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Author: Anoma Ranaweera, Medical Writer, Auckland, New Zealand. DermNet NZ Editor in Chief: Adjunct A/Prof Amanda Oakley, Dermatologist, Hamilton, New Zealand. Copy edited by Gus Mitchell. May 2018.
In March 2018, tildrakizumab (Ilumya™; Sun Pharma, Mumbai, India) received US Food and Drug Administration (FDA) approval for the treatment of moderate-to-severe plaque psoriasis in patients who are candidates for systemic therapy or phototherapy. This monoclonal antibody, which selectively binds to the p19 subunit of interleukin (IL) 23 and inhibits its interaction with the IL-23 receptor, was licensed by Sun Pharma from Merck and Co. (New Jersey, USA) in 2014.
Tildrakizumab is the second approved biological therapy that selectively blocks only IL-23, a cytokine that plays a key role in plaque psoriasis.
Tildrakizumab received FDA approval based on safety and efficacy data from the Phase III reSURFACE clinical trials that compared tildrakizumab to placebo and etanercept. In both studies, tildrakizumab was linked to significant improvements versus placebo and etanercept at Week 12 as measured by the Psoriasis Area Sensitivity Index (PASI) and Physician's Global Assessment (PGA) scores.
Almirall has been granted rights to develop and commercialise the drug in Europe. Almirall filed the drug for regulatory approval with the European Medicines Agency in March 2017.
Tildrakizumab is currently not available in New Zealand.
The approval of tildrakizumab was based on two Phase III trials.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data from Phase III randomised, placebo-controlled trials were pooled to evaluate the safety of tildrakizumab. The table below summarises the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the tildrakizumab 100-mg group compared to placebo.
Table. Adverse reactions in ≥ 1% of subjects treated with tildrakizumab
|Adverse reaction||Tildrakizumab 100mg (n = 705)||Placebo|
|Upper respiratory infections||98 (14%)||41 (12%)|
|Injection site reactions||24 (3%)||7 (2%)|
|Diarrhoea||13 (2%)||5 (1%)|
Respiratory infections observed as an adverse reaction in patients treated with tildrakizumab include:
Injection site reactions observed as an adverse reaction in patients treated with tildrakizumab include:
Adverse reactions that occurred in < 1% of the tildrakizumab group and at a higher rate than in the placebo group include:
Cases of angioedema and acute urticaria have occurred in tildrakizumab-treated subjects in clinical trials. If a serious hypersensitivity reaction occurs, the drug should be discontinued immediately and an appropriate therapy should be initiated.
The rates of serious infections for patients in the tildrakizumab group and the placebo group were ≤ 0.3%. Treatment with tildrakizumab should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.
Phase III studies with tildrakizumab have shown great promise regarding tildrakizumab's efficacy and short-term safety. However, larger, long-term studies and evidence from everyday practice are needed to confirm these assumptions. Head-to-head randomised controlled trials in comparison with current therapies, such as ustekinumab and guselkumab, are needed to understand tildrakizumab's relative efficacy. The main advantage of tildrakizumab is that it is dosed in a maintenance regimen of 12 weeks (similar to ustekinumab), and this is likely to encourage treatment adherence.
As the understanding of the immunopathogenesis of psoriasis grows, the emphasis has turned toward more specific targets for psoriasis drugs. The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis.
Agents that target the p40 subunit common to both IL-12 and IL-23 (such as ustekinumab) have shown robust clinical activity. However, selectivity for IL-23p19 could offer advantages in efficacy and safety with respect to the anti-p40 blockade. Acting upstream in the IL-23/IL-17 cytokine pathway is likely to reduce the expression of multiple pro-inflammatory cytokines acting on keratinocytes, including IL-17F, IL-21, and IL-22, in addition to IL-17A.
Based on that understanding, the selective targeting of the IL-23p19 subunit has emerged as an attractive therapeutic option and led to the development of a new category of biological agents (eg, guselkumab and tildrakizumab) for the treatment of moderate-to-severe psoriasis. Safety data thus far suggest that these drugs might be devoid of some of the adverse effects of IL-17A blockade demonstrated by secukinumab and brodalumab (eg, mucocutaneous candida infections or the triggering or worsening of inflammatory bowel disease).
Biological drugs targeting these cytokines and their receptors have proven to be effective and safe in clinical trials and have offered greater efficacy than pre-existing biologicals, as evidenced by the large proportions of patients achieving not only PASI 75 but also 90% and 100% improvement in PASI score (PASI 90 and PASI 100).
New Zealand approved datasheets are the official source of information for these prescription medicines, including approved uses and risk information. Check the individual New Zealand datasheet on the Medsafe website.
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