Dataset Information

Exposure-response characterisation of tildrakizumab in chronic plaque psoriasis: Pooled analysis of 3 randomised controlled trials.

ABSTRACT:

Aims

In this exposure-response analysis, the dosing regimen for tildrakizumab, an antibody for treating moderate-to-severe chronic plaque psoriasis, was determined using data from 3 randomised controlled trials (P05495/NCT01225731: phase 2b, n = 355; reSURFACE 1/NCT01722331: phase 3, n = 772; reSURFACE 2/NCT01729754: phase 3, n = 1090).

Methods

A maximum drug effect (E_max ) logistic-regression exposure-efficacy model was used to describe the week 12 Psoriasis Area and Severity Index (PASI) responses with average concentration of tildrakizumab during weeks 1-12 (C_avg12 ) as exposure metric. The impact of covariates (e.g., body weight, region) was tested. Exposure-safety, longitudinal pharmacokinetic-pharmacodynamic and risk-benefit analyses were also conducted.

Results

At week 12, E_max was estimated at 62.2, 37.9 and 14.6% of responders for PASI75/90/100, respectively. Exposure-response curves plateaued at exposures >5 μg mL^-1 . Heavier subjects had a lower response rate to placebo as measured by PASI75/90/100 than lighter subjects. PASI100 placebo response was less in subjects with higher baseline PASI score and older age. Simulated week 12 PASI75 increased by ≤4% on increasing the dose from 100 to 200 mg every 12 weeks (Q12W). The pharmacokinetic-pharmacodynamic model adequately described the time course of PASI change after treatment in the entire population and in each subject. Risk-benefit profiles were favourable for the 100- and 200-mg doses in different weight subgroups.

Conclusions

Patients with moderate-to-severe psoriasis should receive 100-mg subcutaneous tildrakizumab Q12W. Patients with high body weight (>90 kg) may benefit from a higher dose (200-mg Q12W).

SUBMITTER: Kerbusch T

PROVIDER: S-EPMC7444761 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Psoriasis affects 1-3% of the population, in some people causing changes to the nails and joints in addition to skin lesions. We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of systemic drug treatments, topical drug treatments, and non-drug treatments (other than ultraviolet light) for chronic plaque psoriasis? What are the effects of ultraviolet light treatments for chronic plaque psoriasis? What are the effects of combined treatment with drugs plus ultraviolet light on chronic plaque psoriasis? What are the effects of combined systemic plus topical drug treatments for chronic plaque psoriasis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). We found 122 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, adding calcipotriol (topical) to psoralen plus ultraviolet light A or ultraviolet light B, adding oral retinoids to psoralen plus ultraviolet A (PUVA), alefacept, balneotherapy, ciclosporin, dithranol, T cell-targeted therapies, cytokine blocking agents, emollients (alone or plus ultraviolet light B), etanercept, fish oil supplementation, fumaric acid derivatives, Goeckerman treatment, heliotherapy, infliximab, Ingram regimen, keratolytics (salicylic acid, urea), leflunomide, methotrexate, oral pimecrolimus, phototherapy plus balneotherapy, psoralen plus ultraviolet A, psychotherapy, oral retinoids (alone or with ultraviolet light B), systemic drug treatments plus topical vitamin D derivatives, tars, tazarotene, topical corticosteroids (alone or plus oral retinoids), topical Vitamin D derivatives, ultraviolet light A, and ultraviolet light B.

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