Association of a Risk Evaluation and Mitigation Strategy Program With Transmucosal Fentanyl Prescribing
Authors: William Fleischman, Doris Auth, Nilay D. Shah, Shantanu Agrawal, Joseph S. Ross
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Transmucosal immediate-release fentanyl (TIRF) drugs are potent, rapid-acting opioids approved to treat breakthrough pain in patients with cancer who are tolerant to other around-the-clock opioid analgesics. In March 2012, a US Food and Drug Administration–approved Risk Evaluation and Mitigation Strategy (REMS) was implemented, mandating prescribers, distributors, pharmacies, and patients to enroll in the REMS to prescribe, dispense, or receive TIRF drugs. <h3>Objective</h3> To evaluate the association of the TIRF-REMS Access Program with TIRF prescribing. <h3>Design, Setting, and Participants</h3> Cohort study using an interrupted time series analysis of TIRF prescriptions to Medicare Part D beneficiaries nationwide from 2010 to 2014. Data were analyzed from August 2017 through July 2018. <h3>Main Outcomes and Measures</h3> Prescribing of TIRF per 100 000 Medicare Part D beneficiaries, overall and stratified by cancer status; percentage of TIRF prescriptions for patients without cancer, overall and by brand; and percentage of TIRF prescriptions for patients without known opioid tolerance, defined as patients prescribed at least 60 morphine milligram equivalents per day, overall and by brand. <h3>Results</h3> There were 99 601 TIRF prescriptions written by 8619 clinicians to 10 472 patients. Most of the patients (79%) were younger than 65 years (mean [SD] age, 56 [13] years), and most (67%) did not have cancer. Implementation of TIRF-REMS was associated with a 26.7% relative level decrease in TIRF prescribing (95% CI, −33.3% to −19.4%;<i>P</i> &lt; .001) but was followed by 2.0% monthly increases in prescribing (95% CI, 1.3% to 2.7%;<i>P</i> &lt; .001). Sensitivity analyses that accounted for overall opioid prescribing trends were consistent with these findings. Furthermore, there were no significant changes associated with REMS implementation in the level (0.47%; 95% CI, −5.36% to 4.69%;<i>P</i> = .85) or trend (0.16%; 95% CI, −0.06% to 0.37%;<i>P</i> = .15) of the percentage of prescriptions for patients without cancer. However, a sensitivity analysis that used a broader cancer definition found implementation was associated with a 7.2% (95% CI, −13.5% to −0.48%;<i>P</i> = .04) level decrease in the percentage of TIRF prescriptions for patients without cancer. Lastly, the TIRF-REMS was associated with a 22.5% level decline in the percentage of TIRF prescriptions for patients without known opioid tolerance (95% CI, −36.1% to −5.95%;<i>P</i> = .01) followed by 1.98% monthly decreases (95% CI, −3.19% to −0.80%;<i>P</i> = .001). <h3>Conclusions and Relevance</h3> Implementation of the TIRF-REMS Access Program, a restrictive drug distribution program, was associated with a temporary reduction in the rate of TIRF prescribing to Medicare Part D beneficiaries, and with a sustained decrease in the percentage of TIRF prescriptions for patients without known opioid tolerance. Implementation may have also been associated with a temporary decrease in the percentage of TIRF prescriptions for patients without cancer.