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

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

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

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%).

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

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

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%).

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)

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 

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%)

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.

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%).

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)

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

Thankyou Questions ?

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, https://doi.org/10.1093/rheumatology/kew479 Published:  27 February 2017  Article history

1. Ther Clin Risk Manag. 2018; 14: 105–116. Published online 2018 Jan 9. doi: 10.2147/TCRM.S154745 PMCID: PMC5767093 PMID: 29386902 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

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