Risankizumab in psoriasis: prior biologics failure does not impact on short-term effectiveness

KEYWORDS:

• Psoriasis
• risankizumab
• interleukin-23
• real-world data
• therapy-systemic
• biologics
• effectiveness

Dear editor,

We read with great interest the recent article published by Al-Janabi et al. [1] that summarizes clinical trial data and meta-analysis for the treatment of moderate to severe psoriasis with risankizumab. We want to complement these findings and add our data from the real world on the effectiveness and safety of risankizumab in patients with moderate-to-severe plaque psoriasis [2].

Psoriasis is a multisystem chronic inflammatory disease that preferentially affects the skin and joints, which may significantly impact patients [3]. Risankizumab is a humanized monoclonal antibody and one of three currently licensed as systemic therapy for moderate to severe plaque psoriasis that targets the p19 subunit of interleukin-23 (IL-23) [4]. In 2019 risankizumab was approved by the Food and Drug Administration (FDA) and European Medical Agency (EMA), and in the Autonomous Community of Madrid (ACM), this agent is available in most hospitals from April 2020. In Spain, risankizumab is reimbursable by the national health care system as the second line of treatment of patients with moderate-severe plaque psoriasis candidates with any contraindication for systemic therapy, inadequate response, or intolerance to conventional systemic therapies or psoralen plus ultraviolet-A photochemotherapy (PUVA) [5]. However, although the treatment with risankizumab, with indication after anti-TNF failure, has demonstrated significant improvements in outcomes for patients with moderate-to-severe plaque psoriasis [6], there is currently limited evidence for its use in real-world clinical practice [7–9].

With the aim of analyzing the short-term effectiveness and tolerability of risankizumab in patients with moderate-to-severe plaque psoriasis in a real-life setting, we carried out a multicenter, Spanish retrospective study. We conducted a retrospective clinical records review on adult patients treated with risankizumab at seven hospital centers in Madrid from April 2020 to December 2020. Patients were included if they had moderate-to-severe plaque psoriasis, had started risankizumab treatment and received at least one dose according to routine clinical practice. Response to the treatment was assessed with the absolute PASI score of ≤ 2 and ≤ 3 at each follow-up visit (1 and 3 months). At the same time, the safety profile was evaluated by treatment-emergent adverse events (AEs) and the number and causes of withdrawals during the treatment. Furthermore, we analyzed the impact of factors potentially associated with effectiveness results according to gender, age, body mass index (BMI), prior biologic experience, psoriasis duration, and PASI scores at baseline. All data were collected in an anonymized database, and a descriptive statistical analysis was performed. Continuous variables were reported as mean (standard deviation -SD-), while categorical variables were reported as number and percentage of cases and distribution of frequencies. In addition, logistic multivariable regression models were fitted to assess the impact of the variables with potential impact on results. Statistical analyses were performed using the Statistical Analysis Software (SAS) (version 9.4), and a p-value of < 0.05 was considered statistically significant.

Data from 44 patients with moderate-to-severe plaque psoriasis were available, with a mean (SD) age of 52.8 (15.5) years, and mostly male (n/N = 29/44, 65.9%). At baseline, the mean BMI of the patients was 30.2 (6.1) kg/m². Mean duration of psoriasis since the first diagnosis was 22.5 (13.5) years, and mean baseline PASI scores were 12.3 (6.7). Our cohort of patients used on average 2.7 (1.9) conventional systemic agents, and 84% had been treated in the past with at least one biologic agent with a mean of 1.9 (1.4), such as an anti-tumor necrosis factor (TNF) agent (n/N = 24/44, 64.8%), ustekinumab (n/N = 19/44, 51.3%), anti-IL-17 (n/N = 12/44, 32.4%) or guselkumab (n/N = 1/44, 2.2%). Among our patients, most of the patients (81.8%) had at least one comorbidity, with hepatic steatosis (n/N = 18/44, 40.9%), dyslipidemia (n/N = 18/44, 40.9%) and hypertension (n/N = 17/44, 38.6%) being the most prevalent. Eight patients (18.8%) had psoriatic arthritis, and two (4.5%) had previous malignancy. Latent tuberculosis was diagnosed in 14 patients (31.8%), and one patient had active tuberculosis in the past, which was treated appropriately. Other reported infections in our cohort were human immunodeficiency virus (HIV) (n/N = 2/44, 4.5%), hepatitis B (n/N = 5/44, 11.3%) and hepatitis C (n/N = 2/44, 4.5%). Seven patients (16%) did not receive an induction dose.

In terms of risankizumab short-term effectiveness, the mean (±SD) PASI score fell from 12.3 (±2.8) at baseline to 5.3 (±0.9) after one month of risankizumab treatment. A further reduction in the mean PASI score was observed after 3 months to 1.3 (±2.0). Reductions in PASI scores were more pronounced in the patient subgroup treated with risankizumab-induction than the non-induced subgroup in both 1 (from 12.3 to 5.2 vs from 11.8 to 6.6, respectively) and 3 months of follow-up (from 12.3 to 0.7 vs from 11.8 to 2.8, respectively), but the difference was not statistically significant. The absolute PASI scores of ≤ 2 and ≤3, which were achieved in 7 (19.4%) and 15 (41.6%) patients at month 1, and in 16 (80.0%) and 17 (85.0%) patients at month 3, respectively. Almost half of the patients (45%) reached complete skin clearance after 3 months of treatment. In addition, further analyses showed that previous biologic therapy did not have a relevant impact on the absolute PASI scores responses. In fact, of all biologics-naïve patients (only 7), 80.0% and 100% demonstrated absolute PASI scores of ≤2 and ≤3 responses after 3 months of therapy (respectively) compared with 80.0% of non-biologic-naïve patients. In terms of safety, risankizumab was generally well tolerated. Only four patients (9.0%) reported AEs during the 3 months of therapy. During this period, the reported AEs among risankizumab recipients were arthralgia, headache and hypertension. In addition, intercurrent appendicitis after two doses of risankizumab led to permanent discontinuation of treatment in one patient. There were no new cases of active tuberculosis or reactivation even in the patient with non-treated latent tuberculosis disease after 3 months of follow-up. Regarding the findings for the multivariable analysis exploring predictors of differential treatment response, none of the tested variables (sex, age, BMI, prior biologic therapies, psoriasis duration, and baseline PASI scores) was associated with differential therapeutic response to risankizumab. Thus, prior biologic therapy did not affect risankizumab effectiveness in a statistically significant manner since better outcomes were found in both biologics-naïve patients and non-biologic-naïve patients at 1 and 3 months in terms of absolute PASI scores 0 (p = 0.41 and p = 0.06, respectively), ≤2 (p = 0.34 and p = 1.00, respectively) and ≤3 (p = 0.65 and p = 0.27, respectively). Basal PASI >12 scores were not associated with worse results in terms of achieving absolute PASI scores of ≤ 2 and ≤3 responses at 3 months (p = 1.00).

In line with our work, the benefits of risankizumab have been reported in three phase-3 clinical trials (UltIMMa-1, UltIMMa-2, IMMvent) [10–12]. In these studies, high levels of efficacy and safety have been demonstrated, and a high number of patients achieved PASI 90 (75.3% of the patients at week 16) and PASI 100 responses (59.5% of the patients at week 52) [12]. Otherwise, the patients included in clinical trials are often dissimilar to those seen in daily clinical practice due to the strict exclusion criteria (i.e. excluding patients with a history of malignancy) and the use of washout period for previous biologic therapy. Indeed, our cohort differed from the phase-3 clinical trial population because patients were older and had lower mean baseline PASI scores and a greater number of prior biological treatments. Nevertheless, despite these population differences, our analyses showed similar percentages of patients achieving absolute PASI ≤ 3 scores (85.0% at 3 months vs 82.9% at 16 weeks, respectively) than recent analyses based on risankizumab clinical trials [13,14]. Commonly, published real-life data on risankizumab are limited to studies with short follow-up and small sample sizes. For example, a multicenter study [9] from December 2019 to May 2020 in Italy included a total of 57 patients with a follow-up of 12 weeks. In this study, the authors found that females were more responsive to risankizumab at week 16, probably due to a high frequency of female BMI <25 (68.4%) compared to males (28.9%). However, although overweight and obese patients experienced a worse outcome than normal-weight patients in our cohort, we did not find statistical differences. Additionally, in an observational and retrospective study [7] of real clinical practice in three public hospitals of another Spanish region (Andalusia), the authors reported a decrease in the levels of absolute PASI clinically significant at 4 weeks in 20 patients.

In conclusion, our initial data from 44 patients in a real-life setting support the findings reviewed by Al-Janabi et al. [1] and the clinical trial promising results on risankizumab as a high-effective, safe and well-tolerated biologic for patients with moderate-to-severe plaque psoriasis in clinical practice up to 3 months following initiation. Moreover, our multicenter study shows that the risankizumab short-term effectiveness is regardless of patient demographics (age, gender, BMI, prior biologic therapies) and disease characteristics (psoriasis disease duration and baseline PASI scores). Although further data are needed to integrate both a higher patient number and a longer follow-up, we hope these findings help develop more affordable, safer, and more effective biologic drugs and contribute to improving the quality of life of patients with moderate-to-severe psoriasis.

Declaration of interests

R Rivera has acted as a consultant and/or speaker and/or investigator for AbbVie, Amgen, Almirall, Boehringer, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer and UCB. Mar Llamas-Velasco has acted as a consultant and/or speaker and/or investigator for AbbVie, Amgen, Almirall, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis and UCB. Mercedes Hospital has acted as a consultant and/or speaker and/or investigator for AbbVie, Amgen, Almirall, Biogen, Celgene, Lilly, Janssen, Leo Pharma, Novartis, and UCB. Isabel Martin has acted as a consultant and/or speaker for AbbVie, Amgen, Almirall, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer and UCB. Ofelia Banjadrés has acted as a consultant and/or has received speakers ́ fees from Janssen-Cilag, AbbVie, Pfizer, Novartis, Lilly, Celgene, Leo Pharma and Almirall. Diana Ruiz Genao has acted as a consultant and/or speaker and/or investigator for AbbVie, Amgen, Almirall, Boehringer, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer and UCB. Pablo de la Cueva has acted as a consultant, advisory board member, honorary for speaking and participation in clinical trials with the following pharmaceutical companies: Abbvie, Almirall, Astellas, Biogen, Boehringer, Celgene, Janssen., LEO Pharma, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB. Carmen García-Donoso has served as speaker for Abbvie, Novartis, Janssen, Leo-Pharma and Lilly. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

The Editorial board member who reviewed this letter to the editor has no relevant financial relationships or otherwise to disclose.

Acknowledgments

The authors would like to thank Carmen Romero Ferreiro (from Scientific Unit Support of Research Institute. Hospital Universitario 12 de Octubre- Madrid), who had collaborated in the statistical analysis.

Additional information

Funding

This study was independent. The medical writer for this manuscript was supported by AbbVie with no input into the preparation, review, approval and writing of the manuscript. The authors maintained complete control over the manuscript content, and it reflects their opinions.