Table 4.

Common immunosuppressive therapies utilized in CTD‐ILD

Medication and mechanism	Dosage	Adverse effects	Screening and monitoring
Corticosteroids Bind to the intracellular glucocorticoid receptor → inhibits cytokine transcription → (1) ↓ T cells (IL2 inhibited) (2) Eosinophil apoptosis (directly or by inhibition of IL5) (3) Macrophage inhibition (blocking IL1 and TNF‐α) (4) Leucocytosis B cells are not significantly inhibited	Start 0.5 mg/kg/day. Aim to taper down to 10–20 mg maintenance	Diabetes Weight gain Hypertension Myopathy Osteoporosis Accelerated atherosclerosis Sleep disturbance Cataracts Glaucoma Dyspepsia Pregnancy risk category A	BP Serum glucose Lipid profile Eye examination Bone densitometry
AZA Inhibits DNA and RNA synthesis in mainly T cells but also B cells	2.0–2.5 mg/kg/day if TPMT within normal limits	Bone marrow suppression GI intolerance Hepatotoxicity Increased malignancy risk (skin and lymphoproliferative) Avoid allopurinol Pregnancy risk category D	TPMT FBC and LFT
MMF and enteric‐coated mycophenolate sodium Inhibits DNA synthesis in T and B cells	MMF: start 500 mg bd, titrating to 2–3 g daily (in two divided doses) MMF 500 mg = enteric‐coated mycophenolate sodium 360 mg	Diarrhoea Bone marrow suppression Hepatotoxicity Increased malignancy risk (skin and lymphoproliferative) Progressive multifocal leucoencephalopathy Pregnancy risk category D contraindicated in pregnancy (category D)	FBC, LFT, renal function
Cyclophosphamide Alkylating agent toxic to all human cells to differing degrees with haematopoietic cells forming a sensitive target	600 mg/m2, maximum dose 1000 mg Monthly for maximum 6 months	Toxicity to bladder and gonads <250–300 mg/kg cumulative dose to avoid gonadal toxicity <360 mg/kg cumulative to minimize risk of malignancy Contraindicated in pregnancy (category D)	Maintain adequate fluid intake to avoid bladder toxicity Monthly urinalysis FBC and LFT
Tacrolimus Prevents calcineurin‐dependent gene transcription in T cells	Start 1 mg bd titrating by 1–2 mg daily with at least 7 days between adjustments. Aim for 12 h trough level 5–8 ng/mL	Increased vascular constriction → ↑BP, ↓ renal perfusion Contraindicated in pregnancy (category D)	Trough levels 10–14 days after initiating and at regular intervals Monitor BP, BGL, FBC, EUC, LFT, lipids
Rituximab B‐cell depletion by targeting CD20 lasting 6–9 months	Initiation: two 1 g infusions, 2 weeks apart Maintenance: 1 g every 6–12 months	Hepatitis B reactivation Should not be taken in pregnancy (category C) Hypogammaglobulinaemia	Screen for hepatitis B (surface antigen and core antibody)
Methotrexate Inhibits dihydrofolate reductase	Start 5–15 mg/week, escalating by 5 mg/month to maximum 25–30 mg/week	Pulmonary toxicity Hepatotoxicity Bone marrow suppression Alopecia Mouth ulcers Contraindicated in pregnancy (category D)	FBC, LFT, EUC

AZA, azathioprine; bd, twice daily; BGL, blood glucose level; BP, blood pressure; CTD‐ILD, connective tissue disease‐associated interstitial lung disease; EUC, electrolyte and urea concentration; FBC, full blood count; GI, gastrointestinal; LFT, liver function test; MMF, mycophenolate mofetil; TNF, tumour necrosis factor; TPMT, test for thiopurine methyltransferase.