1. Monitoring of DMARDS and use in pregnancy.
Dr Sarah Levy
Consultant Rheumatologist
CUH.

2. Recent guidelines
Hydroxychloroquine Retinopathy screening. February 2018.
BSR and BHPR guideline for the prescription and monitoring of non-biologic disease- modifying anti-rheumatic drugs. June 2017
BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding—Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Sept 2016

3. DMARD monitoring
Common DMARDS – Methotrexate, Leflunomide, Sulphasalzine, Hydroxychloroquine, Azathioprine, Mycophenolate Mofatil.
Less commonly used - Tacrolimus/Ciclosporin/MepacrineApremilast
Generic advice
Additional screening

4. Generic recommendations for all DMARDS.
FBC, U+E, LFT ( ALT/albumin) every 2 weeks for 6 weeks (and after dose increase) then:
Monthly for 3 months.
12 weekly minimum (using judgement based on patient risk) ongoing.
Vaccinations against pneumococcus and influenza are recommended (GRADE 1C, 97%).

5. Blood Monitoring. Standard Blood Monitoring No Blood monitoring
Extra blood monitoring
FBC, U+E, LFT ( ALT/albumin) every 2 weeks for 6 weeks (and after dose increase) then monthly for 3 months then 12 weekly minimum (using judgement based on patient risk)
Azathioprine
Hydroxychloroquine
Methotrexate + Leflunomide monthly for at least 1 year
Leflunomide
Mepacrine
Tacrolimus – monthly
Methotrexate
Ciclosporin - monthly
Mycophenolate
Sulphasalazine
Sulphasalazine after 1 year stable

6. Drugs with extra monitoring
Hydroxychloroquine
Retinal screening (see later slide)
Leflunomide
BP/ weight 3- 6 monthly
Ciclosporin/Tacrolimus
BP/ glucose each visit
Gold
Urinalysis on every visit

7. Drug specific extras
Methotrexate: All patients should be co- prescribed folic acid supplementation at a minimal dose of 5 mg once weekly (GRADE 1B, 97%).
Azathioprine: Patients should have baseline thiopurine methyltransferase (TPMT) status assessed. (GRADE 1A, 97%).

8. Hydroxychloroquine (2018)
Change from yearly optician eye checks (baseline in clinic) and safe dose 6.5mg/kg.
Safe dose 5mg/kg.
Patients should have baseline formal ophthalmic examination (by opthalomology service), optical coherence tomography (OCT) , within 1 year of commencing an antimalarial drug (GRADE 2C, 88%)
Then at 5 years yearly assessment for OCT for duration of treatment.
Baseline and yearly OCT in high risk (Tamoxifen, eGFR < 60, dose over 5mg/kg)

9. Surgery
Steroid exposure should be minimized prior to surgical procedures, and increases in steroid dose to prevent adrenal insufficiency are not routinely required (GRADE 2B, 95%).
DMARD therapy should not routinely be stopped in the perioperative period, although individualized decisions should be made for high-risk procedures 

10. Infections
During a serious infection, MTX, LEF, SSZ, AZA, apremilast, MMF, CSA and tacrolimus should be temporarily discontinued until the patient has recovered from the infection (GRADE 1A–C, 97%)

11. Shared care – Croydon.
Currently for MTX oral and sub cut ( problems with waste in Croydon currently)
Leflunomide
Not needed for SZ / Hydroxychloroquine, Azathioprine – but combined SCG are being prepared for the region.

12. Shared care
The prescriber has responsibility for ensuring patients are adhering to monitoring guidance (GRADE 1C, 97%).
When prescribing takes place in primary care, it should be supported by local written shared care agreements, highlighting responsibilities of each party (patient, secondary care, primary care; GRADE 1C, 97%).

13. SC MTX
Why?
Bioavailability of oral MTX of over 20 mg/week highly variable and significantly lower than detected with SC MTX.
Oral bioavailability can be 2/3 of equivalent SC dose.
Increased efficacy in Rheumatoid / JIA/ PSA- cw oral
Safety profile is equivalent to oral (less GI sx)
Lower costs if switched to SC MTX ( save on biologics)

14. Pregnancy and common DMARDS BSR 2016
Drug
Peri conception
1st trimester
2nd/3rd trimester
Breast
feeding
Paternal use
Prednisolone
yes
Hydroxychloroquine
Methotrexate
Stop for 3 months no
Sulphasalazine
Yes (fertility)
Leflunomide
No cholestyramine washout
Azathioprine
Mycophenolate
Stop 6 weeks

15. Thankyou
Questions ?

17. BSR and BHPR guideline for the prescription and monitoring of non-biologic disease-modifying anti-rheumatic drugs 
Jo Ledingham Nicola Gullick Katherine Irving Rachel Gorodkin Melissa ArisJean Burke Patrick Gordon Dimitrios Christidis Sarah Galloway Eranga Hayes ... Show more
Rheumatology, Volume 56, Issue 6, 1 June 2017, Pages 865–868, 
Published:
 27 February 2017
 Article history

18. 1. Ther Clin Risk Manag. 2018; 14: 105–116.
Published online 2018 Jan 9. doi:  /TCRM.S154745
PMCID: PMC
PMID: 
Update on subcutaneous methotrexate for inflammatory arthritis and psoriasis
Gino Antonio Vena,1,2 Nicoletta Cassano,1,2 and Florenzo Iannone3
Author information Copyright and License information Disclaimer

19. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding—Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids 
Julia Flint Sonia Panchal Alice Hurrell Maud van de Venne Mary GayedKaren Schreiber Subha Arthanari Joel Cunningham Lucy Flanders Louise Moore Rheumatology, Volume 55, Issue 9, 1 September 2016, Pages 1693–1697