Guselkumab shows highest drug survival among systemic treatments

In a comparison of 5 commonly used systemic treatments for psoriasis, guselkumab demonstrated the highest drug survival and adalimumab the lowest in a prospective cohort study from the BADBIR. If the drug was discontinued due to ineffectiveness of treatment, drug survival was also affected by prior lines of biologic therapy.

“Drug survival essentially measures the time between starting and stopping a treatment and that serves as a proxy marker for a treatment’s effect,” Dr Zenas Yiu (University of Manchester, UK) explained [1]. He pointed out that real-world evidence on drug survival is still inconsistent and previous study results have been limited by a lack of data on discontinuation reasons or previous biologic therapies.

To gain more insight, a prospective cohort study was conducted using data between 2007 and 2021 from the longitudinal, pharmacovigilance registry on patients with moderate-to-severe psoriasis: the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). “There are currently 165 recruiting centres, over 20,400 registrations and over 76,000 patient-years,” Dr Yiu said.

Therapy discontinuation was defined as a treatment gap of more than 90 days. The study included data on the most widely used agents for psoriasis: adalimumab (TNF inhibition), guselkumab (IL-23 inhibition), ustekinumab (IL-12/23 inhibition), ixekizumab and secukinumab (IL-17A inhibition). Drug survival was analysed at 1 and 2 years, and flexible parametric survival models were fitted to evaluate possible effect modification by variables like age, sex, body mass index, or history of prior biologic therapy.

As the investigated drugs have been on the market for different time-spans, the number of evaluated patients differed. For example, the adalimumab cohort comprised 6,607 participants, while the ixekizumab and the guselkumab groups had 703 and 730 participants, respectively. Follow-up time also varied between 1.1 and 2.7 years, and the mean age of patients ranged from 45 to 48 years. The study participants were predominantly men. As might be expected, the rate of biologic-naïve patients was comparatively lower for the newer therapeutic agents. It extended from 74.8% in the adalimumab arm to 18.2% for ixekizumab and 23.6% for guselkumab.

The functions of drug survival were determined according to ineffectiveness or adverse events as reasons for discontinuation. “Across all of the outcomes and years, guselkumab has the highest drug survival, and adalimumab the lowest,” highlighted Dr Yiu (see Figure).

Figure: Crude drug survival for discontinuation due to either ineffectiveness or adverse events [2]
Reprinted from Yiu ZZN, et al. Br J Dermatol 2020;182(2):294–302 under the terms of the Creative Commons CC BY.

At years 1 and 2, the drug survival for discontinuation due to ineffectiveness: adalimumab 0.81/0.76, secukinumab 0.86/0.75, ustekinumab 0.89/0.83, ixekizumab 0.86/0.75, and guselkumab 0.94/0.92.

The respective results for drug survival for discontinuation as a result of side effects were: adalimumab 0.91/0.88, secukinumab 0.94/0.0.90, ustekinumab 0.94/0.91, ixekizumab 0.92/0.87, and guselkumab 0.96/0.93. “You can see great drug survival for all our treatments for safety but again it demonstrates that guselkumab has higher drug survival compared with the comparators,” Dr Yiu commented. He further pointed out that an effect modification was detected by previous biologic treatment history.

“Guselkumab had the highest drug survival for both effectiveness and safety out of the treatments looked at here. Previous biologic experience was an effect modifier for discontinuation due to ineffectiveness, and this reduction-effect for drug survival over treatment lines seems to be most pronounced for the IL-17A inhibitors,” Dr Yiu concluded.

 

1. 
   
   1. Yiu ZZN. Drug survival of guselkumab, ixekizumab, secukinumab, ustekinumab and adalimumab for psoriasis: a prospective cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR). FC20, Psoriasis from Gene to Clinic 2021, 9–11 December.
   2. Yiu ZZN, et al. Br J Dermatol 2020;182(2):294–302.

 

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Posted on 2 February 20223 February 2022