Secukinumab without the initial loading dose in the treatment of plaque‐type psoriasis – a simplified dosing regimen at the expense of efficacy?

Short abstract

Linked Article: https://doi.org/10.1111/bjd.18015.

Treatment of psoriasis vulgaris, a chronic and as yet incurable disease, has been revolutionized by the introduction of biological therapies in the early 2000s.1 Newer biologics such as the interleukin (IL)‐17 or IL‐17RA antagonists or IL‐23p19 inhibitors allow for Psoriasis Area and Severity Index (PASI) 90 response rates of up to 80% after 52 weeks.2, 3 Most biologics have an induction phase in which the treatment is given in shorter time intervals and/or at increased doses to accelerate the therapeutic response and thus to enhance patients’ adherence to treatment. Whereas many studies present data on the short‐term outcome only, long‐term results such as PASI or Physician Global Assessment at week 48 or later are in general of much greater relevance for patients and physicians given the chronicity of the disease.

Secukinumab is a first‐in‐class fully human monoclonal antibody against IL‐17A for chronic plaque psoriasis administered by subcutaneous injections at the labelled dose of 300 mg at weeks 0, 1, 2, 3, 4 (loading dose) and every 4 weeks thereafter (maintenance dose).4

In this issue of the BJD, Gisondi et al. report on a retrospective observational study from Italy on the efficacy of secukinumab with or without an initial loading dose in individuals with chronic plaque‐type psoriasis.5 The study comprised 156 subjects who were alternately assigned to one of these two regimens. The two groups of patients were well matched with respect to psoriasis severity as well as age, sex, weight and duration of psoriasis. Of note, almost 50% of the participants had concomitant psoriatic arthritis and half of the patients had previously been treated with an antitumour necrosis factor‐α blocking agent and/or ustekinumab. Patients not receiving the loading dose had a significantly lower response at weeks 8 and 12 and discontinued treatment significantly more often by week 8 because of lack of efficacy compared with patients treated according to the labelled dose (25% vs. 13%). Interestingly, lack of response was significantly associated with a higher body weight. However, when looking at later time points, the difference in efficacy between the two treatment groups levelled off and was insignificant from week 16 onwards until week 48.5

Due to the uncontrolled retrospective study design and the particular characteristics of the study cohort the findings of this study need to be interpreted with caution but might nevertheless have a significant bearing on the future treatment of patients with psoriasis with secukinumab. A simplified administration schedule that omits the loading dose not only is much more comfortable for the patients but also associated with significant costs savings. These advantages are counterweighed by a slower onset of the therapeutic response and a higher rate of premature discontinuation of treatment. However, in the latter context it is important to point out that Gisondi et al. treated a selected group of severely affected patients with long‐standing disease. It is thus conceivable that the therapeutic advantage of an initial loading dose will be much lower or even negligible in biological‐naïve patients, patients without associated psoriatic arthritis and, in particular, patients of normal weight. A prospective randomized, controlled trial is required to confirm the findings of this study and to better delineate which patients are candidates for secukinumab without the initial loading dose.

Conflicts of interest

None to declare.