Real-world effectiveness of fremanezumab in patients with migraine switching from another mAb targeting the CGRP pathway: a subgroup analysis of the Finesse Study.

BACKGROUND: Monoclonal antibodies targeting the CGRP pathway are effective and safe for prophylactic treatment of episodic (EM) and chronic migraine (CM). In case of treatment failure of a CGRP pathway targeting mAb, physician has to decide whether using another anti-CGRP pathway mAb is useful. This interim analysis of Finesse Study evaluates effectiveness of the anti-CGRP mAb fremanezumab in patients with a history of other prior anti-CGRP pathway mAb treatments (switch patients). METHODS: FINESSE, a non-interventional, prospective, multicentre, two-country (Germany-Austria) study observing migraine patients receiving fremanezumab in clinical routine. This subgroup analysis presents data on documented effectiveness over 3 months after the first dose of fremanezumab in switch patients. Effectiveness was evaluated based on reduction in average number of migraine days per month (MMDs), MIDAS and HIT-6 scores changes as well as in number of monthly days with acute migraine medication use. RESULTS: One hundred fifty-three out of 867 patients with a history of anti-CGRP pathway mAb treatment prior to initiation of fremanezumab were analysed. Switch to fremanezumab led to ≥ 50% MMD reduction in 42.8% of migraine patients, with higher response rate in EM (48.0%) than in CM patients (36.5%). A ≥ 30% MMD reduction was achieved by 58.7% in CM patients. After three months, monthly number of migraine days decreased by 6.4 ± 5.87 (baseline: 13.6 ± 6.5; p < 0.0001) in all patients, 5.2 ± 4.04 in EM and 7.7 ± 7.45 in CM patients. MIDAS scores decreased from 73.3 ± 56.8 (baseline) to 50.3 ± 52.9 (after 3 months; p = 0.0014), HIT-6 scores decreased from 65.9 ± 5.0 to 60.9 ± 7.2 (p < 0.0001). Concomitant use of acute migraine medication had decreased from 9.7 ± 4.98 (baseline) to 4.9 ± 3.66 (3 months) (p < 0.0001). CONCLUSIONS: Our results show that about 42.8% of anti-CGRP pathway mAb-non-responder benefit from switching to fremanezumab. These results suggest that switching to fremanezumab may be a promising option for patients experiencing poor tolerability or inadequate efficacy with prior other anti-CGRP pathway mAb use. TRIAL REGISTRATION: FINESSE Study is registered on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS44606).

Drug utilization patterns of flupirtine following implementation of risk minimization measures in Germany.

Objectives: This report characterizes flupirtine prescribing patterns before and after the implementation of risk minimization measures (RMM) in Germany as a complementary analysis to support previous study findings. Methods: A retrospective analysis was conducted using a patient-level longitudinal prescription database (IMS LRx) in Germany. The study population included patients who were prescribed flupirtine-containing products. One-year periods before (2012) and after (April 2015-March 2016) RMM implementation were assessed for the following measures: flupirtine use of up to two weeks, flupirtine use when other analgesics are contraindicated and concomitant use of drugs with a known potential to induce liver injury. Results: The number of flupirtine users decreased by 41.0% from 248,738 patients in the pre-RMM implementation period to 146,764 in the post-implementation period. The proportion of patients prescribed flupirtine for up to 14 days increased significantly by 22.7%, from 67.9% to 90.6% in the pre- to post-implementation periods, respectively. Over half the patients received long-term medications for conditions contraindicated with the use of other analgesics within 12 months prior to the first flupirtine prescription in the pre- and post-implementation periods (57.1% and 52.3%, respectively). Concomitant prescriptions of drugs with known potential hepatotoxic effects were recorded in 36.6% and 34.2% of flupirtine prescriptions during the pre- and post-implementation periods, respectively. Conclusions: While physicians generally restricted flupirtine prescriptions to the short-term treatment duration recommended in the labeling, the other labeling recommendations were not as stringently adopted. Findings of this investigation support a previous study conducted in an electronic medical record database.

The impact of risk minimization measures on compliance and prescribing practices of flupirtine in Germany.

Objective: In response to safety concerns, risk minimization measures (RMM) for flupirtine were implemented in Europe in 2013 to reduce hepatotoxicity risk. This study aims to characterize compliance and prescribing practices of flupirtine before and after RMM implementation.Research design and methods: A retrospective pre-post design cohort study was conducted in the outpatient setting using a longitudinal electronic medical record database in Germany. The study population included patients who initiated flupirtine. One-year pre- and post-implementation periods were assessed.Main outcome measures: Six RMM elements were evaluated, including indication of acute pain, use for maximum of 2 weeks, use when other analgesics are contraindicated, no pre-existing liver disease or alcohol abuse, no concomitant drug induced liver injury, and weekly liver function tests.Results: The number of flupirtine users decreased by 34.4% from 18,291 in the pre-implementation period (2012) to 12,000 in the post-implementation period (April 2015 to March 2016). Elements of RMM with substantial improvement included flupirtine prescription duration, where the proportion of patients with duration ≤14 days increased significantly by 16.5% from 74.8% to 91.3% in the pre- and post-implementation periods, respectively. RMM with a moderate-to-high degree of compliance during the post-implementation period, although with a very small or no change from the pre- implementation period, included restriction of flupirtine prescribing to patients with acute pain when other analgesics are contraindicated, and avoiding use in patients with either pre-existing liver disease or concomitant drugs known to have a potential hepatotoxic effect. Weekly liver function tests had a low degree of compliance.Conclusions: These findings demonstrate that, while physicians restricted flupirtine prescriptions to short-term use in the target population of acute pain, not all drug labeling elements were followed to the same extent in routine practice.