Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis

Abstract

A randomized, double-blind, placebo-controlled, multicenter study of secukinumab to demonstrate the efficacy at 24 weeks and to assess the long term safety, tolerability and efficacy up to 2 years in patients with active psoriatic arthritis List of tables List of figures Glossary of termsAssessment A procedure used to generate data required by the study Control drug A study drug used as a comparator to reduce assessment bias, preserve blinding of investigational drug, assess internal study validity, and/or evaluate comparative effects of the investigational drug Enrollment Point/time of patient entry into the study; the point at which informed consent must be obtained (i.e. prior to starting any of the procedures described in the protocol)Inadequate response to TNFα Active disease despite stable treatment with anti-TNFa for at least 3 months at a stable dose or for at least one dose in the case of lack of tolerance Investigational drugThe study drug whose properties are being tested in the study; this definition is consistent with US CFR 21 Section 312.3 and is synonymous with "investigational new drug."Medication number A unique identifier on the label of each study drug package in studies that dispense study drug using an IVR systemPatient number A number assigned to each patient who enrolls in the study. When combined with the center number, a unique identifier is created for each patient in the study. PeriodA minor subdivision of the study timeline; divides phases into smaller functional segments such as screening, baseline, titration, washout, etc.Phase A major subdivision of the study timeline; begins and ends with major study milestones such as enrollment, randomization, completion of treatment, etc.Premature patient withdrawal Point/time when the patient exits from the study prior to the planned completion of all study drug administration and assessments; at this time all study drug administration is discontinued and no further assessments are plannedRandomization number A unique identifier assigned to each randomized patient, corresponding to a specific treatment arm assignment Stop study participation Point/time at which the patient came in for a final evaluation visit or when study drug was discontinued whichever is later Study drug Any drug administered to the patient as part of the required study procedures; includes investigational drug and any control drugs Study drug discontinuation Point/time when patient permanently stops taking study drug for any reason; may or may not also be the point/time of premature patient withdrawal Variable Information used in the data analysis; derived directly or indirectly from data collected using specified assessments at specified timepointsThis document (090095a88362b521 in docbase CREDI_BS) has been digitally signed with external signatures using Entrust PKI. Protocol synopsisTitle of study: A randomized, double-blind, placebo-controlled, multicenter study of secukinumab to demonstrate the efficacy at 24 weeks and to assess the safety, tolerability and...

Secukinumab improves psoriasis symptoms in patients with inadequate response to cyclosporine A: A prospective study to evaluate direct switch

“…In agreement with the concept, the present direct switch study showed no new or unexpected safety signals during the 16‐week treatment, with a safety profile consistent with that reported in the pivotal secukinumab phase III trials 12, 14, 16, 17. It is noteworthy that the incidence of AE during the 4‐week induction period was lower (29.4%) than that of the 16‐week entire study period (70.6%), suggesting a smooth switch to secukinumab without major safety concerns.…”

“…Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL‐17A, has been shown to have a significant efficacy in the treatment of moderate‐to‐severe psoriasis11, 12, 13, 14 and psoriatic arthritis,15, 16, 17 showing a rapid onset of action and sustained responses with a favorable safety profile. Secukinumab has been approved for the treatment of multiple indications, such as moderate‐to‐severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis in USA and Europe 15, 17, 18. In Japan, it is approved for plaque psoriasis, psoriatic arthritis and generalized pustular psoriasis 19.…”

Phase II Study of ABT‐122, a Tumor Necrosis Factor– and Interleukin‐17A–Targeted Dual Variable Domain Immunoglobulin, in Patients With Psoriatic Arthritis With an Inadequate Response to Methotrexate

“…The PASI90 skin responses in particular suggest that ABT‐122 is functioning largely through its effects on anti‐TNF activity, since the greater efficacy expected with the addition of IL‐17A inhibition 13, 14 was not seen.…”

“…Levels of TNF and IL‐17A–producing CD8+ T cells are elevated in the synovial fluid of patients with PsA 4, 9. Inhibition of either TNF or IL‐17A alone has demonstrated efficacy in improving joint inflammation, features of skin disease, and quality of life in patients with PsA 10, 11, 12, 13, 14, 15, 16, suggesting that TNF and IL‐17A may both contribute to the pathophysiology of PsA. An unanswered question has been whether, assuming that the contributions of TNF and IL‐17A are at least partly independent of one another, dual neutralization of TNF and IL‐17A may provide the opportunity to achieve better control of inflammation in patients with PsA compared to neutralization of either target alone.…”

Brief Report: Secukinumab Provides Significant and Sustained Inhibition of Joint Structural Damage in a Phase III Study of Active Psoriatic Arthritis

“…In the placebo‐controlled, double‐blind, phase III FUTURE 1 study, secukinumab provided rapid, significant, and sustained improvements in key clinical domains of PsA, including signs and symptoms, physical functioning, and quality of life 7. Moreover, secukinumab significantly reduced radiographic progression, as measured by change from baseline to week 24 in the modified total Sharp/van der Heijde score (SHS) for PsA 8, compared with placebo 7. The current report describes 52‐week radiography results from FUTURE 1, and presents the results of analyses related to previous anti–tumor necrosis factor (anti‐TNF) therapy with concomitant methotrexate (MTX).…”