PAS Statement on the Publication of the NICE Guideline

STATEMENT FROM THE PERNICIOUS ANAEMIA SOCIETY ON THE PUBLICATION OF THE NICE GUIDELINE

Vitamin B12 deficiency in over 16s: diagnosis and management 6^th March 2024

The Pernicious Anaemia Society welcomes the publication of the NICE vitamin B12 deficiency guideline. We sincerely hope this NICE guideline will lead to a better awareness, increased education and better knowledge in the health care profession. We also call for dedicated research in this area. This must be the start to better diagnosis and treatment for people who have a B12 deficiency regardless of the cause of that deficiency.

As key stakeholders in the process, we appreciate the work the NICE Committee has put in. We are grateful for their adoption of many of our comments and their acknowledgement of our feedback during the process.

The Pernicious Anaemia Society is the charity which originally petitioned for a NICE guideline on Pernicious Anaemia, and we are disappointed that during the formation of the NICE Committee and in the early meetings, the focus moved to a more general NICE guideline on B12 deficiency as a symptom and not Pernicious Anaemia as a condition. We believe there is still a need for better guidance on the diagnosis, treatment, and ongoing monitoring of Pernicious Anaemia.

We remain concerned by two significant points which, in our view, have not been addressed adequately during this process.

The first is that the NICE Committee have consistently refused to acknowledge the use of the term Pernicious Anaemia throughout the guideline as the name of the condition. We understand that the term ‘Pernicious Anaemia’ has limitations, notably in cases where anaemia may not be present, the fact that the condition is no longer pernicious (meaning deadly), and its failure to clearly denote the intrinsic factor deficiency aspect of the condition.

Our primary concern centres on the NICE Committee’s decision to avoid the term ‘Pernicious Anaemia’ in favour of ‘autoimmune gastritis’. This is fundamentally flawed, as it is possible to have autoimmune gastritis without Pernicious Anaemia, with Pernicious Anaemia typically manifesting in the later stages of the condition. Furthermore, the UK does not routinely conduct endoscopies for individuals suspected of having Pernicious Anaemia as a means of diagnosing autoimmune gastritis. Notably, a survey involving over a 1000 individuals with Pernicious Anaemia revealed that only 9% had undergone an endoscopy. This reclassification neglects the condition’s historical name, under which many in the UK have been diagnosed and which patients and doctors are familiar with. It also overlooks cases where individuals exhibit positive autoimmune Intrinsic Factor Antibody tests without signs of gastritis. This approach by the NICE Committee will lead to further confusion and exclude or misrepresent a significant portion of the affected population.

The rationale provided for this shift — ‘PA in its true sense of life-threatening anaemia’ — neglects the fact that untreated PA can indeed result in anaemia and ultimately a fatal outcome. This justification, as the reason not to call the condition Pernicious Anaemia, is doing a huge disservice and will cause psychological damage to those with this as their current diagnosis.
Furthermore, the NHS, existing research and various healthcare guidance publications predominantly refer to the condition as Pernicious Anaemia, not autoimmune gastritis. This points to a significant disconnect between the NICE guideline and current medical practice and literature. This discrepancy introduces more confusion than the current lack of specificity in the name. Many research papers and review papers that refer to Pernicious Anaemia have formed part of the material the NICE Committee used to prepare this NICE guideline. The insistence by the NICE Committee on what seems to be a desire to ‘cancel’ or diminish the use of Pernicious Anaemia is both a mystery and a disappointment to our Society.

While we acknowledge the complexities and imperfections associated with the term ‘Pernicious Anaemia’, we express concern over the sudden and unclear reclassification proposed by the NICE guideline. We believe that maintaining the use of ‘Pernicious Anaemia’ in the NICE guideline is crucial for avoiding confusion and ensuring that both patients and healthcare professionals have clear, consistent guidance on the diagnosis and management of this condition.

Looking ahead, should there be a drive towards renaming the condition, such an initiative must be approached with thought. It necessitates a precise dissemination strategy and must encompass patients and clinicians in the decision-making process for the name change. Engaging with these key stakeholders is crucial to ensure any change is meaningful and accepted and avoids negative repercussions for patients and healthcare professionals. Without such action, a name change risks misunderstanding and misdiagnosis, impacting patient care.
Our second concern is that the NICE guideline is limited to Over 16’s due to lack of evidence for children and young adults. With growing interest in plant-based diets, highly processed diets, and current financial impacts on people being able to afford a healthy diet, as well as the possibility of autoimmune conditions in under 16s we feel that greater effort to find the necessary expertise in this area should have been found to advise the NICE Committee. In the alternative, the NICE guideline should at least recommend future research and an additional NICE guideline for children and young adults.

Despite our concerns, there are some good outcomes in the NICE guideline, in particular:

• The reminder to know and treat the patient as an individual.
• The statement that vitamin B12 replacement dose, frequency and method of delivery may need to be adjusted or changed for it to work properly.
• The importance of continuing with treatment so symptoms do not return or get worse and, for those with autoimmune gastritis (and for this must be interpreted to include the term Pernicious Anaemia whether with or without a positive IFA) is lifelong.

We welcome the recommendation¹ that diagnostic testing for B12 deficiency should be based on one common symptom and one risk factor. We appreciate that GP’s might push back against this, fearing an increase in workload and costs. We accept there could be reasons for similar symptoms, but it is our experience, through our membership feedback, that delays in diagnosis and unnecessary referrals and tests are far more costly and draining on a GP’s time than ruling out a B12 deficiency and trialing treatment. As stakeholders we would have preferred for the list of symptoms to be more inclusive of the many that are listed on our website and for the risk factor to carry less weight than symptoms because we fear that with a too formulaic application of this recommendation, there remains the possibility that diagnosis will be delayed or missed.

We welcome the inclusion of Active B12 (serum holotranscobalamin) to the initial test for diagnosis as routine and hope that those providing the assay testing will invest in more accurate and aligned ranges. There needs to be greater awareness in the healthcare profession of the limitations of the Serum and Active B12 tests. We also support the advice to test before B12 replacement has begun and for clinicians to take into account any B12 replacement which the patient already started. We know that many of our members first try to resolve their own symptoms by dietary changes with fortified foods and drinks or supplements, especially since these are often promoted in the media. This can skew their test results. However, the NICE guideline is not clear enough in this area for people with Pernicious Anaemia where deficiencies in iron and folate as well as other vitamins and minerals might also be indicating factors.

We welcome the table simplification² of thresholds for interpretating B12 deficiency results but would caution healthcare professionals from over-reliance on the cut-off points and in their use of this NICE guideline since treating symptoms is far more important to the patient than a certain number, especially when the test results are not reliable.

We welcome the recommendation that an IF Antibody test³ be carried out only if a previous positive test has not already been done. We note the important confirmation⁴ that a negative test does not rule out autoimmune gastritis or Pernicious Anaemia. Our members frequently report requests by GP’s to repeat IFAb tests or to carry out new tests on seeing a different doctor or changing surgeries. We are also aware that many initial tests for our members have been lost or not documented. It is completely unnecessary to repeat or request IFAb tests if treatment is reported as working (i.e. resolving symptoms) by the patient. A better and more accurate test for IF Antibodies needs to be developed.

We welcome the acknowledgement⁵ that symptoms can take a long time to improve and may get worse initially.

We see as a positive reminder to the healthcare profession, the recommendation for treatment for malabsorption as a confirmed or suspected cause⁶ is lifelong intramuscular B12 replacement for those with autoimmune gastritis/Pernicious Anaemia. We sincerely hope that there will be a significant reduction in incidences of our members contacting our charity where GP practises stop treatment, threaten to stop treatment, or insist on change from injections to oral dosing without any basis or evidence of the need for such a change.

We welcome the recommendation that in the cases of ‘other causes of malabsorption’ the guideline offers the option of both high dose (1mg) oral replacement and injections. We also note the acknowledgement throughout the process of preparing this NICE guideline that there is no evidence that oral doses are as effective as intramuscular injections. This vital message must be communicated to primary care who regularly misquote research or mislead patients in this area. We remain concerned however that the NICE guideline does not adequately address the causes of malabsorption and do not mention important conditions like Crohn’s, Colitis etc.

Regarding malabsorption and the use of oral replacement, we question the logic that if there is a malabsorption cause, how can oral dosing be sufficiently effective for severe symptoms? The Pernicious Anaemia Society would like to see further research into this area and until there is clarity patients should be offered injections to treat severe symptoms of B12 deficiency regardless of the cause.

We welcome the recommendations for research about self-administration⁷ either intramuscular or sub-cutaneous. This is an important step to giving people with Pernicious Anaemia control back over their lives and relief from their symptoms. Research into self-administration will lead towards more constructive and flexible dosing according to the return of symptoms, whilst relieving the pressure on appointments at GP practises.

We are pleased to see a recommendation about follow-up appointments to discuss symptoms and improvement (if any) and hope that this is put in place. There is a real need for constructive conversations to take place between GP’s and patients about dosage and frequency that improve the quality of the patient’s life. We know from our member feedback that following a diagnosis of Pernicious Anaemia, routine follow up appointments are not offered. Rarely is there any constructive consideration taken by the GP to amending treatment when there is a change of circumstances, additional health issue diagnosis, or return of symptoms.

Regarding stopping treatment⁸ we see it as very important to remind GP’s that it is only an option if symptoms have resolved and the cause has been addressed. If the diagnosis is Pernicious Anaemia the cause will never be addressed and treatment is lifelong. We also welcome the very clear statement⁹ about not repeating initial diagnostic testing for people on Vitamin B12 replacement. It is clear from this NICE guideline¹⁰ that the best way forward is to increase frequency of injections until symptoms are resolved.

We welcome the recommendations about monitoring¹¹ for people with autoimmune gastritis/Pernicious Anaemia to have a referral to gastroenterology. However, since the risk of gastric tumours is higher in those with Pernicious Anaemia and very difficult to detect until late stage, we would have preferred to have seen a more active primary care follow up recommended for people with a diagnosis of Pernicious Anaemia. As an example, a review every 3-5 years to discuss symptoms and provide advice to the patient on what to look for in terms of symptoms for gastric cancer, would seem to be a good starting point. We welcome the call for research on what should be included in a follow up and monitoring gastric cancer¹².

The Pernicious Anaemia Society fully supports the recommendations for further research recommended in the NICE guideline on B12 deficiency and would like to see these recommendations and those identified in the James Lind Alliance Priority Setting Partnership on Pernicious Anaemia prioritized for funding. Many of our members would be delighted to see research into more cost effective, simplified administration and controlled dosing/frequency of their vitamin B12 replacement. They would embrace the opportunity to avoid having sometimes painful intramuscular injections if a replacement effective delivery system can be developed for those who cannot absorb through digestion or supplementation. Improvements that put the control of symptoms and administration of replacement B12 in the hands of the patient will contribute to better quality of life and reduce the drain on cost and time for GP’s.

The work the Pernicious Anaemia Society did with the James Lind Alliance identified that better tests for identification of the cause of B12 deficiency are vital. It is shameful that here in the UK we are worse off today in diagnosing Pernicious Anaemia than we were in the 1980’s since no adequate replacement for the Schilling test has been funded or developed.

We are grateful that the publication of this NICE guideline gives organisations like the Pernicious Anaemia Society, other research specialists like those in cluB-12 and many others who represent patient groups, the opportunity to raise awareness, dispel myths and improve the day to day lives of people who suffer with debilitating symptoms caused by a B12 deficiency.

Find the NICE Guideline here.