French guidelines to treating psoriasis

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Phototherapy (NBUVB, home‐based NBUVB, PUVA, bath PUVA)
Dosing scheme:

• NBUVB (outpatient or at home when available): 3 sessions/week (Grade A), 20–30 sessions (Grade A).
  
• PUVA: use oral psoralen (8‐methoxypsoralen) at 0.6 mg/kg followed 2–3 h later by exposure to UVA irradiation: 2–3 sessions per week, for 20–30 sessions (Grade A).
  
• A lack of improvement after 20 sessions is considered as a failure (Grade D).
  
• Bath PUVA: prepare the bath by diluting a 0.75% solution of psoralen in 80–100 L of water to obtain a concentration of 2.6 mg of psoralen per litre (Grade C). The bath should last 15 min and be followed by irradiation immediately after drying. The recommended doses of UVA are lower than those used for oral PUVA.
  

Number of cumulative sessions of phototherapy during a lifetime should not exceed 200 (Grade C).
Efficacy (Monotherapy)
Onset of clinical effect: after 1 or 2 weeks. Efficacy assessment: after 20 sessions.

• NBUVB: PASI 75 = 62–70%.
  
• Home‐based NBUVB: no difference in efficacy compared to classical NBUVB.
  
• PUVA: PASI 75 = 73–80%.
  
• Bath PUVA: PASI 75 = 47%.
  

Optional combination therapy

• Acitretine (10‐20 mg daily, to start 10‐14 days before phototherapy: Grade A for PUVA, Grade B for NBUVB, Grade B for bath PUVA.
  
• Grade B for MTX, ADA and ETA with NBUVB.
  
• Grade C for USTK with NBUVB.
  

Adverse events
Erythema, itching, blistering, xerosis, hyperpigmentation, photoageing.
The risk of skin malignancies is significantly increased with PUVA, limited data are available for NBUVB.
For oral PUVA, nausea, abdominal pain may also occur.
Main contraindications
Absolute contraindications: increased sensitivity to light, concomitant phototoxic medication. Gene defects with increased photosensitivity or risk of skin cancer. History of melanoma. For PUVA: use of CSA, pregnancy or breastfeeding.
Important relative contraindications: dysplastic nevi syndrome or multiple nonmelanoma skin cancers, patients under immunosuppressive medication, prior therapy with arsenic or ionizing radiation. For PUVA: severe liver or renal impairment, children, use of psoralen for cosmetic purposes. For home‐based NBUVB: lack of compliance/adherence.
Precautions

Vaccination
No specific recommendation. Follow French immunization schedule. Live vaccines are permitted during treatment.
Surgery
Phototherapy can be maintained in patients undergoing surgery if the patient's condition allows it.
Cost in France (2017)
For 3 treatments/week: €250 monthly for NBUVB, €255 monthly for PUVA.

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Methotrexate (MTX)
Dosing scheme:
Starting dose

• In general, 7.5–15 mg/week by oral or s.c. delivery (Grade B).
  
• One RCT suggests a starting dose of 17.5 mg/week s.c. administration with dose escalation to 22.5 mg/week after 8 weeks if the patient has not achieved PASI 50 (Grade A).
  
• No low test dose is mandatory (Grade C).
  
• No weight‐based adaptation. The s.c. administration might reduce gastrointestinal AEs reported in patients treated orally (Grade C) but has not demonstrated superiority compared to the oral route.
  

Maintenance dosage

• 5–25 mg/week depending on efficacy and tolerability (Grade B).
  
• Use the lowest therapeutic dose. Folate supplementation: 5 mg/week of folic acid taken 24 h after administration of MTX (Grade B).
  
• Interrupting treatment after a given cumulative dose is not recommended if MTX is well‐tolerated and the follow up required is completed (Expert opinion).
  

Half‐life
2–7 h.
Efficacy (Monotherapy)
Onset of clinical effect: 4–8 weeks. Efficacy assessment: W12–16.

• Short‐term efficacy (W16): PASI 75: 45% (W12–16)/PASI 90: 18%/DLQI: 9‐point reduction. ACR20 (W12): 41%.
  
• Long‐term efficacy (W52): PASI 75: 73%. Median drug survival: 30.1%, and 15.1% after 3 and 5 years.
  

Optional combination therapy

• Grade A with ETA,
  
• Grade B with NBUVB,
  
• Grade B with INFLI,
  
• Grade C with ADA.
  

Main adverse events
Fatigue, nausea, vomiting, moderate hair loss, transaminase increase, bone marrow suppression, gastrointestinal and mucosal ulcerations, infections, liver fibrosis, interstitial pneumonia.
Main contraindications
Severe infections, serious kidney and liver dysfunction, bone marrow suppression, men and women currently trying to conceive children, pregnancy, breastfeeding, pulmonary fibrosis or poor lung function, alcohol abuse, active peptic ulcer.
Precautions
Inform the patient on how to take the drug (only once a week).
If liver ultrasound is abnormal at baseline: check PIIIP or Fibroscan®.
Fibroscan® should be performed at baseline in obese patients if long‐term treatment is planned.
Adequate contraception for men and women is mandatory. After the end of treatment, contraception is recommended for 3 months in men and only 1 day in women (contraception should be continued until the end of treatment and conception is possible as soon as contraception is stopped).
Vaccination
Follow the French immunization schedule. Primary vaccination and/or boosters for HBV/annual influenza/pneumococcal vaccination. Live‐attenuated vaccines are contraindicated during treatment.
Surgery

• No systematic interruption of MTX required prior to minor surgery (Grade B).
  
• Discuss interruption of MTX (30 h) prior to major surgery in patients with a history of healing disorders or wound infections (Grade C).
  

Cost in France (2017)
For 20 mg/week: between €84/year (oral form) and €1 080/year (s.c. form).

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Cyclosporin (CSA)
Dosing scheme
Starting dose

• 2.5 mg/kg/day by oral delivery, divided in half and taken morning and evening (Grade A).
  In the absence of comorbidity, start with 5 mg/kg for faster action (Grade B).
  
• If there is no adequate response to the starting dose at W4–W8, or when rapid disease control is necessary, increase the dose to a maximum of 5 mg/kg (Grade B).
  
• Use the ideal weight for obese patients (Grade B).
  

Maintenance dosage

• Intermittent therapy (2–4 months of treatment) or continuous therapy with minimal effective dose, depending on the clinical situation (Grade B).
  
• Slow tapering of CSA offers a slight delay in psoriasis relapse (Grade B).
  
• Consider other treatment options when disease relapses rapidly (Expert opinion).
  
• Avoid using CSA continuously for more than 2 years unless disease is severe and other treatment options cannot be used, and collaborate with a nephrologist (Grade C).
  

Half‐life
7 h.
Efficacy (Monotherapy)
Onset of clinical effect: 4 weeks. Efficacy assessment: W8.

• Short‐term efficacy: PASI 75: 60–88.6% at W8–W12/PASI 90: 29% at W12/DLQI: 9.3‐point reduction at W12.
  
• Median drug survival 23.3% at 1 year.
  

Optional combination therapy
Given the lack of robust data on CSA therapy in combination, we recommend not to use CSA with any other systemic treatment, including phototherapy.
Adverse events
Renal impairment, arterial hypertension nausea, diarrhoea, liver dysfunction, gingival hyperplasia, paraesthesia, muscle pain, headache tremors, hypertrichosis, increased blood lipids.
Main contraindications
Impaired renal function, uncontrolled arterial hypertension, severe infectious disease, history of malignancy (possible exceptions: cured basal cell carcinoma, history of in situ squamous carcinoma) or current malignancy, concomitant PUVA therapy.
Precautions

Be aware that CSA increases the risk of nonmelanoma skin cancers in patients already treated with phototherapy.
Vaccination
Follow the French immunization schedule.
Primary vaccination and/or boosters for HBV/annual influenza/pneumococcal vaccination (especially the elderly). Live‐attenuated vaccines are contraindicated during treatment.
Surgery

• No systematic interruption of CSA required prior to minor surgery (Grade B).
  
• Discuss interruption of CSA (35 h) prior to major surgery in patients with a medical history of healing disorders or wound infections (Grade C).
  

Cost in France (2017)
For a dose of 3 mg/kg/day in a 70 kg patient: €3 144/year.

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Acitretin
Dosing scheme
Starting dose

• Use incremental dosing starting from 10 mg/day to achieve a target dose of 0.3–0.5 mg/kg daily (Grade B).
  

Maintenance dose

• To be adapted to the clinical response and tolerance, usually between 0.5 and 0.8 mg/kg daily, with a maximum dose of 50 mg daily (Grade C). The degree of lip dryness may help to determine the maximum tolerated dose (Expert opinion).
  
• Long‐term therapy must be discussed on a case‐by‐case basis according to clinical and biological tolerance.
  
• Treatment must be initiated by a dermatologist.
  

Half‐life
2–5 days.
Efficacy (Monotherapy)
Onset of clinical effect: 4–8 weeks. Efficacy assessment: after 3 or 4 months at the optimum dose; discontinue the treatment if response is inadequate (Expert opinion).
Response rate is difficult to assess because of the low quality of published trials. PASI 75: 30% at W12–24 with a dose of 0.4 mg/kg. Drug survival at first year: 42.3%.
Optional combination therapy

• Level A with PUVA therapy,
  
• Level B with NBUVB,
  
• Level B with ETA,
  
• Level C with INFLI.
  

Adverse events
Teratogenicity, hypervitaminosis A (cheilitis, xerosis), conjunctivitis (contact lenses may become unbearable), hair loss, photosensitivity, hyperlipidaemia, muscle, joint and bone pain, idiopathic intracranial hypertension, decreased colour vision and impaired night vision.
Main contraindications
Severe renal or hepatic impairment. Women of child‐bearing age: pregnancy, breastfeeding, desire to have children or insufficient guarantee of effective contraceptive measures up to 3 years after discontinuation of therapy. Alcohol abuse. Blood donation.
Precautions
Start treatment on the second or third day of the menstrual cycle, after satisfactory contraception for at least 1 month prior to treatment. Double contraception is recommended. Emphasize the need for reliable contraception in women of child‐bearing age for up to 3 years after therapy.
Check pregnancy test before starting treatment, then every month during treatment, and then every month for 2 months after treatment discontinuation.
There is no need for contraception in men.
Vaccination
No specific recommendations. Follow the French immunization schedule. Live vaccines are permitted during treatment.
Surgery
Acitretin can be safely continued in patients undergoing surgery.
Cost in France (2017)
For 25 mg/day: €600/year.

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Infliximab (Remicade) (INFLI)
Dosing scheme
Intravenous administration (day care hospital unit).

• 5 mg/kg given at W0, W2, W6, every 8 weeks thereafter (continuous treatment is recommended, Grade A).
  
• Possibility of increasing dosage or reducing administration intervals (Grade C). If loss of efficacy to standard‐dose maintenance therapy occurs: INFLI 5 mg/kg every 6 weeks (Expert opinion).
  

Half‐life
10 days
Efficacy (Monotherapy)
Efficacy assessment: W14 (after 4 doses).
Induction efficacy (W10):

• PASI 75: 81%/PASI 90: 55%
  
• DLQI: 8.4‐point reduction (median)
  
• ACR 20: 77%.
  

Stop INFLI in patients who have not responded adequately at W14.
Long‐term efficacy (W50):

• PASI 75: 61%/PASI 90: 45%.
  

Median drug survival: 65% 1st year/35% 3rd year.
Optional combination therapy
Level B with MTX 7.5–15 mg/week.
Level C with acitretin.
Main adverse events
Injection‐site reactions, headache and muscle/bone pain, viral, bacterial or fungal infections (including tuberculosis), weight gain, allergic reactions, anaphylactic and anaphylactic‐like reactions, serum sickness or serum sickness‐like reactions, autoimmune processes, worsening of congestive heart failure, neurological disorders, nonmelanoma skin cancers.
Main contraindications
Cardiac insufficiency (NYHA grade III or IV), active tuberculosis or other serious infections, active malignancy, pregnancy, breastfeeding, demyelinating disease, hypersensitivity.
Precautions
See clinical and biological pre‐treatment procedures and surveillance.
Vaccination
Follow the French immunization schedule.
Primary vaccination and/or boosters for HBV/annual influenza/pneumococcal vaccination (especially the elderly).
Live‐attenuated vaccines are contraindicated during treatment.
Surgery

• No systematic interruption of INFLI is required prior to minor surgery (Grade C).
  
• Discuss interruption of INFLI prior to major surgery (3–5 half‐lives = 4–7 weeks) in patients with a medical history of healing disorders or wound infections (Grade C). Surgery may be placed between two infusions (Expert opinion).
  

Cost in France (2017)
Around €12 220 for the first year for Remicade® (5 mg/kg W0–W2–W6, then every 8 weeks for an 80 kg patient), not including the day hospital cost. Biosimilars are available (Inflectra®, Remsina®, Flixabi®).

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Adalimumab (Humira) (ADA)
Dosing scheme

• Loading dose of 80 mg at W0, 40 mg W1, then 40 mg every other week.
  
• If inadequate response at W16: possibility of transient increase in the dosing frequency to 40 mg every week (Grade B). The dose should subsequently be reduced again if an adequate response is achieved. If an adequate response is not achieved 4 months after increasing the dosing frequency, ADA should be stopped (Expert opinion).
  
• No weight—dose adjustment for obese patients.
  

Half‐life
2 weeks
Efficacy (Monotherapy)
Efficacy assessment: W16.
Short‐term efficacy (W16):

• PASI 75: 71%/PASI 90: 45%
  
• DLQI: 7‐point reduction (median)
  
• ACR 20: 52%.
  

Stop ADA in patients who have not responded adequately at W16.
Long‐term efficacy (W48):

• PASI 75: 63%/PASI 90: 48%.
  

Mean drug survival: 79% 1st year/59% 3rd year.
Optional combination therapy

• Level C with MTX 7.5–15 mg/week.
  
• Level B with NBUVB.
  

Main adverse events
Injection‐site reactions, headache and muscle/bone pain, viral, bacterial or fungal infections (including tuberculosis), weight gain, allergic reactions, autoimmune processes, worsening of congestive heart failure, neurological disorders, nonmelanoma skin cancers.
Main contraindications
Cardiac insufficiency (NYHA grade III or IV), active tuberculosis or other serious infection, active malignancy, pregnancy, breastfeeding, demyelinating disease, hypersensitivity.
Precautions
See clinical and biological pre‐treatment procedures and surveillance.
Vaccination
Follow the French immunization schedule.
Primary vaccination and/or boosters for HBV/annual influenza/pneumococcal vaccination (especially the elderly).
Live‐attenuated vaccines are contraindicated during treatment.
Surgery

• No systematic interruption of ADA required prior to minor surgery (Grade C).
  
• Discuss interruption of ADA prior to major surgery (3–5 half‐lives = 6–10 weeks) in patients with a past medical history of healing disorders or wound infections (Grade C).
  

Cost in France (2017)
Around €11 400 for the first year for Humira® (80 mg loading dose and 40 mg every other week, starting W1).
No biosimilar available in France in 2017.

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Etanercept (Enbrel) (ETA)
Dosing scheme

• 50 mg BIW for up to 12 weeks, followed by 50 mg QW is a more effective strategy than 50 mg QW from the beginning of treatment (Grade A).
  
• Possibility of intermittent therapy (grade C).
  
• No weight–dose adjustment for obese patients.
  

Half‐life
70 h (3 days).
Efficacy (Monotherapy)
Efficacy assessment: W12.
Induction efficacy (W12):

• PASI 75: 38% (50 mg QW*)/52% (50 mg BIW)
  
• PASI 90: 15% (50 mg QW*)/25% (50 mg BIW)
  
• DLQI: 6‐point reduction (median)
  
• ACR 20: 59%.
  

Stop ETA in patients who have not responded adequately at W12.
Long‐term efficacy (W96):

• PASI 75: 51%.
  

Median drug survival: 70% 1st year/40% 3rd year.
*25 mg BIW
Optional combination therapy

• Level A with MTX 7.5–15 mg/week.
  
• Level B with NBUVB and acitretin.
  

Main adverse events
Injection‐site reactions, headache and muscle/bone pain, viral, bacterial or fungal infections (including tuberculosis), weight gain, allergic reactions, autoimmune processes, worsening of congestive heart failure, neurological disorders, nonmelanoma skin cancers.
Main contraindications
Cardiac insufficiency (NYHA grade III or IV), active tuberculosis or other serious infection, active malignancy, pregnancy, breastfeeding, demyelinating disease, hypersensitivity.
Precautions
See clinical and biological pre‐treatment procedures and surveillance.
The needle cover on the prefilled syringe contains dry natural rubber and should not be handled by patients allergic to latex.
Vaccination
Follow the French immunization schedule.
Primary vaccination and/or boosters for HBV/annual influenza/pneumococcal vaccination (especially the elderly).
Live‐attenuated vaccines are contraindicated during treatment.
Surgery

• No systematic interruption of ETA required prior to minor surgery (Grade C).
  
• Discuss interruption of ETA prior to major surgery (3–5 half‐lives = 9–15 days) in patients with a past medical history of healing disorders or wound infections (Grade C).
  

Cost in France (2017)
Around €12 670 for the first year for Enbrel® (50 mg BIW up to W12, followed by 50 mg QW).
Biosimilar available (around €11 140 for the first year for Benepali®).

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Ustekinumab (Stelara) (USTK)
Dosing scheme

• 45 mg at Week 0, Week 4 and then every 12 weeks.
  
• Adjusted for patients >100 kg: same scheme, but with a 90 mg dose.
  
• Suggested dose‐escalation strategy (off‐license): USTK 90 mg every 12 weeks (<100 kg) or USTK 90 mg every 8 weeks (>100 kg) (Grade C).
  

Half‐life
3 weeks
Efficacy (Monotherapy)
Efficacy assessment: W28.
Induction efficacy (W28):

• PASI 75: 70 (45 mg)–79% (90 mg)/PASI 90: 45 (45 mg)–48% (90 mg).
  
• DLQI: 8‐point reduction (median).
  
• ACR 20: 42–49%.
  

Stop USTK in patients who have not responded adequately at W28.
Long‐term efficacy (W156):

• PASI 75: 81 (45 mg)–83% (90 mg)/PASI 90: 43 (45 mg)–58% (90 mg).
  

Median drug survival: 89% 1st year/75% 3rd year.
Optional combination therapy
Level C with NBUVB.
Main adverse events
Injection‐site erythema, fatigue and muscle/bone pain, diarrhoea, viral, bacterial or fungal infections (no reactivation or new onset of tuberculosis), allergic reactions, exfoliative dermatitis, MACE.
Main contraindications
Active tuberculosis or other serious infection, pregnancy, breastfeeding, active malignancy, hypersensitivity.
Precautions
See clinical and biological pre‐treatment procedures and surveillance.
In patients with increased cardiovascular risk, initiate the treatment in collaboration with a cardiologist and control risk factors.
The needle cover on the prefilled syringe contains dry natural rubber and should not be handled by patients allergic to latex.
Vaccination
Follow the French immunization schedule
Primary vaccination and/or boosters for HBV/annual influenza/pneumococcal vaccination (especially the elderly).
Live‐attenuated vaccines are contraindicated during treatment.
Surgery

• No systematic interruption of USTK required prior to minor surgery (Grade C)
  
• Discuss interruption of USTK prior to major surgery (3–5 half‐lives = 9–15 weeks) in patients with a past medical history of healing disorders or wound infections (Grade C).
  

Cost in France (2017)
Around €14 920 for the first year for Stelara® (45 or 90 mg W0, W4, then every 12 weeks)
No biosimilar available in France in 2017.

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Secukinumab (Cosentyx) (SEC)
Dosing scheme

• 300 mg, delivered in two injections of 150 mg each.
  
• 300 mg at W0, 1, 2, 3, 4 and then 300 mg every 4 weeks.
  
• No weight–dose adjustment.
  

Half‐life
27 days
Efficacy (Monotherapy)
Efficacy assessment: W16.
Short‐term efficacy (W12): PASI 75: 76–87%/PASI 90: 55–60%/DLQI 0/1: 55.8%/ACR 20: 58.2% (week 24)
Stop SEC in patients who have not responded adequately at W16.
Long‐term efficacy (W104): PASI 75: 88.2%/PASI 90: 58%.
Mean drug survival: unknown at this time.
Intermittent dosing: not validated.
Optional combination therapy
No data for skin psoriasis. Can be used in combination with DMARDs in PsA (Grade C).
Adverse events
Infections (upper respiratory tract, candida), diarrhoea, neutropenia, inflammatory bowel disease onset and flare.
Main contraindications
Hypersensitivity, active infection, pregnancy, breastfeeding, active malignancy.
Precautions
Avoid if possible in patients with a history of inflammatory bowel disease (Grade C).
Close monitoring of patients with psychiatric disorders and/or a history of suicide attempts and/or severe depression (possible class effect – Expert opinion).
In patients with increased cardiovascular risk, initiate in collaboration with a cardiologist and control risk factors (no long‐term safety assessment in patients at high cardiovascular risk – Expert opinion).
Vaccination
Follow the French immunization schedule
Primary vaccination and/or boosters for HBV and HAV/annual influenza/pneumococcal vaccination (especially the elderly). Live‐attenuated vaccines are contraindicated during treatment.
Surgery
No data available about surgery.
We recommend interrupting SEC 4 weeks before performing scheduled surgery. Resume medication after healing (American College of Rheumatology and American Association of Hip and Knee Surgeons recommendations).
Cost in France (2017)
Cosentyx®

• First year: €19.375
  
• then €14 857/year.
  

No biosimilar available in 2017.

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Ixekizumab (Taltz) (IXE)
Dosing scheme

• Loading dose of 160 mg, 80 mg every other week until week 12, then 80 mg every 4 weeks.
  
• No weight–dose adjustment.
  

Half‐life
13 days
Efficacy (Monotherapy)
Efficacy assessment: W16. In case of partial response at week 16, improved response can be observed until week 20.
Induction efficacy (W16):

• PASI 75: 84% (81–88%)/PASI 90: 69% (65–72%) (Grade A)
  
• DLQI 0/1: 59.9%/ACR 20: 57.9%.
  

Stop IXE in patients who have not responded adequately at W16.
Long‐term efficacy (W60):

• PASI 75: 74%/PASI 90: 57% (Grade B).
  

Mean drug survival: NA.
Intermittent dosing: treatment can be stopped in patients who achieve PGA 0/1 at week 12 and then reintroduced in case of relapse (80 mg every 4 weeks) (Grade C).
Optional Combination therapy
No
Adverse events
Infections (upper respiratory tract, candida), injection site reactions, neutropenia, inflammatory bowel disease onset and flare.
Main contraindications
Hypersensitivity, active infection, pregnancy, breastfeeding, active malignancy.
Precautions
Avoid if possible in patients with a history of inflammatory bowel disease (Grade C).
Close monitoring of patients with psychiatric disorders and/or a history of suicide attempts and/or severe depression (possible class effect – Expert opinion).
In patients with increased cardiovascular risk, initiate in collaboration with a cardiologist and control risk factors (no long‐term safety assessment in patients at high cardiovascular risk – Expert opinion).
Vaccination
Follow the French immunization schedule.
Primary vaccination and/or boosters for HBV and HAV/annual influenza/pneumococcal vaccination (especially the elderly). Live‐attenuated vaccines are contraindicated during treatment.
Surgery
No data available about surgery.
We recommend interrupting IXE 4 weeks before performing scheduled surgery. Resume medication after healing (American College of Rheumatology and American Association of Hip and Knee Surgeons recommendations).
Cost in France (2017)
Taltz®

• First year: €18 532,
  
• then €13 421/year
  

No biosimilar available in 2017.

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Apremilast (Otezla) (APR)
Dosing scheme

• One‐week titration for first‐time users. Treatment is started with a dose of 10 mg on day 1 and increased daily by 10 mg over 1 week up to the recommended dose of 30 mg twice a day.
  
• No dose adjustment required, except for severe renal impairment (clearance <30 mL/min): maximal dose: 30 mg once a day.
  

Half‐life
6–9 h
Efficacy (Monotherapy)
Efficacy assessment (W16): PASI 75: 29–33%; PASI 90: 9–10%; ACR 20:32–41%.
Discontinue treatment in non‐responders at W16.
Long‐term efficacy (W52): PASI 75: 42% (Grade C).
Median time to loss of PASI 50/PASI 75 response upon drug discontinuation: 12.4 weeks/5.1 weeks.
Mean drug survival: unknown.
Intermittent dosing: not validated.
Optional combination therapy
No data for skin psoriasis. Can be used in combination with DMARDs in PsA (Grade C).
Adverse events
Diarrhoea (at onset, long‐term persistence possible), nausea, asthenia, insomnia, upper respiratory tract infections, headaches, depression, weight loss.
Main contraindications
Hypersensitivity, pregnancy.
Precautions
Avoid in patients with psychiatric disorders and/or a history of suicide attempts and/or severe depression (Expert opinion).
Vaccination
No specific recommendation was given in the SmPC.
Follow the French immuniation schedule.
No data available about live‐attenuated vaccines.
Surgery
No data available about surgery.
Cost in France (2017)
First year (including titration) = €7061, then €7368/year