Allodynia-associated symptoms, pain intensity and time to treatment: predicting treatment response in acute migraine intervention.

OBJECTIVE: To evaluate the relationship between treatment outcomes and allodynia-associated symptoms (AAS) at the time of treatment with almotriptan. METHODS: Analyses were performed with data collected prospectively from patients in 2 recently completed early intervention trials, AXERT Early miGraine Intervention Study (AEGIS) and AXERT 12.5 mg time vs Intensity Migraine Study (AIMS): 2-hour pain free, 2-hour pain relief (AEGIS only), sustained pain free (SPF), use of rescue medication, and median headache duration (AIMS only), in the presence and absence of pretreatment AAS, which was determined by responses to a questionnaire. Analyses were conducted to evaluate possible prognostic variables. RESULTS: The presence of pretreatment AAS did not have a significant effect on 2-hour pain-free, 2-hour pain-relief or SPF rates, use of rescue medication, or headache duration. Significant factors for most favorable outcomes (greater 2-hour pain-free, 2-hour pain-relief and SPF rates, less use of rescue medication, and shorter headache duration) included treatment with almotriptan 12.5 mg, treatment of mild or moderate headache pain, and treatment within 1 hour of headache onset. CONCLUSION: Almotriptan 12.5 mg was efficacious in providing 2-hour pain free, 2-hour pain relief, SPF, and reducing rescue medication use irrespective of the presence of AAS at the time of treatment. The most optimal efficacy outcomes occurred when patients treated migraine attacks early and before the onset of severe pain. The presence of AAS, which may indicate an early phase of allodynia, did not influence the efficacy of almotriptan therapy.

Efficacy and tolerability of almotriptan in adolescents: a randomized, double-blind, placebo-controlled trial.

OBJECTIVES: To assess the efficacy and safety of almotriptan 6.25 mg, 12.5 mg, and 25 mg vs placebo for acute migraine treatment in adolescents. PATIENTS AND METHODS: In this double-blind, placebo-controlled, parallel-group, multicenter trial, 866 patients aged 12 to 17 years with a >1 year history of migraine (per International Headache Society criteria) were randomized to treat one migraine headache with almotriptan 6.25 mg, 12.5 mg, 25 mg, or placebo. The primary efficacy endpoint was headache pain relief 2 hours after dosing, adjusted for baseline severity, with absence of nausea, photophobia, and phonophobia 2 hours after dosing as coprimary endpoints. RESULTS: The 2-hour pain-relief rate was significantly higher with almotriptan 25 mg compared with placebo (66.7% vs 55.3%; P = .022). The incidence of nausea, photophobia, and phonophobia at 2 hours (adjusted for baseline pain intensity) for the almotriptan 25 mg and placebo groups was not significantly different. The 2-hour pain-relief rates (unadjusted) were significantly higher with almotriptan 6.25 mg (71.8%), 12.5 mg (72.9%), and 25 mg (66.7%) than with placebo (55.3%; P = .001, P < .001, and P = .028, respectively). Rates for sustained pain relief also were significantly greater with almotriptan 6.25 mg (67.2%), 12.5 mg (66.9%), and 25 mg (64.5%) than with placebo group (52.4%), P < .01 for the 6.25- and 12.5-mg doses and P < .05 for the 25-mg dose. Age group subanalysis demonstrated significantly greater 2-hour pain-relief rates with all 3 doses of almotriptan compared with placebo for patients aged 15 to 17 years, a significantly lower incidence of photophobia and phonophobia at 2 hours with almotriptan 12.5 mg compared with placebo for patients aged 15 to 17 years, and a significantly lower incidence of photophobia with almotriptan 12.5 mg compared with placebo for those aged 12 to 14 years. Almotriptan treatment was well tolerated, with the most common adverse events (>2%) of nausea, dizziness, and somnolence. CONCLUSIONS: Oral almotriptan was efficacious for relieving migraine headache pain in adolescents, with the 12.5-mg dose associated with the most favorable efficacy profile with respect to relieving headache pain and associated symptoms of migraine (photophobia and phonophobia). Almotriptan treatment was well tolerated in this adolescent population.

Characteristics of migraine attacks and responses to almotriptan treatment: a comparison of menstrually related and nonmenstrually related migraines.

OBJECTIVES: To compare the clinical characteristics of menstrually related migraines (MRMs) and nonmenstrually related migraines (nonMRMs) and to investigate the efficacy of almotriptan in the treatment of these migraine subtypes. DESIGN/METHODS: These are post hoc analyses of data from the AXERT Early miGraine Intervention Study (AEGIS), a multicenter, double-blind, parallel-group trial that evaluated adults with IHS-defined migraine with and without aura. Patients were randomized 1:1 to treat 3 consecutive headaches with almotriptan 12.5 mg or matching placebo at the first sign of headache typical of their usual migraine, at any level of pain intensity but within 1 hour of onset. MRMs were defined as those occurring +/-2 days of the first day of menstrual flow. Post hoc analyses to describe headache characteristics pooled all migraine attacks experienced by patients who reported > or = 1 menses during the study regardless of assigned treatment group. The post hoc efficacy analyses included outcomes of almotriptan treatment compared with placebo treatment for all migraines in patients with a menstrual record. RESULTS: Of the 275 women in the AEGIS intent-to-treat population, 190 (69.1%; 97 almotriptan, 93 placebo; aged 18-54 years) reported > or = 1 menses during the trial. Of the 506 migraines reported by these patients, 95 (18.8%) occurred +/-2 days of the first day of menstrual flow and were defined as MRM. Aura was associated with 11.7% of MRM and 15.0% of nonMRM. Allodynia-associated symptoms were present with 62.8% of MRM and 57.0% of nonMRM. Prior to treatment, 19.1% of MRM were associated with normal functional ability, 68.1% with disturbed functional ability, and 12.8% required bed rest compared with 18.9%, 68.8%, and 12.3%, respectively, of nonMRM. Pretreatment pain intensity was mild in 40.0%, moderate in 47.4%, and severe in 12.6% of MRM compared with 43.6%, 47.2%, and 9.2%, respectively, of nonMRM. Almotriptan treatment efficacy outcomes for MRM vs nonMRM, respectively, were: 2-hour pain relief, 77.4% vs 68.3%; 2-hour pain free, 35.4% vs 35.9%; and sustained pain free, 22.9% vs 23.8%. Almotriptan was similarly effective in relieving migraine-associated symptoms and improving functional disability associated with both MRM and nonMRM. CONCLUSIONS: Prior to treatment, the presence of migraine-associated characteristics including aura, allodynia-associated symptoms, photophobia, phonophobia, and nausea were similar for both MRM and nonMRM attacks. The pretreatment levels of pain intensity and functional disability were likewise similar across the migraine subtypes. Almotriptan was equally effective in the treatment of both MRM and nonMRM attacks and was associated with an adverse event profile that was similar to placebo treatment.

Effect of early intervention with almotriptan vs placebo on migraine-associated functional disability: results from the AEGIS Trial.

OBJECTIVE: To investigate the effect of early acute migraine intervention with almotriptan vs placebo on functional disability and health-related quality of life (HRQoL) indicators. DESIGN/METHODS: In this multicenter, double-blind, parallel-group trial, adults with international classification of headache disorders-defined migraine, with or without aura, were randomized 1:1 to treat 3 consecutive headaches with either almotriptan 12.5 mg or placebo. Patients were instructed to take their study medication at the first sign of migraine headache pain of any intensity, within 1 hour of onset. Patients recorded level of functional disability (normal, disturbed, bed rest required, emergency room [ER]/hospitalization required) at baseline (pretreatment), 0.5, 1, 2, 4, and 24 hours posttreatment and at time of pain-free. Patients completed the Migraine Disability Assessment Scale (MIDAS) at randomization and completed the Migraine Quality-of-Life Questionnaire (MQoL) at 24 hours after each attack. RESULTS: Results are presented for 315 patients (160 almotriptan, 155 placebo) in the evaluable for efficacy population. At 2 hours posttreatment of Attack 1, 54.4%, 32.5%, 13.1%, and 0%, respectively, of almotriptan-treated patients reported normal function, disturbed function, bed rest required, and ER/hospitalization required compared with 38.1%, 45.2%, 16.1%, and 0.6%, respectively, of placebo-treated patients. The differences in level of functional disability between the 2 treatment groups were statistically significant at 2 hours (P = .007; Cochran-Mantel-Haenszel, stratified by center) and at 4 hours (P < .001). Resolution of pain was associated with a normal level of function; at 2 hours posttreatment, 91.7% of patients in the total population who achieved pain-free reported normal function compared with 44.8%, 8.0%, and 0% of patients with mild, moderate, and severe pain, respectively. The absence compared with the presence of photophobia, phonophobia, and nausea at 2 hours also was associated with less disability (P < .0001 for each symptom). Treatment with almotriptan compared with placebo resulted in consistently better 24-hour MQoL scores with significant results for all 3 migraine headache attacks in the social function and feelings/concern domains. A logistic regression model determined that pretreatment functional level (P = .0117), pretreatment pain intensity (P = .0089), and pretreatment MIDAS score (P = .0152) were significant covariates of the proportion of patients who achieved normal function at 2 hours posttreatment. CONCLUSIONS: Early treatment with almotriptan within 1 hour of migraine pain onset significantly reduced levels of functional disability at 2 and 4 hours posttreatment compared with placebo. Consistency in improvement of HRQoL indicators was observed across 3 headaches treated.

Early intervention with almotriptan: results of the AEGIS trial (AXERT Early Migraine Intervention Study).

OBJECTIVE: To evaluate prospectively the efficacy and safety of almotriptan 12.5 mg as compared to placebo when administered within 1 hour of headache pain onset for the acute treatment of 3 migraine headaches. BACKGROUND: Although clinical trials have reported improved outcomes when triptans were used early or to treat mild pain, acceptance of this treatment strategy has been hampered by both efficacy and tolerability issues. METHODS: In this multicenter, double-blind, placebo-controlled, parallel-group trial, patients with IHS-migraine were randomized in a 1:1 ratio to treat 3 consecutive migraine attacks with either almotriptan 12.5 mg or placebo. Patients were instructed to take their study medication at the first sign of headache pain of any intensity, within 1 hour of onset, and to record their symptoms at multiple time points during their headaches using a personal digital assistant. Clinical trial efficacy results for the first study headache and safety data for the entire study are presented. RESULTS: A total of 378 patients were randomized, 189 to each group; 162 almotriptan-treated patients, and 155 placebo-treated patients were evaluable for efficacy. Almotriptan treatment, compared to placebo, resulted in a significantly greater proportion of patients achieving 2-hour pain free (37.0% vs 23.9%, P= .010), 2-hour pain relief (72.3% vs 48.4%, P < .001) and sustained pain free (24.7% vs 16.1%, P= .040). Significant differences in pain free (P= .026) and pain relief (P= .019) between almotriptan and placebo also were observed at 1 hour. At 2 to 4 hours and 4 to 24 hours after treatment, the mean intensity of phonophobia and photophobia were significantly lower in the patients treated with almotriptan compared to the placebo-treated patients. A greater proportion of patients treating with almotriptan versus placebo reported normal functionality within 2 hours postdose (54.4% vs 38.1%, P= .007) and 4 hours postdose (74.5% vs 54.3%, P < .001). The percentage of patients experiencing 1 or more treatment-emergent adverse events (AE) was 9.8% for almotriptan and 6.4% for placebo. The only treatment-emergent AEs that occurred with a frequency of at least 1% (equivalent to 2 or more patients) in the almotriptan and placebo groups, respectively, were somnolence (1.1% and 2.3%), nausea (1.1% and 1.7%), vomiting (1.1% and 0.6%), and fatigue (1.1% and 0%). CONCLUSION: Treatment with almotriptan within 1 hour of migraine onset resulted in significantly better clinical outcomes than placebo and tolerability similar to placebo. Acute medications, such as almotriptan, that are both effective and well tolerated may encourage patients to access acute treatment earlier.

Effect of pain intensity and time to administration on responsiveness to almotriptan: results from AXERT 12.5 mg Time Versus Intensity Migraine Study (AIMS).

OBJECTIVE: To determine whether time-based early treatment, independent of pain intensity, is superior to a pain intensity-based treatment, where patients are asked to treat at least moderate intensity headaches, resulting in a reduction of overall migraine headache duration. BACKGROUND: Retrospective and prospective trials have reported improved outcomes when triptans were used early or to treat mild migraine headache pain. However, tolerability as well as efficacy may be 2 of several key issues that have prevented this new treatment paradigm from becoming universally accepted. METHODS: In this multicenter, open-label, cluster-randomized study, patients with IHS-defined migraine were instructed to treat 2 sequential migraine headaches with almotriptan 12.5 mg using either Early Treatment (ET, ie, treat at earliest onset of headache pain, within 1 hour) or Standard Treatment (ST, ie, treat when headache pain intensity is moderate or severe). The novel trial design uses total migraine headache pain duration as the primary endpoint. RESULTS: Results are presented for the first headache and include an ITT population of 757 ET and 693 ST patients. Median headache duration (time from onset of headache pain until no pain) was significantly shorter in ET patients compared to ST patients (3.18 vs 5.53 hours, P < .001). An analysis of the ET subgroup treating headache pain within 1 hour of onset revealed pain intensity, ie, treating mild or moderate versus severe pain, was significantly correlated with treatment outcomes defined by total headache duration, 2-hour pain free, sustained pain free, and use of rescue medication. Multivariate analyses comparing ST subgroups that treated within 1 hour versus greater than 1 hour after headache onset, demonstrate that both pain intensity, ie, treating moderate versus severe headache pain, and treating early versus late, were significantly correlated with total headache duration, 2-hour pain free, sustained pain free, and use of rescue medication. The overall incidence of adverse events was low; nausea and dizziness were the only adverse events with an incidence > or =1% in either treatment group (nausea: 2.5% and 1.7% and dizziness 1.1% and 0.7%, in the ET and ST groups, respectively). CONCLUSION: Total headache duration was significantly shorter in the early treatment group compared to the standard treatment group. Considering time to treatment within a relatively early range of 1 hour or less, efficacy results when treating mild versus moderate pain were similar and both were associated with better outcomes than treatment of severe pain. When considering the prognostic variables of time to treatment and headache pain intensity (limited to moderate vs severe), both were independent predictors, with time to treatment a better predictor of headache duration and rescue medication use, and pain intensity a better predictor of 2-hour pain free and sustained pain free.

The impact of topiramate on health-related quality of life indicators in chronic migraine.

BACKGROUND: Chronic migraine is a disabling primary chronic daily headache disorder that significantly impacts the daily activities of patients with this disorder. To our knowledge, this is the first report of a large, randomized, double-blind, placebo-controlled trial that assessed the impact of topiramate on the daily activities, emotional distress, headache-related disability, and global impression of change in patients with chronic migraine. OBJECTIVE: To assess whether topiramate 100 mg/day reduces migraine-related disability and limitations of daily activities in patients with chronic migraine. STUDY DESIGN/METHODS: Patients aged > or =18 years with chronic migraine were randomized 1 : 1 ratio to topiramate 100 mg/day or placebo. The double-blind period lasted 16 weeks. Three patient-reported outcome measures were administered: Migraine Disability Assessment, Migraine-Specific Quality of Life Questionnaire (Domains: Role Function Restrictive and Preventive and Emotional Function), and Subject's Global Impression of Change. Investigators completed a Physician's Global Impression of Change for each patient. Subject's Global Impression of Change and Physician's Global Impression of Change were completed one time, at the end of study, and measured on a 7-point scale (1 = very much improved to 7 = very much worse). The Migraine-Specific Quality of Life Questionnaire was analyzed using analysis of covariance (last observation carried forward) approach. Results were not adjusted for multiplicity. RESULTS: A total of 328 patients were randomized (topiramate, n = 165; placebo, n = 163), and 306 patients were included in the intent-to-treat population. Mean age was 38.2 years, and a majority of the patients were female (85.3%). Fifty-six percent of topiramate-treated patients vs 45% of placebo-treated patients reported >50% improvement from baseline in Migraine Disability Assessment scores (P = .074). The Migraine-Specific Quality of Life Questionnaire analysis demonstrated significant improvements at week 4 in all 3 domains, and at weeks 8 and 16 in both Role Function-Restrictive and Emotional Function domains (P < .05). Role Function-Preventive approached, but did not reach significance, at week 8 (P = .053). Seventy-five percent and 72% of topiramate-treated patients vs 61% and 59% of placebo-treated patients reported improvements on the Subject and Physician's Global Impression of Change scales (P = .025 and P = .037, respectively). CONCLUSION: Compared with placebo-treated patients, topiramate 100 mg/day appears to contribute to reductions in migraine-related limitations on daily activities and emotional distress beginning as early as week 4 and continuing up to week 16 after treatment. Physician's Global Impression of Change results are very similar with Subject's Global Impression of Change, indicating concordance between the physician's and the subject's assessment of improvement.