German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version).

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1-S126, 2006; or http://www.psoriasis-leitlinie.de ).

Introduction

The Deutsche Dermatologische Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the treatment of plaque psoriasis. The full version of the Guidelines has been published in the Journal der Deutschen Dermatologischen Gesellschaft (JDDG 2006 Suppl 2) and is available at http://www.psoriasis-leitlinie.de [149]. This article summarizes the key points of the Guidelines.

Background

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries is 1.5–2% [2]. Studies on the impairment of life quality have shown that, depending on the severity of the disease, a significant burden may exist in the form of a disability or psychosocial stigmatization [3]. Patient surveys have shown that the mental and physical impairment associated with psoriasis is comparable to that of other significant chronic conditions, such as type 2 diabetes or chronic respiratory diseases [4].

Patient surveys have shown that only 25% of psoriasis patients are highly satisfied with the outcome of their treatment, another 50% indicate moderate satisfaction, and approximately 20% report low treatment satisfaction [5]. In addition, there is a high non-compliance rate in the intake of medication of up to 40% [1].

Experience has shown that treatment selection for patients with psoriasis vulgaris is more commonly based on traditional concepts than on evidence-based data on the efficacy of various therapeutic options. In addition, it appears that systemic therapies are occasionally not applied in situations where they are needed due to the increased effort involved in monitoring the patients for unwanted side effects and possible interactions with other drugs.

Goal of the Guidelines

The overall objective of the Guidelines is to provide dermatologists in clinics and private practice with an accepted and evidence-based decision-making tool for the selection and implementation of a suitable and efficacious treatment for patients with psoriasis vulgaris. The focus of the Guidelines is on the induction therapy of mild, moderate, and severe plaque-type psoriasis in adults.

Physicians’ personal experiences and traditional therapeutic concepts should be supplemented and, if necessary, replaced by an evidence-based assessment of the efficacy of individual therapies in psoriasis vulgaris.

The guidelines provide in-depth explanations of the available systemic and topical treatments for psoriasis, including the different photo- and photochemical therapies, and provide detailed descriptions of the administration and safety aspects.

By providing background information on the profile of the available drugs, including efficacy, safety, and aspects of practicality and costs, the Guidelines should facilitate the process of selecting an appropriate treatment for each individual patient. This should help increase compliance and optimize the benefit/risk ratio of psoriasis therapies.

Methods

A detailed description of the methodology employed in developing the Guidelines can be found in the Method Report on the Guidelines (http://www.psoriasis-leitlinie.de).

Basis of data

A systematic search of the literature was carried out in May 2005 with the objective of assessing the effectiveness of individual therapeutic options. This search yielded 6,224 publications of which 142 studies fulfilled the inclusion criteria for the Guidelines (see Box 1) and were therefore included in the assessment of the effectiveness of the relevant treatment. Various other aspects were evaluated on the basis of information presented in available literature, without a systematic analysis, and the years of personal experience of the experts.

Evidence assessment

The efficacy and effectiveness of each intervention was evaluated using evidence-based criteria.

The methodological quality of each individual study was assessed using the following grades of evidence (GE):Individual interventions (i.e., as monotherapy) were rated according to the following levels of evidence (LE):

Meta-analysis that includes at least one randomized study with grade A2 evidence. In addition, the results of the different studies included in the meta-analysis must be consistent with one another.

A high-quality (e.g. sample-size calculation, flow chart, intention-to-treat (ITT) analysis, sufficient size) randomized, double-blind comparative clinical study.

Randomized clinical study of lesser quality or other comparative study (non-randomized, cohort, or case-control study).

Non-comparative study.

Expert opinion.

Intervention is supported by studies with grade A1 evidence or studies with grade A2 evidence whose results are predominantly consistent with one another.

Intervention is supported by studies with grade A2 evidence or studies with grade B evidence whose results are predominantly consistent with one another.

Intervention is supported by studies with grade B evidence or studies with grade C evidence whose results are predominantly consistent with one another.

Little or no systematic empirical evidence

Therapeutic recommendation

A distinct rating of the therapeutic options or a strict clinical algorithm cannot be defined for the treatment of psoriasis vulgaris. The criteria for selecting a particular therapy are complex. The decision for a specific treatment should be based on the profile of the available drugs and the characteristics of a given patient. The decision for or against a therapy remains a case-by-case decision. These Guidelines provide a reasonable form of assistance in deciding on a suitable therapy and are an instrument for optimizing the required therapeutic process.

The recommendations formulated in the text are supported graphically in selected key recommendations by the following indications of the strength of the therapeutic recommendation:The strength of the recommendation reflects both a treatment’s efficacy and the level of evidence supporting it as well as aspects of safety, practicality, and the cost/benefit ratio. A consensus on the strength of the recommendation was reached during the Consensus Conference.

Measure is highly recommended

Measure is recommended

Neutral

Measure is not recommended

Measure is highly inadvisable

Results

Therapeutic options are named and discussed in alphabetical order.

Overview of the therapeutic options evaluated for chronic plaque psoriasis (the therapeutic options are listed alphabetically and do not represent a ranking)

Evaluation of topical and systemic therapies in tabular form

These tables are intended to provide a rough orientation for evaluating the therapeutic options. Cumulative calculations of the individual aspects for the overall evaluation of the therapeutic options are not possible and cannot be drawn upon for the final analysis of a therapeutic option. The product assessment for each individual patient may deviate greatly. A direct comparison between systemic and topical therapies is not possible because of the different severity of the psoriasis lesions of patients treated with topical or systemic treatments. The evaluations reported here were made on the basis of data extracted from the literature and expert opinions.

For further details refer to the Methods Report at www.psoriasis-leitlinie.de

Topical monotherapy

Phototherapy and systemic monotherapy

(a) Efficacy The evaluation of the efficacy column reflects the percentage of patients who achieved a reduction in the baseline Psoriasis Area and Severity Index (PASI) of ≥75%.

The evidence level applies only to the estimate of efficacy.

(b) Safety/tolerance in induction therapy or maintenance therapy This refers to the risk of occurrence of severe adverse drug reactions or the probability of adverse drug reactions that would result in the discontinuation of therapy.

(c) Practicality (Patient) This evaluation analyzes the effort involved in handling and administrating the treatment regimen by the patient.

(d) Practicality (Physician) This aspect considers the amount of work (documentation, explanation, monitoring), personnel and equipment needs, time for physician/patient interaction, remuneration of therapeutic measures, invoicing difficulties/risk of recourse claims from the health insurance companies.

(e) Cost/benefit Consideration of the costs of an induction therapy or a maintenance therapy.

The evaluations of safety/tolerance in induction therapy or maintenance therapy as well as practicality for the physician or patient and the cost/benefit were performed using a scale ranging from poor (–) to good (++++). The gradation between these two extremes was made based on expert opinion and unsystematic literature search. A level of evidence was not given for these evaluations since no systematic literature review was performed.

Evaluation of topical therapies

Calcineurin inhibitors

Corticosteroids

Coal tar

Dithranol

Tazarotene

Vitamin D3 and analogues

Phototherapy

Evaluation of systemic therapies

Efalizumab

Etanercept

Infliximab

Cyclosporine

Fumaric acid esters

Methotrexate

Retinoids

aDouble contraception is recommended (e.g., condom + pill; IUD/Nuva-Ring + pill; cave: no low-dosed progesterone preparations/mini-pills) during and up to 2 years after the end of therapy; effectiveness is reduced by acitretin

Other therapies

Climate/balneotherapy

Psychosocial therapy

Notes on the use of the Guidelines

The presentation of the therapies deliberately focused on those aspects deemed particularly relevant by a panel of experts. Aspects which are not of specific importance for a certain intervention, but which are part of the physician’s general obligations to the patient, such as the investigation of intolerance and allergies toward certain drugs or the exclusion of contraindications, are not individually listed, but it is nevertheless taken for granted that these are part of the physician’s duty to provide care.

It is recommended that each and every user carefully reads and follows the product information and compare it with the recommendations in the Guidelines on dosaging, contraindications, and drug interactions for completeness and currentness. Every dose or application is administered at the user’s own risk. The authors and the publishers kindly request that users inform them of any inaccuracies that they might notice. The users are requested to keep themselves constantly informed of any new findings subsequent to the publication of the Guidelines.

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

Table 1

Tabular summary

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× dailyTacrolimus: 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!

Table 2

Tabular summary

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	–

Table 3

Tabular summary

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

Table 4

Tabular summary

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	–

Table 5

Tabular summary

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	–

Table 6

Tabular summary

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

Table 7

Tabular summary

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, immunosuppressionOnly PUVA: pregnancy and nursing
Important ADRs	Erythema, itching, blistering, malignanciesOnly 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

Table 8

Tabular summary

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

Table 9

Laboratory controls during treatment with efalizumab

aHb (hemoglobin), HCT (hematocrit), erythrocytes, leukocytes, differential blood count, platelets

bALT alanine aminotransferase, AST aspartate aminotransferase

Table 10

Tabular summary

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	–

Table 11

Laboratory controls during treatment with etanercept

Table 12

Tabular summary

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	–

Table 13

Laboratory controls during treatment with infliximab

aHb, HCT, erythrocytes, leukocytes, differential blood count, platelets

Table 14

Tabular summary

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

Table 15

Laboratory controls during treatment with cyclosporine

aErythrocytes, leukocytes, platelets

bALT, AST, AP (alkaline phosphatase), γGT (gamma glutamyl transpeptidase), bilirubin

cSodium, potassium

dRecommended twice (fasting) and week-2 and 0

eOnly with indication (e.g. muscle cramps)

Table 16

Tabular summary

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	–

Table 17

Dosage regimen for Fumaderm therapy

	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

Table 18

Laboratory controls during treatment with fumaric acid esters

aLeukocytes, platelets, erythrocytes, differential blood count

Table 19

Tabular summary

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

Table 20

Laboratory controls during treatment with MTX [137]

aHb, HCT, erythrocytes, leukocytes, differential blood count, platelets

bALT, AST, AP, γGT, albumin, bilirubin, lactate dehydrogenase (LDH)

cLiver biopsy instead of a liver sonography in risk groups

Table 21

Tabular summary

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

Table 22

Laboratory controls during treatment with Acitretin

aHb, HCT, leukocytes, platelets

bPreferably assayed twice (week-2 and 0); HDL, high-density lipidoprotein

Table 23

Tabular summary

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