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Disease Modifying Anti-Rheumatic Drugs- DMARDs

What are they?

DMARDs are inhibitors of the immune response used to suppress disease activity in various inflammatory rheumatic diseases.

There are conventional DMARDs (cDMARDs) and biologic DMARDs (bDMARDs).

There are shared care protocols available for therapies used in the management of rheumatological conditions.

Formulary | Lothian Joint Formulary (nhs.scot)

What are the most commonly used cDMARDs?

The doses and mode of administration of the most commonly used DMARD are summarised below

Drug Typical DoseRoute of administration
Methotrexate 7.5-25mg once a week Oral or SC
Sulfasalazine 1g-4g / day in divided doses Oral 
Leflunomide 10-20mg /day Oral 
Azathioprine 50-150mg /day Oral 
Hydroxychloroquine 200-400mg /day Oral 
Mycophenolate Mofetil2-3gm/dayOral

Do patients on cDMARDs require blood monitoring?

Most DMARDs require some blood monitoring. During induction of treatment, frequent monitoring is required but this can be reduced once the dose has been stabilised, see below

 DrugBloodsFrequency 
 MethotrexateFBC LFTs UEs Two weekly for 6 weeks, then monthly until the dose has been stable for 3 months, then 3 monthly provided the dose remains stable.
Sulfasalazine FBC LFTs UEs Two weekly for 6 weeks, then monthly until the dose has been stable for 3 months, then 3 monthly for 12 months provided the dose remains stable. After 12 months routine monitoring can be stopped.
Leflunomide FBC LFTs UEs Blood pressure monitoring   Two weekly for 6 weeks, then monthly until the dose has been stable for 3 months, then 3 monthly provided the dose remains stable.
Azathioprine FBC LFTs UEs Two weekly until the dose has been stable for 6 weeks, then monthly until the dose has been stable for 3 months, then 3 monthly provided the dose remains stable.
Hydroxychloroquine  Blood monitoring not required. Patients should be reviewed by an optometrist after five years of treatment and annually thereafter.   Test includes OCT( Optical Coherence Tomography) and widefield fundus autofluorescence imaging (FAF)   Annual monitoring is recommended after five years because the incidence of ocular toxicity prior to this is low.    
MycophenolateFBC LFTs UEs Two weekly until the dose has been stable for 6 weeks, then monthly until the dose has been stable for 3 months, then 3 monthly provided the dose remains stable.

What are the main side effects and what should be done if they occur?

InfectionImmunosuppressants can be associated with an increased infection risk. If there is active infection- please stop all DMARDs. Exception to this rule being Hydroxychloroquine and Sulphasalazine,
BreathlessnessRarely methotrexate can cause hypersensitivity pneumonitis which presents with cough and breathlessness. If the patient becomes breathless methotrexate should be stopped immediately. Assess for chest infection. If no infection and still breathless contact rheumatology.  
Abnormal LFTALT rise can occur with methotrexate, sulfasalazine, leflunomide, mycophenylate and azathioprine. If the ALT >2X upper limit of normal follow  abnormal LFT algorithm.  
Reduced WBCThis can occur with methotrexate, sulfasalazine, leflunomide, mycophenylate and azathioprine. See abnormal FBC algorithm.  
Reduced platelet countThis can occur with methotrexate, sulfasalazine, leflunomide, mycophenylate or azathioprine. See abnormal FBC algorithm.  
MacrocytosisMild macrocytosis (MCV 98-104) does not require any action. If MCV is greater than 105, check B12, folate and thyroid function and treat any underlying abnormality.  

Vaccination:

Non-live vaccines can be safely administered to patients on immunosuppressive medication and it is recommended that all patients on DMARD be offered pneumococcal and influenza vaccines.

Live vaccines are contraindicated in patients on immunosuppressive medication.

Pregnancy:

Details on: Pregnancy, DMARDs and Biologic Therapies (nhslothian.scot)

DMARDs to stop: Methotrexate, leflunomide and mycophenolate are contraindicated during pregnancy and should be stopped if the patient is planning a pregnancy. Women of childbearing age on these medicines must use effective contraception.    
DMARDs safe in pregnancy : Hydroxychloroquine is safe during pregnancy and can be continued. Sulfasalazine is generally considered to be safe, but discuss with rheumatology service if the patient wishes to get pregnant. Azathioprine can also be used in pregnancy after a careful risk assessment (please discuss with rheumatology service). Anti-TNF drugs  

Surgery:

Perioperative Management Guideline for DMARDs and Biologics

  cDMARDs: There isn’t any evidence to suggest  cDMARDs increase the risk of infection or significantly alter wound healing after surgery and therapy can usually be continued as normal. If needing to stop cDMARD- they can be stopped 1-2 weeks prior to surgery and restarted post operatively provided there is no infection  
  Biologics: These will need to be stopped prior to surgery and can be restarted post surgery if there is no active infection  

M.A & H.B/S.R 25-01-24