Secukinumab for plaque psoriasis: Results from the 4-year extension of ERASURE and FIXTURE

Secukinumab, an anti-IL-17A monoclonal antibody, is recommended at a dose of 300 mg in patients with plaque psoriasis.¹ The safety and efficacy of secukinumab has previously been confirmed in the phase III SCULPTURE trial (NCT01406938). More recently, the phase III ERASURE (NCT01365455) and FIXTURE (NCT01358578) trials investigated the safety and efficacy of secukinumab at two different doses to treat moderate-to-severe plaque psoriasis.¹ Here, we discuss data from the combined extension phase of ERASURE and FIXTURE up to 5 years from trial initiation.

Study design¹

In the double-blind core studies of ERASURE and FIXTURE (up to Year 1), patients were randomized to receive either 300 mg or 150 mg of secukinumab. A total of 1,366 patients completed the core trials to Year 1, with 1,146 entering the extension; 934 patients completed up to Year 3 of the extension study, with 883 patients entering the open-label period; and 777 completed up to Year 5, the end of the extension phase. The study design of the ERASURE–FIXTURE extension study is shown in Figure 1.

Figure 1. ERASURE and FIXTURE core and extension design* 

IGA, Investigator Global Assessment; PASI, Psoriasis Area and Severity Index; PFS, pre-filled syringe; Q4W, every four weeks; SC, subcutaneous.
*Adapted from Langley, et al.^1
†Partial response defined as PASI 50 responders.
^‡In the core trials, patients received secukinumab 150 mg or 300 mg weekly from baseline to Week 4, then every 4 weeks to Week 48.
^§Patients on placebo who relapsed were returned to secukinumab treatment.

Results¹

In the core trials, the majority of patients were male and had achieved a 75% improvement in Psoriasis Area and Severity Index (PASI 75) from baseline. Patient characteristics at baseline of the extension phase are shown in Table 1.

Table 1. Patient characteristics in randomized cohort in extension*

Safety

The median duration of secukinumab exposure for both doses was 1,438 days. Safety analysis did not reveal an increased incidence of adverse events over the 5 years; the overall incidence rates of adverse events throughout the entire extension period are shown in Table 2. There were two deaths reported, both were not considered treatment related.

Table 2. Adverse events across the entire study period*

Efficacy

The proportion of patients treated with secukinumab 300 mg in both the response and partial-response groups achieving PASI 75, PASI 90, and PASI 100 remained consistent from Year 3 to 5, as shown in Figure 2.

Figure 2. Proportion of patients treated with secukinumab 300 mg achieving PASI 75, PASI 90, and PASI 100* 

PASI, Psoriasis Area and Severity Index.
*Adapted from Langley, et al.¹

The mean PASI score increased from 1.84 to 2.61 from Year 1 to 5 in patients who achieved a response or partial response in the core study and proceeded to receive secukinumab 300 mg in the extension. At Year 1 and 5, this represents a 91.8% and 88.1% decrease in mean PASI score from baseline, respectively. The percentage of patients achieving Investigator’s Global Assessment 0/1 decreased from Year 1 to Year 5, as illustrated in Figure 3.

Figure 3. A Mean PASI score in patients treated with secukinumab 300 mg and B the percentage of patients treated with secukinumab 300 mg who achieved IGA 0/1* 

IGA, Investigator’s Global Assessment; PASI, Psoriasis Area and Severity Index.
*Adapted from Langley, et al.¹

Quality of life measures

Using Dermatology Life Quality Index (DLQI) measurements, quality of life benefits were maintained up to Year 5 of treatment. The mean DLQI score was 1.8 at Year 1, increasing to 2.7 at Year 3, and 3.3 at Year 5. Figure 4 shows the percentage of patients treated with secukinumab 300 mg who achieved a DLQI score of 0 or 1 (the condition is having little or no impact on the quality of life).

Figure 4. Percentage of patients treated with secukinumab 300 mg achieving a DLQI of 0 or 1* 

DLQI; Dermatology Life Quality Index.
*Adapted from Langley, et al.¹

Conclusion 

In the extension study of ERASURE and FIXTURE, secukinumab demonstrated sustained efficacy at 5 years in patients with moderate-to-severe plaque psoriasis; however, loss of response was observed in some patients. In recent data from the FIXTURE and CLEAR (NCT02074982) trials, a bodyweight <90 kg and not having experienced a failed biologic therapy was associated with more durable responses to secukinumab; this could explain a reduced response in this subset of patients. In addition, a higher BMI score has been associated with poorer PASI responses at Week 78 of secukinumab treatment, which may be linked to secukinumab plasma levels; during the FIXTURE trial, there were higher efficacy rates in patients with higher secukinumab plasma levels.

Data from real-world studies is needed to fully elucidate the efficacy and safety of secukinumab; however, these findings may be limited by differences in treatment sequencing, prior biologic exposure, and less rigorous follow-up compared with clinical trials.

The efficacy and safety data reported in these trials were similar to results of the previous SCULPTURE trial, with no additional safety signals observed in the extension phase. For the majority of patients, this suggest that secukinumab could be safely used for prolonged periods while maintaining responses.