Importance of Regular and Maintenance Therapy Adherence in Neuromyelitis Optica (NMO): Lessons from a Repeating Relapse Case.

BACKGROUND Neuromyelitis optica (NMO) is a rare demyelinating disease of the central nervous system; NMO predominantly affects the spinal cord and optic nerves. The diagnosis is based on history, clinical presentation, seropositive NMO-IgG antibody, and notably, exclusion of other diseases. Despite the absence of definitive therapeutic strategies for NMO, methylprednisolone pulse therapy and plasma exchange are used for acute phase treatment, while immunosuppressive agent(s) are recommended to prevent relapses and improve prognosis. Here, we report a repeating relapse NMO case due to lack of regular and maintenance therapy. CASE REPORT A 58-year-old female with chronic NMO presented with a three-day history of new-onset right leg weakness and pain. The patient was diagnosed with NMO three years ago and presented with her fourth attacks. During her initial diagnosis, she was initiated on steroids. One year later, she developed the first relapse and was treated with steroids and rituximab, leading to 1.5-year remission. After the second relapse, steroids and rituximab was still given as maintenance therapy, but was not followed. Thus, the third relapse occurred in five months. During this hospitalization, she received initially high-dose solumedrol (1 g daily for five days) in addition to gabapentin 100 mg (gradually increased to 300 mg) three times a day for muscle spasms. Due to worsening of paresthesia and hemiparesis, it was decided to place her on plasma exchange treatment. After two plasma exchanges, the patient's condition was improved and she regained strength in her lower extremity. She completed five more cycles of plasma exchange, and was then discharged on steroid therapy (prednisone 20 mg daily for 10 days then taper) as maintenance therapy and with follow-up in neurology clinic. CONCLUSIONS Over the span of three years, the patient has had three relapses since her NMO diagnosis where her symptoms have worsened. Steroid therapy alone seemed not insufficient in managing her more recent relapses. Nonadherence to NMO treatment likely increased her risk for recurrence, thus regular and long-term maintenance therapy is imperative to delay the progression and prevent relapse in NMO.

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.

Efficacy of sumatriptan tablets in migraineurs self-described or physician-diagnosed as having sinus headache: a randomized, double-blind, placebo-controlled study.

BACKGROUND: Many patients and physicians interpret episodic headache in the presence or absence of nasal symptoms as "sinus' headache, while ignoring the possible diagnosis of migraine. OBJECTIVE: The purpose of this study was to assess the efficacy and tolerability of sumatriptan succinate 50-mg tablets in patients with migraine presenting with "sinus" headache. METHODS: A randomized, double-blind, placebo-controlled, multicenter study was conducted in adult (aged 18-65 years) migraine patients presenting with self-described or physician-diagnosed "sinus" headache. From November 2001 to March 2002, patients meeting International Headache Society criteria for migraine (with > or =2 of the following: unilateral location, pulsating quality, moderate or severe intensity, aggravation by moderate physical activity; and > or =1 of: phonophobia and phonophobia, nausea and/or vomiting) and with no evidence of bacterial rhinosinusitis were enrolled and randomized in a 1:1 ratio via computer-generated randomization schedule to receive either 1 sumatriptan 50-mg tablet or matching placebo tablet. The primary efficacy end point was headache response (moderate or severe headache pain reduced to mild or no headache pain) at 2 hours after administration. The presence or absence of migraine-associated symptoms and sinus and nasal symptoms was also measured. Tolerability was assessed through patient-reported adverse events (AEs). RESULTS: Two hundred sixteen patients with self-described or physician-diagnosed "sinus" headache received a migraine diagnosis and treated 1 migraine attack with sumatriptan 50 mg. The efficacy (intent-to-treat) analysis included 215 patients treated with sumatriptan 50 mg (n = 108; mean [SD] age, 39.6 [12.3] years; mean [SD] weight, 77.7 [17.7] kg; sex, 71% female; race, 69% white) or placebo (n = 107; mean [SD] age, 41.0 [11.3] years; mean [SD] weight 80.7 [20.9] kg; sex, 69% female; race, 64% white). Significantly more patients treated with sumatriptan 50 mg achieved a positive headache response at 2 and 4 hours after administration compared with those treated with placebo (69% vs 43% at 2 hours and 76% vs 49% at 4 hours, respectively; both, P < 0.001). Significantly more sumatriptan-treated patients were free from sinus pain compared with placebo recipients at 2 hours (63% vs 49% placebo, P = 0.049) and 4 hours (77% vs 55%, P = 0.001). All treatments were generally well tolerated. The most common drug-related AEs reported in the sumatriptan and placebo groups, respectively, were dizziness (5% vs < 1%), nausea (3% vs 2%), other pressure/tightness (defined as sense of heaviness; heaviness of upper body, upper extremities; jaw tension; neck tension) (4% vs 0%), and temperature sensations (defined as warm feeling of back of neck, or flushing) (2% vs 0%). No patients experienced any serious AEs. CONCLUSIONS: Sumatriptan 50-mg tablets were effective and generally well tolerated in the treatment of these patients presenting with migraine headaches that were self-described or physician-diagnosed as sinus headaches.

Valdecoxib for treatment of a single, acute, moderate to severe migraine headache.

OBJECTIVE: To evaluate the analgesic efficacy and safety of a single 20- or 40-mg dose of valdecoxib compared with placebo in treatment of a single, acute, moderate or severe migraine headache, with or without aura. BACKGROUND: Valdecoxib, an oral COX-2 specific inhibitor, is indicated for relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis and treatment of primary dysmenorrhea. This study assessed the optimal dose of valdecoxib for treatment of a single, acute, moderate to severe migraine headache. METHODS: This was a double-blind, randomized, placebo- and active-controlled, multicenter, single-dose (primary end point) and multiple-dose (secondary end point), 56-day study of valdecoxib in the treatment of a single, acute, moderate or severe migraine headache, with or without aura. Migraine headaches were diagnosed according to International Headache Society (IHS) criteria. The primary efficacy end point was headache response (defined as reduction of headache pain intensity from moderate or severe to mild or none) at 2 hours postdose. Patients assessed their headache pain intensity and presence or absence of migraine-associated nausea, vomiting, phonophobia, and photophobia at intervals from 0 to 24 hours postdose. Sumatriptan 50 mg (encapsulated, in standard method, to maintain blinding) was included as a positive control for assay sensitivity. No statistical comparisons were performed between active treatment arms (valdecoxib 20 mg, valdecoxib 40 mg, and sumatriptan 50 mg). Adverse events and safety parameters were monitored throughout the study. RESULTS: In the intent-to-treat population of 570 patients (135 valdecoxib 20 mg, 151 valdecoxib 40 mg, 143 sumatriptan, and 141 placebo), no significant differences in baseline demographics among treatment groups were observed. The headache response rate with valdecoxib 40 mg and sumatriptan 50 mg was significantly greater than that with placebo at all time points from 2 to 24 hours postdose. With valdecoxib 20 mg, headache response rate was significantly greater than placebo from 2 to 4 hours. Significantly fewer patients treated with valdecoxib 40 mg, compared with placebo, experienced nausea, vomiting, and phonophobia at 2 hours postdose. CONCLUSIONS: A single 40-mg dose of valdecoxib is effective and well tolerated in treatment of migraine headache pain and associated symptoms.

Pharmacokinetics of frovatriptan in adolescent migraineurs.

Frovatriptan is a selective 5-HT(1B/1D) receptor agonist available for acute treatment of migraine in adults (18 years and older). The objective of this study was to determine key pharmacokinetic parameters of frovatriptan in adolescent migraineurs after a single 2.5-mg oral dose and to compare these results with those from an earlier study completed in adults. Subjects were stratified by age (12-14 and 15-17 years) and gender, and serial blood and urine samples were collected over 48 hours. A total of 25 subjects (13 male, 12 female) completed the study. Pharmacokinetic profiles for adolescent subjects were similar to those observed in adults. The median tmax ranged from 2 (male subjects) to 3 (female subjects) hours. The AUC0-24h and Cmax were slightly lower in adolescent subjects as compared with adults. As seen in adults, AUC0-24h and Cmax values were approximately 2-fold higher in females than in their male counterparts (AUC mean range 40.5-59.8 ng x h/mL vs 21.2-23.5 ng x h/mL and Cmax mean range 4.02-6.14 vs ng x h/mL 2.52-2.99 ng/mL, in female and male adolescent subjects, respectively). Elimination was biphasic, with an approximate terminal elimination half-life (t(1/2)) between 12.2 and 25.5 hours. Renal clearance was similar in adolescents and adults, being somewhat higher in female than male subjects. Frovatriptan was well tolerated with no serious or treatment-related adverse effects. In addition, there were no clinically significant changes in safety parameters. Overall, the pharmacokinetic profile of frovatriptan in adolescents (12-17 years) is similar to that seen in adults, and dosing adjustments are unlikely to be needed.