New guidance for safe prescribing of DMARDs

Article kindly written by Lindsay Turner, Clinical Guidelines Programme Manager, British Society for Rheumatology

Replacing previous guidance from 2017, BSR have undertaken a major review and expansion of their csDMARDs clinical guidelines. The update is based on new evidence and expert consensus and now covers people of all ages with rheumatic disease. 

Shared care

A clear infographic accompanying the guidelines offer a quick-access summary of the key messages. The flow diagram below shows an example of the recommended collaborative management between primary care and specialist providers, although local shared care agreements should be determined by individual ICB commissioning pathways and negotiations between secondary care trusts and primary care providers. 

Recommendation 29    

The management of patients on csDMARD therapy should be a collaborative effort between primary care and specialist rheumatology providers. A shared care protocol should be agreed upon (including in the paediatric age group when shared care exists) delineating the responsibilities of each party (GRADE 1C, SoA 100%). 

Once a patient is stable on csDMARD therapy and agrees to a shared care plan, their secondary care team can submit a shared care request to the patient’s primary care provider. If the primary care team accepts the request, along with the relevant decision form and monitoring schedule, they can assume responsibility for prescribing and monitoring csDMARD therapy. 

The authors acknowledged that there are not shared care documents in place universally for children and young people and hope that, by including them in this guideline and unifying their care, where possible, this will help a move towards wider coverage for shared care agreements.

Blood monitoring

A key area that has been updated in the guidelines is around blood monitoring. Real-world experience gathered during the COVID-19 pandemic has allowed the new guidance to recommend a relaxation of previously more frequent monitoring schedules for most patients; balancing safety with practicality.

When rheumatology specialist teams hand over prescribing to primary care, they will be advising blood monitoring frequency based on the patient’s likelihood of having abnormal blood results or toxicity, which will take account of risk factors – including (but not limited to): cytopenia; raised liver enzymes during initiation phase; CKD stage 3 or worse; age; other medications.

All prescribers, including those in primary and secondary care, should assess changes to a patient’s health status (e.g. hospital admission, changes in medication, or new symptoms indicative of toxicity) which may prompt a reassessment of monitoring requirements. Changes to monitoring should be shared between primary and secondary care via the shared care pathway.

Recommendation 31

Prescribers should assess risk factors for csDMARD toxicity at least annually, adjusting the frequency of monitoring according to the level of risk identified. Changes in risk factors should be communicated between primary care and specialist rheumatology providers (GRADE 1C, SoA 98%). 

Safe prescribing

Methotrexate (MTX) is the most commonly prescribed csDMARD and has a narrow therapeutic index, meaning there is a small margin between its effective and toxic doses. High doses can result in life-threatening adverse events. The common causes of harm related to MTX include prescriptions of the wrong frequency of dose, a lack of/poor monitoring, issues with transfer of care (e.g. hospital admission and discharge) and shortcomings in communication with patients. 

In response to the persistence of such errors, the European Medicines Agency issued new guidance, including providing patients with a reminder card to emphasize the once-weekly schedule and encourage recording their specific day of intake so that patients are less likely to inadvertently take MTX more frequently than intended. 

Co-prescription of folic acid supplementation at a minimum dose of 5 mg per week is also strongly recommended for patients on MTX therapy. Evidence indicates that folic acid significantly reduces the risk of gastrointestinal side effects.

A further cause of considerable harm from one-weekly MTX can arise from inadvertent prescribing of 10 mg instead of 2.5 mg tablets. Only 2.5 mg tablets should be prescribed for adult patients with systemic autoimmune rheumatic diseases (SARDs).

Recommendation 11a

Before prescribing methotrexate, make sure that the patient is able to understand and comply with once-weekly dosing (GRADE 1C, SoA 100%).

Recommendation 11b

All patients on methotrexate should have an agreed day of the week for dosing and be co-prescribed folic acid supplementation at a minimum dose of 5 mg once weekly, not on the day of methotrexate (GRADE 1B, SoA 100%).

Vaccinations

The updated guidelines also provides a series of very helpful recommendations and broad information on vaccinations for those with SARDs. The guidelines recommendations align with The Green Book, which incorporates recommendations from the Joint Committee on Vaccination and Immunisation (JCVI). For example, MTX should usually be withheld for up to 2 weeks following influenza or COIVD-19 vaccination in adults, but the decision to withhold MTX must carefully balance the potential benefits against the risk of SARD flares:

Recommendation 10

Following influenza or COVID-19 vaccination in adults, methotrexate should be withheld for up to two weeks, assuming disease activity/risk of flare allows. In the paediatric age group, this is up to the discretion of the clinician and an individualized approach is needed (GRADE 1A, SoA 99%).

Rheumatology teams are encouraged to focus on patient education related to vaccinations, and clear communication with primary care providers.

Serious infections and csDMARDS

Intercurrent infections are a well-recognized concern in individuals with SARDs, with both the underlying disease and immunosuppressive therapies contributing to increased susceptibility. These infections can be more severe, necessitating prompt and aggressive treatment. For patients with serious infections (for example, those requiring intravenous antibiotics or hospitalization) it is recommended to temporarily discontinue immunosuppressive drugs until the patient has recovered from the infection.

Recommendation 20

Intercurrent infection: During a severe infection (e.g. requiring intravenous therapy or hospitalization), csDMARDs should be temporarily discontinued until the patient has recovered from the infection (GRADE 1B, SoA 98%). 

Retinopathy

New evidence has also led to updated recommendations regarding retinopathy monitoring for those taking hydroxychloroquine, which have adopted the guidance from the Royal College of Ophthalmology:

Recommendation 13a

All patients who have taken hydroxychloroquine for the equivalent of 5 years of continuous treatment or more should have annual retinopathy monitoring (GRADE 1B, SoA 100%). 

Recommendation 13b

Patients who are at high risk of hydroxychloroquine retinopathy should have annual monitoring after 1 year of use. High risk factors include: tamoxifen use, in adults hydroxychloroquine doses >5 mg/kg actual body weight, renal impairment, e.g. eGFR <60 mL/min/1.73 m2  and prior chloroquine use (GRADE 1B, SoA 99%).

Resources

Along with the new guidelines there are a number of resources to help break down the important updates and to implement them in practice, including a podcast and video interview with the authors, the infographic summary diagram and a presentation by the guidelines lead explaining what’s new. These can be freely accessed on the BSR’s guidelines homepage or by logging in to their free e-learning platform to view the complete guideline collection.