Skylar Jeremias is the Managing Editor for The Center for Biosimilars and The American Journal of Managed Care (AJMC).

Skylar Jeremias

Patients with moderate to severe Crohn disease in Spain could experience improved outcomes and lower treatment costs when biosimilar ustekinumab is used as a first-line therapy rather than reserved for later lines, according to a cost-effectiveness analysis 

Early use of ustekinumab biosimilars in Spain shows cost-effective Crohn disease care, boosting QALYs and cutting NHS spend—insights for Europe. |Image credit: mi_viri - stock.adobe.com

Crohn disease imposes a considerable economic burden on national health systems, with annual costs per patient in Spain reported to range from €11,000 to €18,000—differences driven largely by pharmacological expenses rather than other direct health care costs.

 offered important context for why this economic question matters at the bedside.

 Reviewers noted that despite ustekinumab's established efficacy in moderate to severe Crohn disease, its high acquisition cost had historically confined it to later lines of therapy, typically after patients experienced treatment failure on 1 or more antitumor necrosis factor agents. The availability of biosimilar versions, the review argued, carries the potential to shift that calculus—reducing financial barriers and enabling earlier use in the treatment algorithm, where evidence increasingly supports more aggressive initial intervention. Biosimilar ustekinumab candidates have demonstrated comparable efficacy, safety, pharmacokinetics, and immunogenicity to the reference product in studies conducted to date, though the review noted that real-world data specific to Crohn disease remain limited.

As biologic therapies have become the cornerstone of moderate to severe disease management, appropriate sequencing has grown more consequential both clinically and financially.

 The 2024 ECCO guidelines positioned ustekinumab as a first-line induction and maintenance option for moderate to severe Crohn disease, but until recently, the high acquisition cost of reference ustekinumab limited its appeal as an early-line choice in Spain. The entry of biosimilar ustekinumab (bsUST) into the Spanish market in mid-2024, at an assumed 30% price reduction vs the reference product, prompted investigators to formally evaluate whether repositioning bsUST to the front of treatment sequences would be cost-effective from the perspective of Spain's National Healthcare System (NHS).

Markov Model Evaluated Seven Biosimilar-Inclusive Treatment Sequences

Investigators developed a Markov model with 2-week cycles and a lifetime horizon to compare 7 treatment sequences in adults with moderate to severe Crohn disease. Health states included active disease, response, remission, surgery, and death. Funnel states simulated induction periods, and patients who lost response transitioned to the next treatment line after a 3-month delay to reflect real-world clinical practice. Surgery was considered only after 4 pharmacological lines had been exhausted.

The sequences incorporated biosimilar adalimumab (bsADA), biosimilar intravenous infliximab (bsIFX), bsUST, risankizumab, upadacitinib, and vedolizumab. Sequence 1—bsADA followed by bsUST, upadacitinib, risankizumab, and surgery—served as the reference comparator because it carried the lowest total lifetime cost at €157,224 per patient.

Patient characteristics were drawn from the UNITI-2 trial (NCT01369329) population and validated against Spanish real-world data from the ENEIDA registry. The modeled cohort had a mean age of 39.2 years, was 46.7% women, and had a mean weight of 73.4 kg. Clinical efficacy data were sourced from a published network meta-analysis, with maintenance efficacy for biologic-experienced patients drawn from pivotal trials. A willingness-to-pay (WTP) threshold of €27,000 per quality-adjusted life year (QALY), a benchmark commonly referenced in Spain, was used to assess cost-effectiveness.

Only One Sequence Met Spain's Cost-Effectiveness Threshold

Of the 7 sequences evaluated, only sequence 2—which placed bsUST first, followed by bsADA, upadacitinib, risankizumab, and surgery—met the €27,000/QALY threshold. That sequence yielded an incremental cost-effectiveness ratio (ICER) of €8,672.6/QALY compared with the reference, representing a gain of 0.36 QALYs at an incremental cost of €3080 per patient. All other sequences exceeded the threshold, with ICERs ranging from €42,594/QALY to €372,446/QALY.

Within the base case, the first treatment line in sequence 2 had a mean duration of 3.9 years, compared with 2.2 to 3.3 years in the remaining sequences. Time to surgery ranged from 7.9 years in sequences 2 and 4 to 9 years in sequences 6 and 7.

Probabilistic sensitivity analysis, based on 10,000 Monte Carlo simulations, confirmed the robustness of these findings: sequence 2 was identified as cost-effective in 98.03% of simulations at the €27,000/QALY threshold. Deterministic sensitivity analysis indicated that the ICER was most sensitive to patient weight, first-line pharmacological costs, and the probability of achieving remission during maintenance.

In an alternative reference-analysis setting with sequence 2 as the comparator, all remaining sequences were either dominated or associated with QALY losses, thereby reinforcing the economic case for early bsUST placement.

Cost Savings Driven by Efficacy and Lower Acquisition Costs

The investigators attributed sequence 2's favorable profile to a combination of bsUST's clinical durability and its lower biosimilar price point. "Positioning bsUST as a first line of treatment appears to be cost effective and an efficient alternative from the NHS perspective in Spain," they wrote, adding that "bsUST may significantly impact Crohn disease management in Spain, improving patient access due to its lower drug acquisition costs."

The study carried several limitations. Markov models assume transition probabilities depend only on the current health state, which may not fully capture the influence of prior treatment history. Efficacy for third- and fourth-line treatments was estimated by carrying forward second-line biologic-experienced data, a conservative approach driven by limited available data. The number of analyzed sequences, while validated by expert gastroenterologists, did not capture all possible treatment pathways. Additionally, the existence of a dual pricing system in Spain, with confidential reimbursement prices negotiated separately from official list prices, means that actual per-sequence costs in practice could differ from those modeled.

Rodríguez-Lago I, Peinado-Fabregat JI, Guigini M, Cerezales M, Ibáñez F, Crespo C, Barreiro-de Acosta M. Cost-effectiveness analysis of sequential treatment strategies for moderate to severe Crohn's disease in Spain: where should biosimilar ustekinumab be positioned? 

 2026;10:557-566. doi:10.1007/s41669-026-00642-1

D'Amico F, Bencardino S, Gonçalves A, et al. Unlocking hope: the future of ustekinumab biosimilars in Crohn's disease treatment. 

 2025;13(2):186-200. doi:10.1002/ueg2.12682

Articles

Early use of ustekinumab biosimilars in Spain shows cost-effective Crohn disease care, boosting QALYs and cutting NHS spend—insights for Europe.

Positioning Biosimilar Ustekinumab Early Reduces Burden on Spain's National Health System

Wide variation in how countries define, evaluate, and approve biosimilar medications may be undermining access to more affordable biological treatments—and a new comparative analysis lays out exactly where those gaps are widest.

Global review reveals uneven biosimilar rules on waivers, interchangeability, and safety tracking—barriers to cheaper biologics and approvals. | Image credit: Tex vector - stock.adobe.com

 examined biosimilar regulatory frameworks across all 6 World Health Organization (WHO) regions, finding persistent inconsistencies in how countries approach comparability requirements, clinical study waivers, interchangeability designation, and pharmacovigilance—differences that may complicate the approval process and limit medication availability.

Why Regulatory Divergence Matters for Biosimilar Access

Clinicians and policymakers who review biosimilar data from other countries often assume those data were produced under standards similar to their own. That assumption, the researchers noted, may be incorrect—and acting on it could introduce bias about a biosimilar's validated safety and efficacy profile. Although the WHO, FDA, and European Medicines Agency (EMA) have each issued guidance frameworks, countries have adopted them unevenly. The need to map those differences systematically became the foundation of the review.

That concern is not new to the field. A 2025 descriptive review 

Therapeutic Innovation & Regulatory Science

 examined individual national regulatory requirements and guidelines for biosimilars in more than 70 countries as of July 2024—including both emerging countries and those with extensive biosimilar experience—and similarly identified key differences that complicate global development efforts.

 Together, the 2 analyses paint a consistent picture of a regulatory landscape that has yet to cohere around shared standards.

The present scoping review followed PRISMA Extension for Scoping Reviews (PRISMA-ScR) methodology, searching CINAHL, PubMed, and Scopus databases through March 1, 2026, and drawing on 37 regulatory guidance documents from 19 countries.

 Twelve were classified as emerging and developing economies and 7 as advanced economies by the International Monetary Fund. The advanced economies—Canada, France, Germany, Japan, South Korea, the UK, and the US—served as comparators given their longer histories of biosimilar development. Emerging and developing economies spanned all 6 WHO regions, including Brazil, China, Egypt, India, Indonesia, Mexico, Nigeria, the Philippines, Poland, Saudi Arabia, Tanzania, and Turkey. No patient demographic data were collected, as the study examined regulatory documents rather than clinical outcomes.

Where Countries Agreed—and Where They Didn't

Most countries (n = 17 of 19; 89%) had adopted WHO biosimilar terminology, and the same proportion defined biosimilarity as the absence of meaningful differences in quality, safety, and efficacy compared with the reference product. Sixteen countries explicitly required comparability exercises, although Mexico, Indonesia, and China did not clearly include this requirement.

Gaps widened on more complex regulatory questions. All 7 advanced economies allowed waivers of clinical efficacy and immunogenicity testing when sufficient analytical data were available—consistent with updated 2022 WHO guidance. Among emerging and developing economies, only a subset had adopted comparable waiver policies, with Tanzania still requiring clinical efficacy studies in every case.

Interchangeability guidance, which determines whether a biosimilar can be substituted for its reference product, sometimes at the pharmacy level without physician consultation, appeared in the guidance documents of only 2 of the 12 emerging and developing economies studied: Nigeria and Poland. Nigeria's guidance, notably, explicitly discouraged substitution, citing pharmacovigilance concerns.

"These findings highlight areas in which the global regulatory framework requires greater harmonization to optimize access to biosimilar medications and to improve support for policy research and cross-country comparisons," the authors wrote.

Pharmacovigilance and Naming Requirements Add Complexity

Eleven countries required a pharmacovigilance plan as part of a biosimilar application. Japan, the Philippines, and the Republic of Korea were the only countries that explicitly mandated postmarketing pharmacovigilance studies. Guidance on biosimilar naming and labeling—important for adverse event tracking—was present in only 8 of the 19 countries examined.

Some official guidance documents were only available in their country's native language, creating the possibility of translation errors despite the use of DeepL Translate software. The researchers also could not confirm they had captured every official guidance document, as some countries distribute regulatory requirements across multiple publications. Guidance documents drafted but not made publicly available would not have been captured. Additionally, Indonesia was reclassified from the WHO South-East Asia region to the Western Pacific region in mid-2025, although all 6 WHO regions remained represented in the final analysis.

For US payers and managed care organizations tracking global biosimilar pipelines, the findings underscore the risk of equating international biosimilar evidence with FDA-reviewed data. The study also signals opportunity: the FDA's June 2024 draft guidance eliminating the requirement for switching studies, and its November 2025 draft guidance reducing the need for comparative clinical efficacy data in favor of analytical justifications, may position the US as a potential model for streamlined approval that other national regulatory agencies could follow.

Watanabe JH, Strand MW, Walvekar M, Alfonso-Cristancho R. Regulatory definitions and classification of biosimilar medications across the 6 regions of the World Health Organization: a scoping review. 

. 2026;7(5):e261642. doi:10.1001/jamahealthforum.2026.1642

Kirchlechner TM, Cohen HP. Global harmonization of biosimilar development by overcoming existing differences in regional regulatory requirements — outcomes of a descriptive review. 

. 2025;59(2):245-255. doi:10.1007/s43441-024-00740-4

Global review reveals uneven biosimilar rules on waivers, interchangeability, and safety tracking—barriers to cheaper biologics and approvals.

Global Biosimilar Rules Diverge Across WHO Regions, Limiting Patient Access

Most people with multiple sclerosis had never heard of biosimilars—even while taking them—a new Italian study reveals, raising urgent questions about patient education gaps in MS care.

The study findings revealed the substantial—yet largely untapped—role of MS nurses in shaping patient knowledge and therapeutic decision-making. | Image Credit: © Robert Kneschke - stock.adobe.com

Biosimilar Blindspot: Over 60% of MS Patients Reported No Prior Awareness

Despite the growing availability and clinical adoption of biosimilar therapies for multiple sclerosis (MS), a large majority of people actively treated with these agents had never heard of them before beginning therapy, according to the cross-sectional study 

. The finding underscores a significant informational deficit that may be shaping—and limiting—biosimilar acceptance across the MS care continuum.

Biosimilar therapies have emerged as a central strategy for improving affordability and expanding patient access to high-cost biologic treatments, including agents used in relapsing forms of MS. The recent approval of biosimilar natalizumab (studied in the Antelope phase 3 trial, 

 Yet patient resistance to initiating or switching to biosimilars remains a documented challenge—one that researchers increasingly attribute not to entrenched opposition but to gaps in health literacy and what is known as the nocebo effect, wherein negative expectations drive perceived adverse outcomes.

To better understand how informational experiences and health literacy shape biosimilar acceptance in this population, researchers in Italy conducted a multicenter observational study using a newly developed, theory-informed questionnaire structured around 4 health literacy domains: access, understand, appraise, and apply.

The study was conducted from March to May 2025 across multiple Italian health care facilities through the Italian Network of Multiple Sclerosis Nurses. A total of 99 adults with confirmed MS diagnoses—representing a 49.5% response rate—completed the questionnaire. Participants had a mean (SD) age of 44.3 years (11), and 71.7% were female. Most were married or cohabiting (62.6%), and the sample was highly educated, with nearly half holding a university degree (47.5%). The majority of participants resided in Southern and Central Italy, with the largest proportion from Puglia (46.5%).

The questionnaire was developed through an iterative process that included interdisciplinary expert review and patient focus groups using a think-aloud method, ultimately yielding a 23-item instrument.

Knowledge Gaps Ran Deep Across All 4 Health Literacy Domains

In the access domain, 62.6% of participants reported never having heard of biosimilar drugs before beginning treatment. Most participants—94.9%—had received some information from a health care professional, but verbal explanation alone accounted for 91.5% of all informational delivery; printed materials and structured educational sessions were used in only 2.1% and 1.1% of cases, respectively.

Comprehension-related findings were similarly concerning. The item assessing perceived adequacy of information yielded the lowest mean (SD) score of the 4 domains (2.68 [1.04]), with 38.4% of participants disagreeing or strongly disagreeing that they felt adequately informed—compared with only 21.2% who agreed or strongly agreed.

In the appraise domain, trust in health care professionals was relatively high (mean [SD], 3.29 [0.94]), yet 35.3% disagreed or strongly disagreed that clinicians had provided complete information. Nearly half of respondents (45.4%) reported independently seeking additional information beyond what providers had shared—a pattern the researchers flagged as a potential vulnerability to misinformation.

The apply domain offered some encouraging findings. Acceptance of biosimilars for first-line treatment initiation showed the strongest positive response, with 49.5% of participants agreeing or strongly agreeing they would use a biosimilar if recommended by their physician. Nurse advice was reported as decisive or very influential on treatment decisions by 82.8% of participants, while physician advice reached that threshold among 92.9%.

MS Nurses Identified as Underutilized but Pivotal in Biosimilar Education

A key finding of the study was the substantial—yet largely untapped—role of MS nurses in shaping patient knowledge and therapeutic decision-making. Nurses were the first source of information about biosimilars for 36.4% of participants, compared with 52.5% who first received information from a physician. The authors noted that, given their frequency of patient contact and continuity of care, nurses are uniquely positioned to reinforce education and address informational gaps across the entire treatment journey.

As the authors wrote, "Biosimilar acceptance in MS appears to be shaped more by difference in health literacy processes than by negative attitudes. MS nurses play a pivotal role in addressing these gaps, supporting informed understanding, reducing uncertainty, and guiding therapeutic decision-making."

The authors acknowledged several limitations. The cross-sectional design prevents causal conclusions. The relatively small sample (n = 99), convenience sampling strategy, and geographic concentration in Southern Italy limit generalizability. The sample's high educational attainment and female predominance may not reflect the broader MS population. All data were self-reported, introducing potential recall and social desirability bias. Additionally, the questionnaire used in this study has not yet undergone formal psychometric validation for reliability or construct validity, meaning the results should be interpreted as exploratory.

These findings carry practical relevance for managed care organizations and health systems working to promote biosimilar uptake. Patient education remains a critical and potentially modifiable barrier to biosimilar adoption—one that nurse-led communication strategies may be well-positioned to address. Strengthening structured, tailored educational interventions delivered by MS nurses could represent a cost-effective lever for improving biosimilar acceptance and, ultimately, supporting sustainable biologic prescribing.

Pastore F, Cicolini G, Forastefano B, et al. Health literacy and biosimilar acceptance in people with multiple sclerosis: a cross-sectional study. 

 2026;25(1):482. doi:10.1186/s12912-026-04660-6

Hemmer B, Wiendl H, Roth K, et al. Efficacy and safety of proposed biosimilar natalizumab (PB006) in patients with relapsing-remitting multiple sclerosis: the Antelope phase 3 randomized clinical trial. 

 2023;80(3):298-307. doi:10.1001/jamaneurol.2022.5007

Italian study finds most MS patients start biosimilars unaware, exposing education gaps and highlighting MS nurses as key to boosting trust and uptake.

Low Biosimilar Awareness in MS Patients Points to Critical Gap in Nurse-Led Education

The growing availability of biosimilar disease-modifying antirheumatic drugs (DMARDs) and the emergence of generic Janus kinase inhibitors (JAKi) have helped reshape how rheumatologists are advised to sequence treatments for people with rheumatoid arthritis (RA), according to updated guidance from the European Alliance of Associations for Rheumatology (EULAR).

People with RA who do not respond adequately to initial methotrexate therapy should move directly to biologic DMARDs, according to updated EULAR recommendations that eliminate the previous requirement for prognostic risk stratification—a shift driven in part by the expanding availability and declining costs of biosimilars. | Image credit: เด็กชาย นุ่มนิ่ม - stock.adobe.com

, the 2025 EULAR recommendations for the management of RA with synthetic and biologic DMARDs represent the most streamlined version of EULAR's guidance to date, consolidating 11 prior recommendations into 9.

 The update was conducted because 3 years had passed since the 2022 revision and new evidence from strategic clinical trials—as well as evolving safety data on JAKi—warranted a reassessment of the therapeutic algorithm.

A 50-member international task force convened by EULAR undertook 2 systematic literature reviews (SLRs) covering efficacy and safety data published through January 2025. The group included rheumatologists from Europe, Asia, Latin America, North America, and Africa, along with patient research partners, nonphysician health professionals, and an infectious disease specialist. The steering committee first met in November 2024 in Washington, DC, with the full task force convening in Amsterdam in March 2025. Because no new DMARDs had received regulatory approval in Europe or the US since the 2022 update, the task force's primary focus was on refining therapeutic strategy and incorporating insights from newer trials.

The most consequential change in the 2025 update was the removal of prognostic risk stratification as a prerequisite for advancing to biologic DMARDs (bDMARDs) after initial methotrexate failure. Previously, the 2022 guidelines directed clinicians to assess prognostic risk factors—such as elevated autoantibody titers, early erosions, and high acute phase reactants—before deciding whether to add a bDMARD or try an additional conventional synthetic DMARD (csDMARD). The 2025 task force voted 98% in favor of eliminating that stratification step, citing evidence that people with RA who did not respond adequately to methotrexate showed limited benefit from further csDMARD cycling and that methotrexate failure itself constitutes an adverse prognostic sign.

Going forward, the algorithm directs clinicians to add a bDMARD when the treatment target is not achieved with an initial csDMARD strategy, with JAKi remaining an option provided relevant risk factors—including history of major adverse cardiovascular events, malignancy, and thromboembolic events—are evaluated first. The task force voted 81% in favor of keeping JAKi safety caveats unchanged from 2022, noting that no new randomized controlled trials on cardiovascular or malignancy risk had been published since the ORAL Surveillance trial (

The task force also strengthened language around DMARD continuation in sustained remission. Recommendation 9 now explicitly states that DMARDs should be continued after glucocorticoid discontinuation, with dose reduction as an option rather than cessation, given data indicating that stopping therapy leads to disease flares in the majority of people with RA.

 That change passed with 96% approval. Other recommendations retained from 2022 included the primacy of methotrexate as first-line therapy, short-term glucocorticoid bridging when initiating or changing csDMARDs (endorsed by 98% of the task force), and treat-to-target (T2T) strategies aimed at remission or low disease activity within 6 months. Levels of agreement across all 9 recommendations and 5 overarching principles exceeded a mean score of 9 out of 10—the first time in the history of these EULAR recommendations that all items achieved that threshold.

What This Means for Payers and Formulary Decisions

For managed care decision-makers, the elimination of the prognostic stratification step carries practical significance: It removes one algorithmic reason to keep people with RA on additional rounds of csDMARDs after methotrexate failure, potentially accelerating the transition to bDMARDs or JAKi. The task force pointed to the declining costs of biosimilar bDMARDs and the availability of generic tofacitinib as factors that weighed in favor of this change, reducing the cost differential that had previously supported delaying biologic initiation.

The recommendations are intended to apply broadly to adults who have received a clinical diagnosis of RA, with particular emphasis on initiating therapy as early as possible. The task force noted that these recommendations do not address people in a "pre-RA" state who have not yet developed clinical joint swelling, as trials of DMARDs in that population have demonstrated only a delay in RA classification rather than disease prevention. The guidelines also acknowledge that biosimilar and generic JAKi availability varies across countries, and that economic considerations remain relevant in less affluent health care settings.

The task force acknowledged that no new randomized controlled trial data on JAKi cardiovascular or malignancy risk were available for this update, meaning safety caveats continue to rest largely on ORAL Surveillance data and observational studies that have not consistently replicated those findings.

 The SLRs were also limited to literature published through January 2025.

Additionally, the recommendations do not provide individualized guidance on sequencing within the bDMARD class, as head-to-head comparative efficacy data remain limited and all licensed targeted DMARDs appear broadly similar in efficacy at the group level. Predictors of individual treatment response remain an unmet need, with no validated biomarkers yet available to guide drug selection.

Smolen JS, Edwards CJ, Konzett V, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs: 2025 update. 

 2026;85(6):991-1009. doi:10.1016/j.ard.2026.01.023

van der Kooij SM, de Vries-Bouwstra JK, Goekoop-Ruiterman YP, et al. Limited efficacy of conventional DMARDs after initial methotrexate failure in patients with recent onset rheumatoid arthritis treated according to the disease activity score. 

 2007;66(10):1356-1362. doi:10.1136/ard.2006.066662

Erhardt DP, Cannon GW, Teng CC, Mikuls TR, Curtis JR, Sauer BC. Low persistence rates in patients with rheumatoid arthritis treated with triple therapy and adverse drug events associated with sulfasalazine. 

 2019;71(10):1326-1335. doi:10.1002/acr.23759

Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. 

 2022;386(4):316-326. doi:10.1056/NEJMoa2109927

New EULAR guidelines speed RA treatment switches as rheumatoid arthritis biosimilars and cost savings push earlier biologics use.

Biosimilar Expansion, Lower Costs Drive Shift in RA Treatment Guidelines

Biologic therapy reaches fewer than half of eligible patients with ankylosing spondylitis in many health care systems—not because the treatments don't work, but because they cost up to $30,000 a year per patient.

Biosimilar tumor necrosis factor inhibitors, which offer cost reductions of 15% to 35% compared with reference biologics, have emerged as a strategy to expand treatment access for people with ankylosing spondylitis, a chronic inflammatory condition that causes progressive spinal pain and stiffness. | Image credit: MQ-Illustrations - stock.adobe.com

A structured narrative review published in 

 synthesized evidence from randomized controlled trials (RCTs), real-world registries, and regulatory approval programs to assess whether people with ankylosing spondylitis who were stable on reference tumor necrosis factor (TNF) inhibitors could safely transition to biosimilar formulations.

Researchers from Yunnan University of Chinese Medicine conducted the review in response to a recognized evidence gap: although biosimilar switching guidance had been developed for rheumatoid arthritis, ankylosing spondylitis-specific switching data—most of which emerged after 2018—had not been systematically synthesized. 

The review covered literature published between January 2013 and March 2025 across PubMed, EMBASE, and the Cochrane Library. Although the authors are based in China, the evidence they synthesized spans multinational registries and trials conducted across Europe, Asia, and North America, making the findings relevant to US payers and health systems navigating biosimilar formulary decisions.

Ankylosing spondylitis affects an estimated 0.2% to 0.5% of adults worldwide, and reference TNF inhibitors—approved for AS between 2003 and 2016—carry annual costs ranging from $15,000 to $30,000 per patient in the US. Biosimilar alternatives typically offer 15% to 35% cost reductions, with deeper discounts available through competitive procurement. Despite this economic case, clinical uptake has depended on confidence that switching stable patients does not disrupt disease control. Ankylosing spondylitis poses unique considerations compared with other inflammatory conditions: patients often require prolonged biologic therapy, use different validated monitoring instruments, and may experience chronic axial pain in ways that heighten susceptibility to the nocebo effect.

The most methodologically rigorous switching data came from the PLANETAS extension study, which followed 174 people with ankylosing spondylitis after an initial 54-week trial establishing equivalence between the infliximab biosimilar CT-P13 and reference infliximab in 250 treatment-naive patients. 

In the extension, 88 patients continued CT-P13, and 86 switched from reference infliximab to CT-P13. At week 102, Assessment of SpondyloArthritis International Society (ASAS)-20 response rates were 80.7% in the maintenance group and 76.9% in the switching group, with ASAS-40 and partial remission rates similar between groups. 

Anti-drug antibody positivity was 23.3% in the maintenance group and 27.4% in the switching group—a difference that was not statistically significant and did not indicate increased immunogenic risk after the transition. Adverse event-related discontinuation occurred in 3.3% of people who maintained CT-P13 and 4.8% of those who switched.

A separate 18-month Greek RCT randomized 88 people with ankylosing spondylitis in clinical remission to either switch to a biosimilar (n = 45) or continue the reference product (n = 43). All patients who completed the study maintained clinical remission, with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP showing no significant between-group differences. Erythrocyte sedimentation rate and C-reactive protein (CRP) values remained stable and comparable across groups.

Registry evidence from multiple countries corroborated trial findings at a larger scale. The Korean College of Rheumatology Biologics (KOBIO) registry reported a 4-year retention rate of 66% among 244 people receiving CT-P13, with BASDAI remaining well-controlled throughout follow-up. A propensity score-matched KOBIO analysis of 248 patients found 3-year retention rates of 64.2% for CT-P13 vs 55.6% for reference infliximab—a nonsignificant difference. 

The French ReFLECT study, which followed 411 patients with rheumatic diseases, including ankylosing spondylitis, over 24 months, reported a retention rate of 74.9%, with inflammatory markers remaining stable in patients who had switched. A Nordic collaborative analysis pooling data across five countries found no significant retention differences between biosimilars and reference products for either infliximab or etanercept in 2,334 biologic-naive people with spondyloarthritis.

The authors identified several important caveats. The PLANETAS extension used an open-label design, introducing potential bias in patient-reported outcomes such as BASDAI, which depends entirely on self-report. The Greek RCT was limited by a small sample size and performed a completers analysis rather than intention-to-treat, meaning patients who discontinued—including 4 in the biosimilar group attributed to nocebo effects—were excluded before efficacy analysis. 

Registry studies could not fully exclude selection bias or unmeasured confounders, as clinicians may have preferentially switched more clinically stable patients. Existing datasets also rarely distinguished between clinician-initiated and administratively mandated switching, which the review identified as a meaningful gap given evidence that mandated switching without patient engagement drove higher discontinuation rates.

The available switching evidence was also heavily concentrated on CT-P13; data for etanercept and adalimumab biosimilars in ankylosing spondylitis populations remained sparse, drawn largely from mixed inflammatory arthritis cohorts with small AS subgroups.

The review emphasized that nocebo effects—symptom worsening driven by negative expectations rather than pharmacological change—contributed meaningfully to switching discontinuations in mandatory programs. 

Dutch data showed approximately 25% of people discontinued biosimilar therapy within 6 months when switching occurred as a payer-mandated policy without individualized clinical assessment, with many discontinuations linked to subjective complaints unsupported by objective inflammatory markers. 

Programs that incorporated shared decision-making and patient education reported lower discontinuation rates.

Zhu W, He X, Cheng K, et al. Ankylosing spondylitis: etiology, pathogenesis, and treatments. 

. 2019;7:22 doi:10.1038/s41413-019-0057-8

Cai L, Chen X, Fang Y, et al. Clinical evidence and implementation guidance for biosimilar switching in ankylosing spondylitis. 

. 2026;17:1803260. doi:10.3389/fphar.2026.1803260

Evidence shows biosimilars switching in ankylosing spondylitis maintains disease control with biologics, cuts costs, and highlights nocebo risks.

Biosimilar Switching Maintained Disease Control in People With Ankylosing Spondylitis

This article was originally published by 

FDA approved | Image credit: Ticha - stock.adobe.com

The FDA has approved interchangeable biosimilars that reference Johnson & Johnson’s Simponi and Simponi Aria, which treat patients with rheumatoid arthritis and ulcerative colitis.

Immgolis (golimumab-sldi) is administered by subcutaneous injection in a single-dose, prefilled syringe. Immgolis Intri (golimumab-sldi) is administered as an intravenous infusion prepared from a single-dose vial. As interchangeable biosimilars, Immgolis and Immgolis Intri can be substituted at the pharmacy for patients with rheumatoid arthritis and ulcerative colitis.

Immgolis and Immgolis Intri were developed by Bio-Thera Solutions, which will maintain responsibility for manufacturing and product supply. The biosimilars will be marketed in the United States by Accord BioPharma, the U.S. specialty division of Intas Pharmaceuticals. They will be available in the fourth quarter of this year.

Golimumab products are human monoclonal antibodies that bind to a protein called tumor necrosis factor alpha (TNFα). By binding TNFα, golimumab stops it from triggering inflammation, which helps improve signs and symptoms of these diseases. Immgolis and Immgolis Intri have the same indications as Simponi and Simponi Aria. The prescribing information can be found 

In a news release, the FDA said that the approval of Immgolis and Immgolis Intri was based on the totality of evidence. Comparisons of the biosimilars with Simponi were made across a range of structural and functional product quality attributes and the impact on safety and efficacy.

The most common expected side effects of Immgolis/Immgolis Intri, like Simponi/Simponi Aria, are upper respiratory tract infection, nasopharyngitis, and injection site reactions.

Immgolis and Immgolis Intri have the same indications as Simponi and Simponi Aria, treating patients with rheumatoid arthritis and ulcerative colitis. The biosimilars will be available in the fourth quarter of this year.

FDA Approves First Biosimilars Interchangeable With Simponi/Simponi Aria

 To quantify the impact of biosimilar adoption on oncology provider financial risk under the Oncology Care Model (OCM) using real-world data.

 Retrospective study of Medicare fee-for-service beneficiaries potentially eligible for an OCM episode of care initiating between January 2019 and June 2021.

 Cancer treatment episodes were identified from the Medicare 5% Limited Data Set (LDS). The study sample consisted of episodes with use of any of the following agents or their biosimilars: bevacizumab, rituximab, trastuzumab, epoetin alfa, filgrastim, and pegfilgrastim. Financial risk was defined as the difference in observed total cost of care vs OCM benchmark episode cost. The primary outcome was the difference in financial risk (expressed in nominal US$) under observed use of reference agents and/or biosimilars vs hypothetical use of 100% reference product.

 The sample included 8851 episodes. Biosimilar adoption resulted in a mean cost reduction of $1023 per 6-month episode vs hypothetical 100% use of reference agents. Biosimilar use increased markedly over the study horizon—with use in 65% of episodes initiating in half 1 (H1) of 2021. The mean cost of care reduction in episodes initiating in H1 2021 ($2060; 4.1% of mean episode benchmark price) improved nearly 10-fold vs H1 2019 ($201; 0.4% of mean episode benchmark price).

 Rapid adoption of biosimilars for Medicare beneficiaries included in the LDS led to substantial cost savings for cancer episodes evaluated under the OCM methods—suggesting that adoption of biosimilars is a key strategy that providers should consider to manage financial risk in value-based payment models.

We estimate that adoption of oncology biosimilars in Medicare value-based payment (VBP) models resulted in cost savings of $1023 per 6-month episode of care (2.07% reduction vs mean episode benchmark).

A biosimilar adoption strategy is important to reduce cost and mitigate provider risk in 2-sided oncology VBP models.

We believe this is the first study to apply biosimilar real-world data to oncology VBP models to quantify the incremental cost and performance impacts.

Our findings inform policy decisions regarding cost of care and provider performance impacts of biosimilars and highlight priority cancers and biologics to maximize impact.

medicare | Image credit: japhoto - stock.adobe.com

In response to the rising cost of cancer care in the US, policy makers and health care stakeholders have increasingly turned to value-based payment (VBP) models as a potential solution.

 Broadly, these models are designed to align reimbursement with patient outcomes and the overall value of care, and they have shown promise in both controlling costs and enhancing the quality of oncological care.

 However, the translation of these models into widespread practice requires careful consideration of structural, clinical, and financial challenges and must be supported by ongoing research and policy refinement.

Biosimilars represent a promising group of drugs within the context of VBPs, as they meet high standards for comparability to existing approved biological products (or 

) in terms of structure, quality, safety, and efficacy and typically have an average sales price (ASP) more than 25% lower than reference products.

 Additionally, biosimilars are highly prevalent in oncology indications, with FDA-approved biosimilars for 8 molecules in oncology as of April 2026.

 As such, biosimilars could be critical tools to help providers manage VBP-related financial risk while still delivering high-quality care.

The objective of this study was to quantify the impact of biosimilar adoption on total cost of care and oncology provider financial risk in VBP models using real-world data. To provide a concrete, quantitative underpinning to our evaluation, we employed the methodology of Medicare’s oncology VBP models as an exemplar. Medicare has been a leader in the oncology VBP space, having launched 2 of the largest oncology VBP models in the US to date: most recently, the Enhancing Oncology Model (EOM), which launched in July 2023 and reopened for new participants from May to September 2024, and the Oncology Care Model (OCM), which ran from July 2016 to June 2022, with final evaluation of the program published in May 2024.

 Broadly, in these programs, provider cost of care is compared to benchmarks calculated from retrospective analyses of patients treated outside the context of a VBP. Providers exceeding cost benchmarks can owe a recoupment to CMS, and those below cost benchmarks are eligible for performance-based (additional) payments. Although key parameters of the EOM payment methodology are still uncertain, the OCM and EOM have significant overlap in their episode identification, cost, and benchmark pricing methodologies, allowing us to use available data and the fully finalized OCM methodology to provide timely and actionable information to providers.

This study takes the perspective of cancer care providers facing choices between use of biosimilars or their reference products in the context of VBP models. Our findings can help these providers understand the impacts of choosing biosimilars in this context on total cost of care and performing favorably in VBP models. Our findings may be particularly beneficial for providers who are new to value-based care arrangements and elected to participate in the second EOM cohort, which began in July 2025.

The Medicare 5% Limited Data Set (LDS) analytic files from 2019 to 2021 were used to evaluate the impact of biosimilar adoption on provider risk and financial performance in VBP models in the context of the OCM payment methodology.

 We used LDS data from 2016 to 2021 to implement required components of the OCM methodology.

Prices for biologic reference products and biosimilars were taken from the Medicare ASP Drug Pricing File

 from the year and quarter indicated by the date of service on the claim for the product.

Biosimilars that met the following criteria were selected: (1) biologic products designated by the FDA as biosimilar to a corresponding reference product and commercially available prior to December 31, 2021 (the last possible date for claims in episodes included in OCM performance period [PP] 10)

; (2) biosimilar products with an FDA indication related to at least 1 of the 21 OCM-eligible cancers

; and (3) assigned an individual Healthcare Common Procedure Coding System (HCPCS) code no later than the October 2021 CMS quarterly HCPCS code update.

 The following 6 sets of biologic products met our inclusion criteria: bevacizumab (Avastin) biosimilars,

The unit of analysis was a 6-month patient episode of care as defined by the OCM methodology, which included episode triggers, episode termination criteria, cancer assignment, and overall OCM inclusion/exclusion criteria.

The primary outcome of the study was the cost impact of observed biosimilar use relative to a counterfactual with the corresponding reference product. The primary outcome was defined as the difference in episode total cost of care (TCOC) with the observed use of reference and biosimilar products compared with TCOC with use of reference products only. Methods for calculating the OCM TCOC benchmark are explained in detail in the 

The study used the OCM simulation module in the Tuple Health RWE Technology Platform, which operationalizes all key facets of the OCM methodology including OCM TCOC calculation, episode framing, cancer attribution, risk adjustment, and the OCM’s inclusion/exclusion criteria.

 Tuple Health’s OCM simulation module was previously cross-validated using empirical OCM data, independent of this study. Modeled predictions for OCM TCOC targets were greater than 99.9% accurate compared with the episode targets provided by Medicare.

This core OCM methodology implementation was extended to include simulated Part D costs and Part D enrollment for OCM episodes to address key gaps in publicly available research data sets.

 Part D cost ranges were initially estimated from a random sample of OCM data, and zero-inflated γ distributions for sampling were assumed to construct the models.

From the initial set of episodes with patterns of care that qualified for inclusion in the OCM, we identified all episodes utilizing reference products corresponding to the biosimilars of interest and any episodes from the LDS data using one of the study biosimilars. We referred to these as 

 (BAEs). These reference products and their corresponding biosimilars were considered 

Episodes in the study population initiated between January 2, 2019, and July 1, 2021, corresponding to OCM PP 6 to PP 10. For each episode in the study population, we computed the TCOC and performed episode cost truncation (winsorization) in accordance with the OCM methodology. Costs for each BAE were computed first under the observed use of biosimilar and reference products, then again under the assumption of the use of reference products only. Costs for BAPs were calculated using the number of billed units in the episode (inclusive of drug waste) for each BAP multiplied by the per-unit prices for the product taken from the Medicare ASP Drug Pricing File from the year and quarter corresponding to the service date of the claim associated with the use of the product.

Of the 3,641,034 beneficiaries present in the 2019-2021 LDS data, 24,845 beneficiaries met the conditions (eg, cancer type, treatment type, and lack of COVID-19 diagnosis, among others) for triggering a potentially eligible VBP episode of care, with a total of 39,571 potentially eligible episodes of care identified (Table 1). Of those potentially reconciliation-eligible episodes of care, 8851 were determined to be BAEs (see eAppendix for additional product-specific details). Aggregated across the entire study period, 55.3% of BAEs had use of reference BAPs only. The observed use of biosimilar BAPs resulted in cost reductions of $1023 per 6-month episode compared with the hypothetical use of only reference products, corresponding to a cost reduction equivalent to 2.1% of the mean episode benchmark price.

, biosimilar use increased steadily over the study period. Among episodes initiating in half 1 (H1) of 2019, 24.3% had use of a biosimilar. By H1 2021, 65% of BAEs had use of a biosimilar. This increased use was primarily driven by biosimilar antineoplastics (1.4% of episodes in H1 2019 to 36.4% in H1 2021) but was also due to the adoption of supportive care biosimilar agents (23.0% in H1 2019 to 34.1% in H1 2021). Mean financial risk reduction improved nearly 10-fold with the rapid adoption of biosimilars over this period, from $201 per episode (representing a cost reduction equivalent to 0.4% of the mean benchmark price) in H1 2019 to $2060 (4.1% of mean benchmark price) in H1 2021.

 compares the rates of biosimilar adoption and resulting financial impact by product class (antineoplastic vs supportive therapies). Averaged over the study period, adoption of biosimilar antineoplastics led to a mean financial risk reduction of $880 per episode. Risk reduction grew rapidly in each period, from $14 in H1 2019 to $2077 in H1 2021. Adoption of biosimilar supportive therapies led to a mean financial risk reduction of $142 per episode. The use of biosimilar supportive therapies led to risk reduction in the first 4 periods but resulted in a risk increase of $22 in the final period, due primarily to significant decreases in the reimbursement costs for reference pegfilgrastim over the study period.

, the 5 most prevalent cancer types assigned to BAEs were breast (19.8%), lymphoma (19.1%), small intestine/colorectal (12.2%), lung (12.0%), and prostate (6.8%). On a per-episode basis, the impact of biosimilar use was most cost saving in renal cancer ($2487), central nervous system (CNS) tumors ($1998), small intestine/colorectal cancer ($1721), lymphoma ($1523), and chronic leukemia ($1407). On a per-episode basis, the impact of biosimilar substitution was least cost saving in endocrine tumors ($54), prostate cancer ($148), pancreatic cancer ($227), bladder cancer ($267), and head and neck cancer ($309). Biosimilar use was more beneficial in cancers included in the EOM ($1085 per episode) than in non-EOM cancers ($831).

In our study, we assessed the impact of biosimilar adoption on provider risk and financial performance in VBP models by applying the Medicare OCM methodology to Medicare fee-for-service claims in the 2019-2021 period. We found that rapid adoption of biosimilars led to substantial TCOC savings and reduction in provider financial risk for exceeding VBP model cost of care benchmarks. Evaluated under the methodology of the OCM, biosimilar use resulted in a mean cost reduction of $1023 per episode relative to a counterfactual with only reference products. Due to declining biosimilar price and increased utilization, the mean cost reduction increased by a factor of 10 in H1 2021 vs H1 2019 ($2060 per episode vs $201 per episode). We found that the overall impact of biosimilar adoption was driven by increases in the use of biosimilar antineoplastics, from 1.4% of episodes in H1 2019 to 36.4% in H1 2021. Over this time, mean financial risk reduction attributed to biosimilar antineoplastic use increased from $14 to $2077 per episode. In subgroup analyses, we found that cancer types for which monoclonal antibody therapies are typically given in larger doses or for longer durations (eg, in maintenance therapy) exhibited even greater savings (breast cancer, small intestine/colorectal cancer, lymphoma, chronic leukemia, ovarian cancer, liver cancer, CNS tumors, and kidney cancer).

When we similarly applied our analytic approach to episodes with cancer types included in the newer Medicare EOM, we found that the included cancer types had particularly high uptake of biosimilars—especially biosimilar antineoplastics. We found that BAEs assigned to a cancer type included in the EOM (75.5% of all BAEs) had disproportionately high use of antineoplastic BAPs (representing 84.4% of BAEs with use of a BAP antineoplastic). For this reason, we expect the cost impact of biosimilar substitution to be particularly pronounced in EOM-included cancers. If biosimilar adoption remains at the level observed in our study population in H1 2021, we estimate that total episode costs across EOM episodes would be approximately 1.3% lower ($748) than they would be without the use of any biosimilars (eAppendix). This could result in providers needing to meet lower benchmark prices or represent an opportunity to more readily meet incentive thresholds. Further, this is likely an underestimate of the cost impact of biosimilars for episodes triggering after new provider enrollment into the EOM. Beginning in 2025, the EOM definition of total cost of care for Part D agents began reflecting Medicare’s reduced responsibility (from 80% of gross drug cost above the catastrophic threshold to 40% for generic drugs and 20% for brand-name drugs) as required by the Inflation Reduction Act. The net effect of this change will be a reduction in expected episode cost (and thus EOM cost benchmarks), increasing the proportion of episode cost that could be saved via biosimilar substitution.

VBP models can theoretically align the economic incentives of health care payers including Medicare with the medical practices of oncologists—achieving high-quality outcomes at a lower cost of care. However, the highly protocolized nature of modern cancer diagnosis, treatment, and monitoring leaves few opportunities for oncologists to bend the cost curve without sacrificing standard components of testing, imaging, therapy, and/or follow-up that can have implications for quality of care. As such, substitution of biosimilar antineoplastic and supportive care therapies for their more costly reference products represents a uniquely feasible strategy to optimize provider performance in the context of VBP. Over time, it is possible that increased biosimilar use could function to decrease VBP price benchmarks, which could make it more difficult for providers to earn performance-based payments. Nonetheless, choosing biosimilars in this context would still benefit providers because they would be expected to have a lower likelihood of owing recoupments for exceeding cost benchmarks.

This study has several limitations that should be noted. Although we applied the detailed OCM methods to Medicare LDS records during the period when the OCM was conducted, we did not limit our analysis to patients who received care from an OCM participant. As a result, our analysis assumes that the average TCOC effects of biosimilar substitution observed in the broader set of included Medicare patients are representative of the OCM cohort. We believe that this is a reasonable assumption because analysis of OCM PPs 1 through 11 (H2 2016-H2 2021) found that, although statistically significant, the difference in total episode payments between OCM and non-OCM practices was quite small relative to episode cost.

 Additionally, we focused our analysis on the subset of patients eligible for treatment in the OCM with the potential to be treated with biosimilars (BAEs). As such, the average cost impacts of biosimilar substitution would be lessened if averaged over the entire OCM-eligible population in a manner analogous to the analysis reported by Keating et al.

 Finally, our analysis assesses observed cost of care in patients with BAEs vs a hypothetical counterfactual where only reference products are used. This analysis demonstrates the maximum degree to which observed levels of biosimilar uptake can decrease TCOC. If a provider’s baseline use of biosimilars is higher, potential for biosimilar-attributable savings may be diminished, but the benefit of reduced risk of owing recoupments will remain. Although OCM methods for cost impact estimation in the EOM are likely valid, the accuracy of our estimates would be improved with the necessary parameters to conduct EOM benchmarking.

From 2019 to 2021, rapid adoption of biosimilars for Medicare fee-for-service beneficiaries included in the LDS led to substantial cost savings and reduction in financial risk for cancer episodes evaluated under the VBP methods. Broad adoption of biosimilars is a key strategy that providers in oncology VBP models should consider for managing TCOC and optimizing performance.

 Tuple Health (BC, AY, LT), Washington, DC; Pfizer Inc (AS, JAR), New York, NY; Mailman School of Public Health, Columbia University (AS), New York, NY; Comparative Health Outcomes, Policy, and Economics Institute, School of Pharmacy, University of Washington (JAR), Seattle, WA.

 Dr Chaudhry, Dr Yue, and Ms Tran are employees of Tuple Health, which was a paid consultant to Pfizer in connection with the development of this manuscript. Dr Yue also served on an advisory board for Johnson & Johnson in December 2024, which was a roundtable hosted by 

 on value-based care agreements and reimbursement models. Drs Shelbaya and Roth are employees and stockholders of Pfizer.

 Concept and design (BC, AY, AS, JAR); acquisition of data (BC, AY); analysis and interpretation of data (BC, AY, AS, JAR); drafting of the manuscript (BC, AY, AS, LT, JAR); critical revision of the manuscript for important intellectual content (BC, AY, AS, JAR); statistical analysis (BC, AY, JAR); obtaining funding (BC, LT, JAR); administrative, technical, or logistic support (LT); and supervision (BC, JAR).

 Basit Chaudhry, MD, PhD, Tuple Health, 4800 Hampden Ln, Ste 200, Bethesda, MD 20814. Email: basitchaudhry@tuplehealth.com.

1. Promoting value, affordability, and innovation in cancer drug treatment. President’s Cancer Panel. March 2018. Accessed August 13, 2024. 

https://web.archive.org/web/20240802081004/https://prescancerpanel.cancer.gov/report/drugvalue/index.html

2. The current cancer care landscape: an imperative for change. In: Levit L, Balogh E, Nass S, Ganz PA, eds. 

Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis

. National Academies Press; 2013. Accessed August 13, 2024. 

https://www.ncbi.nlm.nih.gov/books/NBK202145/

3. Cox JV, Sprandio JD, Barkley R. Understanding and surviving the transition to value-based oncology. 

. 2013;33(1):e361-e368. doi:10.14694/EdBook_AM.2013.33.e361

Evidence suggests that adoption of oncology biosimilars in Medicare value-based payment models has produced substantial cost savings and improved provider financial performance.

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