Comparing methotrexate, ciclosporin, and acitretin for moderate plaque psoriasis
Lead Clinical Reviewer: Dr Tsui
Article Review Status
Answer
For an adult with moderate chronic plaque psoriasis requiring conventional systemic therapy in specialist care, here is a practical comparison.
Bottom line
- Methotrexate: usually the default first choice for longer-term control. [1]
- Ciclosporin: best when you need rapid control or short-term rescue. [1]
- Acitretin: generally less favoured for plaque psoriasis; NICE suggests it when methotrexate/ciclosporin are unsuitable or have failed. It is more often useful when pustular disease is present. [1]
Comparison
| Feature | Methotrexate | Ciclosporin | Acitretin |
|---|---|---|---|
| Typical role | First-choice systemic for most patients [1] | First-choice if rapid/short-term control needed, or if conception is being considered [1] | Consider if MTX/ciclosporin not appropriate or have failed [1] |
| Speed of action | Weeks; SPC suggests response usually within 4-8 weeks [2] | Fastest; can be used when rapid improvement is required, with response expected within weeks and assessment at 1-3 months [3] | Slower; maintenance effect in psoriasis often needs 6-8 weeks after the initial phase, and NICE asks you to assess at 4 months [4][1] |
| How it is given | Once weekly, usually oral; strict once-weekly dosing is critical [2] | Daily oral, split into 2 doses [3] | Daily oral with meals/milk [4] |
| Main toxicity concern | Bone marrow suppression, hepatotoxicity, pulmonary toxicity [2] | Nephrotoxicity and hypertension; also hyperlipidaemia, tremor [3] | Mucocutaneous dryness, hyperlipidaemia, hepatotoxicity, bone changes with long-term use [4] |
| Monitoring burden | FBC, LFTs, renal function; vigilance for cough/dyspnoea and dosing errors [2] | Frequent BP and renal monitoring; lipids, potassium, magnesium, uric acid; sometimes drug levels [3] | LFTs and fasting lipids; pregnancy testing where relevant; sometimes skeletal surveillance if long-term [4] |
| Pregnancy / conception | Contraindicated in pregnancy and breastfeeding; requires contraception during treatment and for at least 6 months after [2] | NICE specifically supports use when conception is being considered and systemic treatment cannot be avoided [1]; SPC says pregnancy only if benefit outweighs risk [3] | Highly teratogenic; contraindicated in pregnancy and breastfeeding. Women of childbearing potential need strict contraception for 3 years after stopping and no alcohol during treatment/for 2 months after because of etretinate formation [4] |
| Best fit clinically | Long-term plaque psoriasis, especially if there is psoriatic arthritis too [1] | Flares, unstable disease, need for quick clearance, or conception planning [1] | Patients unsuitable for MTX/ciclosporin, or with pustular phenotypes; less attractive for straightforward plaque disease [1] |
Practical take-home
- Choose methotrexate if you want a standard longer-term systemic and can monitor closely.
- Choose ciclosporin if you need rapid suppression or a short bridge.
- Choose acitretin only if the other two are unsuitable/failed, and be very cautious in anyone with pregnancy potential.
Key cautions
- Methotrexate: avoid in pregnancy, breastfeeding, significant liver disease, significant renal impairment, blood dyscrasias, severe infection. [2]
- Ciclosporin: avoid/limit in hypertension or renal impairment; watch for nephrotoxicity and drug interactions. [3]
- Acitretin: avoid in pregnancy, breastfeeding, hyperlipidaemia, liver disease; strict contraception requirements are the major limiting issue. [4]
References
- NICE. Psoriasis: assessment and management. Guidance CG153, recommendations.
- Methotrexate 2.5mg tablets. Summary of product characteristics. Active substance: methotrexate. Last read 25 June 2026.
- Capimune 50mg soft capsules. Summary of product characteristics. Active substance: ciclosporin. Last read 25 June 2026.
- Acitretin 25mg capsules. Summary of product characteristics. Active substance: acitretin. Last read 25 June 2026.