Post Hoc Subanalysis of Two Randomized, Controlled Phase 3 Trials Evaluating Diclofenac Potassium for Oral Solution: Impact of Migraine‐Associated Nausea and Prior Triptan Use on Efficacy

• Published in: Headache 2017-05, Vol.57 (5), p.756-765
• Main Authors: Lipton, Richard B., Schmidt, Pete, Diener, Hans‐Christoph
• Format: Article
• Language: English
• Subjects: Adult; Cyclooxygenase Inhibitors - administration & dosage; Cyclooxygenase Inhibitors - pharmacology; Diclofenac - administration & dosage; Diclofenac - pharmacology; diclofenac potassium; Double-Blind Method; Female; Humans; Male; Middle Aged; migraine; Migraine Disorders - complications; Migraine Disorders - drug therapy; nausea; Nausea - drug therapy; Nausea - etiology; oral solution; Outcome Assessment (Health Care); Research Submissions; triptan; Tryptamines - therapeutic use; vomiting
• ISSN: 0017-8748; 1526-4610
• DOI: 10.1111/head.13073

Objective To determine whether baseline nausea or prior triptan treatment for migraine impact the effectiveness of diclofenac potassium for oral solution in treating acute migraine. Background A great deal of variability exists in patients' response to migraine medications. Migraine‐associated nausea is common and debilitating and can reduce the effectiveness of oral medications. It may cause patients to delay taking oral medications, which is known to diminish therapeutic outcomes, or to avoid taking them altogether. Gastroparesis, which may be associated with nausea, also inhibits drug absorption, resulting in lower bioavailability. Studies have shown that having nausea at the time of drug administration predicts a poorer response to triptan treatment. It is of interest to understand how effective other migraine medications are in patients with a poor response to triptans. Methods Data from two randomized, double‐blind, placebo controlled trials were pooled and post hoc subgroup analyses were performed in patients with and without nausea at baseline, and in patients with and without prior triptan treatment. Efficacy assessments included the percentage of patients who, at 2 hours postdosing, were headache pain‐free (2hPF, primary endpoint), without photophobia, without phonophobia, without nausea, or without a severe degree of disability. A Cochran–Mantel–Haenszel test, stratified by analysis center was used to evaluate treatment effect. Effects of nausea or prior triptan use were determined using logistic regression with factors of treatment group, analysis center, nausea or prior triptan use at time of dosing, and interaction of treatment group by nausea or prior triptan use at time of dosing. Results The modified intent to treat population consisted of 1272 patients, 644 on active drug and 628 on placebo. The majority of patients (85%) were female. At the time of dosing, 783 (62%) patients reported nausea with the treated attack. Prior triptan use was recorded in 570 (45%). For headache pain, nausea, photophobia, and phonophobia, patients in the active treatment group had a statistically significantly better response than those receiving placebo, regardless of whether they had nausea at baseline. In logistic regression analysis only treatment group predicted a response for these parameters with no detectable group interaction. Baseline nausea, as well as treatment group, predicted whether patients recorded severe disability at 2 hours. While patients i