This report provides an overview of the evolving therapeutic landscape for moderate to severe ulcerative colitis (UC), including recent changes to clinical practice guidelines, key trends in therapeutic strategies, and new or emerging treatment options, with a focus on biologics and small-molecule therapies. Recent guidelines on the medical management of patients with UC include those of the American Gastroenterological Association (AGA), American College of Gastroenterology (ACG), and European Crohn’s and Colitis Organisation (ECCO), which were published in 2019, 2020, and 2022, respectively. These guidelines provide an accurate reflection of how clinical practice has changed to incorporate newer therapies that have entered the market and newer evidence that has been published since the release of the Canadian guidelines in 2015. The ACG, AGA, and ECCO guidelines all recommend use of a tumour necrosis factor (TNF) antagonist, vedolizumab, or tofacitinib for induction of remission in patients with moderate to severe UC; the AGA and ECCO guidelines also recommend ustekinumab as an option and recommend vedolizumab over adalimumab, whereas the AGA guidelines recommend early use of biologic drugs over a step-up approach after failure of 5-aminosalicylates. Two important trends in therapeutic strategies for UC include changes in the use and definition of treatment targets and recommendations regarding therapeutic drug monitoring (TDM). The 2021 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE-II) guidelines provide contemporary consensus recommendations for using new and updated targets throughout an individualized treatment timeline in patients with inflammatory bowel disease (IBD). Although histologic remission is not considered a formal UC treatment target in STRIDE-II, it is acknowledged as an adjunctive measure to endoscopic remission to represent a deeper level of healing and is the focus of many current studies. The use of TDM emerged from challenges associated with the use of older biologics (primarily TNF antagonists), which posed difficulties related to immunogenicity and dosing. The relevance of TDM for newer biologics with different mechanisms of action, reduced immunogenicity, and fixed dosing (e.g., vedolizumab and ustekinumab) is a topic of ongoing debate. Although AGA guidelines on TDM in IBD and expert consensus statements support the use of reactive TDM for patients with UC who lose response to a TNF antagonist, evidence gaps remain regarding appropriate use of proactive TDM, utility of TDM for small molecules and biologics outside of the TNF antagonist class, and consistent target concentration thresholds to guide dose changes. There is a substantial pipeline of new and emerging drugs for the treatment of adults with moderate to severe UC, with many in phase IIb or III of clinical development; several notable trends of emerging pharmacotherapies exist, including an increasing number of Janus kinase inhibitors, several therapies with biologic targets that are new in UC (e.g., interleukin-23 antibodies, TNF-like ligand 1A inhibitors), an increasing number of oral therapies, and the first combination of 2 biologic therapies in UC. The Canadian health care system should be prepared to adapt to the rapidly evolving treatment landscape and potential clinical practice changes in moderate to severe UC. Drugs with new mechanisms of action in the treatment area and the new paradigm of combination therapy with multiple biologics of different classes may lead to improved patient outcomes but can also further complicate the treatment decision-making process. Therefore, it is important for health care providers to stay up to date on new and upcoming treatment options, which may require educational initiatives for both providers and patients as well as updates to the Canadian treatment guidelines. Overall, potential changes on the horizon may have substantial implications for the health care system given the prevalence of UC in Canada, the costs of advanced therapies, and the increasing number of available treatment options.

Unlike the new-generation biologics (interleukin [IL]-17 and IL-23 inhibitors), all old-generation biologics (anti–tumour necrosis factor [TNF] and anti–IL-12/23 biologics) for plaque psoriasis (PsO) have now lost their exclusivity status and most were launched prior to the pan-Canadian Pharmaceutical Alliance. In addition, biosimilar versions of the old-generation biologics have had limited uptake and delayed launches in Canada spanning multiple years, suggesting a significant opportunity cost paid for these drugs after loss of exclusivity. Modern clinical evidence, which is more rigorous than the evidence supporting the old-generation drugs and includes head-to-head trials comparing IL-17 and IL-23 inhibitors with anti-TNF and anti–IL-12/23 biologics, have demonstrated greater efficacy with the new-generation biologics. In Canada, despite access to newer and more efficacious treatments, physicians continue to prescribe old-generation drugs to patients newly initiating a biologic for PsO (25% of patients in 2020), and the new-generation biologics are also less costly on an average per patient basis at list price compared with the most utilized old-generation biologic (ustekinumab). Public payers have spent $28 million (at list price) on biologics initiated for PsO beyond their loss of exclusivity from 2016 to 2020 ($600 million for biologics initiated for any indication), and that figure is likely much higher today. Notably, some IL-17 biologics will lose data protection within the next 2 years, which will further increase this opportunity cost. It is prudent that decision-makers review the place in therapy of biologics for PsO. Based on the findings of this report, the policy recommendation is to assess the clinical and economic value of old-generation biologics in the context of current evidence standards in PsO. The promotion of the use of new-generation biologics should be considered by payers to support the appropriate use of biologics in PsO, which would improve patient outcomes with budget savings or neutrality (assuming no confidential pricing agreements with the old-generation biologics) versus the status quo.

Health Canada has approved 7 targeted immune modulators for the treatment of adults with moderate to severe ulcerative colitis, which include 5 biologics (adalimumab, infliximab, golimumab, ustekinumab, and vedolizumab) and 2 small molecules (tofacitinib and ozanimod). Biosimilars for adalimumab and infliximab and generics for tofacitinib are currently available in the Canadian market; however, although their patent protection has expired, there are no biosimilars for golimumab and ustekinumab. All targeted immune modulators have undergone pan-Canadian Pharmaceutical Alliance negotiations and concluded with a Letter of Intent except for ustekinumab, which is the only targeted immune modulator not included on any public formularies for ulcerative colitis. Coverage is consistent across all drug plans except for golimumab and tofacitinib, which is not covered by all jurisdictions for ulcerative colitis. Most public drug plans have implemented or have announced a biosimilar policy to promote the use of biosimilars over originator biologics. The listing status for targeted immune modulators in ulcerative colitis is similar across public drug plans; however, there is heterogeneity in criteria requirements for prior treatments and diagnosis definitions. Considering these factors and the emergence of new data, it would be important to reassess these drugs and evaluate their place in therapy. Further research, such as horizon scanning, utilization analyses, and long-term effectiveness and safety studies, is warranted for targeted immune modulators to ensure the appropriate use of these drugs in the treatment of moderate to severe ulcerative colitis.

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.

For rheumatoid arthritis (RA), treatment guidelines and clinical evidence support the combination (either dual or triple) of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) before accessing a biologic DMARD (bDMARD). Federal, provincial, and territorial (FPT) drug plans currently have different coverage criteria for bDMARD eligibility in RA. To align their criteria, these plans should consider the inclusion of at least 1 line of combination csDMARDs before a bDMARD: For dual csDMARDs: Saskatchewan, Veterans Affairs Canada, and Canadian Armed Forces would need to change their current coverage criteria to include at least 1 line of dual csDMARDs before access to a bDMARD. For triple csDMARDs: Alberta, Saskatchewan, Manitoba, Veterans Affairs Canada, and Canadian Armed Forces would need to alter their current coverage criteria because each of these FPT drug plans only consider csDMARD monotherapy or dual csDMARDs in their current coverage criteria. Most FPT drug plans require a failure of at least 2 lines to 3 lines of csDMARD therapy before a bDMARD, except British Columbia, Ontario, Newfoundland and Labrador, Veterans Affairs Canada, and Canadian Armed Forces, which offer an option to access bDMARDs after 1 line of combination csDMARDs. British Columbia, Ontario, the Atlantic provinces, Yukon, Correctional Service of Canada, and Non-Insured Health Benefits include triple csDMARDs in their coverage criteria. Alberta, Manitoba, Veterans Affairs Canada, and Canadian Armed Forces include dual, but not triple, csDMARDs in their criteria; however, Veterans Affairs Canada and Canadian Armed Forces do not require a trial of dual csDMARDs if 2 lines of csDMARD monotherapy have been attempted. Saskatchewan is the only jurisdiction that only requires csDMARD monotherapy. Canadian private insurers have also reached a consensus to implement a trial requirement of dual csDMARDs before a bDMARD across their formularies. Evidence-based guidelines, including the 2012 Canadian Rheumatology Association guidelines, recommend csDMARD monotherapy (methotrexate [MTX] is preferred unless contraindicated) as first-line treatment for RA, although a guideline published in 2018 by the Brazilian Society of Rheumatology stated that combination therapy with 2 or more csDMARDs may also be used as a first-line treatment. These guidelines generally recommend combination csDMARDs after csDMARD monotherapy is deemed ineffective. A network meta-analysis found that triple csDMARDs is more efficacious than dual csDMARDs, etanercept monotherapy, and 4 mg/kg tocilizumab monotherapy and comparable to other bDMARDs (alone or in combination with MTX), targeted synthetic DMARDs in combination with MTX, and biosimilars in combination with MTX. Additionally, economic evidence demonstrated that triple csDMARDs is more cost-effective than etanercept plus MTX combination therapy. Time to first bDMARD was, on average, longer in Alberta, British Columbia, and Ontario than in Saskatchewan, Manitoba, and the Atlantic provinces by approximately 4 months, which may be partially explained by differences in coverage criteria for the number of prior lines of csDMARD therapy required. Increasing the time to initiating a bDMARD could lead to budget savings without impacting clinical outcomes.