a number needed to treat of 6.8 and 8.1 people, respectively, to have one person achieve pain relief at 2 hours attributable to the drug,” Dr. Loder said.
“Although there are no head to head studies comparing ubrogepant to triptans, for reference the [number needed to treat] for a 100-mg oral dose of sumatriptan is on the order of 3.5 for pain relief at 2 hours, meaning that one needs to treat just 3.5 people with sumatriptan in order to have one person achieve pain relief at 2 hours attributable to the drug,” she said (Cochrane Database Syst Rev. 2014;5:CD009108. doi: 10.1002/14651858.CD009108.pub2).
“The bottom line is that in the ACHIEVE II study, ubrogepant appears, on average, to be modestly better than placebo to treat migraine. It does not appear to be in the same league as sumatriptan. Instead, as Dr. Tfelt-Hansen and I said in our article, the results look comparable to those likely to be achieved with inexpensive nonprescription medications such as NSAIDs.”
Dr. Loder called for a trial comparing ubrogepant and other therapies. “I challenge the authors and the company to conduct a large, placebo-controlled trial comparing ubrogepant to 100 mg of oral sumatriptan and to 650 mg of aspirin,” Dr. Loder said.
Dr. Loder has no financial connections with any pharmaceutical or device companies and is paid for her work as the head of research for the British Medical Journal.
SOURCE: Lipton RB et al. JAMA. 2019;322(19):1887-98. doi: 10.1001/jama.2019.16711.