Canadian Journal of Health Technologies

Dostarlimab (Jemperli)

CADTH; Test Contributor — Wed, 24 Jul 2024 00:00:00 +0000

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
This review assesses dostarlimab (JEMPERLI), 500mg/10 mL (50 mg/mL), 500 mg every 3 weeks for 6 cycles followed by 1,000 mg every 6 weeks, solution for IV infusion.
Indication: In combination with carboplatin and paclitaxel for the treatment of adult patients with primary advanced or recurrent deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) endometrial cancer who are candidates for systemic therapy.

Cannabidiol (Epidiolex)

CADTH — Tue, 23 Jul 2024 00:00:00 +0000

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
This review assesses cannabidiol (Epidiolex), 100 mg/mL, oral solution.
Indication: Cannabidiol is indicated for use as adjunctive therapy for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome or tuberous sclerosis complex in patients 2 years of age and older.

Inebilizumab (Uplizna)

CADTH — Mon, 22 Jul 2024 00:00:00 +0000

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
This review assesses inebilizumab (Uplizna), 10 mg/mL, single-dose vials containing 100 mg inebilizumab in 10 mL solution, IV infusion.
Indication: As monotherapy for the treatment of adult patients with neuromyelitis optica spectrum disorder (NMOSD) who are seropositive for anti-aquaporin-4 immunoglobulin G (AQP4-IgG). Treatment should be administered under the supervision of a qualified healthcare professional.

Sotorasib (Lumakras)

CADTH — Mon, 22 Jul 2024 00:00:00 +0000

Reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
This review assesses sotorasib (Lumakras), 120 mg, oral tablet.
Indication: For the treatment of adult patients with KRAS G12C-mutated, locally advanced (not amenable to curative therapy) or metastatic non–small cell lung cancer (NSCLC) who have received at least 1 prior systemic therapy.

Nirmatrelvir-Ritonavir (Paxlovid)

CADTH — Tue, 09 Jul 2024 00:00:00 +0000

CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
This review assesses nirmatrelvir-ritonavir (Paxlovid), 150 mg nirmatrelvir; 100 mg ritonavir, tablets, co-packaged for oral use.
Indication: For the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with positive results of direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.

National and International Policies on the Use of Biosimilars: An Environmental Scan

Jaemin Kim, Jessica Arias, Scott Gavura — Thu, 04 Jul 2024 00:00:00 +0000

Biosimilars are biologic drugs that are highly similar to their reference biologics that were already authorized for sale.
Interchangeability is a term used to describe when 1 drug can be exchanged for another and is expected to have the same clinical effect. Interchangeability may allow 1 medicine to be substituted for another at the time of dispensing (automatic substitution). However, the decision to allow automatic substitution is made by each jurisdiction according to its own regulations.
Interchangeability of a reference biologic (the originator product) and a biosimilar is a designation in the US and Finland. The US, France, Germany, Norway, and Australia allow automatic substitution between reference biologics and biosimilars, whereas other countries do not. Interchangeability is limited to select products in the US and Australia.
The countries included in this Environmental Scan (N = 13) endorse starting patients who have not yet received treatment on a biosimilar. Switching between reference biologics and biosimilars is generally allowed in all the countries included in this review; however, many jurisdictions prefer switching be clinician led with ongoing clinical monitoring of patients.
Practices such as target setting, quotas, and financial incentives, as well as guidelines and recommendations for prescription of biosimilars, can be effective ways to encourage biosimilar use. Mandatory switching is also implemented in 11 Canadian jurisdictions.
Extrapolation is the regulatory and scientific process of granting a clinical indication to a medicine without clinical efficacy and safety data to support that indication. Extrapolation of indications for reference biologics to biosimilars is reasonable, provided several factors are comparable: mechanism of action across indications, pharmacokinetics and biodistribution, safety, immunogenicity, and other factors that affect the safety and efficacy for each indication and patient population.
Pricing and procurement practices vary internationally. Some countries implement policies controlling the list price of a biosimilar (and its reference drug less commonly) at the time of biosimilar launch. Pricing policies include a free-pricing policy (i.e., manufacturers are free to set the price of biosimilars) and mandatory price reductions. Tendering is the most common practice in procurement to achieve lower prices and to increase biosimilar uptakes in 8 countries reviewed in this Environmental Scan.
Biosimilar-related policies and markets are rapidly evolving, so recent changes might have not been fully captured in this Environmental Scan. Therefore, caution is required in interpreting the findings.

Pembrolizumab (Keytruda)

CADTH — Mon, 15 Jul 2024 00:00:00 +0000

CADTH recommends that Keytruda should be reimbursed by public drug plans for the treatment of locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2) positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumours express programmed cell death-ligand 1 (PD-L1) if certain conditions are met.
Keytruda should only be covered to treat adult patients who have not received previous treatment for advanced or metastatic esophageal or GEJ cancer and have good performance status.
Keytruda should only be reimbursed if prescribed in combination with trastuzumab, fluoropyrimidine, and platinum-containing chemotherapy by a clinician with expertise and experience in treating gastric and GEJ cancer.

CRISPR Technologies for In Vivo and Ex Vivo Gene Editing

CADTH — Fri, 19 Jul 2024 00:00:00 +0000

What Is the Issue?

The first therapeutics based on clustered regularly interspaced short palindromic repeats (CRISPR) technologies are entering the market. These gene editing technologies have the potential to change treatment paradigms and may be used to treat conditions that cannot be treated or cured with current methods. This report aims to provide an overview of the technologies and their current and potential roles in health care.

What Are the Technologies?

CRISPR is a part of bacterial immune systems that can cut DNA strands and is used as a gene editing tool. A guide ribonucleic acid (RNA) sequence leads the CRISPR-associated nuclease to the target DNA sequence where the cut is made. These edits change the function of the gene, making genes nonfunctional or replacing the coding sequence for 1 gene with another. CRISPR can also be used to increase or decrease the expression of specific genes.

What Is the Potential Impact?

CRISPR-based technologies have a variety of potential applications in health care, including:

treating genetic diseases
understanding the genetic mechanisms of diseases and investigating the relevance of potential drug treatments
managing infectious diseases through detection, treatment, and elimination.

What Else Do We Need to Know?

Ethical issues pertinent to the use of CRISPR include the ability to obtain adequately informed consent, the potential future consequences of gene editing and its potential unintended effects, and the impact gene editing could have on future generations. The long-term effects of CRISPR-based therapies are currently unknown. Further research into emerging applications is required. Long-term follow-up of the patients who have received the first CRISPR-based therapeutics will help inform understanding of the safety and effectiveness of these treatments. While the first of these therapies have been granted regulatory authorization, the next viable CRISPR-based therapies are still in the early phases of development, with the pivotal clinical trials not expected to be completed until at least 2027.

Re-Treatment With Immune Checkpoint Inhibitors

CADTH — Tue, 23 Jul 2024 00:00:00 +0000

We did not find any evidence regarding the clinical effectiveness and safety of second re-treatment with pembrolizumab for non–small cell lung cancer, classical Hodgkin lymphoma, and advanced melanoma.
We did not find any evidence regarding the clinical effectiveness and safety of second re-treatment with cemiplimab for cutaneous squamous cell carcinoma.
We did not find any evidence-based guidelines regarding the second re-treatment with immune checkpoint inhibitors for non–small cell lung cancer, classical Hodgkin lymphoma, advanced melanoma, and cutaneous squamous cell carcinoma.

Auditory Verbal Therapy for Children With Hearing Loss

CADTH — Thu, 18 Jul 2024 00:00:00 +0000

What Is the Issue?

Children with hearing loss may experience delays in language, speech, and cognitive development, which can have long-lasting implications if unaddressed.
Early hearing detection and intervention programs aim to identify and avoid long-term impacts of hearing loss for infants and children. Interventions include the use of hearing devices (e.g., cochlear implants, hearing aids) and habilitation with the intent to minimize delays in development.
Auditory verbal therapy (AVT) is a specialized habilitation intervention that focuses on improving listening skills while avoiding visual cues to communicate. The overall goal is to minimize the difference in speech and language capabilities between children with hearing loss and their peers without hearing loss. It requires certified professionals to deliver.
The effectiveness of AVT for children with hearing loss compared to other habilitation approaches remains unclear.

What Did We Do?

To inform decisions regarding the use of AVT, we summarized evidence that compared the effectiveness of AVT to alternative habilitation approaches for children with hearing loss using cochlear implants, bone-conduction hearing devices, or conventional hearing aids. We also sought to identify evidence-based guidelines regarding appropriate habilitation approaches for this population.
We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened articles for inclusion based on predefined criteria.

What Did We Find?

For children with cochlear implants, AVT may result in better speech and language outcomes than standard habilitation, oral communication, total communication, or the bilingual-bicultural approach. However, AVT did not result in a significant difference in speech and language skills compared to sign and spoken language (1 systematic review).
AVT may result in better executive function compared to standard auditory training for children with cochlear implants (1 randomized controlled trial).
We did not find any evidence-based guidelines regarding appropriate habilitation approaches that met the predefined criteria for this rapid review. We also did not identify relevant evidence for children using bone conduction hearing devices and conventional hearing aids.

What Does It Mean?

Limited and low-quality evidence suggests that AVT is more effective than some alternative habilitation approaches for children using cochlear implants. High-quality studies are needed with rigorous methodology, detailed reporting of results, and analysis controlling for confounding factors to make definitive conclusions about the performance of AVT against alternative habilitation for this population.
Although the literature comparing AVT to alternative approaches is limited, findings from before-and-after studies suggest that AVT improves speech, language, and executive function for children with cochlear implants. Decisions around the use of AVT may also depend on the individual needs and goals of the child and their parents or guardians and the resources needed to ensure capacity to deliver AVT, such as time and costs to certify professionals.

Review of Guidelines on Second-Line Therapy for Patients With Relapsing-Remitting Multiple Sclerosis: A 2024 Update

CADTH — Thu, 18 Jul 2024 00:00:00 +0000

What Is the Issue?

Multiple sclerosis is a chronic autoimmune disorder that causes damage to central nervous system cells. Relapsing-remitting multiple sclerosis is characterized by relapses (episodes of new or worsening symptoms) followed by periods of partial or complete recovery (remission).
First-line therapies for multiple sclerosis include interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide. Second-line therapies include natalizumab, alemtuzumab, and fingolimod.
The considerations for switching from a first-line to a second-line therapy for patients with relapsing-remitting multiple sclerosis are unclear.

What Did We Do?

To inform decisions around switching patients with relapsing-remitting multiple sclerosis from a first-line to a second-line therapy, we sought to identify and summarize recommendations from evidence-based guidelines.
We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included guidelines, and narratively summarized the findings.

What Did We Find?

We identified 2 evidence-based guidelines that included recommendations around switching from a first-line to a second-line therapy in patients with relapsing-remitting multiple sclerosis.
One guideline from Spain classified therapies as moderate-efficacy (interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide) and high-efficacy (fingolimod, cladribine, ocrelizumab, natalizumab, and alemtuzumab). The guideline recommends that patients switch from a moderate-efficacy disease-modifying therapy to a high-efficacy disease-modifying therapy for a variety of reasons including suboptimal response, adverse events, comorbidities, pregnancy plans, confirmed progression of disability, and tolerability issues. The guideline also included several recommendations specific to switching to natalizumab as well as washout periods when switching from a moderate-efficacy therapy.
One guideline from France included recommendations regarding washout periods for switching from a first-line therapy. The guideline recommends that when switching from a first-line therapy, a second-line therapy or an induction therapy could be started without a washout period if the patient has normal biological results. The guideline also recommends validating the indication, timing, and washout period of a switch to a second-line therapy or induction therapy with a multiple sclerosis expert centre or in a multidisciplinary consensus meeting. The guideline also included specific considerations for washout periods for dimethyl fumarate and teriflunomide.

What Does It Mean?

The considerations for switching from a first-line to a second-line therapy in patients with relapsing-remitting multiple sclerosis — including the timing of a switch, choice of second-line therapy, and washout periods — depend on treatment response, individual patient characteristics, and the specific first-line therapy being used.
Additional evidence-based guidelines that use comprehensive methods for identifying evidence and include clear links between identified evidence and recommendations will help to reduce uncertainty around considerations for switching from first-line to second-line therapies in patients with relapsing-remitting multiple sclerosis.

Trends in Public Drug Plan Expenditures for Patients With Crohn Disease and Ulcerative Colitis Initiating Targeted Immune Modulator Therapy

CADTH — Fri, 12 Jul 2024 00:00:00 +0000

The objective of this analysis was to examine the changes in drug expenditures with the initiation of targeted immune modulator (TIM) treatment in patients diagnosed with Crohn disease (CD) and ulcerative colitis (UC).
Patient cohorts for CD and UC were identified from hospitalizations in Canada. Expenditure data for TIMs with a Health Canada–approved indication for the treatment of CD or UC were extracted from all provincial drug plans (except Quebec) and Yukon from 2016 to 2021, and a descriptive analysis was performed to assess the expenditure patterns.
Annual expenditures on TIMs for patients with CD increased each year from 2016 to 2019 before decreasing in 2020 and 2021, whereas expenditures on TIMs in UC increased each year, generally by a greater percentage than was observed in CD (peak percentage growth of 92.5% for UC versus 15.9% for CD in 2018).
Expenditures associated with TIM initiation among patients with CD and UC were driven by infliximab and adalimumab, with the 2 drugs accounting for nearly all expenditures in both indications in 2016 and most expenditures in 2021.
In both CD and UC, vedolizumab expenditures increased over time, as did the proportions of TIM expenditures on ustekinumab in CD and tofacitinib in UC, albeit to a lesser extent than vedolizumab.