FormalPara Key Points

Real-world patients with psoriasis who switch to ixekizumab after discontinuing another biologic show improvements in disease severity and patient-reported outcomes at 6 months.

These improvements were largely similar irrespective of the immediate prior biologic class; however, patients who switched class (from a TNFi or IL-12/23i, or IL-23i) were more likely to achieve response for some disease severity outcomes compared to patients who switched from a prior IL-17i.

1 Introduction

Biologic therapies have made an important contribution in treating psoriasis in the last two decades. These include tumor necrosis factor inhibitors (TNFi), the biologic class approved first, along with newer therapeutic classes such as interleukin-17a inhibitors (IL-17i), interleukin-12/23 inhibitors (IL-12/23i), and interleukin-23 inhibitors (IL-23i). With the increasing number of available biologic therapies, patient switching between biologic therapies (within therapeutic class or to another class) is becoming a common practice and may be due to several factors, including treatment failure, adverse events, economic factors, and patient preferences [1,2,3]. Not all switches, however, lead to improved outcomes [1]. Due to lack of strong evidence, there are no specific US guideline recommendations for switching biologic treatments [1]. More data from real-world sources are needed to fill this evidence gap.

Many studies have reported similar effectiveness of ixekizumab, an IL-17i, between biologic-experienced and biologic-naïve patients [4,5,6], whereas few studies have examined the effectiveness of ixekizumab following a switch from an IL-23i. Mastorino et al. found that out of 769 patients, seven patients switched to an IL-17i after treatment failure with an IL-23i [7]. They reported a rapid response in all patients and that five of the seven achieved ≥ 100% improvement in the Psoriasis Area Severity Index (PASI100) at 28 weeks.

We previously conducted a study of 419 patients enrolled through September 2020 in the CorEvitas Psoriasis Registry to compare the effectiveness of ixekizumab between patients who previously failed secukinumab (within class; another IL-17i) and those who failed other biologics (composite of TNFi, IL-12/23i, and IL-23i) [8]. All patients who initiated ixekizumab demonstrated improvements in measures of disease severity and patient-reported outcomes after 6 months. We also found that those who switched from secukinumab demonstrated fewer improvements than patients who switched from other biologic therapies. Due to limited sample size, we were unable to compare patients switching from an IL-23i specifically or from the IL-17 receptor blocker brodalumab.

Since September 2020, increasing numbers of patients initiating newer biologic therapies within the CorEvitas Psoriasis Registry and additional patient follow-up have facilitated examination of the effectiveness of ixekizumab after a switch from an IL-23i. Furthermore, while prior real-world studies have identified several factors that impact response to biologic therapy, including sex, employment status, smoking, weight, psoriasis in high-impact sites, and disease activity at biologic initiation [9, 10], it is unclear whether these factors influence ixekizumab effectiveness after switching from other biologic therapies. To add to the growing data surrounding switching of biologic therapies, the objective of this analysis was to determine whether 6-month effectiveness of ixekizumab is impacted by prior biologic class, by stratifying our results into three groups of prior biologic class (TNFi or IL-12/23i, IL-17i [excluding ixekizumab], and IL-23i). In addition, we sought to examine factors impacting 6-month effectiveness following any biologic switch.

2 Methods

2.1 Description of the CorEvitas Psoriasis Registry

The CorEvitas Psoriasis Registry is a prospective, multicenter, non-interventional registry, launched in April 2015 in collaboration with the National Psoriasis Foundation, for patients with psoriasis under the care of a dermatologist. The registry design has been previously described [11]. Patients were enrolled if they were 18 years or older, had psoriasis diagnosed by a dermatologist, and initiated or switched to a US Food and Drug Administration (FDA)-approved systemic or biologic psoriasis treatment at registry enrollment or within 12 months before enrollment.

Data are collected from dermatologists and patients during routine clinical visits occurring at approximately 6-month intervals. All participating investigators were required to obtain full board approval for conducting research involving human subjects. All registry subjects were required to provide written informed consent prior to participating.

2.2 Study Population

The current study included patients who switched to ixekizumab after discontinuing another biologic therapy at or after enrollment into the registry (baseline visit) beginning on 22 March 2016, the approval date of ixekizumab. Further, included patients were required to have a corresponding 6-month follow-up visit (within a 5- to 9-month window) as of February 2023. Biologic-naïve patients initiating ixekizumab were excluded.

2.3 Measures

2.3.1 Prior Biologic Class

Patients were classified into one of three mutually exclusive groups based on their immediate prior biologic class: (1) TNFi (adalimumab, certolizumab, etanercept, infliximab, golimumab) or IL-12/23i (ustekinumab); (2) non-ixekizumab IL-17i (secukinumab, brodalumab); and (3) IL-23i (guselkumab, tildrakizumab, risankizumab). No patients with prior bimekizumab were included.

2.3.2 Outcomes

Disease activity measures: Psoriasis Area and Severity Index (PASI) [12], body surface area (BSA) [13], and Investigator’s Global Assessment (IGA) [14] were measured at the baseline and 6-month follow-up visits, and mean changes from baseline were calculated at follow-up. Also at follow-up, the proportions of patients achieving ≥ 75% improvement in PASI (PASI75), ≥ 90% improvement in PASI (PASI90), and ≥ 100% improvement in PASI (PASI100) were ascertained. In addition, the proportions of patients maintaining or achieving PASI ≤ 3, acceptable response (BSA ≤ 3% or BSA improvement ≥ 75% from baseline) or target response (BSA ≤ 1%) [15], and IGA 0/1 [14] at follow-up were determined.

Patient-reported outcomes: At the baseline and follow-up visits, skin itch/pruritus, skin pain, fatigue, and current health status (EQ-5D-3L) were measured using visual analog scales (VAS, 0-100) in all patients, and, in patients with comorbid psoriatic arthritis, joint pain due to psoriatic arthritis and Patient Global Assessment (PGA) were measured using a visual analog scale (VAS; 0–100) [16]. Lower scores indicate better health for itch, skin and joint pain, fatigue, and PGA, while higher scores indicate better health for EQ-5D-3L. Mean changes in these scores and in Dermatology Life Quality Index (DLQI) [17] were calculated from baseline to follow-up. Additionally, proportions of patients maintaining or achieving DLQI 0/1 at follow-up were determined [18].

2.3.3 Covariates

Baseline visit variables included sociodemographics, lifestyle characteristics, comorbidity burden, psoriasis disease characteristics, and psoriasis-specific measures. Medications included past and concomitant psoriasis therapies (non-biologic systemics (apremilast, methotrexate, cyclosporine, acitretin), phototherapy and topical agents, and previous biologic therapies, including the number of prior biologics (categorized as 0, 1, or ≥ 2)).

2.4 Statistical Analysis

Patient characteristics and disease severity measures at the baseline visit were summarized using descriptive statistics stratified by prior biologic class. Summary measures for continuous variables included number of observations, means, standard deviations (SDs), medians, and 25th and 75th percentiles, while categorical variables were summarized using frequency counts and percentages. Baseline differences in means or proportions of characteristics between prior biologic class groups were calculated using Cohen’s f (for continuous variables) and Cohen’s w (for categorical variables), each a type of standardized effect size that assesses global imbalance among all groups (i.e., any difference in characteristic between two prior biologic class groups). Thresholds for small, medium, and large differences were, respectively, 0.10, 0.25, and 0.40 for Cohen’s f, and 0.10, 0.30, and 0.50 for Cohen’s w.

For each continuous outcome, an analysis of covariance (ANCOVA) model was used to calculate and compare unadjusted and multivariable-adjusted mean absolute change in continuous outcomes at 6 months within and between prior biologic class groups. For each dichotomous outcome, disease response at 6 months was summarized by prior biologic class using frequencies and percentages. Modified Poisson regression models with robust standard errors were fit to calculate the relative risk (RR) and 95% confidence intervals (CIs) to estimate the likelihood of response by prior biologic class relative to non-ixekizumab IL-17i group for response outcomes. Modified Poisson regression allows for direct estimation of the RR and applies the robust error variance to correctly estimate CIs [19]. All models were adjusted a priori for age, gender, race, duration of psoriasis, psoriatic arthritis, number of prior biologics, and baseline outcome measure. Additional patient characteristics were reviewed for potential inclusion in the models; none demonstrated at least a moderate difference between strata with ≤ 5% missing values, and therefore none were added to the models. No adjustments were made for multiple comparisons in this study. A p-value < 0.05 was considered statistically significant.

In a secondary analysis, factors likely to be associated with a disease activity outcome (achieving PASI75) and a patient-reported outcome (maintaining or achieving DLQI 0/1) were evaluated in separate univariable analyses for each factor using modified Poisson regression with robust standard errors. Factors with p-value ≤ 0.10 in the univariable models and ≤ 5% missing values were included in a multivariable modified Poisson regression model for each outcome and removed individually via backward selection until all remaining variables were significant (p < 0.05). Stata version 16.1 (StataCorp, LLC, College Station, TX, USA) was used for all analyses.

2.5 Ethics

The study was performed in accordance with the Declaration of Helsinki and the Guidelines for Good Pharmacoepidemiology Practice (GPP). All participating investigators were required to obtain full board approval for conducting non-interventional research involving human subjects with a limited dataset. Sponsor approval and continuing review was obtained through a central Institutional Review Board (IRB, Advarra, Protocol number Pro00051221). For academic investigative sites that did not receive a waiver to use the central IRB, full board approval was obtained from the respective governing IRBs and documentation of approval was submitted to CorEvitas, LLC, prior to the initiation of any study procedures. All patients in the registry were required to provide written informed consent and authorization prior to participating.

3 Results

3.1 Patient Characteristics

As of 10 February 2023, among the 18,556 patients enrolled in the Psoriasis Registry, there were 2689 initiations of ixekizumab, of which 1948 were among biologic experienced patients. Among these initiations, 1516 had a baseline visit and 743 had a 6-months follow-up visit after initiation of ixekizumab. Therefore, a total of 743 patients were included in the analysis and stratified by their immediate prior biologic class with 405 (54.5%) in the TNFi or IL-12/23i group, 237 (31.9%) in the non-ixekizumab IL-17i group, and 101 (13.6%) in the IL-23i group. The patient flowchart is shown in Fig. 1.

Fig. 1
figure 1

Patient flowchart. Baseline visit = Those who had a baseline visit associated with ixekizumab initiation

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Patient demographic and clinical characteristics for the overall study cohort are summarized in Table 1. Patients reported a mean age of 51.0 years (SD 13.4 years) and were 51% female, 79% White, and 7% of Hispanic or Latino ethnicity. There were similarities in patient demographics, lifestyle characteristics, comorbidity burden, and psoriasis disease characteristics. Psoriasis disease severity was slightly higher among patients initiating ixekizumab who previously discontinued TNFi or IL-12/23i compared to patients in the prior non-ixekizumab IL-17i and IL-23i groups with mean BSA of 12.5% (SD 15.4) versus 10.8% (SD 14.6) and 9.0% (SD 11.6), mean PASI of 8.2 (SD 8.0) versus 7.0 (SD 8.1) and 5.6 (SD 5.7), and mean IGA of 2.8 (SD 0.9) versus 2.5 (SD 1.1) and 2.6 (SD 1.1), respectively. Patient-reported outcome measures at baseline were similar across prior biologic groups.

Table 1 Patient demographic and clinical characteristics at baseline visit for all ixekizumab initiators who switched from another biologic in the CorEvitas Psoriasis Registry, overall and stratified by prior biologic class
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Treatment characteristics at baseline visit are shown in Supplemental Table 1 (Online Supplemental Material (OSM)). The duration between prior biologic discontinuation and initiation of ixekizumab was longer among patients who previously discontinued TNFi or IL-12/23i compared to patients who previously discontinued non-ixekizumab IL-17i and IL-23i. Larger proportions of patients who switched to ixekizumab from either another IL-17i or an IL-23i had received two or more prior biologics compared with patients who switched to ixekizumab from a TNFi or IL-12/23i. Among patients with baseline reporting of the reasons for discontinuing their prior biologic, the prior non-ixekizumab 17i group had a lower proportion of discontinuation due to primary non-response (inadequate initial response) compared to the prior TNFi or IL-12/23i and IL-23i groups. Similar proportions were observed for secondary non-response (failure to maintain initial response), lack of effectiveness, patient doing well, and contraindications across groups.

3.2 Six-Month Outcomes Overall

Mean absolute changes in continuous disease activity and patient-reported outcomes from baseline to 6 months are shown in Fig. 2a and b. Statistically significant improvements from baseline were observed in PASI (mean change − 4.9; 95% CI − 5.4, − 4.3) and BSA (mean change − 7.5; 95% CI − 8.5, − 6.4). There were statistically significant improvements in all patient-reported outcomes: patient-reported itch (mean change − 22.2; 95% CI − 24.9, − 19.5), skin pain (mean change − 15.5; 95% CI − 18.0, − 13.0), fatigue (mean change − 9.7; 95% CI − 11.8, − 7.6), EQ-5D health status (mean change 5.4; 95% CI 4.0, 6.9), and DLQI (mean change − 3.5; 95% CI − 4.0, − 3.0). Among the subset of patients with psoriatic arthritis, there were statistically significant improvements in joint pain due to psoriatic arthritis (mean change − 17.6; 95% CI − 20.8, − 14.5) and PGA (mean change − 18.3; 95% CI − 21.5, − 15.2).

Fig. 2
figure 2

A and B Mean absolute changes at 6 months, and C proportions of patients achieving outcomes at 6 months, for all ixekizumab initiators who switched from another biologic in the CorEvitas Psoriasis Registry. BSA, body surface area, DLQI Dermatology Life Quality Index, EQ-5D current health status, PASI Psoriasis Area and Severity Index, PASI75 ≥ 75% improvement in PASI, PASI90 ≥ 90% improvement in PASI, PASI100 ≥ 100% improvement in PASI, PGA Patient Global Assessment. *Among patients with comorbid psoriatic arthritis

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Outcomes at 6 months for the dichotomous measures are shown in Fig. 2c. Among the 741 patients with PASI, 54%, 41%, and 31% achieved PASI75, PASI90, and PASI100, respectively. Over 72% of patients maintained or achieved PASI ≤ 3. Similarly, 74% of patients maintained or achieved BSA ≤ 3% or experienced at least 75% improvement in BSA, and 54% of patients maintained or achieved BSA ≤ 1%. Half (50%) of patients maintained or achieved IGA 0/1, and 48% maintained or achieved DLQI 0/1.

3.3 Mean Changes from Baseline by Prior Biologic Class

3.3.1 Within-Group Changes

Among ixekizumab initiators switching from TNFi + IL-12/23i, there were statistically significant changes from baseline to 6 months in all disease activity and patient-reported outcomes after adjusting for a priori baseline covariates (PASI: mean change − 4.88; 95% CI − 5.30, − 4.47; BSA: mean change − 7.62; 95% CI − 8.39, − 6.84; DLQI: mean change − 3.60; 95% CI − 4.09, − 3.10; EQ-5D health status: mean change 5.64; 95% CI 3.96, 7.31; itch: mean change − 23.29; 95% CI − 26.22, − 20.36; skin pain: mean change − 16.73; 95% CI − 19.21, − 14.25; and fatigue: mean change − 10.75; 95% CI − 13.15, − 8.35) (OSM Table 2). Among the subset of patients with psoriatic arthritis, there were statistically significant changes in joint pain (mean change − 18.99; 95% CI − 22.69, − 15.29) and PGA (mean change − 19.40; 95% CI − 23.04, − 15.77).

Among those switching from non-ixekizumab IL-17i, there were statistically significant changes from baseline to 6 months in all disease activity and patient-reported outcomes after adjusting for a priori baseline covariates (PASI: mean change − 4.48; 95% CI − 5.03, − 3.93; BSA: mean change − 6.83; 95% CI − 7.86, − 5.81; DLQI: mean change − 3.25; 95% CI − 3.90, − 2.61; EQ-5D health status: mean change 6.20; 95% CI 4.01, 8.39; itch: mean change − 19.57; 95% CI − 23.41, − 15.73, skin pain: mean change − 14.10; 95% CI − 17.35, − 10.84; and fatigue: mean change − 8.76; 95% CI − 11.91, − 5.60) (OSM Table 3). Among the subset of patients with psoriatic arthritis, there were statistically significant changes in joint pain (mean change − 17.78; 95% CI − 22.72, − 12.85) and PGA (mean change − 18.64; 95% CI  − 23.49, − 13.78).

Among ixekizumab initiators switching from IL-23i, there were statistically significant changes from baseline to 6 months in most disease activity and patient-reported outcomes after adjusting for a priori baseline covariates (PASI: mean change − 5.19; 95% CI − 6.02, − 4.36; BSA: mean change − 7.81; 95% CI − 9.34, − 6.27; DLQI: mean change − 3.37; 95% CI − 4.35, − 2.39; itch: mean change − 22.20; 95% CI − 28.03, − 16.38; skin pain: mean change − 12.83; 95% CI − 17.76, − 7.90; and fatigue: mean change − 7.78; 95% CI − 12.58, − 2.97). The exception was EQ-5D health status (mean change 1.95; 95% CI − 1.38, 5.28) (OSM Table 4). Among the subset of patients with psoriatic arthritis, there were statistically significant changes in joint pain (mean change − 12.48; 95% CI − 20.12, − 4.83) and PGA (mean change − 14.32; 95% CI − 21.83, − 6.81).

3.3.2 Between-Group Changes

In the unadjusted models, patients who switched to ixekizumab from a TNFi or IL-12/23i had larger mean changes in all observed outcomes relative to patients who switched to ixekizumab from a prior non-ixekizumab IL-17i or IL-23i. Statistically significant differences were observed across the three prior biologic groups for mean changes from baseline in PASI, BSA, EQ-5D health status, itch, and skin pain (all p-values < 0.05, data not shown).

When adjusting for patient age, gender, race, psoriasis duration, psoriatic arthritis, line of therapy and the baseline value of the outcome, there were no statistically significant between-group differences in the continuous outcomes at 6 months (Fig. 3a and b). Adjusted mean change in disease activity measures of PASI (− 4.5 vs. − 4.9 vs. − 5.2) and BSA (− 6.8 vs. − 7.6 vs. − 7.8) were similar between prior non-ixekizumab IL-17i, TNFi or IL-12/23i and IL-23i groups, respectively. Likewise, adjusted mean change in patient-reported outcomes of itch (− 19.6 vs. − 23.3 vs. − 22.2), skin pain (− 14.1 vs. − 16.7 vs. − 12.8) and fatigue (− 8.8 vs. − 10.8 vs. − 7.8) were similar between prior non-ixekizumab IL-17i, TNFi or IL-12/23i and IL-23i groups, respectively.

Fig. 3
figure 3

Adjusted mean changes in A disease activity measures and B patient-reported outcomes at 6 months among ixekizumab initiators by prior biologic class. BSA body surface area, DLQI Dermatology Life Quality Index, EQ-5D current health status, IL-17i interleukin-17 inhibitor, IL-12/23i interleukin-12/23 inhibitor, IL-23i interleukin-23 inhibitor, Ixe ixekizumab, PASI Psoriasis Area and Severity Index, PGA Patient Global Assessment, TNFi, tumor necrosis factor inhibitor, VAS visual analog scale. *Among patients with comorbid psoriatic arthritis

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Among patients with psoriatic arthritis, there were no statistically significant between-group differences in unadjusted or adjusted mean changes in joint pain or PGA. Changes in joint pain were numerically slightly larger for patients with prior non-ixekizumab IL-17i or prior TNFi or IL-12/23i than for patients with prior IL-23i.

3.4 Likelihood of Response Compared to Prior Non-Ixekizumab IL-17i Group

In unadjusted modified Poisson regression models comparing likelihood of achieving dichotomous response outcomes at 6 months in the prior TNFi or IL-12/23i and IL-23i groups versus the non-ixekizumab IL-17i group, patients in the prior TNFi or IL-12/23i group had an increased likelihood of achieving disease severity response (PASI75: RR 1.18; 95% CI 1.01, 1.38; PASI90: RR 1.34; 95% CI 1.08, 1.65; PASI100: RR 1.37; 95% CI 1.05, 1.79; and IGA 0/1: RR 1.27; 95% CI 1.07, 1.52; data not shown). Additionally, patients in the prior IL-23i group had an increased likelihood of achieving disease severity response (PASI90: RR 1.40; 95% CI 1.07, 1.85; PASI100: RR 1.61; 95% CI 1.16, 2.25; and IGA 0/1: RR 1.35; 95% CI 1.07, 1.70; data not shown).

Adjustment for age, gender, race, psoriasis duration, psoriatic arthritis, line of therapy (one prior vs. two+ prior biologics) and baseline outcome yielded similar results to the unadjusted models. In the adjusted models (Fig. 4), there were statistically significant differences between groups with the prior TNFi or IL-12/23i group more likely to achieve PASI100 (RR 1.31; 95% CI 1.01, 1.69) and IGA 0/1 (RR 1.32; 95% CI 1.11, 1.57) and the prior IL-23i group more likely to achieve PASI90 (RR 1.45; 95% CI 1.10, 1.91), PASI100 (RR 1.55; 95% CI 1.12, 2.13), and IGA 0/1 (RR 1.39; 95% CI 1.12, 1.73) compared to the prior non-ixekizumab IL-17i group. There were no statistically significant between-group differences in achievement of PASI75, PASI ≤ 3, BSA ≤ 3% or ≥ 75% improvement, BSA ≤ 1%, or DLQI 0/1.

Fig. 4
figure 4

Adjusted relative risks for maintaining/achieving disease and patient-reported outcome response, relative to non-ixekizumab IL-17i group. BSA body surface area, DLQI Dermatology Life Quality Index, IGA Investigator Global Assessment, IL-17i interleukin-17 inhibitor, IL-12/23i interleukin-12/23 inhibitor, IL-23i interleukin-23 inhibitor, PASI75 ≥ 75% improvement in Psoriasis Area and Severity Index (PASI), PASI90 ≥ 90% improvement in PASI, PASI100 ≥ 100% improvement in PASI, TNFi tumor necrosis factor inhibitor

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3.5 Factors Associated with PASI75 and DLQI 0/1

Factors positively associated with achieving PASI75 in the adjusted multivariable model included psoriatic arthritis (RR 1.35; 95% CI 1.18, 1.55), higher baseline PASI (RR 1.02; 95% CI 1.02, 1.03) and months between ixekizumab initiation and 6-month visit (RR 1.17; 95% CI 1.13, 1.22), whereas female patients were less likely to achieve PASI75 (RR 0.85; 95% CI 0.75, 0.97) (OSM Table 5).

Factors positively associated with maintaining or achieving DLQI 0/1 in the adjusted multivariable model included months between ixekizumab initiation and 6-month visit (RR 1.18; 95% CI 1.13, 1.24), whereas non-White race (RR 0.71; 95% CI 0.56, 0.89), current smoking (RR 0.81; 95% CI 0.65, 1.00), having psoriasis in high impact sites (RR 0.81; 95% CI 0.70, 0.93), and higher baseline DLQI (RR 0.96; 95% CI 0.94, 0.97) were associated with lower likelihood of achieving DLQI 0/1 (OSM Table 6). Prior biologic class was not significantly associated with achieving either PASI75 or DLQI 0/1 in the final adjusted models.

4 Discussion

This study identified improvements in disease severity and patient-reported outcomes at 6 months in real-world settings in patients with psoriasis who switched to ixekizumab after discontinuing another biologic. Compared to patients making intra-class switches from another IL-17i, patients switching class from a TNFi or IL-12/23i were more likely to achieve PASI100 and IGA 0/1, and patients switching class from an IL-23i were more likely to achieve PASI90 in addition to PASI100 and IGA 0/1. Other improvements were consistent regardless of prior biologic class.

Effectiveness of ixekizumab has been demonstrated in real-world settings [20,21,22]. Our updated findings for switching to ixekizumab are consistent with those of our earlier study [8], in which patients who switched to ixekizumab from any biologic other than the IL-17i secukinumab (i.e., TNFi, IL-12/23i, or IL-23i) had greater likelihood of achieving PASI75, PASI90, PASI100, IGA 0/1, and BSA ≤ 3% compared to those switching from secukinumab. This consistency is logical given that patients from the earlier study were also included in the present study. A more recent observational study in the Czech BIOREP registry showed treatment success in intra-class IL-17i switching at 24 weeks [23], while a systematic review and meta-analysis demonstrated that prior IL-17i exposure does not appear to impact effectiveness of another IL-17i [24]. Indeed, the IL-17i brodalumab was found to be effective in patients who failed other IL-17is [25]. By contrast, a longer-term study found low drug survival of brodalumab at 50 weeks after switching from ixekizumab [3]. These studies, however, did not compare patients switching within the IL-17i class to those switching from other classes.

Given the more recent entrance to the market of the IL-23i class and limited information on switching class from an IL-23i to an IL-17i, we were particularly interested in the patients who switched to ixekizumab from an IL-23i. In the small study by Mastorino and colleagues, five of seven patients who switched to an IL-17i after treatment failure with an IL-23i achieved PASI100 at 28 weeks and three of seven achieved PASI100 at 40 weeks [7]. The findings in our larger patient population, which included patients who switched regardless of reason, affirm these with statistically significant changes from baseline in most disease activity and patient-reported outcomes at 6 months. As the IL-23i class gains popularity, our results suggest that ixekizumab may be a good option for switching after IL-23i discontinuation.

Conversely, emerging evidence from a phase 3b open-label single-arm trial suggests that the IL-23i risankizumab may improve psoriasis response and symptoms for up to 1 year in patients who had suboptimal response to secukinumab or ixekizumab [26]. However, over 60% of patients in the open-label trial had switched from secukinumab, and treatment response in the open-label trial was lower than in the original IMMhance trial of risankizumab in which only 26% of patients had prior IL-17i use [27]. This follows a prior report of effectiveness of TNFi and IL-12/23i in patients with non-response to secukinumab [28] and small studies that have shown benefits of intra-class IL-23i switches [29, 30]. Future studies will be needed to confirm these findings in larger real-world patient populations and to determine patient characteristics associated with success within and between classes.

4.1 Limitations and Strengths

Limitations of the study include that the CorEvitas registry consists of a sample of adults with psoriasis who are not necessarily representative of all adults with psoriasis in the USA and Canada. In particular, these patients have attended at least two clinical visits with dermatologists. In addition, history of medication use prior to enrollment is derived from reports by patients and their current dermatologists within the registry. Given that IL-23i are the newest class of medications included in the study, there are fewer patients who switched from IL-23i than from the other classes. It is worth noting that the reasons for switching therapeutic classes varied, and not all patients reported a reason. Similarly, the reason for each visit is not captured, although the assumption can likely be made that the dermatology visit is related to psoriasis. The registry captures physician-reported prescribing without measures of patient adherence. Further, our findings are subject to limitations inherent in all observational studies, including the potential for unmeasured confounding and unknown patient factors linked to healthcare access.

Nevertheless, the study also has many strengths resulting from the CorEvitas Psoriasis Registry, a longitudinal prospective registry collecting data from both patients and providers on psoriasis treatment and a wide range of both physician- and patient-reported disease outcomes. This provides a unique resource of large sample size, and longitudinal follow-up on the real-world use of biologic drugs in the USA and Canada. The registry enables examination of response patterns based on measures relevant to patient-physician encounters and a large set of patient histories and characteristics to use as predictors of response. Moreover, the registry contains clinical data (e.g., disease activity scores and patient-reported outcomes data) that are not available in claims databases.

5 Conclusions

These updated findings with IL-23i data reaffirm that real-world patients with psoriasis who switch to ixekizumab after discontinuing another biologic demonstrate improvements in disease severity and patient-reported outcomes at 6-month follow-up. These improvements were largely similar irrespective of the immediate prior biologic class; however, patients who switched class (from a TNFi or IL-12/23i, or IL-23i) were more likely to achieve response for some dichotomous disease severity outcomes compared to patients who switched from a prior IL-17i. In our regression analysis, we did not find that PASI75 and DLQI 0/1 were impacted by prior biologic class. The results advance the evidence base for offering patients a holistic, personalized approach to psoriasis management by tailoring treatment to patient needs [31,32,33]. Further research in real-world data sources is needed to evaluate the persistence of ixekizumab response long term after switching from other biologics.