Efficacy and safety of DFN-15, an oral liquid formulation of celecoxib, in adults with migraine: a multicenter, randomized, placebo-controlled, double-blind, crossover study.

BACKGROUND: The objective of this proof-of-concept study was to assess the safety, efficacy, and potential for dose response of a new oral liquid formulation of celecoxib, DFN-15, in adults with migraine. Variability in patient-identified most bothersome symptom (MBS) across 3 migraine attacks was also evaluated. METHODS: This was a randomized, placebo-controlled, double-blind, 3-treatment, 6-sequence, 3-period, crossover study of 3 treatments (DFN-15 120 mg, DFN-15 240 mg, and placebo) administered at the onset of moderate to severe headache. RESULTS: Of 63 randomized subjects, 56 (89%) took single doses of DFN-15 120 mg and 240 mg and completed all 3 treatment periods. Most subjects were female (75.0%) and white (86.7%), with a mean age of 43.6 years. Both doses of DFN-15 achieved a higher 2-hour pain-free response than placebo (29.1% for 120 mg, 26.1% for 240 mg, and 17.6% for placebo), but the differences were not statistically significant. Photophobia was most commonly reported as the MBS, but for 53% of subjects (27/51), their identified MBS varied across the 3 studied attacks. The most common treatment-emergent adverse events with DFN-15 were dysgeusia (≤11.8%) and nausea (≤5.9%). CONCLUSION: Both doses of DFN-15 outperformed placebo for the 2-hour pain-free end point, but due to a carryover effect with placebo, the differences were not statistically significant. Since response to both doses was similar, DFN-15 120 mg is being further developed for the management of acute migraine. Further study is needed to determine whether the current findings are altered by larger or different trial designs (ClinicalTrials.gov identifier: NCT02472418).

Allodynia Is Associated With Initial and Sustained Response to Acute Migraine Treatment: Results from the American Migraine Prevalence and Prevention Study.

OBJECTIVE: In a population sample of persons with migraine treating with a single category of acute migraine medication, to identify rates and factors associated with acute treatment outcomes, including 2-hour pain freedom (2hPF), 24-hour pain response (24hPR), and 24-hour sustained pain response (24hSPR). Key predictors include acute treatment type (triptans and other medication categories), the influence of allodynia on response to medication, and the interaction between medication category and presence of allodynia in response to treatment among people with migraine. BACKGROUND: Cutaneous allodynia was previously associated with inadequate 2hPF, 24hPR, and 24hSPR (sustained response at 24 hours among those with adequate 2hPF) among people with migraine in the American Migraine Prevalence and Prevention (AMPP) Study. METHODS: The AMPP Study obtained data from a representative US sample of persons with migraine by mailed questionnaire. The 2006 survey included 8233 people with migraine aged 18 or over who completed the Migraine Treatment Optimization Questionnaire (mTOQ). mTOQ was used to assess acute treatment outcomes including 2hPF, 24hPR, and 24hSPR. Eligible individuals used only a single category of acute prescription migraine treatments (n  =  5236, 63.6%). This sample was stratified into 5 categories of type of acute prescription headache medication used (triptans, nonsteroidal anti-inflammatory drugs, barbiturate-combinations, opioids, and opioid combinations and ergot alkaloids). Separate binary logistic regression models evaluated: (1) triptans vs other medication types; (2) presence of allodynia vs no allodynia; and (3) the interaction of medication category with allodynia. Sociodemographic variables, health insurance status, over-the-counter and preventive medication use were included as covariates. Odds ratios (OR) and 95% confidence intervals (CI) were generated for each acute treatment outcome. RESULTS: Among eligible participants, the mean age was 46 years, and 82.5% were women. The triptan use group had better outcomes than other medication groups for 2hPF (OR range: 2.00-2.63, all significant except ergot alkaloids) and 24hPR (OR range: 2.10-6.22, all significant). No significant medication effects were found for the 24hSPR outcome. The presence of allodynia was associated with significantly worse outcomes for both 2hPF (OR range: 1.42-1.55, all significant) and 24hPR (OR range: 1.30-1.32, all significant, except for ergot alkaloids, P  =  .051). Allodynia effects were not significant for the 24hSPR. The interaction between medication and allodynia was also not significant (OR range for 2hPF: .68-2.02; OR range for 2hPR: .35-1.34; OR range for 24hSPR: 1.21-2.72) in any of the models, suggesting allodynia is an important predictor of treatment response regardless of the medication group prescribed. CONCLUSIONS: The use of triptan medication was associated with significantly better 2hPF (except vs ergot alkaloids) and significantly better 24hPR outcomes compared with other acute medication categories. The presence of allodynia significantly increased the likelihood of an inadequate treatment response for both of these outcomes. Triptan use was generally associated with the best outcomes. Because allodynia was associated with inadequate outcomes for all medication groups, we suggest that allodynia is an area of unmet treatment need.

Predicting Inadequate Response to Acute Migraine Medication: Results From the American Migraine Prevalence and Prevention (AMPP) Study.

BACKGROUND: Pain freedom at 2 hours and sustained pain response at 24 hours are important outcomes of acute migraine therapy. Some studies have examined rates and predictors of successful treatment outcomes for single attacks in clinical trials. However, little is known about predictors of typical response to acute treatment over multiple attacks in the population. OBJECTIVES: To identify sociodemographic features, headache characteristics, comorbidities and treatment-related factors that predict acute treatment success or failure at 2 hours and 24 hours post dose in a US population sample of persons with episodic migraine. METHODS: Eligible respondents completed the 2006 American Migraine Prevalence and Prevention Study survey, met criteria for episodic migraine, reported the use of acute treatment for migraine and answered questions on acute treatment outcomes from the Migraine Treatment Optimization Questionnaire (mTOQ). One question focused on 2 hour pain free (2hPF) response and the other focused on pain relief at 2 hours and 24 hours (24hPR). For each question, responses were considered adequate if they were achieved "half the time or more" and inadequate if they were achieved "never," "rarely," or "less than half the time." Models were run to identify predictors of outcomes in relation to usual acute treatment: (1) Inadequate 2hPF response; (2) Inadequate 24hPR response; and (3) Inadequate 24 hour Sustained Pain Freedom (24hSPF), which was a conditional analysis of pain freedom at 24 hours among those who initially had an adequate pain freedom response at 2 hours. Binary logistic regression models were used to separately predict each of the 3 outcomes adjusting for covariates. Potential predictor variables were analyzed independently and variables that did not contribute significantly to outcome prediction were trimmed. The retained variables were entered into a final multivariable binary logistic regression that included age, sex, and the covariates that survived the trimming process. Odds ratio (OR) and 95% confidence interval (CI) statistics were generated for each variable. A value of P ≤ .05 was used to identify statistically significant variables. RESULTS: Among 8233 eligible respondents with episodic migraine, 56.0% of respondents reported Inadequate 2hPF response to usual acute treatment and 53.7% reported Inadequate 24hPR. Among the 44.0% of individuals who achieved Adequate 2hPF (N = 3621), 25.7% reported Inadequate 24hSPR or recurrence. Significant predictors of Inadequate 2hPF response included demographic variables (male sex and higher body mass index [BMI]), headache features (higher headache pain intensity, cutaneous allodynia, more headache days per month), comorbidity (depression), and migraine pharmacologic treatment factors (not using preventive migraine medications). Significant predictors of Inadequate 24hPR included headache features (more headache days per month, higher migraine symptom severity composite score, cutaneous allodynia), comorbidity (depression), and migraine pharmacologic treatment factors (medication overuse). Significant predictors of Inadequate 24hSPR were greater monthly headache day frequency, cutaneous allodynia, depression, medication overuse, and higher migraine symptom severity composite score. CONCLUSIONS: These results provide a snapshot of the effectiveness of usual acute treatment as well as predictors of inadequate acute treatment response in a large population sample of people with episodic migraine. These results highlight the high rates of unmet treatment needs in people with migraine. Similarities and differences in predictors vary with outcome for reasons that are discussed.