Public Drug Plan Research Articles

Cenobamate (Xcopri)


 CADTH recommends that Xcopri should be reimbursed by public drug plans as adjunctive therapy in the management of partial onset seizures in adults with epilepsy whose seizures are not satisfactorily controlled with conventional therapy, if certain conditions are met.
 Xcopri should only be reimbursed for the management of partial onset seizures in adults with epilepsy whose seizures are not satisfactorily controlled with conventional therapy, according to the criteria used by the public drug plans for other third generation antiseizure medication (ASMs) that are currently reimbursed for the management of partial onset seizures in adults with epilepsy whose seizures are not satisfactorily controlled with conventional therapy.
 Xcopri should only be reimbursed if the daily cost of Xcopri is the same as or lower than the daily cost of other third generation adjunctive therapies (lacosamide, brivaracetam, eslicarbazepine, and perampanel), and if the potential budget impact of funding Xcopri is addressed.

Roflumilast (Zoryve)


 CADTH recommends that Zoryve be reimbursed by public drug plans for the treatment of plaque psoriasis, including treatment of psoriasis in the intertriginous areas, in patients 12 years of age and older if certain conditions are met.
 Zoryve should only be covered to treat patients who have a clinical diagnosis of plaque psoriasis with an Investigator Global Assessment (IGA) score of at least 2 (mild) and an area of plaque psoriasis appropriate for topical treatment covering a body surface area of 2% to 20% (inclusive).
 Zoryve should be discontinued if a response has not been demonstrated by 8 weeks. A response to treatment is defined as at least a 2-grade improvement from baseline in IGA score or an IGA score of “clear” or “almost clear” (0 or 1). The cost of Zoryve should not exceed the drug program cost of treatment with the least costly topical therapy reimbursed for the treatment of plaque psoriasis.

Avacopan (Tavneos)


 CADTH recommends that Tavneos not be reimbursed by public drug plans as adjunctive treatment for adults with severe active antineutrophil cytoplasmic autoantibody-associated vasculitis (ANCA-AV) (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]).
 One clinical trial demonstrated that Tavneos in combination with ANCA-AV background therapy (including glucocorticoids and drugs that reduce immune system function) was as good as oral prednisone (60 mg dose reduced over 20 weeks) in combination with ANCA-AV background therapy for showing a reduction in disease symptoms at week 26 and was better than oral prednisone for maintaining symptom improvement at week 52. However, it was unclear if Tavneos offered a meaningful clinical benefit over other treatments used for ANCA-AV mainly because rituximab was not used as maintenance therapy in the trial, as is currently recommended by Canadian guidelines, and there is uncertainty around the clinical meaningfulness of the differences between the treatment groups for outcomes that assessed renal function, relapse, and Short Form [36] Health Survey version 2 (SF-36v2).
 There was not enough evidence to conclude that Tavneos met patients’ needs for a treatment that reduces or eliminates the use of glucocorticoids and their side effects as well as improves their health-related quality of life (HRQoL).

Deucravacitinib (Sotyktu)


 CADTH recommends that Sotyktu not be reimbursed by public drug plans for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
 The evidence from 2 clinical trials was insufficient to determine that Sotyktu offered treatment benefits over the currently available advanced treatments in Canada for the treatment of moderate to severe plaque psoriasis in adults.
 No evidence was found that directly compared Sotyktu to newer interleukin (IL)-17 and IL-23 biologics, and the indirect evidence suggested that Sotyktu was less effective at improving skin plaques than several biologics (including IL-17 and IL-23 biologics) that are available and reimbursed in Canada.
 CADTH concluded that there was not enough evidence to show that Sotyktu met the needs of patients with moderate to severe plaque psoriasis not already addressed by other available treatments.

Ravulizumab (Ultomiris)


 CADTH recommends that Ultomiris should not be reimbursed by public drug plans for the treatment of adult patients with anti-acetylcholine receptor (AChR) antibody–positive generalized myasthenia gravis (gMG).
 Although evidence from a clinical trial (CHAMPION) suggested that Ultomiris contributed to improvement in activities of daily living and gMG disease severity after 26 weeks, it is uncertain if immunosuppressive therapy (IST) was optimized at the time of study enrolment. Patients in both Ultomiris and placebo groups of the CHAMPION trial received stable doses of IST; however, it was unclear if IST was optimized in both groups. The eligibility criteria for duration of IST treatment and duration of stable IST dosing in the CHAMPION trial were below the estimated range of time to maximal response according to the clinical experts consulted by CADTH. Although some evidence (mean time frame since MG diagnosis, mean corticosteroid treatment durations) was available, without dose information, it is unclear if corticosteroid was optimized for patients at the time of study enrolment.
 Feedback from patient and clinician groups identified an unmet need for patients with gMG who have symptoms but are not considered refractory to IST. There is an unmet need for effective therapy for patients with refractory gMG, but the CHAMPION trial did not require patients to be refractory. Therefore, it is unknown how many patients in the CHAMPION trial were refractory and if the results observed in the trial would be the same in these patients. As a result, the ability of Ultomiris to fill the unmet need for patients who are refractory to IST is limited by the CHAMPION trial design, which used Ultomiris earlier in the treatment paradigm for gMG and did not require participants to be refractory to IST.
 The CHAMPION trial did not provide evidence on the efficacy or harms of Ultomiris compared with other therapies used in clinical practice, such as rituximab, IV immunoglobulin, and plasma exchange. Therefore, the potential therapeutic benefit is unknown compared to what is used in clinical practice.

Utilization of Opioid Agonist Therapies in Canada


 Canada continues to experience an opioid crisis that has had a devastating impact on public health, highlighting the importance of management strategies for opioid use disorder (OUD). Several opioid agonist therapies (OATs) for the management of OUD are available in Canada, including recent approvals of new brand name drugs and generic versions of widely used OATs.
 Coverage criteria for OATs are comparable across public drug plans in Canada. Methadone hydrochloride (HCL) and the combination of buprenorphine HCL and naloxone HCL (buprenorphine HCL-naloxone HCL) are typically listed as regular or open benefits; generics for these 2 medications have been available since 2020 and 2013, respectively. Sublocade and Probuphine — long-acting buprenorphine preparations approved by Health Canada in 2018 — have varied coverage that is often dependent on prior therapy requirement.
 The annual number of public claims for OATs decreased by 19.5% from 2018 to 2022. The market share of claims during this period was dominated by methadone HCL and buprenorphine HCL-naloxone HCL, with an increase in claims market share for buprenorphine over time (starting in 2020) and a negligible contribution by buprenorphine HCL. Additionally, in a subanalysis on the number of OAT claimants, the results did not indicate a decrease in individual beneficiaries for these medications; therefore, the decrease in OAT claims was likely driven by increased usage of OATs that require fewer claims per patient, as opposed to decreased OAT use in the population.
 Despite the decrease in annual OAT claims during the analysis period, total OAT expenditures increased every year, with a 67.0% increase from 2018 to 2022 (5-year total of $307 million). The increase was initially driven by buprenorphine HCL-naloxone HCL, which increased from $27 million (58.9% of OAT expenditures) in 2018 to $39 million (67.2% of OAT expenditures) in 2019. Thereafter, expenditures for buprenorphine drove overall OAT cost increases from 2020 onward, accounting for $22 million (28.2% of OAT expenditures) in 2022. In contrast, methadone HCL accounted for a decreasing proportion of expenditures each year ($19 million or 41.1% of OAT expenditures in 2018 to $16 million or 21.0% of OAT expenditures in 2022), despite having the greatest proportion of claims throughout the study period.
 The availability of new OAT formulations and generic versions of existing products, as well as other notable regulatory policy changes (e.g., Health Canada’s removal of the need for an exemption to prescribe methadone HCL) and reimbursement decisions (e.g., positive reimbursement recommendations from CADTH for the newer branded OATs, Sublocade and Probuphine), impacted the observed utilization and expenditure patterns, and will likely continue to influence decision-making, particularly where coverage has recently changed or has yet to change to reflect the evolving landscape. If the utilization of injectable buprenorphine (Sublocade) continues at the rate observed in this analysis, it will likely continue to drive increases in OAT expenditures; Sublocade has several patents and the earliest patent expiry is not until 2031, so generic versions of this formulation will likely not be available for several more years. Overall, the findings of this analysis may help to inform jurisdictions in funding decisions regarding OATs for the treatment of OUD.

Difelikefalin (Korsuva)


 CADTH recommends that difelikefalin should not be reimbursed by public drug plans for the treatment of moderate to severe pruritus associated with chronic kidney disease (CKD-aP) in adult patients on hemodialysis (HD).
 The CADTH Canadian Drug Expert Committee could not conclude whether treatment with difelikefalin resulted in clinically meaningful improvements. Evidence from 2 randomized controlled trials (KALM-1 and KALM-2) demonstrated that treatment with difelikefalin was associated with statistically significant improvements in itch; however, whether the improvement is clinically meaningful to patients is unclear due to a high placebo response and the trials measuring itch in a way that is inconsistent with clinical practice. As such, it is difficult to determine the actual treatment effect of difelikefalin.
 Patients living with moderate to severe CKD-aP on HD expressed a need for treatments that improve quality of life (QoL). Based on the available evidence, it is unclear if difelikefalin is associated with an improvement in QoL.
 There is a lack of evidence to show that difelikefalin would meet the needs identified by patients, such as reducing hospital visits and the amount of overall medication required, improving sleep quality and reducing sleep disturbance, and reducing side effects.

Trastuzumab Deruxtecan (Enhertu)


 CADTH recommends that Enhertu be reimbursed by public drug plans for the treatment of adult patients with unresectable or metastatic HER2-low breast cancer if certain conditions are met.
 Enhertu should only be covered to treat adult patients with HER2-low breast cancer that is unresectable (cannot be removed by surgery) or metastatic (has spread to other parts of the body) who have received a prior chemotherapy for metastatic disease or had their cancer come back after surgery within 6 months of completing adjuvant chemotherapy. If the patient is hormone receptor (HR)-positive, they should have been treated with at least 1 endocrine therapy (ET) and no longer be considered candidates for further ET treatment. Patients receiving Enhertu should be in relatively good health (i.e., have a good performance status, as determined by a specialist). Patients in whom the cancer has spread to the brain or spinal cord, for whom there is spinal cord compression causing symptoms, or those with interstitial lung disease or pneumonitis should not be eligible for coverage.
 Enhertu should only be reimbursed if prescribed by clinicians with experience and expertise in treating advanced breast cancer in centres, if it is not used with other cancer treatments, and if the cost of Enhertu is reduced. Patients who experience disease progression while taking Enhertu or who cannot tolerate the drug would not be eligible for continued coverage.

Vericiguat (Verquvo)


 CADTH recommends that Verquvo be reimbursed by public drug plans for the treatment of chronic heart failure (HF) as an adjunct to standard of care therapy if certain conditions are met.
 Verquvo should only be covered to treat adult patients: whose heart is unable to pump enough blood to keep up with the body’s needs because the heart is too weak (i.e., HF with reduced ejection fraction); who are considered to be symptomatic (e.g., slight limitation in physical activity, defined as New York Heart Association [NYHA] functional classification class II; a marked limitation in physical activity, defined as NYHA class III; or symptoms even at rest, defined as NYHA class IV); and who had a recent hospitalization or needed to receive IV medicines.
 Verquvo should only be reimbursed if the price of Verquvo is reduced.

Atogepant (Qulipta)


 CADTH recommends that Qulipta be reimbursed by public drug plans for the prevention of episodic migraine, if certain conditions are met.
 Qulipta should only be reimbursed for adults with episodic migraine, according to the criteria used by public drug plans for other calcitonin gene-related peptide (CGRP) inhibitors for the prevention of episodic migraine.
 In addition to following the pre-existing criteria for other CGRP inhibitors, Qulipta should not be used in combination with other CGRP inhibitors. Qulipta should only be reimbursed if the cost is reduced such that the total treatment cost of Qulipta does not exceed the total treatment cost of the least costly CGRP inhibitor reimbursed for the preventive treatment of episodic migraine in adults.

Sex-specific medication trajectories in older adults newly diagnosed with diabetes

BackgroundPeople with diabetes tend to use many medications to treat diabetes and comorbidities. Nevertheless, the evolution of polypharmacy in newly diagnosed males and females has been little studied. ObjectiveThe objective of this paper was to identify and describe medication trajectories in incident diabetes cases according to sex. MethodsData were obtained from the Quebec Integrated Chronic Disease Surveillance System. We built a population-based cohort of community-dwelling individuals aged >65 years diagnosed with diabetes in 2014 who were alive and covered with the public drug plan until March 31, 2019. Latent class models were used to identify medication trajectory groups in males and females separately. ResultsOf the 10,363 included individuals, 51.4% were males. Females were older and more likely to have more medication claims than males. Four trajectory groups were identified for males and five for females. Most trajectories showed sustained and stable number of medications over time. For each sex, only one of the trajectory groups included a mean annual number of medications lesser than five. Slight increasing trends of medication use were detected in the trajectories composed of very high users, which included older, more comorbid individuals frequently exposed to potentially inappropriate medications. ConclusionsMost males and females with incident diabetes had a high burden of medication following the year of diagnosis and were classified in a group of sustained medication use over time. The largest increase in medication was among those who had higher level of polypharmacy of questionable quality at baseline, raising concerns about the innocuity of such medication trajectories.

Risankizumab (Skyrizi)


 CADTH recommends that Skyrizi be reimbursed by public drug plans for the treatment of moderately to severely active Crohn disease (CD) if certain conditions are met.
 Skyrizi should only be covered to treat adult patients with moderately to severely active CD who do not respond to, stop responding to, or who cannot tolerate conventional or biologic therapies.
 Skyrizi should only be reimbursed if prescribed by a physician experienced in the diagnosis and management of CD, if it is not used in combination with other biologics, and if the cost of Skyrizi is reduced so that it does not cost the drug programs more than the least costly biologic therapy. Patients must respond to treatment in the first 12 weeks of starting Skyrizi to continue receiving the drug.

Palovarotene (Sohonos)


 CADTH recommends that Sohonos be reimbursed by public drug plans to reduce the formation of heterotopic ossification (HO) in adults and children aged 8 years and above for females and 10 years and above for males with fibrodysplasia ossificans progressiva (FOP), if certain conditions are met.
 Sohonos should only be covered to treat patients who have a clinical diagnosis of FOP and the R206H ACVR1 mutation as confirmed by genetic testing, and who do not have completely fused joints over the whole body.
 Sohonos should only be reimbursed if prescribed by an expert in the diagnosis and management of FOP and if the cost of Sohonos is reduced. While receiving Sohonos, patients (and their caregivers, for pediatric patients) and their physicians should have ongoing and regular discussions to assess the benefits and risks of treatment with Sohonos.

Upadacitinib (Rinvoq)


 CADTH recommends that Rinvoq be reimbursed for the treatment of adults with active ankylosing spondylitis (AS) who have had an inadequate response to a biologic disease-modifying antirheumatic drug (bDMARD) or when use of those therapies is inadvisable only if certain conditions are met.
 Eligibility for Rinvoq should be based on the criteria used by each of the public drug plans for reimbursement of bDMARDs for the treatment of adult with active AS who have had an inadequate response to a bDMARD, are intolerant, or who have contraindications to bDMARDs.
 Rinvoq should only be reimbursed if it is prescribed by a rheumatologist. For patients with other manifestations, an ophthalmologist, gastroenterologist, or dermatologist may be consulted. Rinvoq should not be reimbursed when used in combination with bDMARDs or other Janus kinase (JAK) inhibitor treatments for active AS. The cost of Rinvoq should not exceed the drug program cost of treatment with the least expensive bDMARD reimbursed for the treatment of AS.

Fostemsavir (Rukobia)


 CADTH recommends that Rukobia be reimbursed by public drug plans for the treatment of HIV type 1 (HIV-1) infection in heavily treatment-experienced adults with multidrug-resistant (MDR) HIV-1 infection for whom it is otherwise not possible to construct a suppressive antiviral regimen due to resistance, intolerance, or safety considerations if certain conditions are met.
 Rukobia should be covered for patients living with HIV-1 whose disease does not respond to the majority of antiretroviral therapies (ARVs) available (ARVs in at least 3 classes) because the available ARVs no longer work, for those who cannot tolerate side effects, or for those who have other safety concerns. In addition, patients should have 1 fully active available drug left in no more than 2 ARV classes based on current and/or documented historical resistant testing. Lastly, Rukobia should be covered for patients who have a viral load that suggests poor control of their infection (≥ 400 copies/mL of HIV-1 ribonucleic acid [RNA]).
 Rukobia should only be reimbursed if it is initially prescribed by, or in conjunction with, a physician who specializes in the management of HIV-1 infection and if the cost of Rukobia is reduced. Reimbursement of Rukobia should be discontinued if the patient’s viral load is not improving, as this suggests that treatment is not working.

Selumetinib (Koselugo)


 CADTH recommends that Koselugo be reimbursed by public drug plans for the treatment of pediatric patients aged 2 years and above, with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PNs), if certain conditions are met.
 Koselugo should only be covered to treat patients who are aged between 2 and 18 years with a diagnosis of NF1 with PNs that are causing symptoms and cannot be completely removed by surgery.
 Koselugo should only be reimbursed if prescribed by specialists with experience in managing NF1 and PNs, and the cost of Koselugo is reduced. To continue treatment with Koselugo longer than 18 months, the treating physician must provide proof that the patient is responding to treatment, including but not limited to reductions in symptoms of pain, improved motor function, and/or stabilization of disease, or proof of shrinking of tumours.

Ciltacabtagene Autoleucel (Carvykti)


 CADTH recommends that Carvykti should be reimbursed by public drug plans for the treatment of adult patients with multiple myeloma (MM) who have received at least 3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody, and who are refractory to their last treatment if certain conditions are met.
 Carvykti should only be covered to treat patients who have MM; received at least 3 prior treatments including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody; did not respond to their last treatment, and are in relatively good health (i.e., have a good performance status, as determined by a specialist). Carvykti should not be reimbursed to treat patients whose MM is affecting their brain or spinal cord or patients showing signs that the tissue layers protecting the brain and spinal cord are affected by MM. It also should not be reimbursed in patients who have previously received a treatment that targets B-cell maturation antigen.
 Carvykti should only be reimbursed for patients who have not yet been treated with chimeric antigen receptor (CAR) T-cell therapy, if it is prescribed and administered in a hospital setting with adequate resources by specialists with expertise in MM, and if the cost of Carvykti is reduced.

Crisantaspase Recombinant (Rylaze)


 CADTH recommends that Rylaze be reimbursed by public drug plans as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients 1 year or older who have developed hypersensitivity to Escherichia coli–derived asparaginase if certain conditions are met.
 Rylaze (crisantaspase recombinant) should only be covered to treat patients who have ALL or LBL with documented hypersensitivity to (or silent inactivation of) an coli–derived asparaginase.
 Rylaze should only be reimbursed as part of a multicomponent treatment regimen to replace pegylated coli–derived asparaginases (pegaspargase), following hypersensitivity or silent inactivation of the E. coli–derived asparaginase. Rylaze should be prescribed by clinicians with expertise in the management of ALL or LBL, and the cost of Rylaze should be reduced.

Classifying Polypharmacy According to Pharmacotherapeutic and Clinical Risks in Older Adults: A Latent Class Analysis in Quebec, Canada.

The simplistic definition of polypharmacy, often designated as the concomitant use of five medications or more, does not distinguish appropriate from inappropriate polypharmacy. Classifying polypharmacy according to varying levels of health risk would help optimise medication use. We aimed to characterise different types of polypharmacy among older adults and evaluate their association with mortality and institutionalisation. Using healthcare databases from the Quebec Integrated Chronic Disease Surveillance System, we selected a community-based random sample of the population ≥ 66 years old covered by the public drug plan. Categorical indicators used to describe polypharmacy included number of medications, potentially inappropriate medications (PIMs), drug-drug interactions, enhanced surveillance medications, complex route of administration medications, anticholinergic cognitive burden (ACB) score and use of blister cards. We used a latent class analysis to subdivide participants into distinct groups of polypharmacy. Their association with 3-year mortality and institutionalisation was assessed with adjusted Cox models. In total, 93,516 individuals were included. A four-class model was selected with groups described as (1) no polypharmacy (46% of our sample), (2) high-medium number of medications, low risk (33%), (3) medium number of medications, PIM use with or without high ACB score (8%) and (4) hyperpolypharmacy, complex use, high risk (13%). Using the class without polypharmacy as the reference, all polypharmacy classes were associated with 3-year mortality and institutionalisation, with the most complex/inappropriate classes denoting the highest risk (hazard ratio [HR] [95% confidence interval]: class 3, 70-year-old point estimate for mortality 1.52 [1.30-1.78] and institutionalisation 1.86 [1.52-2.29]; class 4, 70-year-old point estimate for mortality 2.74 [2.44-3.08] and institutionalisation 3.11 [2.60-3.70]). We distinguished three types of polypharmacy with varying pharmacotherapeutic and clinical appropriateness. Our results highlight the value of looking beyond the number of medications to assess polypharmacy.

Mavacamten (Camzyos)


 CADTH recommends that Camzyos be reimbursed by public drug plans for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM) of New York Heart Association (NYHA) class II to III in adult patients if certain conditions are met.
 Camzyos should only be covered to treat patients who have a documented left ventricular ejection fraction (LVEF) of 55% or greater at rest, determined by echocardiography, a left ventricular (LV) wall thickness of 15 mm or more (or ≥ 13 mm with a family history of hypertrophic cardiomyopathy [HCM]), and a left ventricular outflow tract (LVOT) peak gradient of 50 mm Hg or greater at rest, after Valsalva maneuver, or postexercise as confirmed by echocardiography. To be eligible, patients must also experience either worsening of symptoms or echocardiographically demonstrated deterioration while taking a beta-blocker (BB) or calcium channel blocker (CCB).
 Camzyos should only be reimbursed if patients are under the care of a cardiologist and if the cost of Camzyos is reduced.