study to demonstrate the efficacy, safety and tolerability of intravenous secukinumab up to 52 weeks in subjects with active psoriatic arthritis

Conditions: Psoriatic Arthritis

Summary: the purpose of this study was to provide up to 52 weeks of efficacy, safety and tolerability data to support registration of intravenous (i.v.) secukinumab (initial dose of 6 mg/kg at baseline (bsl) followed thereafter with 3 mg/kg administered every four weeks) in patients with active psoriatic arthritis (psa) despite current or previous non-steroidal anti-inflammatory drugs (nsaids), disease-modifying antirheumatic drugs (dmards) and/or anti-tumor necrosis factor (tnf) therapy.

this multicenter study used a randomized, double-blind, placebo-controlled, parallel-group design. a screening (scr) period running up to 10 weeks before randomization was used to assess subject eligibility followed by a treatment period of 52 weeks. at baseline, 381 patients with active psoriatic arthritis were randomized to one of the two treatment groups in a 1:1 randomization: group 1: approximately 190 patients with active psoriatic arthritis; these patients received secukinumab 6 mg/kg i.v. at bsl, followed by the administration of secukinumab 3 mg/kg i.v. every four weeks starting at week 4. group 2: approximately 190 patients with active psoriatic arthritis; these patients received i.v. placebo at bsl and at weeks 4, 8, and 12, followed by the administration of secukinumab 3 mg/kg i.v. every four weeks starting at week 16. study consisted of 4 periods: a screening period (up to 10 weeks), treatment period 1 (total duration of 16 weeks) and treatment period 2 (total duration of 36 weeks) followed by a safety follow up period of 8 weeks after the end of treatment visit (i.e., week 52). primary endpoint analysis will be performed with week 16 data (last patient completing treatment period 1 (week 16). long-term efficacy and safety assessments will be performed up to week 52.

Eligibility criteria:
patients eligible for inclusion in this study had to fulfill all of the following criteria: * diagnosis of psa classified by caspar criteria and with symptoms for at least 6 months with moderate to severe psa who must have at baseline ≥3 tender joints out of 78 and ≥3 swollen out of 76 (dactylitis of a digit counts as one joint each) * rheumatoid factor and anti-ccp antibodies negative at screening * diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or documented history of plaque psoriasis * subjects with psa should have taken nsaids for at least 4 weeks prior to randomization with inadequate control of symptoms or at least one dose if stopped due to intolerance to nsaids * subjects taking corticosteroids must be on a stable dose of ≤10 mg/day prednisone or equivalent for at least 2 weeks before randomization and should remain on a stable dose up to week 16 * subjects taking mtx (≤ 25 mg/week) are allowed to continue their medication if the dose is stable for at least 4 weeks before randomization and should remain on a stable dose up to week 52. patients fulfilling any of the following criteria are not eligible for inclusion in this study: * 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 * subjects taking high potency opioid analgesics (e.g. methadone, hydromorphone, morphine) * previous exposure to secukinumab or other biologic drug directly targeting il-17 or il-17 receptor * ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, uv therapy) at randomization. the following wash-out periods need to be observed: * oral or topical retinoids- 4 weeks * photochemotherapy (e.g. puva)- 4 weeks * phototherapy (uva or uvb)- 2 weeks * topical skin treatments (except in face, eyes, scalp and genital area during screening, only corticosteroids with mild to moderate potency)- 2 weeks * any intramuscular or intravenous corticosteroid treatment within 4 weeks before randomization. * any therapy by intra-articular injections (e.g. corticosteroid) within 4 weeks before randomization. * subjects who have previously been treated with more than 3 different tnf inhibitors (investigational or approved). * subjects who have ever received biologic immunomodulating agents, investigational or approved except for those targeting tnfα. * previous treatment with any cell-depleting therapies including but not limited to anti-cd20 or investigational agents (e.g., campath, anti-cd4, anti-cd5, anti-cd3, anti-cd19)

Keywords: active psoriatic arthritis intravenous secukinumab psa