Efficacy of secukinumab without the initial weekly loading dose in patients with chronic plaque psoriasis

Abstract

Summary Background Secukinumab is administered at the labelled dose of 300 mg at weeks 0, 1, 2, 3, 4 (loading dose) and every 4 weeks thereafter. Objectives To investigate the efficacy of secukinumab administered without the initial loading dose in patients with psoriasis. Methods This was a retrospective observational study including adult patients with psoriasis (n = 156) treated with secukinumab 300 mg administered either according to the labelled dose (n = 75) or without the initial loading dose (n = 81). Efficacy was evaluated by comparing the Psoriasis Area and Severity Index (PASI) 75 and PASI 90 response rates at week 8, 12, 16, 32 and 48. Results For patients who received the labelled dose vs. those who did not, PASI 75 response rates were achieved at week 8, 12, 16, 32 and 48 by 60% vs. 40% (P < 0·01), 72% vs. 61% (P < 0·01), 77% vs. 75%, 85% vs. 77% and 79% vs. 78%, respectively. PASI 90 responses were achieved at the same time points by 45% vs. 31% (P < 0·01), 49% vs. 40% (P < 0·01), 54% vs. 47%, 55% vs. 47% and 57% vs. 54% for those who received the labelled dose vs. those who did not, respectively. A greater proportion of patients receiving secukinumab without the loading dose discontinued treatment because of inefficacy (25% vs. 13%, P < 0·05), particularly those with body weight greater than 80 kg. Conclusions Secukinumab administered without the loading dose is associated with a higher proportion of primary inefficacy, and achieved inferior results compared with the labelled dose at week 8 and week 12, but showed similar efficacy thereafter. What's already known about this topic? Secukinumab is an interleukin (IL)‐17A inhibitor 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). Dose adjustment is common in clinical practice, and can consist of dose reduction when a prolonged remission is obtained or a dose increase in order to improve efficacy. What does this study add? The efficacy of secukinumab administered without the initial weekly loading dose was significantly inferior compared with the labelled dose in the short term, but was similar after week 16 and up to week 48. A greater proportion of patients receiving secukinumab without the loading dose showed primary inefficacy, particularly those with body weight greater than 80 kg.

Gradually increasing the dosing interval of Secukinumab for moderate to severe plaque psoriasis: A single‐center, uncontrolled, prospective study in 36 weeks

“…A GAIN study by Reich et al revealed the potential benefit of the Q2W dosing in some suboptimal responders but did not reach statistical significance compared with the Q4W dose 13 . Another therapeutic administered without the initial weekly loading dose was inferior to secukinumab at the labeled dose 14 . The feasibility of gradually increasing the dosing interval of secukinumab for treatment is still unknown.…”

“… 13 Another therapeutic administered without the initial weekly loading dose was inferior to secukinumab at the labeled dose. 14 The feasibility of gradually increasing the dosing interval of secukinumab for treatment is still unknown. Herein, we designed a modified therapy that gradually increases the dosing interval of secukinumab based on the response of the PASI score.…”

Real‐world experience of secukinumab in moderate to severe psoriasis patients in Thailand: Characteristics, effectiveness, and safety

“…Our findings reaffirm the association between initial weekly loading dose and treatment effectiveness. Gisondi et al 28 reported significantly greater PASI 75 and PASI 90 response rates at week 12 in psoriatic patients who received the labeled loading dose versus those who did not. The absence of loading dose was also associated with a higher proportion of primary inefficiency.…”

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

“…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 …”

“…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 . The study comprised 156 subjects who were alternately assigned to one of these two regimens.…”