Evaluation of TWEAK in Plaque Psoriasis and Psoriatic Arthritis Patients

Psoriasis vulgaris is associated with significant comorbidity including depression, increased risk of cardiovascular events, diminished quality of life, as well as overall increased mortality.

Moreover, concomitant psoriatic arthritis is present in up to 40% of psoriasis patients or will develop in the future.

To enhance quality of life and potentially lower the risk of concomitant disease in psoriasis patients, effective treatment of this immune-mediated systemic inflammatory disease is required

Psoriasis vulgaris is associated with significant comorbidity including depression, increased risk of cardiovascular events, diminished quality of life, as well as overall increased mortality.

The cytokine tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK), in cooperation with its sole receptor, Fn14, is involved in miscellaneous biological and pathological processes .

The main role of TWEAK is in the induction of pro-inflammatory cytokines and chemokines. The upregulation of TWEAK and Fn14 occurs in many human skin disorders, including cutaneous lupus erythematosus, bullous pemphigoid, and dermatomyositis . There is a lack of studies examining the role of TWEAK in patients with psoriasis or psoriatic arthritis.

The introduction of anti-tumor necrosis factor-α inhibitors (anti-TNF agents) has significantly improved outcomes among patients with PsA but a proportion of patients have an inadequate response or poor tolerability to these agents.

Adalimumab treatment continuation in routine clinical practice may lead to benefits for remission and low disease activity among patients with psoriasis, psoriatic arthritis, or axial spondyloarthritis who did not achieve their treatment goals at 12 weeks, according to recent findings.

Methotrexate (MTX)was approved for the treatment of psoriasis by the US Food and Drug Administration (FDA). At present, the drug is indicated for the treatment of practically all forms of moderate or severe psoriasis, including psoriatic arthritis .

Eligibility Criteria:
Inclusion Criteria:

* Patients of both sexes with psoriasis vulgaris and Psoriatic arthritis.
* Active PsA with three or more tender and swollen joints and met the CASPAR, despite previous treatment with NSAIDs, DMARDs or anti-TNFs

Exclusion Criteria:

* Previously received biologic immunomodulating agents, except for those targeting TNF
* Previously been treated with three or more different TNF inhibitors
* Active, ongoing inflammatory diseases other than PsA
* Active TB (patients with latent TB had to commence treatment for latent TB before study entry)
* A history of hepatitis B or C, human immunodeficiency virus, or any active systemic infection within the 2 weeks before baseline
* History of ongoing, chronic or recurrent infections, or evidence of active TB infection
* History of malignancy within the past 5 years (except for basal cell carcinoma or actinic keratosis that has been treated with no evidence of recurrence in the past 3 months, in situ cervical cancer or non-invasive malignant colon polyps that had been removed)
* Underlying metabolic, hematological, renal, hepatic, pulmonary, neurological, endocrine, cardiac, infectious or gastrointestinal conditions which, in the opinion of the investigator, immunocomprimised the patient and/or placed the patient at unacceptable risk for participation
* Pregnant or nursing (lactating) women and women of child-bearing potential unwilling to use effective contraception during the study and for 16 weeks after stopping treatment