DFN-15 safe, effective in episodic migraine
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DFN-15, a 120 mg oral celecoxib solution, was shown to be safe and effective among patients with episodic migraine in two phase 3 studies presented at the American Headache Society Annual Meeting.
“As known, NSAIDs inhibit prostaglandin synthesis by blocking two cyclooxygenase isoforms, COX-1 and COX-2 enzymes,” Sagar Munjal, MD, vice president of clinical development and medical affairs at Dr. Reddys Inc., said during the virtual presentation. “There has been a lot of evidence that NSAIDs are effective in the treatment of episodic migraine; however, [with] celecoxib, a COX-2 inhibitor, the evidence is very minimal.”
To gather more evidence, researchers conducted two identically designed, randomized, double-blind, placebo-controlled studies at multiple centers to assess the safety and efficacy of DFN-15 in patients with episodic migraine.
Overall, 631 patients in study 1 and 622 patients in study 2 were randomly assigned to receive 25 mg/mL of DFN-15 or placebo with their first migraine attack at a moderate or severe pain level and were randomly assigned again at their second migraine attack at any pain level.
Safety
When evaluating the safety of DFN-15, the researchers did not identify any treatment-emergent adverse events or death.
In study 1, Munjal and colleagues found that 10.7% of participants who received DFN-15 and 9.9% of those who received placebo reported a treatment-emergent adverse event.
The most common treatment-emergent adverse events were nausea and dysgeusia. Although the second round of treatment had similar findings, there was a lower incidence of adverse events among participants, according to the researchers.
In study 2, 13.3% of participants treated with DFN-15 and 8.9% of those given placebo reported a treatment-emergent adverse event. In 9.1% of participants who received DFN-15 and 6% of participants who received placebo, the researchers considered the adverse event related to the study.
As in study 1, the most common adverse event among participants in both treatment arms was nausea and dysgeusia, and there were fewer adverse events during the second round of treatment.
Only one participant who had been receiving placebo discontinued treatment because of a treatment-emergent adverse event of vomiting, and one severe adverse event — diarrhea — was reported in a participant who received placebo in study 2.
Munjal and colleagues did not identify remarkable findings in laboratory tests, vital signs, ECGs or other safety assessments, and therefore concluded that DFN-15 could possibly be a well-tolerated alternate to treatment with oral triptans for migraine.
Efficacy
In an efficacy analysis, Munjal and colleagues reported that the proportion of participants who were pain free at 2 hours was significantly different between treatment arms. Among participants, 32.8% of those who received DFN-15 and 23.5% of those who received placebo in study 1, as well as 35.6% of those who received treatment and 21.7% of those who received placebo in study 2, were pain free after 2 hours.
In addition, more participants who received DFN-15 were relieved of their most bothersome symptom after 2 hours, with 58.1% of those who received treatment and 43.9% of those who received placebo in study 1 experiencing relief. Similarly, 57.8% of those receiving treatment and 44.8% of those receiving placebo in study 2 reported being free from this symptom after 2 hours.
The researchers observed similar results in pain relief at 2 hours in both studies, with a prevalence of 67.9% in study 1 and 74.5% in study 2 among those who received treatment, compared with 55.3% in study 1 and 60.5% in study 2 among those who received placebo.
Munjal and colleagues also found that the prevalence of those who were free from pain for 2 to 24 hours was significantly higher in those who received treatment compared with placebo.
Therefore, the researchers determined that DFN-15 could be an effective alternate to oral triptans.
“Overall [in] the two phase 3 placebo-controlled studies, DFN-15 was found to be effective for the treatment of acute migraine,” Munjal said in the virtual presentation.
References:
Munjal S, et al. Abstract #842761. Presented at: American Headache Society Annual Meeting; June 15-30, 2020; Virtual.
Munjal S, et al. Abstract #842787. Presented at: American Headache Society Annual Meeting; June 15-30, 2020; Virtual.
Perspective
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Holly Yancy, DO
I think the combined results of these two studies are optimistic, supporting another option for acute migraine therapy — a category of treatments that providers are always in need of given the varied response of patients to abortive treatments for migraine. This is a choice available both for neurologists and primary care providers, and it offers a unique delivery method for rapid absorption in migraine patients — important since many patients with migraine have gastroparesis, or nausea and vomiting, during attacks.
Selective Cox-2 inhibitor medications likely have not been a popular choice for abortive treatment previously because two of them were discontinued in the early 2000s due to related cardiovascular (CV) complications. Another — celecoxib, the subject of these studies — was allowed to remain on the market with further ongoing investigation. Based on that investigation, an FDA review panel stated that, when used for arthritis, celecoxib did not pose a significantly higher risk for CV complications compared with prescription doses of other NSAIDs, such as naproxen or ibuprofen, although there are some CV risks with NSAIDs. That panel recommendation likely led to the study of celecoxib for other pain indications, such as migraine.
These randomized and double-blind studies show that celecoxib was effective for treatment of acute migraine when used by patients on two separate occasions, and that it was generally well-tolerated with the most common adverse effects being nausea and unpleasant or altered taste.
For select patients, then, celecoxib may be an alternative to triptans, other NSAIDs, or some newer acute treatment options that may be either ineffective or have debilitating side effects. Consideration of CV risk factors should always be taken into account with patients using NSAIDs, and although there was no evidence of CV side effects in these studies, further study with more consistent use will be necessary for patients who have risks for stroke and heart attack, as well as patients on blood-thinning medications or with kidney disease.
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Munjal S, et al. Abstract #842761. Presented at: American Headache Society Annual Meeting; June 15-30, 2020; Virtual.
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