Outcomes in Bimekizumab Treated Psoriasis Patients With Prior IL-17 Inhibitor Failure

Background and Purpose

Psoriasis is a chronic, systemic, inflammatory skin disorder with an estimated global prevalence of 2-4%. ¹ The burden of uncontrolled psoriasis has been well described, with an impact on quality of life comparable to cancer and chronic lung disease. ² Studies have shown higher levels of skin clearance to be positively correlated with various quality-of-life measures. ³ While advancements in psoriasis therapeutics have led to significant levels of skin clearance, many patients still struggle to achieve or maintain complete skin clearance. Several guidelines have been published on treatment sequencing after initial biologic failure, with the general recommendation to stay within the class for secondary non-responders (loss of initial efficacy) while switching out of the class for primary non-responders (eg, < PASI 50). ⁴ Most phase 3 trials have excluded patients exposed to the same drug class under study (eg, prior failure to an IL-17 inhibitor would exclude a patient from an investigational study with another IL-17 inhibitor). Bimekizumab is a humanized IgG1 antibody that selectively targets IL-17 A/F and is approved for adults with moderate-to-severe plaque psoriasis and active psoriatic arthritis.^14-19 In their phase 3 development program, 53% of patients had prior IL-17 inhibitor experience.^14-17 However, exposure to a medication does not necessarily mean treatment failure or intolerance; therefore, one cannot extrapolate these results to real-world patients who have failed a prior IL-17 inhibitor. Moreover, clinical trials are highly regulated with strict inclusion and exclusion criteria, which oftentimes leads to a population that doesn’t accurately reflect the heterogeneity of our real-world clinical practice. To that end, we report our real-world experience using bimekizumab in patients who failed a prior IL-17 inhibitor to demonstrate efficacy, safety, and tolerability in this difficult-to-treat population.

Research Design

We conducted a multicenter, retrospective study of adult patients who failed a prior IL-17 inhibitor and were treated with bimekizumab. Patients were identified from practice data using ICD-10 codes corresponding to psoriasis and a documented history of treatment failure with an IL-17 inhibitor. Patient consent to be included in this study was obtained at a subsequent encounter. Those on multiple systemic therapies for concurrent immune-mediated disorders were excluded due to the difficulty of assessing treatment tolerability and safety. Patients treated with other biologic classes were also included in this analysis as long as they had failed a prior IL-17 inhibitor (eg, patients did not have to be treated with an IL-17 inhibitor immediately before switching to bimekizumab). Of these patients who had failed a previous IL-17 inhibitor, 2 patients were on another (Guselkumab or Adalimumab) immediately prior to initiation of bimekizumab.

Baseline demographics, prior treatment history, and clinical outcomes are summarized in Table 1. While investigators were prompted to choose the type of treatment failure, it was up to their discretion how they defined a primary and secondary failure and a partial responder. Efficacy was assessed by body surface area (BSA) and investigator global assessment (IGA) scores at the time of switch to bimekizumab and at least 16 weeks on therapy. Adverse events of special interest, including candidiasis, liver serologic abnormalities, injection site reactions, new-onset inflammatory bowel disease, and suicidal ideation and behavior, were recorded when appropriate.

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Table 1.

Demographic information of patients included in this study, organized per demographics and specific subgroup IL-17 agent failure. Subgroups were broken out to reflect which drugs were attempted prior, their mean period attempted, and starting points of disease severity.

Demographic data	Patients	SD	% of patients
Mean age (years) + SD	50	14.2
Sex n(%): (n = 50)
1. Male	25		50%
2. Female	25		50%
PsA present at baseline n(%): (n = 50)	29		58%
No. failed biologics prior to bimekizumab, mean + SD	3.5	2.0
Previous biologic prior to bimekizumab n(%): (n = 50)
1. Ixekizumab	34		68%
2. Secukinumab	11		22%
3. Brodalumab	5		10%
Number of prior biologics (n = 50)
≥1	50
≥2	44
≥3	30
Number of months treated with agent prior to initiation of bimekizumab, mean + SD
1. Ixekizumab	23	23.2
2. Secukinumab	10	9.1
3. Brodalumab	35	53.1
Baseline IGA n(%): (n = 50)*
≥1	45		90%
≥2	43		86%
≥3	40		80%
≥4	21		42%
Baseline BSA, mean + SD	10.0	13.1
sPGA x BSA prior to initiation of bimekizumab + SD*	35.0	53.1
*sPGA x BSA prior to initiation: of n = 50, 5 patients had an undocumented baseline IGA

Data Analysis and Results

Baseline demographics, prior treatment history, and treatment response with bimekizumab are summarized in Figure 1. Fifty patients met the inclusion criteria, with 50% female and a mean age of 50 years (range: 18-77 years). 29/50 of patients had clinician-diagnosed concomitant psoriatic arthritis, of which 4 patients were evaluated by rheumatology as well. Patients were treated with an average of 3.5 biologics before initiating bimekizumab. The average treatment duration on a previous IL-17 inhibitor was 16.8 months, with the most common reason for switching being a partial responder or secondary non-responder. The average duration of time on bimekizumab was 11.5 months. 43/50 patients had improved skin clearance after switching to bimekizumab, with 82 % achieving IGA 0/1. 9/50 of patients had persistent scalp involvement at the time of the switch to bimekizumab, with 5 of these patients eventually achieving either partial or complete scalp clearance. 7 patients switched to bimekizumab due to uncontrolled psoriatic arthritis, in which 4 patients experienced improvement in joint symptoms. One patient reported worsening back, hip, wrist, and hand pain after starting bimekizumab, which improved after switching to a combination of adalimumab and deucravacitinib.OPEN IN VIEWER

Treatment response to bimekizumab based on IL-17 inhibitor failure type is summarized in Figure 2. Given the non-uniformity in how treatment failure was defined amongst the investigators, one cannot draw any conclusions on treatment response based on treatment failure type. Still, our data demonstrate that in those who were primary failures, secondary failures, and partial responders to an IL-17 inhibitor, 100%, 81%, and 71% achieved sPGAxBSA of 75%, respectively (Table 2).OPEN IN VIEWER

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Table 2.

Efficacy Data

	Patients
Bimekizumab responders at week 16 (n = 50)
sPGA x BSA 75%	35
sPGA x BSA 90%	31
sPGA x BSA 100%	18
IXE
sPGA x BSA 75%	23
sPGA x BSA 90%	20
sPGA x BSA 100%	13
total Responders	28
SEC
sPGA x BSA 75%	10
sPGA x BSA 90%	10
sPGA x BSA 100%	5
total Responders	10
BRO
sPGA x BSA 75%	3
sPGA x BSA 90%	3
sPGA x BSA 100%	3
total Responders	5

Bimekizumab adverse effects and discontinuation rates are summarized in Table 3. Bimekizumab was discontinued in 3 patients for reasons including severe fatigue and diarrhea, worsening psoriatic arthritis (case above), and a persistent diffuse eczematous eruption. Two patients reported oral candidiasis, and one additional patient experienced fatigue with diarrhea, but none of these led to treatment discontinuation. There were no reports of injection site reactions, liver serologic abnormalities, inflammatory bowel disease, or suicidal ideations and behavior.

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Table 3.

Adverse Events on Bimekizumab

	Patients
Total patients who completed >16wks on bimekizumab	50
Oral candidiasis	2
Eczematous eruption *D/c < 8wks on bimekizumab	1
Fatigue and/or diarrhea *1 patient D/c < 8wks on bimekizumab
Worsening psoriatic arthritis *1 patient D/c < 33wks on bimekizumab	2

Conclusion

Guidance on treatment sequencing after initial biologic failure remains highly relevant given the unexpectedly high drug discontinuation and switching rates reported with even our most effective psoriasis therapies. ⁵ Switching to another class (inter-class switching) has been the preferred approach for non-responders, but there may be compelling reasons to stay within the class, particularly to treat comorbid diseases such as psoriatic arthritis. Furthermore, studies have shown that there can be notable differences in binding affinity, epitope surface area, half-life, and immunogenicity amongst biologics within the same class, which may have implications on treatment efficacy and safety. ⁶ In the phase 3b/4 BE RADIANT study, bimekizumab demonstrated superiority over secukinumab in PASI 100 achievement at 16 weeks. ⁷ In addition, 79% of patients who were PASI 90 non-responders on secukinumab at 48 weeks achieved this stringent endpoint after switching to open-label bimekizumab after 48 weeks of treatment. ⁸

Several published studies have reported intra-class switching with IL-17 inhibitors, including secukinumab to ixekizumab, ⁹ and secukinumab and/or ixekizumab to brodalumab. ¹⁰ More recently, Sood et al ¹¹ published a 52-week real-world study of bimekizumab in a Canadian cohort, which included 59 patients with prior IL-17 inhibitor exposure. While 76.6% (23/30) of these patients achieved an IGA 0/1 after switching to bimekizumab, this study did not differentiate prior experience vs prior failure to an IL-17 inhibitor.

Our study has several notable strengths. Patients were collected from various practice settings, ranging from independent private practices to larger group practices and academic centers across different geographic regions. All authors in the study specialize in psoriasis, so clinical outcomes were meticulously documented. While not specifically assessed for, our study also captured efficacy data in special site areas, including scalp and genital psoriasis, as well as psoriatic arthritis. Finally, we included patients who were non-responders to brodalumab, which has been widely considered to be the most effective treatment for multiple biologic failures. ¹²

Our study also has limitations. The definition of primary non-responder, secondary non-responder, and partial responder was not standardized amongst investigators and was left open to their interpretation. Therefore, response rates based on prior treatment failure type should be interpreted with caution. Laboratory tests were not consistently collected, and there may be differences in how patients were screened for suicidal ideation and behavior and inflammatory bowel disease. Additional patient selection metrics such as age, gender and ethnicity were not collected as this was not central to the studies central focus but does overall pose a limitation on the study. Treatment duration on bimekizumab is also limited, so one cannot conclude how durable, safe, and well-tolerated bimekizumab would be with longer drug exposure. Finally, a BSAxPGA composite was used to measure disease severity and treatment response rather than a psoriasis area severity index (PASI) score, which is the standard in clinical trials. However, several studies have validated the utility of a BSAxPGA composite as a proxy for PASI in the real world. ¹³

Collectively, our data demonstrate that even in a treatment-refractory population that was enriched for prior IL-17 inhibitor failure, bimekizumab is a viable treatment option. This adds to the growing body of literature on biologic switching and provides clinicians with another set of data points to optimize the management of patients who have inadequately responded to an IL-17 inhibitor.