Introduction
Background
Goal of the Guidelines
Methods
Basis of data
Evidence assessment
Therapeutic recommendation
Results
Therapeutic strategies
Evaluation of topical and systemic therapies in tabular form
Topical monotherapy
Phototherapy and systemic monotherapy
Scale | Systemic therapy | Topical therapy |
---|---|---|
++++ | Approx. 90% | Approx. 60% |
+++ | Approx. 70% | Approx. 45% |
++ | Approx. 50% | Approx. 30% |
+ | Approx. 30% | Approx. 15% |
+/− | Approx. 10% | Approx. 5% |
– | Not defined | Not defined |
Evaluation of topical therapies
Calcineurin inhibitors
Calcineurin inhibitors | |
---|---|
First approved in Germany | |
Pimecrolimus (Elidel®) | 2002 (Atopic dermatitis, not approved for psoriasis vulgaris) |
Tacrolimus (Protopic®) | 2002 (Atopic dermatitis, not approved for psoriasis vulgaris) |
Recommended initial dosage | Pimecrolimus cream: 1× to 2× daily Tacrolimus: 1× to 2× daily (application on the face: Begin with 0.03% salve; increase later dosage to 0.1% salve) |
Recommended maintenance dosage | Individual therapeutic adjustment |
Expected beginning of clinical effect | After approximately 2 weeks |
Response rate | No data available |
Important contraindications | Pregnancy and nursing (due to lack of experience) skin infections, immune suppression |
Important adverse drug reactions (ADRs) | Burning sensation on skin, skin infections |
Important drug interactions | None known |
Other |
Cave: Do not combine with phototherapy! Photoprotection!
|
Corticosteroids
Corticosteroids | |
---|---|
First approved in Germany | 1956 (Psoriasis vulgaris) |
Recommended control parameters | None |
Recommended initial dosage | One to two times daily |
Recommended maintenance dosage | Gradual reduction following onset of effect |
Expected beginning of clinical effect | After 1–2 weeks |
Response rate | Betamethasone dipropionate, two times daily: marked improvement or clearance of the skin lesions in 46–56% patients after 4 weeks (LE 1) |
Important contraindications | Skin infections, rosacea, perioral dermatitis |
Important ADRs | Skin infections, perioral dermatitis, skin atrophy, hypertrichosis, striae |
Important drug interactions | None |
Other | – |
Coal tar
Coal tar | |
---|---|
First approved in Germany | Listed active ingredient since 2000 (DAC on page 170), historical application, various tar-containing externals are licensed as drugs, application of tar as anti-psoriatic following publication by Goeckermann in 1925 |
Recommended control parameters | After long-term application/application on large areas: if needed clinical controls for potential development of skin carcinoma |
Recommended initial dosage | 5–20% salve preparations or gels for local therapy, 1× daily |
Recommended maintenance dosage | No long-term application (max. 4 weeks, DAC 2000) |
Expected beginning of clinical effect | After 4–8 weeks, efficacy improves in combination with UV application |
Response rate | There is insufficient data available on the response rate as a monotherapy (LE 4) |
Important contraindications | Pregnancy and nursing |
Important ADRs | Color, odor, carcinogenic risk, phototoxicity—which is part of the desired effect |
Important drug interactions | Not known with topical use |
Other | DAC 2000 (on page 170), Hazardous Goods Directive Appendix 4 No. 13 |
Dithranol
Dithranol | |
---|---|
First approved in Germany | |
Psoralon | 1983 (Psoriasis vulgaris) |
Psoradexan | 1994 (Psoriasis vulgaris) |
Micanol | 1997 (Psoriasis vulgaris) |
Recommended control parameters | Intensity of irritation |
Recommended initial dosage | Begin with 0.5% preparation for long-term therapy or 1% for short-contact therapy, then increase if tolerated |
Recommended maintenance dosage | Not recommended for maintenance therapy |
Expected beginning of clinical effect | After 2–3 weeks |
Response rate | Marked improvement or clearance of skin lesions in 30–50% of the patients (LE 2) |
Important contraindications | Acute, erythrodermic forms of psoriasis vulgaris; pustular psoriasis |
Important ADRs | Burning and reddening of the skin in >10% |
Important drug interactions | – |
Other | – |
Tazarotene
Tazarotene | |
---|---|
First approved in Germany | 1997 (psoriasis vulgaris) |
Recommended control parameters | Check development of skin irritations |
Recommended initial dosage | Begin with one treatment daily of tazarotene gel 0.05% in the evening for approximately 1–2 weeks |
Recommended maintenance dosage | If necessary continue for 1–2 weeks with tazarotene gel 0.1% |
Expected beginning of clinical effect | After 1–2 weeks |
Response rate | After 12 weeks therapy with 0.1% tazarotene gel improved findings of at least 50% in approximately 50% of the patients (LE 2) |
Important contraindications | Pregnancy, nursing |
Important ADRs | Pruritus, burning sensation of skin, erythema, irritation |
Important drug interactions | Avoid concomitant use of preparations with irritating and drying properties |
Other | – |
Vitamin D3 and analogues
Vitamin D3 and analogues | |
---|---|
First approved in Germany | |
Calcipotriol | 1992 (Psoriasis vulgaris) |
Tacalcitol | 1994 (Psoriasis vulgaris) |
Calcitriol | 1999 (Psoriasis vulgaris) |
Calcipotriol/Betamethasone | 2002 (Psoriasis vulgaris) |
Recommended control parameters | Monitor for skin irritations |
Recommended initial dosage | Calcipotriol: 1× to 2× daily to affected locations, up to a maximum of 30% of the body surface |
Tacalcitol: 1× daily to affected locations, up to a maximum of 20% of the body surface | |
Calcitriol: 2× daily to affected locations, up to a maximum of 35% of the body surface | |
Recommended maintenance dosage | Calcipotriol: 1× to 2× daily, up to 100 g/week for up to 1 year |
Tacalcitol: 1× daily for 8 weeks, for up to 18 months, on a maximum of 15% of the body surface with up to 3.5 g daily | |
Calcitriol: insufficient experience with the application for more than 6 weeks | |
Expected beginning of clinical effect | After 1–2 weeks |
Response rate | Between 30 and 50% of the patients demonstrated a marked improvement or clearance of the lesions after 4–6 weeks (LE 1) |
Important contraindications | Diseases with abnormal calcium metabolism, severe liver and renal diseases |
Important ADRs | Skin irritation (reddening, itching, burning) |
Important drug interactions | Drugs which elevate the calcium levels, (e.g. thiazide diuretics), no concomitant application of topical salicylic acid preparations (inactivation) |
Other | Exposure to UV light results in inactivation of the vitamin D3-analogues |
Phototherapy
Phototherapy | |
---|---|
First approved in Germany | Clinical experience, depending on the modality for >50 years |
Recommended control parameters | Regular skin inspection (UV erythema) |
Recommended initial dosage | Individual dose depends on skin type; options: |
• UVB: 70% of minimum erythema dose (MED) | |
• Oral PUVA (photochemotherapy): 75% of the minimum phototoxic dose (MPD) | |
• Bath/cream PUVA: 20–30% of MPD | |
Recommended maintenance dosage | Increase according to degree of UV erythema |
Expected beginning of clinical effect | After 1–2 weeks |
Response rate | In >75% of the patients PASI, 75 after 4–6 weeks (LE 2) |
Important contraindications | Photo-dermatoses/photosensitive diseases, skin malignancies, immunosuppression Only PUVA: pregnancy and nursing |
Important ADRs | Erythema, itching, blistering, malignancies Only oral PUVA: nausea |
Important drug interactions | Drugs causing phototoxicity or photoallergy |
Other | Combination with topical preparations acts synergistically, PUVA may not be combined with cyclosporine |
Evaluation of systemic therapies
Efalizumab
Efalizumab | |
---|---|
First approved in Germany | September 2004 (psoriasis vulgaris) |
Recommended control parameters | Prior to therapy exclusion of significant infections, complete blood count, liver values |
Recommended initial dosage | 0.7 mg/kg body weight (BW) per week |
Recommended maintenance dosage | 1 mg/kg BW per week |
Expected beginning of clinical effect | After 4–8 weeks |
Response rate | PASI 75 for approximately 30% of the patients after 12 weeks (LE 1) |
Important contraindications (limited selection) | Chronic or acute infections, pregnancy, malignant diseases, immune deficiencies, no vaccinations before or during treatment |
Important ADRs (limited selection) | Flu-like injection reactions, leukocytosis and lymphocytosis, rebound, exacerbation and arthralgia, thrombocytopenia |
Important drug interactions | Not known |
Other | Stop therapy due to the risk of exacerbation and rebound if a PASI reduction of 50% is not achieved after 12 weeks |
Etanercept
Etanercept | |
---|---|
First approved in Germany | 2002 (Psoriasis arthritis )/2004 (psoriasis vulgaris) |
Recommended control parameters | Prior to therapy exclusion of tuberculosis, complete blood count, liver and renal values, urinanalysis |
Recommended initial dosage | Twice 25 mg per week or 2× 50 mg/week |
Recommended maintenance dosage | Twice 25 mg per week |
Expected beginning of clinical effect | After 4–8 weeks, at the latest after 12 weeks |
Response rate | PASI 75 in 34% (2 × 25 mg) or 49% (2 × 50 mg) of the patients at the end of the induction phase (12 weeks) (LE 1) |
Important contraindications (limited selection) | Infections, pregnancy, nursing, heart failure NYHA III–IV |
Important ADRs (limited selection) | Local reactions, infections |
Important drug interactions (limited selection) | Anakinra (IL-1 receptor antagonist) |
Other | – |
Infliximab
Infliximab | |
---|---|
First approved in Germany | 2004 (Psoriasis arthritis)/2005 (psoriasis vulgaris) |
Recommended control parameters | Prior to therapy exclusion of tuberculosis, during therapy: leukocyte and platelet counts, liver value controls, signs of clinical infection |
Recommended initial dosage | 5 mg/kg BW at week 0, 2, 6 |
Recommended maintenance dosage | 5 mg/kg BW in dosage intervals of 8 weeks |
Expected beginning of clinical effect | After 1–2 weeks |
Response rate | PASI 75 in ≥80% of the patients with moderate to severe psoriasis vulgaris (LE 1) |
Important contraindications (limited selection) | Acute or chronic infections, tuberculosis, cardiac failure NYHA III–IV, pregnancy and nursing |
Important ADRs (limited selection) | Infusion reactions, severe infections, progression of heart failure NYHA III–IV, very rare liver failure, autoimmune phenomena |
Important drug interactions (limited selection) | Anakinra (IL-1 receptor antagonist) |
Other | – |
Cyclosporine
Cyclosporine | |
---|---|
First approved in Germany | 1983 (Transplantation medicine) |
1993 (Psoriasis vulgaris) | |
Recommended control parameters | Interview/examination: |
• Status of skin and mucous membranes | |
• Signs of infection | |
• Neurological, gastrointestinal symptoms | |
• Blood pressure | |
Laboratory controls: see Table 14
| |
Recommended initial dosage | 2.5–3 (max. 5) mg/kg BW |
Recommended maintenance dosage | Interval therapy (between 8 and 16 weeks) with dosage reduction at the end of the induction therapy (e.g., 0.5 mg/kg BW every 14 days) or |
Continuous long-term therapy with dosage reduction (e.g. by 50 mg every 4 weeks after week 12) and a dosage increase by 50 mg with relapse | |
Maximum total duration of therapy: 2 years | |
Expected beginning of clinical effect | After approximately 4 weeks |
Response rate | Dose-dependent: after 8–16 weeks with 3 mg/kg BW; PASI 90 in approximately 30–50% of patient and PASI 75 in approximately 50–70% of patients (LE 1) |
Important contraindications (limited selection) | Absolute: |
Reduced renal function, insufficiently controlled arterial hypertension, uncontrolled infections, relevant malignancies (current or previous, in particular hematologic diseases and cutaneous malignancies with the exception of basal cell carcinoma) | |
Relative:
| |
Relevant hepatic dysfunction, pregnancy and nursing, concomitant use of substance which interacts with cyclosporine, concomitant UV-therapy or prior PUVA-pre-therapy with cumulative dosage >1000 J/cm², concomitant application of other immunosuppressives, retinoids or long-term prior-therapy with methotrexate (MTX) | |
Important ADRs (limited selection) | Renal failure, increase of blood pressure, liver failure, nausea, anorexia, vomiting, diarrhea, hypertrichosis, gingival hyperplasia, tremor, weariness, parasthesia, hyperlipidemia |
Important drug interactions (limited selection) | Increase of the cyclosporine level (CYP3A inhibition) through: |
Allopurinol, calcium antagonists, amiodarone, antibiotics (macrolides, clarithromycin, josamycin, ponsinomycin, pristinamycin, doxycycline, gentamicin, tobramycin, ticarcillin, quinolones), ketoconazole, oral contraceptives, methylprednisolone (high dosages), ranitidine, cimetidine, grapefruit juice | |
Decrease of the cyclosporine level (CYP3A induction) through: Carbamazepine, phenytoin, barbiturates, metamizole, St. John’s wort | |
Possible reinforcement of nephrotoxic adverse drug reactions through: Aminoglycosides, amphotericin B, ciprofloxacin, acyclovir, non-steroidal antiphlogistics | |
Specific interactions: | |
Potassium-saving substances: increased risk of hyperpotassemia | |
Reduced clearance of: Digoxin, colchicine, prednisolone, HMG-CoA reductase inhibitors (e.g. lovastatin), diclofenac | |
Other | Increased risk of lympho-proliferative diseases in transplant patients. Increased risk of squamous cell carcinoma in psoriasis patients following excessive phototherapy. |
Only moderately effective in and not approved for psoriatic arthritis | |
Also used successfully in the therapy of chronic-inflammatory diseases in children |
Fumaric acid esters
Fumaric acid esters | |
---|---|
First approved in Germany | 1995 (Psoriasis vulgaris) |
Recommended control parameters | Serum creatinine, transaminases/γGT, complete blood count including differential blood count, urinanalysis |
Recommended initial dosage | According to recommended dosage regimen see Table 17
|
Recommended maintenance dosage | Individually adapted dosage |
Expected beginning of clinical effect | After approximately 6 weeks |
Response rate | PASI 75 in 50–70% of the patients at the end of the induction phase after 16 weeks (LE 2) |
Important contraindications (limited selection) | Chronic diseases of the gastrointestinal tract and/or the kidneys and chronic diseases, which are accompanied by an impairment of the leukocyte count or functions, malignant diseases, pregnancy and nursing |
Important ADRs (limited selection) | Gastrointestinal complaints, flush, lymphopenia, eosinophilia |
Important drug interactions | None known |
Other | – |
Fumaderm initial | Fumaderm | |
---|---|---|
Week 1 | 1-0-0 | |
Week 2 | 1-0-1 | |
Week 3 | 1-1-1 | |
Week 4 | 1-0-0 | |
Week 5 | 1-0-1 | |
Week 6 | 1-1-1 | |
Week 7 | 2-1-1 | |
Week 8 | 2-1-2 | |
Week 9 | 2-2-2 |
Methotrexate
Methotrexate | |
---|---|
First approved in Germany | |
Lantarel®
| 1991 (Psoriasis vulgaris) |
Metex® 7.5/10 mg | 1992 (Psoriasis vulgaris) |
Metex® 2.5 mg | 2004 (Psoriasis vulgaris) |
Recommended control parameters | Complete blood count (Hb, HCT, differential blood count, platelets), renal function (serum creatinine, urea, urine sediment), liver values (serum transaminases), III-procollagen amino terminal propeptides |
Recommended initial dosage | 5–15 mg per week |
Recommended maintenance dosage | 5–22.5 mg per week depending on effect |
Expected beginning of clinical effect | After 4–8 weeks |
Response rate | PASI 75 in approximately 60% of the patients at the end of the induction phase of 16 weeks (LE 3) |
Important contraindications (limited selection) | Absolute contraindications: |
Desire to have children (for both men and women), pregnancy and nursing, inadequate contraception, drug consumption, alcoholism, known sensitivity to active ingredient methotrexate (e.g. pulmonary toxicity), bone marrow dysfunction, severe liver disease, severe infections, immunodeficiency, active peptic ulcers, hematologic changes (leucopenia, thrombocytopenia, anemia), renal failure | |
Relative contraindications: | |
Kidney disorders, liver disorders, history of arsenic consumption , chronic congestive cardio-myopathy, adiposity, old age, diabetes mellitus, history of hepatitis, lack of patient compliance, ulcerative colitis, diarrhea, NSAID use, gastritis | |
Important ADRs (limited selection) | Liver fibrosis/cirrhosis, pneumonia/alveolitis, bone marrow depression, renal damage, alopecia (reversible), nausea, weariness, vomiting, elevated transaminases, infection, gastrointestinal ulcerations, nephrotoxicity |
Important drug interactions (limited selection) | Cyclosporine, salicylates, sulfonamides, probenecide, penicillin, colchicin, NSAIDs (naproxene, ibuprofene, etc.), ethanol, co-trimoxazole, pyrimethamine, chloramphenicol, sulfonamides, prostaglandin synthesis inhibitors, cytostatics, probenecide, barbiturates, phenytoin, retinoids, sulfonamides, sulfonylurea, tetracyclines, co-trimoxazol, chloramphenicol, dipyridamole, retinoids, ethanol, leflunomide |
Other | Consistent avoidance of alcohol, X-ray of the lungs prior to beginning therapy |
Retinoids
Acitretin | |
---|---|
First approved in Germany | 1992 (Psoriasis vulgaris) |
Recommended control parameters | Erythrocyte sedimentation rate (ESR), complete blood count, liver values, renal values, blood lipid values, pregnancy test, x-ray control of the bones in case of long-term therapy |
Recommended initial dosage | 0.3–0.5 mg/kg BW per day for approximately 4 weeks, then 0.5–0.8 mg/kg BW |
Recommended maintenance dosage | Individual dosaging dependent on the results and tolerance |
Expected beginning of clinical effect | After 4–8 weeks |
Response rate | Widely variable and dose-dependent, no definite statement possible, partial remission (PASI 75) in 25–75% of the patients (30–40 mg per day) (LE 3) in studies |
Important contraindications (limited selection) | Renal and liver damage, desire to have children in female patients of child-bearing age, pregnancy, nursing, alcohol abuse, manifest diabetes mellitus, wearing of contact lenses, history of pancreatitis, hyperlipidemia requiring drug treatment |
Important ADRs (limited selection) | Hypervitaminosis A (e.g., cheilitis, xerosis, nose-bleeding, alopecia, increased skin fragility) |
Important drug interactions (limited selection) | Phenytoin, tetracyclines, methotrexate, alcohol, mini-pill |
Other | Contraception up to 2 years after discontinuation in female patients of child-bearing age |
Other therapies
Climate/balneotherapy
Climate/balneotherapy | |
---|---|
First approved in Germany | Clinical experience with balneotherapy has existed for more than 200 years |
Recommended control parameters | Regular skin inspection |
Recommended initial dosage | Therapy regimens vary depending on the institution/location |
Recommended maintenance dosage | Therapy regimens vary depending on the institution/location |
Expected beginning of clinical effect | Varies greatly |
Response rate | Varies greatly (LE 4) |
Important contraindications | Dependent on modality selected |
Important ADRs | Dependent on modality selected |
Important drug interactions | Not applicable |
Other | Balneotherapy and climate therapy are frequently combined |