Effect of Secukinumab in the Treatment of Psoriatic Arthritis

Patients Inclusion Criteria: * Patients with active psoriatic arthritis (fulfilling CASPAR criteria) affecting ≥2 peripheral joints (swollen and tender) that have not responded to at least one standard DMARDs * All meet CASPAR criteria for diagnosis of PsA, * Be rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) negative at screening, * Have had no prior exposure to biologic therapy, * Not have received parenteral glucocorticosteroids in the 6 weeks prior to the baseline assessment, * If taking oral glucocorticoids remain on a stable dose of \<10mg throughout the study with no change in dose in the 6 weeks prior to baseline assessment, * If taking methotrexate or other DMARDs remain on a stable dose throughout the study and not have changed dose or therapy for 6 weeks prior to the baseline assessment Patients Exclusion Criteria: * Active or chronic infection including mycobacterium tuberculosis, HIV, hepatitis B or C * Absence of active psoriatic arthritis * Patients who are starting anti-TNF therapy for treating PsA * Pregnancy and planning pregnancy 1. WOCBP who are unwilling or unable ot use acceptable method to avoid pregnancy for study duration plus timeframe as specified in section 5.2.5. 2. Women who are pregnant or breastfeeding 3. Sexually active fertile men not using effective birth control if their partners are WOCBP. * Malignancy * Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process obtained within 3 months prior to Screening and evaluated by a qualified physician. * Patients with hyponatraemia and nephrotic syndrome * Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor. * Use of any investigational drug and/or devices within 4 weeks before registration or a period of 5 half-lives of the investigational drug, whichever is longer. * Significant comorbidity that, in the opinion of the investigator, would impact on ability to participate * Any change in the dose of oral glucocorticosteroids or DMARDS in the prior 6 weeks prior to the Baseline visit or use of i.v. intramuscular or intra-articular glucocorticosteroid during the last 6 weeks prior to the enrolment visit. * Patients who have previously been treated with TNFα inhibitors (investigational or approved). * History of hypersensitivity to the study drug or its excipients or to drugs of similar classes. * Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19). * Active ongoing inflammatory diseases other than PsA that might confound the evaluation of the benefit of secukinumab therapy. * Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine,cardiac, infectious or gastrointestinal conditions which in the opinion of the Investigator immunocompromise the patient and/or place the patient at unacceptable risk for participation in an immunomodulatory therapy. * Significant medical problems or diseases, including but not limited to the following: uncontrolled hypertension (≥ 160/95 mmHg), congestive heart failure (New York Heart Association status of class III or IV), uncontrolled diabetes. * History of clinically significant liver disease or liver injury as indicated by abnormal liver function tests (LFT) such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, or serum bilirubin. The Investigator should be guided by the following criteria: 1. Any single parameter may not exceed 2 x upper limit of normal (ULN). A single parameter elevated up to and including 2 x ULN should be re-checked once more as soon as possible, and in all cases, at least prior to enrollment/registration, to rule out laboratory error. 2. If the total bilirubin concentration is increased above 2 x ULN, total bilirubin should be differentiated into the direct and indirect reacting bilirubin. In any case, serum bilirubin should not exceed 1.6 mg/dL (27 μmol/L). * History of renal trauma, glomerulonephritis, or patients with 1 kidney only, or a serum creatinine level exceeding 1.5 mg/dL (132.6 μmol/L). * Screening total white blood cell (WBC) count \< 3 000/μL, or platelets \< 100 000/μL or neutrophils \< 1 500/μL or hemoglobin \< 8.5 g/dL (85 g/L). * Active systemic infections during the last 2 weeks (exception: common cold) prior to registration. * History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis according to local practice/guidelines) or a positive QuantiFERON TB-Gold test or TB-Spot Test (as indicated in Section 4.1 and Table 6-1). Patients with a positive test may participate in the study if further work up (according to local practice/guidelines) establishes conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is established then treatment according to local country guidelines must have been initiated. * Known infection with human immunodeficiency virus, hepatitis B or hepatitis C at Screening or registration. * History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 3 months, carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed). * Use of Vitamin D containing supplements. * Inability or unwillingness to undergo repeated venepuncture (e.g. because of poor tolerability or lack of access to veins). * Patients who have received a live vaccine within 4 weeks prior to planned registration must be excluded. Healthy Controls Inclusion Criteria: * 10 healthy control blood samples. * The healthy controls will be recruited from staff at the University of Liverpool or Aintree University hospitals and who are not taking nor have taken over the preceding 6 months, any immunosuppressive agent including systemic corticosteroids and whose health is otherwise good. There will be an equal balance of males to females. Matching to biologic or DMARD controls is not required. The healthy controls will provide one sample of blood for neutrophil studies.