Trial in Patients With Psoriasis Treated With Methotrexate Using an Optimized Treatment Schedule (METOP)

Inclusion Criteria:

1. Are 18 years of age or older at time of informed consent; may be men or women.

2. Are MTX naïve

3. Moderate to severe plaques psoriasis (according rule of ten (PASI ≥10 or BSA ≥ 10 orDLQI ≥ 10) for at least 6 months with or without psoriatic arthritis (however, highlyactive psoriatic arthritis is excluded, defined by. > 5 swollen tender joints or solesand C-Reactive Protein (CRP) >2 x UNL) .

4. Women of childbearing potential and all men must be using a highly effective method ofcontraception (pearl index < 1%) as defined blow and must agree to continue to usesuch measures and not become pregnant or plan a pregnancy until 6 months afterreceiving the last injection of Investigational Medicinal Product (IMP).Highlyeffective method is defined as: Use of oral, injected or implanted hormonal methods,intrauterine device (IUD) or intrauterine system (IUS), barrier methods ofcontraception: condom or occlusive cap (diaphragm or cervical/vault caps) withspermicidal foam/gel/film/cream/suppository.

5. Able to adhere to the study visit schedule and other protocol requirements.

6. Capable of giving informed consent. The informed consent must be obtained prior to anystudy related procedures.

7. Must avoid prolonged sun exposure and avoid use of tanning booths or other ultravioletlight sources during study.

8. Must agree not to receive a live virus or live bacterial vaccination 4 weeks prior tothe first IMP s.c. administration, during the trial and up to 3 months after the lastinjection.

9. Chest X-ray investigation within the last 6 months prior to first s.c. administrationof IMP and show no clinically relevant abnormalities

Exclusion Criteria:

1. Currently have non-plaque forms of psoriasis (eg, erythrodermic, guttate, orpustular).

2. Have current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbationof psoriasis from beta blockers, (hydroxy-) chloroquine, or lithium).

3. Are pregnant, nursing, or planning pregnancy (both men and women) while enrolled inthe study.

4. Have screening laboratory test results for the following parameters outside the statedranges (please refer also to :

5. Hemoglobin < 10 g/dL

6. White blood cells < 3.0 x 109/L

7. Neutrophils < 1.5 x 109/L

8. Platelets < 100 x 109/L

9. Creatinine clearance (calculated according to Cockcroft-Gault) < 50 mL/min)

10. Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), and GammaGlutamyltransferase (γ-GT) levels must be > 2 times the upper limit of normalrange

11. Bilirubin > 5mg/dl (85,5 μmol/l)

12. Hypalbuminemia <3,5 g/dl

13. Have used any other IMP within the previous 4 weeks or 5 times the half-life of aninvestigational agent prior to the first s.c. administration of the IMP of this study,whichever is longer.

14. Not able or willing to wash out any prohibited medications as listed below.

• Any biologics; washout 5 times of half-life

• Phototherapy or any systemic medications that could affect the psoriasis (including but not limited to oral or injectable corticosteroids, retinoids, 1,25dihydroxy vitamin D3 and analogues, sulfasalazine, hydroxyurea, or fumaric acidderivates), within 4 weeks

• Any topical medications that could affect the psoriasis (e.g. corticosteroids,anthralin, calcipotriene, topical vitamin D derivates, retinoids, tazarotene),within 2 weeks

• Any systemic immunosuppressants (e.g. azathioprine, cyclosporine, 6-thioguanine,mercaptopurine, mycophenolate mofetil, hydroxyurea, and tacrolimus) ,within 4weeks

• lithium, antimalarial agents To be stopped directly prior to first s.c.administration of IMP

• Intramuscular gold ,Within 4 weeks Patients who take prohibited medications thatcannot be washed out within 4 weeks or at least 5 times of the half-life of theinvestigational agent prior to first s.c. administration of IMP should not be asked to participate in the trial.

7. Have a history of chronic or recurrent infectious disease or had a serious infectionor have been hospitalized or received i.v. antibiotics for the treatment of aninfection within 2 months prior to screening.

8. History of radiotherapy or planed concomitant radiotherapy

9. Ulcers of the oral cavity (e.g. ulcerative stomatitis) and/or known gastrointestinalulcer disease

10. A known B12/cobalamin deficiency

11. Known diagnosed ascites or pleural effusions

12. Have a history of latent or active Tuberculosis (TB) (prior to screening).

13. Have current signs or symptoms of severe, progressive, or uncontrolled renal (specifically with calculated creatinine clearance < 20), hepatic (especially withbilirubin > 5mg/dl (85,5 mol/l), hematological, gastrointestinal, endocrine,pulmonary, cardiac, neurologic, cerebral, or psychiatric disease.

14. Have any known malignancy or have a history of malignancy (with the exception of basalcell carcinoma, squamous cell carcinoma in situ of the skin, or cervical carcinoma insitu that has been treated with no evidence of recurrence, or squamous cell carcinomaof the skin that has been treated with no evidence of recurrence within 5 years priorto the first administration of study agent).

15. Have shown a previous immediate hypersensitivity response, including anaphylaxis, tothe folic acid

16. Are unable or unwilling to undergo multiple venipunctures because of poor tolerabilityor lack of easy access to veins.

17. Are known to have had a substance abuse (drug or alcohol) problem within the previous 12 months.

18. Staff or relatives/partner of any clinical research site