Treatment persistence and switching in triptan users: a systematic literature review.

OBJECTIVE: To conduct a systematic review to evaluate persistence to and switching of triptan therapy for the acute treatment of migraine. BACKGROUND: Migraine affects over 12% of adults in Western countries and an estimated 36 million people in the United States. Triptans are an abortive treatment option in patients with moderate to severe migraine. Despite the safety and efficacy of triptans reported in clinical trials, observational studies have consistently demonstrated low persistence to therapy and frequent switching among products over time. METHODS: The following databases were researched: Medline, CENTRAL, and EMBASE. Detailed inclusion and exclusion criteria were specified a priori before conducting abstract and full-text screening. Included studies were required to: (1) report triptan use for migraine treatment; (2) report measures of persistence and/or switching patterns; (3) study migraineurs aged 18 years or older; and (4) conduct an observational study. Studies were excluded if they (1) incorporated interventional study design; (2) lack information or relevance to outcome of interest; (3) were not original research; (4) did not clearly state the results; and (5) were not written in English. Abstracts and full-text articles were reviewed independently by two investigators. RESULTS: Out of 595 studies identified, 380 studies were included for abstract screening. A total of 12 articles met the eligibility criteria after full-text screening of 44 studies, including four studies from reference search. The proportion of patients that remained persistent up to six refills of an index triptan ranged from 3.2% to 12.6% and the proportion of patients that never refilled their index triptan ranged from 38% to 65.8%. In addition to those patients who discontinued, several studies reported that 5-9% of newly initiating triptan users switch to a different triptan before refilling their original medication. Finally, several studies reported the 1-year probability of discontinuation among a general group of triptan users (not limited to treatment naïve patients) to be between 30% and 60%. CONCLUSIONS: Triptans can be a valuable option for acute treatment of migraine. However, studies have shown that treatment persistence is low. This, along with frequent switching behaviors, suggests that a significant unmet clinical need remains despite the wide availability of triptans.

Adherence, persistence, and switching patterns of dabigatran etexilate.

OBJECTIVE: To investigate adherence, persistence, and switching in patients initiating dabigatran. STUDY DESIGN: Descriptive analysis using pharmacy claims databases. METHODS: Patients with a claim for dabigatran and who were continuously enrolled in pharmacy benefits for 180 days prior to and 180 days following the initiation of dabigatran were identified and stratified by whether there was a history of warfarin treatment prior to dabigatran initiation. Medication adherence was calculated as the proportion of days covered (PDC). Persistence to treatment at 180 days was measured. Among patients who discontinued dabigatran, time to initiating warfarin was determined. RESULTS: In the overall population, 39.9% of 17,691 patients were nonpersistent to dabigatran. The PDC for the warfarin-naïve cohort was 0.674 (standard deviation [SD] 0.364), and 0.712 (SD 0.354) for the warfarin-experienced cohort. For patients persistent to dabigatran, the PDCs for warfarin-naïve and warfarin-experienced cohorts were 0.935 (SD 0.075) and 0.937 (SD 0.074), respectively. In patients discontinuing dabigatran, 16.1% of warfarin-naïve and 41.1% of warfarinexperienced patients initiated warfarin. Among patients discontinuing dabigatran, the mean time to discontinuation in warfarin-naïve and warfarinexperienced cohorts, respectively, was 59.8 (SD 36.2) and 59.6 (SD 36.2) days. The mean time to initiating warfarin in warfarin-naïve and warfarin experienced cohorts, respectively, was 62.5 (SD 47.2) and 60.5 (SD 43.0) days. CONCLUSIONS: Two in 5 patients discontinued dabigatran therapy within 6 months, and the majority of these patients were not anticoagulated with warfarin upon discontinuation. These findings highlight potential gaps in the care of patients treated with dabigatran in routine practice.

Evidence for mutation showers.

Mutants in the Big Blue transgenic mouse system show spontaneous clustered multiple mutations with unexpectedly high frequency, consistent with chronocoordinate events. We tested the prediction that the multiple mutations seen within the lacI mutation target sometimes occur in the context of chronocoordinate multiple mutations spanning multiple kilobases (mutation showers). Additional sequencing of mutants was performed in regions immediately flanking the lacI region (total of 10.7 kb). Nineteen additional mutations were found outside the lacI region ("ectomutations") from 10 mutants containing two or more lacI mutations, whereas only one ectomutation was found in 130 mutants with a single mutation (P < 0.0001). The mutation showers had an average of approximately one mutation per 3 kb. Four mutants showed closely spaced double mutations in the new sequence, and analysis of the spacing between these mutations revealed significant clustering (P = 0.0098). To determine the extent of the mutation showers, regions (8.5 kb total) remote from the lacI region (approximately 16-17 kb away) were sequenced. Only two additional ectomutations were found in these remote regions, consistent with mutation showers that generally do not extend more than approximately 30 kb. We conclude that mutation showers exist and that they constitute at least 0.2% and possibly 1% or more of mutational events observed in this system. The existence of mutation showers has implications for oncogenesis and evolution, raising the possibilities of "cancer in an instant" and "introns as sponges to reduce the deleterious impact of mutation showers."