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Rapid responses are electronic comments to the editor. They enable our users to debate issues raised in articles published on bmj.com. A rapid response is first posted online. If you need the URL (web address) of an individual response, simply click on the response headline and copy the URL from the browser window. A proportion of responses will, after editing, be published online and in the print journal as letters, which are indexed in PubMed. Rapid responses are not indexed in PubMed and they are not journal articles. The BMJ reserves the right to remove responses which are being wilfully misrepresented as published articles or when it is brought to our attention that a response spreads misinformation.

From March 2022, the word limit for rapid responses will be 600 words not including references and author details. We will no longer post responses that exceed this limit.

The word limit for letters selected from posted responses remains 300 words.

Re: The role of physician associates in the NHS Kieran Walshe. 388:doi 10.1136/bmj.r437

Dear Editor

Introduction of PA could have been a major breakthrough in NHS if it was developed as an alternative route to become a registered medical practitioner rather than an alternative to replace a doctor. It will be much more productive to debate how best to harness the potential of PAs to progress to a career as a doctor. As per GMC data 15% of all entries to Specialist Register in 2024 were through the portfolio route [1], hence a similar approach to the primary qualification would be beneficial and practical.

PA role has an excellent potential to be developed to meet the UKs demand of doctors and thus reducing the reliance on overseas trained doctors over long term. Instead of being a dead-end job, PAs are a valuable resource who can progress to qualification similar to MBBS through ongoing training modules, portfolio development, assessments and passing a qualifying examination like Medical Licencing Assessment (MLA). Converting a proportion of MBBS places in universities to PA route to a registered medical qualification can also reduce the burden on school students of making a career choice and intense competition at an early age.

PAs can be provided with an option to continue medical education one or more days a week to complete requirement of MBBS qualification over a period of few years. Once all modules are passed, they may appear in MLA examination. Simultaneously, they can maintain a portfolio demonstrating completion of foundation year (FY1) competencies. The two together should allow GMC to give registration as licenced practitioner equivalent to the MBBS. Based on my experience as a trainer for medical students from conventional route as well as graduate entry students, it is highly likely that once qualified PAs with substantial portfolios can be more competitive than their conventional MBBS peers to gain entery to specialty medical training posts. Significantly better academic performance of graduate entry students at a UK university compared to the undergraduate entrants supports this view [2].

For some PAs continuing the role as an associate to physician may be the preferred option if they elect not to pursue further studies or take on the responsibility to work as an independent medical practitioner. It is however important that at the time of applying for the PA qualification it is emphasized that it does not guarantee progression to become a doctor.

1. https://www.gmc-uk.org/about/what-we-do-and-why/data-and-research/statis...
2. Knight, James & Stead, Anthony & Geyton, Thomas. (2017). Comparing the academic performance of graduate-entry and undergraduate medical students at a UK medical school. Education for Health. 30. 75. 10.4103/efh.EfH_157_15.

Competing interests: No competing interests

26 March 2025
Arun Jain
Consultant Urologist
The Royal Oldham Hospital, Northern Care Alliance NHS Foundation Trust
Oldham, UK
Re: UK welfare reforms threaten health of the most vulnerable Gerry McCartney, Lucinda Hiam, Katherine E Smith, David Walsh. 388:doi 10.1136/bmj.r593

Dear Editor

Whilst I agree with much of this response to the recent government proposal of violence against the UK’s disabled population, I am yet again disappointed that carers are erased from the discourse. Especially distressing and frustrating that this is coming from a significant representative of the medical community.

According to carersuk.org 60% of carers have a long term health condition or disability, and “the rate of poverty amongst unpaid carers is 50% higher in comparison to those who do not provide unpaid care”. These cuts will push families such as mine (a disabled lone parent caring for disabled adult children) into crisis. I don’t have a choice but to provide care and support, they are my children. The lack of consideration for the subsequent impact on carers health and wellbeing is always shocking to me. We plug the gaps poor health care leaves, which often detrimentally impacts our own health. Unpaid carers are subject to the same poor health care provision as the people we care for. Currently we’re already impacted by benefit cuts given Carers Allowance is effectively taken from our universal credit each month, pound for pound, and replaced with a UC premium around half its value.
Any discourse around systemic failures in health and social care and the benefits system MUST include unpaid carers. It’s our labour that plugs the gap. Literally our bodies. Until a consideration of unpaid carers is made at foundational levels of the medical community you’re failing service users and carers, and failing to move towards a healthier nation.

Give solid consideration to my response before replying.

Regards
Abby

Competing interests: No competing interests

26 March 2025
Abby Harrison
Unpaid carer
NW England
Re: Laws that would make abortion homicide in nine US states Rebecca B Reingold, Lauren Karpinski, Paulina Macías Ortega, Laura Dragnic Tohá. 388:doi 10.1136/bmj.r481

Dear Editor

In 2023, the UN Human Rights Committee, in its review of the United States' adherence to the International Covenant on Civil and Political Rights (ICCPR), stated unequivocally that abortion bans across various US states constitute serious infringements upon women's rights. The Committee urged the United States to completely decriminalise abortion and called for the removal of criminal penalties at federal, state, and local levels. It emphasised that prosecuting women and healthcare providers violates fundamental rights to life, privacy, equality, and freedom from cruel treatment (1).

The moral calibre of any civilised society can be measured by how it treats vulnerable groups and women, especially women. Women's rights are central indicators of societal justice and civilisation. According to a 2022 Pew Research Center survey, 72% of US adults support a woman's right to decide on abortion (2). Another survey showed only around 24% of American men and 15% of women support charging women who have abortions with murder (3), highlighting that equating abortion with homicide is a minority viewpoint, sharply at odds with mainstream values of autonomy and compassion.

Since the overturning of Roe v. Wade in 2022, several distressing cases have highlighted the severe consequences of criminalising abortion, turning women's personal tragedies into criminal offences (4). Nine US states now propose to classify abortion as homicide, potentially subjecting women to severe penalties, including the death penalty. Driven by extremist ideology, these proposals contradict mainstream public opinion and ethical standards, further isolating the US internationally.

It remains deeply troubling that women today continue to be victims of religious conflict and political agendas. It is vital that we unite broadly to oppose such legislation, which threatens medical ethics, human rights, and democratic values.

References
1. IPAS. UN experts say U.S. abortion bans violate human rights. 2023. https://www.ipas.org/news/un-experts-say-u-s-abortion-bans-violate-human...
2. Pew Research Center. America’s Abortion Quandary. 2022. https://www.pewresearch.org/religion/2022/05/06/americas-abortion-quanda...
3. Khaled F. Murder Charges for Women Getting Abortion Backed by 24% of Men: Poll. 2022. https://www.newsweek.com/murder-charges-women-getting-abortion-backed-24...
4. Rubin M.Texas prosecutor disciplined for allowing murder charge against woman who self-managed an abortion. 2024. https://www.texastribune.org/2024/03/01/Starr-county-district-attorney-a...

Competing interests: No competing interests

26 March 2025
Yong Wu
associate professor
Shenzhen Baoan Women's and Children's Hospital, Shenzhen, China
56 Yulv road, Shenzhen 518102, China
Re: Removing diversity, equity, and inclusion infrastructure in medicine, public health, and science: the cost of overcorrection Amy S Gottlieb, Reshma Jagsi. 388:doi 10.1136/bmj.r468

Dear Editor,

We share the conclusions of this article but want to add our concerns. The recent decision by the Trump administration to identify the words they don’t like to be used in official communication by civil servants or scientists, are no less than a kind of peekaboo, but this time, a decision with dramatic consequences. Flagging certain words like "racism", “health equity” or “injustice" raises significant issues. While the Trump administration is playing peekaboo, the reality is that injustice or inequities in health care and beyond still do exist. The problem is no one is allowed to denounce it or link certain politics to unfair allocation of means, chances or capabilities. These situations are damaging and hurt, especially “people in vulnerable situations”. Today in the US, conducting research on that, making reports of it and taking action to improve the situation in the field, is no longer possible, at least doing it openly. It sets a huge burden, not only for science and health care in the US but also abroad and for people worldwide collaborating with American scientists and healthcare professionals. Some institutions already change the names of their departments or units to escape censorship. Understandably, this means that the identity and scientific scope of these institutes is likely to disappear or induce a 'culture of double speak'.

Flagging words is an ideological gesture the Trump administration pretended to fight, shouting out loud how, in their view, “wokism” had put us in a situation where people were cancelled because they used certain vocabulary. While wokism had for sure certain radical outbursts, it had the merit of pointing us to existing discrimination of people, at an individual or systemic level. Playing peekaboo does not have this merit. It only puts us in a situation of censorship and denial of reality.

Using a list of flagged words is a symptom of what French philosopher Michel Foucault called the representation of a shift in the “episteme” of a certain era. As the shift in our era restricts the language available to scientists and healthcare workers, thereby limiting their ability to address and communicate about inequities and injustices in health care, we are worried about the repercussions for the future of science and health care in the US and globally. We are worried because if we are no longer able to address inequities and injustices effectively, the consequences will be dramatic. The potential negative impact on patient care and outcomes is huge. Next to that, censoring existing unfairness can reduce public awareness and understanding of critical social issues and therefore also the support of the public for policy making to reduce inequity and injustice, leading to more sickness, poorer quality of life and a higher mortality rate within society.

By raising our voices and keeping on telling the world the narratives which represent the ongoing reality behind the peekaboo, we want to challenge the atrocities of the Trump policies that undermine the ability to address health disparities and promote social justice. Foremost, we don’t do this because of certain political ideas. We simply want to safeguard the principles of equity, solidarity, justice, and integrity for patients in our healthcare systems since they are a matter of democracy and basic rights, which should be evident in our era. Unfortunately, they are not.

We therefore call scientists, scientific journals, health care professionals and policy makers to spread the word - pun intended - and withstand the evolution sketched above. We need to stand up against the censorship by engaging ourselves to fight against injustice and inequity, in health care and in society in general.

Competing interests: No competing interests

25 March 2025
Ignaas Devisch
Senior professor philosophy of medicine & ethics
Prof. Sara Willems, Prof. Em. Jan De Maeseneer, Prof. Oliver Van Hecke, Prof. Peter Decat, Prof. Ann van Hecke, Laurence Hendrickx, department of public health and primary care, Ghent University; Prof. Olivier Degomme, chair of the department of Public Health and Primary Care; Prof. Piet Hoebeke, dean of the faculty of medicine & health sciences, Ghent University; Prof. Em. Marleen Temmerman, UGent, Prof Aga Khan University, Nairobi. Kenya
Ghent University - Department of Public Health and Primary Care
Campus UZ Gent Ingang 42, 6K3 – Corneel Heymanslaan 10 9000 Gent – Belgium
Re: Risk of Bias in Network Meta-Analysis (RoB NMA) tool B Hutton, J M Wright, Areti-Angeliki Veroniki, P F Whiting, et al. 388:doi 10.1136/bmj-2024-079839

Dear Editor

Rethinking the Tools of Science: When "Subjective Judgments" Become the Invisible Enablers of Bias

Medical research is often likened to a compass that guides medical decisions. But if the compass itself is misaligned, the consequences can be fatal. Carole Lunny, et al. recently introduced RoB NMA, a new tool for assessing the risk of bias in network meta-analyses (NMA), which claims to identify "invisible vulnerabilities" in studies (1). However, as I perused the article, I found that a key issue was understated: the tool was highly dependent on the subjective judgment of the evaluator, which could turn "correcting" into "creating" bias.

The article emphasizes that the use of the RoB NMA requires "collaboration between clinical and methodological experts" and acknowledges the need for "a combination of professional judgment" in the assessment. This seems reasonable, but in fact it hides a contradiction. For example, when assessing whether an intervention is a reasonable combination, experts need to empirically judge the similarity of different treatment options. But in reality, experts' definitions of "similar" can vary wildly—some strictly by dose, others by mechanism. This subjectivity is a double-edged sword: it gives tools flexibility, but it also sows the seeds of disagreement.

More critically, the authors do not delve into how this subjectivity affects the reliability of the conclusions. Imagine that the same study is evaluated by different teams, and the conclusion may be "low risk" or "high risk," depending on the background of the experts. The paper mentioned that the median evaluation took 79 minutes, but it didn't say how to train the evaluators to reduce bias. Without uniform standards, tools can become bias amplifiers, turning supposedly objective scientific assessments into contests of expert intuition (2).

The root of such problems lies in the design logic of scientific tools. RoB NMA is like an "open recipe," with clear steps but customized condiments. For example, in deciding whether a study has publication bias, the evaluator must decide whether missing evidence affects the results. However, without quantitative thresholds or case-base support, such judgments are highly susceptible to being dominated by personal experience. When a tool relies too much on qualitative descriptions rather than quantitative indicators, its scientific nature may be diluted by subjectivity.

The solution is not to negate the value of subjective judgments, but to create guardlines for them. For example, a companion decision flow chart or a base of common dispute cases can be developed to help evaluators anchor judgment criteria. At the same time, the evaluation results of different teams on the same study are disclosed, and the tool is continuously optimized through data feedback. The progress of medical research needs tools, but the vitality of tools lies in "more accurate" rather than "once and for all."

The birth of RoB NMA is an important step, but if we ignore the "human" variable, even the perfect tool may fail in reality. The essence of science is to reduce uncertainty, not to wrap uncertainty into authority. Only when tools and human intelligence form a closed loop of "calibration-feedback" can we truly polish the compass of medical research.

References
1. Lunny C, Higgins J P T, White I R, Dias S, Hutton B, Wright J M et al. Risk of Bias in Network Meta-Analysis (RoB NMA) tool BMJ 2025; 388 :e079839 doi:10.1136/bmj-2024-079839
2. Hess, Konstantin, et al., "Efficient and Sharp Off-Policy Learning under Unobserved Confounding." arXiv preprint arXiv:2502.13022 (2025).

Competing interests: No competing interests

25 March 2025
Du Zhicheng
PhD candidate
Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
Shenzhen
Re: Amend the Children’s Wellbeing and Schools Bill to protect children from assault Andrew G Rowland, Grace Hastie. 388:doi 10.1136/bmj.r566

Dear Editor

After banning corporal punishment, what else do we need to do?

Every child deserves to grow up in safety, but how can the law truly be their shield? A recent opinion article called for an amendment to the bill to ban corporal punishment of children in England altogether (1). This is undoubtedly a big step forward, but after reading the article, I felt a little uneasy: If the law is passed, then what?

The core logic of the article is clear and powerful—to remove the "reasonable punishment" defense and free children from violence just as much as adults (2). The authors support this with positive data from other countries that have banned corporal punishment, such as Finland and Sweden, where rates of corporal punishment have declined. This is compelling, but the problem is that these countries did not succeed solely on the basis of a ban. There is a whole support system behind them, from rental education to changing social attitudes. The article says almost nothing about it.

Will a law banning corporal punishment end violence?
The authors' assumption that changes to the law will automatically lead to behavioral change may be too optimistic. Imagine that a parent who is used to beating and scolding is suddenly told that "this is illegal, but there are no alternative methods; the result may be twofold: either fear of the law to suppress emotions, accumulating greater family conflicts, or going "underground" and hiding the violence. The real challenge is not the legislation itself, but getting it on the ground.

More important than a ban is teaching people "how not to use corporal punishment."
Corporal punishment often stems from a sense of powerlessness—when parents or teachers don't know how to respond to a child's behavior, violence becomes the quickest "solution." After the prohibition of corporal punishment, society needs to provide more specific tools. Schools have added emotional management courses to help teachers deal with classroom conflict. The cost, resource allocation, and policy coherence of these measures are not covered in the article. Without support, laws can become castles in the air and even add to educators' frustration.

Beyond the law, a 'gentle revolution' is needed.
The deeper problem is that the legitimacy of corporal punishment has long been rooted in the cultural notion of "spare the rod, spoil the rod." Laws can be changed overnight, but it takes time to change hearts. The article, on the other hand, only focuses on the parliamentary vote but ignores the importance of mass mobilization and cultural reconstruction. Without public support, the new law may face enforcement resistance and even be stigmatized as "government interference in parenting."

Conclusion: Give the law a pair of walking shoes.
A ban on corporal punishment is necessary, but the law cannot go it alone. What is needed is not just a ban but a one-two punch: from a family education resource pack to a community support network to a reshaping of public awareness. Only in this way can the law be transformed from justice on paper into a smile on the face of a child. Otherwise, the perfect article may stumble in reality—and the price will eventually be borne by the child.

References
1. Rowland A G, Hastie G. Amend the Children’s Wellbeing and Schools Bill to protect children from assault BMJ 2025; 388 :r566 doi:10.1136/bmj.r566.
2. Smith, Anne B. "The state of research on the effects of physical punishment." Social Policy Journal of New Zealand 27 (2006): 114.

Competing interests: No competing interests

25 March 2025
Du Zhicheng
PhD candidate
Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
Shenzhen
Re: NHS England: Government abolishes quango that “delivered less care at huge cost” Zosia Kmietowicz. 388:doi 10.1136/bmj.r521

Dear Editor
The Lansley reforms could have been very successful if combined with a financial uplift of around 30% . It was never going to happen.

Competing interests: No competing interests

25 March 2025
Simon Price
retired GP
nil
Chichester
Re: Medical journals should use the term “public health and social measures” Azeem Majeed, Kamran Abbasi. 388:doi 10.1136/bmj.r409

Dear Editor,

I thank Professor Yong Wu for highlighting key points from our recent article advocating the shift from "non-pharmaceutical interventions" (NPIs) to the more descriptive and inclusive term "public health and social measures" (PHSMs).

As Professor Wu emphasises, the Covid-19 pandemic has underscored the critical role that comprehensive public health strategies play. China's "dynamic zero-Covid" strategy aimed to integrate traditional public health approaches with innovative solutions such as rapid contact tracing, big data analytics, and active community participation. I agree with Professor Wu that categorising such nuanced strategies merely as NPIs inadequately conveys their complexity and importance.

I also appreciate Professor Wu’s recognition of the risks associated with prematurely relaxing these measures, as shown by the spike in global cases following the emergence of the Omicron variant. This illustrates the continued necessity and effectiveness of PHSMs, even in a context where vaccines and other pharmaceutical interventions are available.

Professor Wu’s point regarding the potential negative implications of overly restrictive or prolonged measures is also important. It reinforces the need for balanced and nuanced communication to ensure that public health measures are proportionate, equitable, and sensitive to their economic and social impacts. The shift in terminology from NPIs to PHSMs is indeed intended to facilitate clearer public understanding, promote interdisciplinary collaboration, and emphasise the social dimensions integral to the success of these interventions.

I appreciate Professor Wu’s support for this terminological shift and echo the call for a continued evolution in our language and practices in public health. Such changes not only improve clarity and consensus but also support more effective, equitable and sustainable public health strategies moving forward.

Competing interests: No competing interests

24 March 2025
Azeem Majeed
Professor of Primary Care and Public Health
Imperial College London
Department of Primary Care and Public Health, Imperial College London, London W12 0BZ
Re: Impact of child weight management pilots was hindered by poor uptake, evaluation finds Elisabeth Mahase. 388:doi 10.1136/bmj.r567

Dear Editor:

We are submitting this Rapid Response to share insights based on our experience in community-based children's health management in China. We hope to offer valuable suggestions that could help improve the uptake and completion rates of weight management programmes for children in England. The details are as follows:

Enhancing Children's Weight Management
Elisabeth Mahase calls for increased government investment to enhance the uptake and completion rates of children’s weight management programmes in England (1). Recently, we have been working on community-based child health management projects and have encountered similar challenges. Based on our experience, we offer the following recommendations:

First, family support: Families are a critical support system in managing children's health, and parental education plays a key role in helping children adopt healthier eating and exercise habits. We recommend developing an Artificial Intelligence (AI)-based Family Support System for Child Weight Management, which would include features such as health education, smart reminders, personalized guidance, real-time optimization, progress tracking, a rewards mechanism, and online social and psychological support (2). This system would enhance engagement, responsibility, and motivation among children and their families, increase uptake rates, and improve completion outcomes.

Second, community collaboration: Given the disparities in resources and socioeconomic backgrounds between urban and rural areas in England, it is recommended to strengthen community-level collaboration alongside family support systems (3). By offering localized health management initiatives tailored to the specific needs of each region, uptake rates and long-term outcomes can be improved, particularly in low-income communities and among minority ethnic groups. These initiatives could include support groups, parent education workshops, low-cost activities such as jogging, skipping, and community sports events, as well as simple, practical cooking techniques using locally available ingredients.

Third, school involvement: Schools play a crucial role in fostering healthy lifestyles among children. In addition to offering healthy school meals, essential knowledge about nutrition, physical activity, and mental well-being should be integrated into the curriculum. Regular weight management sessions, using interactive methods, help children understand the importance of healthy eating and exercise. Active school involvement will create a supportive environment, providing children with offline social and psychological support (4). These measures will help facilitate recruitment and promote long-term engagement.

Above all, we recommend developing an AI-based Family Support System for Child Weight Management, combined with community collaboration and school involvement, to create a seamless online-offline experience that would enhance both uptake and completion rates in weight management programmes. While AI systems require a significant upfront investment, they could provide broad, long-term support, helping numerous families overcome weight challenges and fostering lasting lifestyle changes. Furthermore, we recommend prioritizing the promotion of cost-effective, high-quality weight management products through targeted advertising, tangible rewards, and incentives. This approach would reduce government spending while improving programme effectiveness, ultimately leading to more sustainable outcomes.

Reference
1.Mahase E. Impact of child weight management pilots was hindered by poor uptake, evaluation finds. BMJ. 2025;388:r567. doi:10.1136/bmj.r567
2.Majekodunmi A. Future applications of artificial intelligence in primary care. BMJ. 2024;385:q1215. doi:10.1136/bmj.q1215
3.Skouteris H, Marmot M, Bessell S. Creating child-inclusive societies. Lancet Child Adolesc Health. 2025;9(1):71-76. doi:10.1016/S2352-4642(24)00254-2
4.Luttinen J, Watroba A, Niemelä M, Miettunen J, Ruotsalainen H. The effectiveness of targeted preventive interventions for depression symptoms in children and adolescents: Systematic review and meta-analyses. J Affect Disord. 2025;376:189-205. doi:10.1016/j.jad.2025.02.002

Authors
Lan Yang, Department of Pediatrics, People’s Hospital of Funing, Yancheng, China (https://orcid.org/0009-0008-3249-7564). Electronic address: yanglan_yaoli@163.com.
*Guodong Ding, Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (https://orcid.org/0000-0001-6576-9361). Electronic address: dingguodong@sjtu.edu.cn.
Contributors
L.Y. and G.D. contributed equally.
Declaration of Interest Statement
The authors have no conflicts of interest to declare.

Competing interests: No competing interests

24 March 2025
Guodong Ding
Pediatrician
Lan Yang
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
1665 Kongjiang Road, Shanghai 200092, China
Re: Multiple sclerosis: Investigation into side effects of switching patients to natalizumab biosimilar Elisabeth Mahase. 388:doi 10.1136/bmj.r403

Dear Editor,

We are writing to respond to the above article.

We appreciate the author’s shared experience at a particular centre in a London-based hospital under the Imperial College Healthcare NHS Trust, where patients with multiple sclerosis (MS) underwent a treatment switch from Tysabri® (reference natalizumab; Biogen) to Tyruko® (biosimilar natalizumab; Sandoz). No details regarding frequency and severity of the reported adverse events (AE), their outcome and medical assessments were provided in the above publication.

We would like to highlight the following points for consideration:

1. Tyruko® was approved in the EU on 22 September 2023 following a thorough biosimilarity assessment compared with the reference biologic, Tysabri®. Extensive data are available from in vivo and in vitro studies to demonstrate this biosimilarity, with no clinically meaningful difference to Tysabri® in clinical efficacy, safety, and immunogenicity of Tyruko® was observed [1] [2].

2. Tyruko® is available in 9 European countries with an estimated patient exposure till 31 January, 2025 of 4,941 patient treatment years (PTY). Sandoz performs ongoing signal detection activities, the results of these are submitted to EMA and other Global Regulatory Agencies through Periodic Safety Update Reports. Based on these safety assessments, the benefit–risk balance of Tyruko® remains positive, and its safety profile is consistent with product information and the natalizumab reference biologic.

3. Based on our analysis of post-marketing AEs reported to Sandoz’s safety database from first approval until 31 January 2025, the high number of AEs reports from the UK is not in line with AE reports from other European countries where Tyruko® is marketed.

4. Our assessment of the available safety information including these reports from the UK could not establish a potential worsening of underlying MS. Review of reported signs and symptoms as AEs do not commensurate with a particular medical diagnosis or syndrome.

5. Sandoz is collaborating with the MHRA to obtain more complete information on these initial AE reports, including the reporting centre(s), laboratory/diagnostic details, severity and outcome to enable a thorough medical assessment.

6. Sandoz has thoroughly assessed the product quality aspects of the batches used in the UK and no product quality concerns have been identified.

The natalizumab reference biologic and biosimilar are interchangeable where Tyruko® has been launched, including the UK, with no clinically meaningful differences between the two drugs in terms of safety and efficacy.

Tyruko® is the first biosimilar of natalizumab for MS [2]. Published data show that any change of treatment in patients with MS is associated with uncertainty [3], including a switch to a new biosimilar medicine. Further, media reports without supporting evidence can lead to an increase of AE reports of nocebo effects attributed to a particular treatment [4,5]. Potential stimulation of AE reports for Tyruko® related to nocebo effects could occur.

Post-marketing cumulative patient exposure of Sandoz biosimilars exceeds 1.5 billion patient treatment days, and a favourable benefit–risk profile consistent with reference biologics have been demonstrated for Sandoz biosimilars [6]. First real-world evidence has shown that switching from reference biologic to biosimilar natalizumab is safe [7] and further publications from Europe and UK sharing safety experience of switch to natalizumab biosimilar are anticipated.

Sandoz would like to re-assure healthcare professionals (HCPs) and patients that as per regulations it is performing an ongoing evaluation of safety information received by the company and will communicate any change in the benefit–risk balance of Tyruko® to the relevant agencies, HCPs and patients.

Sincerely,

Michael Wiechmann
Global Medical Affairs

Amit Kubavat
Global Program Safety Lead

References
1 Selmaj K, Roth K, Höfler J, et al. Introducing the Biosimilar Paradigm to Neurology: The Totality of Evidence for the First Biosimilar Natalizumab. BioDrugs. 2024;38:755–67. doi: 10.1007/s40259-024-00671-4
2 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. JAMA Neurol. 2023;80:298–307. doi: 10.1001/jamaneurol.2022.5007
3 Manzano A, Eskyté I, Ford HL, et al. Patient perspective on decisions to switch disease-modifying treatments in relapsing-remitting multiple sclerosis. Mult Scler Relat Disord. 2020;46:102507. doi: 10.1016/j.msard.2020.102507
4 Barsky AJ, Saintfort R, Rogers MP, et al. Nonspecific medication side effects and the nocebo phenomenon. JAMA. 2002;287:622–7. doi: 10.1001/jama.287.5.622
5 MacKrill K, Morrison Z, Petrie KJ. Increasing and dampening the nocebo response following medicine-taking: A randomised controlled trial. J Psychosom Res. 2021;150:110630. doi: 10.1016/j.jpsychores.2021.110630
6 Sagi S, Anjaneya P, Kalsekar S, et al. Long-Term Real-World Post-approval Safety Data of Multiple Biosimilars from One Marketing-Authorization Holder After More than 18 Years Since Their First Biosimilar Launch. Drug Saf. 2023;46:1391–404. doi: 10.1007/s40264-023-01371-8
7 Brustad AW, Høgestøl E, Meling M, et al. Real-world safety of switching from originator to biosimilar natalizumab. ECTRIMS 2024 – ePoster. Multiple Sclerosis Journal. 2024;30(3_suppl):681-1137. doi:10.1177/13524585241269221

Competing interests: No competing interests

24 March 2025
Michael Wiechmann
Global Medical Head - Sandoz AG
Amit Kubavat, Global Program Safety Lead
Sandoz AG, Centralbahnstrasse 4, 4051 Basel / CH

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