Table 1.

Non-corticosteroid immunosuppressants and biologics characteristics in SLE

	Immunosuppressive agent	Dose	Main indications in SLE	Adverse events	Special issue
Non-steroidal immunosuppressants	CYC	Low dose  500 mg, iv, biweekly, 4 times High dose  0.75–1.0 mg/m2, iv, monthly, 6 times	Severe organ involvement:  LN  NPSLE  Vasculitis	Cystitis (especially high doses) Gastrointestinal Hematological	Teratogenic effect Premature ovarian failure Malignancies To prevent bladder toxicity—Mesna administration For overall less toxicity—regimen according to Euro-Lupus [51]
	MMF	2.0–3.0 g/day, orally	Hematologic Skin LN in induction and maintenance therapy	Gastrointestinal Hematological	Teratogenic effect
	Calcineurin inhibitors
	CsA	3.0—5.0 mg/kg/day, orally	LN Skin Hematologic	Nephrotoxicity Metabolic (hypertension, hyperglycemia, hyperlipidemia) Hirsutism	Safe during pregnancy and lactation Continuing with folic acid during pregnancy
	Voclosporin	23.7 mg, twice daily, orally	LN	Hypertension Nephrotoxicity Serious infections Malignancies	Combination therapy with MMF in LN Dose adjustment based on eGFR Advantages compared with CsA and tacrolimus with respect to dosing and tolerability
	Tacrolimus	0.2–0.3 mg/kg/day, orally	LN	Nephrotoxicity Cardiomyopathy	Combination therapy with MMF in LN with nephrotic proteinuria
	AZA	1.0–5.0 mg/kg/day, orally Pregnancy and lactation:  ≤ 2.0 mg/kg/day, orally	Hematologic Skin LN in maintenance therapy	Gastrointestinal Hepatotoxicity Hematological	Drug interactions with allopurinol Safe during pregnancy and lactation Mild GCs-sparring effect
	MTX	7.5–25 mg/week, orally/sc	Joints Skin Serositis	Gastrointestinal Hepatotoxicity Hematological	Teratogenic effect Mild GCs-sparring effect Use with caution in elderly patients and in patients with reduced GFR (< 30 ml/min)
Biologics	Belimumab	Iv: 10.0 mg/kg on days 0, 14 and 28, then every 28 days sc: 200 mg/week In LN: 400 mg/week, 4 times; then 200 mg/week	Skin Joints LN	Infections Depression Progressive multifocal encephalopathy	Complementary treatment in seropositive moderate to severe SLE Not recommended in severe NPSLE FDA-approved to treat seropositive, moderate SLE in children 5–17 years of age
	Anifrolumab	300 mg, iv, every 4 weeks	Skin Joints	Infections, especially herpes zoster	Complementary treatment in seropositive moderate-to-severe SLE GCs-sparing effect
	Rituximab	500–1000 mg, iv, on days 0 and 14, the next course to be administered after 6 months	Refractory LN NPSLE	Progressive multifocal encephalopathy Infections	Drug off label Different administration schedules

AZA azathioprine, CsA cyclosporine, CYC cyclophosphamide, eGFR estimated glomerular filtration rate, GCs glucocorticosteroids, FDA Food and Drug Administration, GFR glomerular filtration rate, iv intravenous, LN lupus nephritis, MMF mycophenolate mofetil, NPSLE neuropsychiatric systemic lupus erythematosus, sc subcutaneous