Outcomes With Treatment and Withdraw of Ixekizumab in Patients With Plaque Psoriasis
Status:
Recruiting
Trial end date:
2027-12-31
Target enrollment:
Participant gender:
Summary
Psoriasis (PsO) is a systemic immune disease that affect 2-4% of the population worldwide.
PsO causes tremendous burden in terms of quality of life, psychological impact, disability
and work productivity of affected individuals. PsO is associated with an increased risk of
cardiovascular morbidities and mortality in the long term. Up to 30% of PsO patients develop
psoriatic arthritis (PsA) over time causing joint deformities and further disabilities.
Majority of patients with PsA developed PsO first, and arthritis develop 5-10 years
afterwards. PsA and PsO are increasingly recognized as two entities under the umbrella of
psoriatic diseases.
Advances in biological treatments have greatly improved the prognosis of patients with PsO.
Remarkable efficacies have been demonstrated for patients with moderate to severe PsO in
randomized controlled trials (RCTs). However, the high cost of biological treatment is one of
the major barriers to prescription of biological treatment and many patients may have limited
access to these treatments.
The best strategy of treatment for PsO that takes into account efficacy and cost
effectiveness is unknown. For instance, whether some PsO patients can stop biological
treatment and be retreated with non-biologic medications upon relapse, which may enhance cost
effectiveness of treatment. Preliminary studies have shown that some PsO patients were able
to maintain good control of disease without medications after biologics withdrawal. The
patho-immunological mechanisms behind long term remission after drug withdrawal is poorly
understood. Better understanding on patho-immunological mechanisms on maintenance of
remission and relapses will advance the development of biomarkers that eventually guide
development of best treatment strategies for PsO.
Ixekizumab is a humanized immunoglobulin G4 (IgG4 kappa) monoclonal antibody targeting
interleukin (IL)-17A. It is highly efficacious in the treatment of plague PsO with and
favorable safety profile as shown in randomized controlled trials, and is an approved
treatment for moderate-to-severe PsO by the U.S. Food and Drug Administration and Health
Sciences Authority. With the proven efficacies, ixekizumab could be a choice of first-line
treatment for patients with moderate to severe PsO. The 2013 American Academy of Dermatology
position statement have stated that the old paradigm of stepwise-therapy starting first with
phototherapy and oral systemic therapies before biologic treatment is not required for
patients with moderate to severe PsO. In the recent 2017 update of the European S3 guidelines
also recommend the use of IL-17 inhibitors as either a first- or second-line agent. In a RCT
that evaluated relapses after withdrawal of ixekizumab among patients who achieved a
clearance of PsO, loss of PsO clearance were seen after a median of 20 weeks. Response can be
successfully recaptured in over 80% of patients with retreatment with ixekizumab, suggesting
that the treatment regimen could be interrupted in some patients. However, real-life data on
biologic treatment or withdrawal for moderate to severe PsO is scatty.