Extent of a valsartan drug shortage and its effect on antihypertensive drug use in the Canadian population: a national cross-sectional study.

BACKGROUND: Drug shortages represent a growing global problem, with potentially serious consequences to patients and the health care system. Our study investigates the impacts of a major recall and shortage of valsartan, an angiotensin receptor blocker (ARB), in July 2018 in Canada. METHODS: We conducted a time-series analysis of antihypertensive drugs dispensed in Canada between 2015 and 2019 using commercially available retail prescription data. Using autoregressive integrated moving average (ARIMA) modelling, we evaluated the change in valsartan use after the recall. We also measured the overall use of ARBs, angiotensin-converting-enzyme (ACE) inhibitors and other antihypertensive drug classes for the same period. RESULTS: After the recall in July 2018, valsartan use decreased 57.8%, from 362 231 prescriptions dispensed in June 2018 to 152 892 in September 2018 (difference = 209 339, p < 0.0001). Overall use of the ARB drug class decreased 2.0%, from 1 577 509 prescriptions dispensed in June 2018 to 1 545 591 in September 2018 (difference = 31 918, p = 0.0003), but use of non-valsartan ARBs increased 14.6%, from 1 215 278 to 1 392 699 prescriptions dispensed (difference = 177 421, p < 0.0001) in the same time frame. Although use of ACE inhibitors initially declined, this reduction was not sustained. The valsartan recall was not associated with a significant impact on use of other antihypertensive drug classes. INTERPRETATION: Our findings illustrate the impact of a major drug shortage, with the immediate and substantial reduction of valsartan dispensed and cascading effects on other ARBs, though future research is warranted to understand the consequences of such extensive shortages on clinical outcomes and health system costs. Improved policy strategies are needed to address the underlying causes of drug shortages and to mitigate their effects.

Effect on Patients' Outcomes of a Change to Biosimilar Filgrastim Product in Autologous Stem Cell Mobilization.

BACKGROUND: Following addition of a biosimilar filgrastim product to the formulary, sites in the authors' provincial health authority transitioned from using the originator filgrastim to the biosimilar for autologous stem cell mobilization. OBJECTIVE: To assess the effect on patient outcomes of a universal change to use of the biosimilar filgrastim in stem cell mobilization. METHODS: This retrospective pre-post study included patients undergoing autologous stem cell mobilization at 2 cancer hospitals in Alberta, Canada, between July 1, 2018, and November 30, 2019. Clinical outcomes were investigated for patients treated with a granulocyte colony-stimulating factor (biosimilar or originator product) for mobilization before stem cell transplant, approximately 6 months before and after the defined date of product change. RESULTS: In total, 102 patients were treated with the originator product and 101 patients with the biosimilar. Effectiveness was similar between the originator and biosimilar products, with 98% successful harvest of stem cells in all patients treated. Independent t tests showed no statistically significant differences between patients receiving the originator and those receiving the biosimilar in terms of time from mobilization to collection (difference of means -0.9 days, 95% confidence interval [CI] -2.12 to 0.32), time for neutrophil engraftment (difference of means 0 days, 95% CI -0.36 to 0.36), time for platelet engraftment (difference of means 1 day, 95% CI -0.55 to 2.55), average length of stay (difference of means -0.7 day, 95% CI -2.71 to 1.31), and CD34+ value (difference of means -1 × 106/kg body weight, 95% CI -2.11 to 0.11). A 98% rate of conversion to use of the biosimilar filgrastim was achieved, with an estimated annual drug-cost saving of $67 500. CONCLUSIONS: In this pre-post study, changing to the biosimilar product from the originator maintained clinical effectiveness outcomes while decreasing overall drug expenditures. A well-planned change to the biosimilar product, executed in conjunction with clinician consultation and monitoring of effectiveness outcomes, can ensure appropriate patient therapy while significantly improving the uptake of biosimilars and decreasing expenditures for biologic drugs.

CONTEXTE: À la suite de l'ajout d'un produit filgrastim biosimilaire à la liste des médicaments, les sites relevant de l'autorité sanitaire provinciale des auteurs sont passés de l'utilisation du filgrastim princeps à la version générique pour la mobilisation des cellules souches autologues. OBJECTIF: Évaluer l'effet sur les résultats des patients d'un changement généralisé visant à utiliser le filgrastim générique pour la mobilisation des cellules souches. MÉTHODES: Cette étude rétrospective pré-post comprenait des patients soumis à une mobilisation des cellules souches autologues dans deux hôpitaux de cancérologie en Alberta (Canada) entre le 1er juillet 2018 et le 30 novembre 2019. L'examen des résultats cliniques des patients traités à l'aide d'un facteur stimulant les colonies de granulocytes (G-CSF) (générique ou princeps) pour une mobilisation avant la greffe de cellules souches a eu lieu environ six mois avant et après la date du changement de produit. RÉSULTATS: Au total, 102 patients ont été traités à l'aide du produit princeps et 101 patients à l'aide du générique. Les deux produits présentaient une efficacité similaire, et 98 % de réussite dans la récolte de cellules souches chez tous les patients traités. Des tests t indépendants n'ont montré aucune différence statistique significative entre les patients recevant le princeps et ceux recevant le biosimilaire en termes de temps allant de la mobilisation à la collecte (différence des moyennes −0,9 jour, intervalle de confiance [IC] 95 % −2,12 à 0,32); temps de la prise de la greffe neutrophile (différence des moyennes 0 jour, IC 95 % −0,36 à 0,36); temps de la prise de la greffe des plaquettes (différence des moyennes 1 jour, IC 95 % −0,55 à 2,55); durée moyenne du séjour (différence des moyennes −0,7 jour, IC 95 % −2,71 à 1,31) et valeur CD34+ (différence des moyennes −1 × 106/kg masse corporelle, IC 95 % −2,11 à 0,11). Un taux de conversion de 98 % visant à utiliser le filgrastim générique a été atteint, avec une estimation des économies annuelles sur le coût des médicaments de 67 500 $. CONCLUSIONS: Dans cette étude pré-post, le passage du produit princeps au générique a préservé l'efficacité des résultats cliniques, tout en diminuant les dépenses générales liées au médicament. Un changement bien programmé pour passer au produit générique, mené conjointement avec la consultation d'un clinicien et un contrôle des résultats d'efficacité, peut assurer une thérapie du patient appropriée tout en améliorant grandement la prise de produits génériques et en diminuant les dépenses associées aux médicaments biologiques.

Effect of listing strategies on utilization of antitumor necrosis factor biologics infliximab and etanercept: a cross-sectional analysis from Ontario, Canada.

BACKGROUND: Use of costly biologic drugs for the treatment of chronic inflammatory diseases has increased significantly in recent years. However, biosimilar drugs offer an opportunity to ensure health system sustainability with robust uptake. OBJECTIVE: To study the effect of formulary listing strategies on the use of infliximab and etanercept innovator and biosimilar biologics. METHODS: This is a cross-sectional study of individuals in Ontario, Canada, dispensed a biologic prescription for infliximab or etanercept through Ontario's public drug program between January 1, 2010, and June 30, 2019. Quarterly utilization and costs were forecasted using Holt-Winters' exponential smoothing models to the second quarter (Q2) of 2022. Secondary analyses explored utilization for rheumatic conditions (RC) and inflammatory bowel disease (IBD). RESULTS: From Q1 2010 to Q2 2019, infliximab and etanercept users increased by 75.7% (n = 4,073 to 7,158), with a forecasted increase of 13.7% (n = 8,142; 95% CI = 7,438-8,847) by Q2 2022. Biosimilar users represented 13.8% (n = 539 of 3,905) of total infliximab users in Q2 2019, although this differed by indication with 6.9% for IBD (n = 187 of 2,712) and 26.6% for RC (n = 203 of 764). Etanercept biosimilar users represented 20.2% (n = 659 of 3,256) of total etanercept users for RC in Q2 2019. Biologics expenditures increased 109.7% during the study, amounting to $49.9 million in Q2 2019. CONCLUSIONS: Despite differing reimbursement restrictions between innovator infliximab and etanercept biologics, the uptake of their biosimilars was low and not noticeably different in the treatment of RC. Dynamic policy strategies are needed to improve the uptake of biosimilars, particularly for IBD. DISCLOSURES: Funding for this study was contributed by the Ontario Ministry of Health. The authors have no conflicts of interest to disclose.