Risankizumab for the Treatment of Moderate to Severe Psoriasis: Impact on Health-Related Quality of Life and Psychological Wellbeing

Introduction

Psoriasis is a chronic immune-mediated inflammatory disease the predominantly affects the skin, but also encompasses a significant list of comorbidities such as an increased risk of mortality, cardiovascular disease, diabetes, hyperlipidemia, or diabetes.^1,2

In addition to all of the above is its chronic nature and the feeling of therapeutic failure that often causes a sense of hopelessness and frustration, with an increased risk of suicide compared to the general population. In short, there is the effect of psoriasis at a physical level (due to the psoriasis itself, comorbidities and iatrogenesis), and also at a psychosocial level due to the limitation in social interaction and behavioural changes in daily life. Health-related quality of life (HRQoL) is the sum of physical health, well-being, and participation; it defines the functional effect of a disease or its treatment and how it is perceived by the patient.

The degree of HRQoL alteration is associated with psoriasis-dependent factors, but there are also personal factors that condition the patient’s vulnerability to the disease.³

Due to the profound systemic and emotional impact of this disease, improvements in severity scales such as PASI are not sufficient for assessing the overall effectiveness of treatment, but other scales such as quality of life indices (DLQI, HRQoL, SKINDEX-29, etc.) must be taken into account.⁴

With the advent of biological drugs, the psoriasis treatment paradigm has changed radically, taking into consideration PASI 90–100 therapeutic goals, and thus improvements in health-related quality of life.⁵ Risankizumab (RZB) is a humanized monoclonal antibody that specifically blocks the p19 subunit of interleukin 23, which in turn regulates the activation, differentiation, and survival of Th17. The IL23/Th17 pathway is activated in psoriasis, being responsible for the chronic inflammation and skin manifestations of the disease. In this sense, numerous molecules have proved their efficacy, their safety compared to anti-TNF⁶ however, studies that assess and compare the improvement in other secondary PROs such as the patient’s quality of life are still scarce. It has been observed that low levels of absolute PASI have been related to improvements in the quality of life related to the patient’s health and that even minimal residual disease has been related to a negative impact on the life of patients.⁷

The objective of this paper is to analyze the literature on the impact of treatment with risankizumab on the quality of life of patients and their psychological well-being.

Materials and Methods

A bibliographic search was carried out to identify all the papers published from July 2015 to June 1, 2022, on risankizumab treatment in psoriasis and its impact on health-related quality of life and psychological well-being. The results have been limited to studies conducted in humans and published in Spanish or English.

The studies were identified by searching the following databases: MEDLINE via PubMed, EMBASE, Centre of Review and Dissemination via University of York, Cochrane Library via Cochrane Database of Systematic Reviews, Cochrane Skin Group, Centre of Evidence Based Dermatology at the University of Nottingham, and the TESEO database of doctoral theses.

Additionally, the search has been expanded with the following websites: ClinicalTrials.gov, reec.aemps.es, Clinicaltrialsregister.eu.

Finally, with the aim of identifying the systematic reviews on quality of life related to health and psychological well-being in psoriasis, and more specifically on treatment with risankizumab, which are currently being carried out, an electronic search was conducted in PROSPERO, the International Prospective Register of Systematic Reviews.

The search terms that have been entered to conduct the definitive search for articles, according to the MeSH and DeSC dictionaries, have been: psoriasis, risankizumab, Health-Related Quality Of Life, quality of life.

Inclusion Criteria for the Studies

• Types of studies: Randomized controlled clinical trials; systematic reviews; observational studies with n greater than or equal to 20.
• Population: Psoriasis patients of legal age, regardless of gender, ethnicity, comorbidity, and prior treatment.
• For studies to be considered, they had to include psoriasis patients treated with risankizumab, at any dose for psoriasis.
• They were restricted to the following languages: Spanish and English.

Exclusion Criteria for the Studies

• Studies published outside the established time range.
• Studies that did not use accepted and validated assessment measures to evaluate health-related quality of life and psychological well-being.
• Case series with less than 20 patients.
• Studies in which risankizumab treatment was for psoriatic arthritis.
• Editorials and narrative reviews.

Management, Data Extraction, Data Synthesis, and Analysis of Methodological Quality

The results obtained by the searches were downloaded to a bibliographic reference manager (Mendeley^®), where the papers were filtered based on the title and abstract. During this process, all the duplicate, discarded, and selected references have been recorded in a flow chart (Figure 1). The search was not blind in terms of authors, journal, or institution.

Figure 1 Flowchart of the bibliographic search carried out in the systematic review.

The Jadad scale for randomized trials⁸ has been consulted, and the critical analysis has been based on the CONSORT guide.⁹ To synthesize the data, the OSTEBA tool has been used, since it allows the quality of the evidence from the various types of studies to be assessed, in addition to preparing summary tables of results.¹⁰

Results

Included and Excluded Studies

Of the 218 records obtained, 198 were excluded after evaluating the title and abstract, and due to duplication in the search databases. Twenty articles have been evaluated in full text, of which 8 were excluded because they did not meet the inclusion criteria or had a small number of patients, as well as the systematic reviews whose primary objective was to evaluate only efficacy and safety, (Figure 1).^11–18

Given the small number of clinical trials and systematic reviews, case series have been included, despite the fact that the evaluation of efficacy and effectiveness in them is very limited.^19–30 The studies that have been evaluated are: 8 clinical trials with high evidence,^{19,20,23–26,28,29} 3 case series, one prospective,²¹ and 2 retrospective,^22,27 of which the evidence is of low quality, and a cohort study of medium evidence quality.³⁰

The studies have been carried out in Europe, the United States, and Japan. The follow-up period, the number of patients, the characteristics of the study population, and the applied intervention in the included studies are summarized in Table 1.

Table 1 Summary of the Articles Included in the Review, Number of Patients, Intervention, Type of Study, Results, and Level of Evidence

Sample Size

The number of participants in the included studies varied considerably, with a maximum of 1276²⁵ and a minimum of 20^21,30 with a total of 5035 patients analyzed. The mean number of participants was 419.5.

Participants

All studies included adults over 18 years old with moderate to severe chronic plaque psoriasis, both men and women.^19–29 One study only included patients with genital psoriasis.³⁰

Design

Eight of the twelve included studies are clinical trials,^{2,19,20,23–26,28} and the rest are case series,^21,22,27 and a cohort study.³⁰

Of the studies included, five of them analyze data from the pivotal trials³¹ UltIMMa-1, UltIMMa-2, which include active comparator with ustekinumab (UST) and placebo (PBO).^{19,20,23,25,29}

In addition, Papp et al²⁰ and Lebwohl et al^23,25 use data from the IMMvent and IMMhance clinical trials, with active comparator with PBO and adalimumab (ADA).^32,33 Two studies analyze data from the LIMMitless extension clinical trial.^24,29 Ohtsuki et al²⁶ evaluated data from the SustaIMM trial comparing RZB 75 mg, 150 mg, and placebo. All these trials have a high level of evidence.

Of the studies with a case series design, one of them is based on the BIOREP registry,²⁷ and analyses patients with moderate-severe psoriasis in the Czech cohort treated with RZB; another article from a real clinical practice carried out in Spain analyses the effectiveness and safety of RZB.²¹ Mastorino et al²² studied whether there are differences in response to risankizumab in patients with bio-naive psoriasis versus bio-experience.

Finally, a cohort of patients with genital psoriasis has been included in which the efficacy and safety of risankizumab versus ixekizumab in genital psoriasis has been evaluated.³⁰

Outcome Measures

The results, as well as the methodology and the quality of the evidence, are represented in Table 1. In the included studies, there was some variation in the method of evaluating the outcomes.

Since there are many tools for measuring the quality of life of people with psoriasis and other skin disorders, studies that have used psoriasis-specific measures have been taken into account. These measures can be categorized as psoriasis-specific (Psoriasis Symptoms Scale [PSS];^19,28 skin-specific (Dermatology Life Quality Index [DLQI];^{19–24,26–30} and generic quality of life measures (SF‐36),²⁸ (EQ-5D-5L),^19,28 Hospital Anxiety and Depression Scale (HADS),^19,28 Work Productivity and Activity Impairment Questionnaire (WPAI),²⁵ Patient Global Assessment of Disease Activity (PtGA),²⁸ and Patient Benefit Index (PBI).²⁸

Discussion

Through the analyzed studies, RZB has shown to achieve a very significant improvement in the quality of life of patients compared to other drugs analyzed, especially in those who have not previously received any biological treatment.²² Compared to UST, at week 16, 66.2% of patients achieved a DLQI 0/1 versus 44.7% with UST.¹⁹ In the IMMvent and LIMMitless studies, these improvements were shown to increase to 77% and 78% at weeks 57 and 172, respectively.²⁴ Similar improvements were found when evaluating other scales related to quality of life, such as EQ-5D-5L or HADS.¹⁹

In addition, psoriasis-specific PROs (patient reported outcomes) such as PSS 0, indicating that there are no symptoms of psoriasis, is obtained in 30.3% of patients treated with RZB, compared to 15.1% with UST and 1% with PBO.¹⁹

When compared with fumaric acid esters (FAEs),²⁸ the most frequently prescribed first-line systemic treatment in Germany, patients treated with RZB had a lower PSS score compared to those treated with AEDs, which translates into less redness, itching, and burning associated with psoriasis.

On the other hand, patients randomized to RZB showed significant improvements in SF-36, HADS, PtGA, and EQ-5D-5L (<0.002); the benefit of treatment was even assessed from the patient’s perspective based on the PBI questionnaire on the patient’s therapeutic needs and another on the benefit achieved by the treatment. In this last questionnaire, RZB presented a better score than the FAEs.²⁸

In real clinical practice, similar results have been observed; Ruiz-Villaverde et al²¹ analyzed the effectiveness and safety of risankizumab in an observational and retrospective study, where they showed that the mean DLQI score at the start of treatment was 13.64 ± 4.80 and at week 16 the mean DLQI was less than 1, correlating with both improvements in PASI, BSA, and the visual analogue scale of pruritus.

Another very important piece of information is job productivity and the indirect costs associated with this disease. Lebwohl et al²⁵ through the Work Productivity and Activity Impairment Questionnaire (WPAI). The total work productivity impairment (TWPI) in the RZB trials (N.2046), incremental TWPI relative to RZB was 3.4%/week for UST/ADA, and 17.1%/week for placebo; incremental indirect cost savings for risankizumab were $2179/year vs adalimumab, $2321/year vs ustekinumab, and $11,284/year vs placebo.

Due to the systemic and psychological implications of psoriasis, it is necessary to analyse various PROs, both psoriasis-specific and general, in a combined manner, relating them to efficacy data, which allows us to obtain a global vision of the patient’s situation. Thus, absolute PASI<1 and DLQI 0/1 were compared, showing adjusted differences of 22.1% [15.2, 29.1 (95% CI)] in patients treated with RZB versus those treated with UST at week 16, and 30.3% [23.1, 37.6 (95% CI)] at week 52.²⁹ Similarly, the LiMMItless study showed that more than half of patients achieved both PASI 90 and DLQI 0/1 at 16 weeks of treatment (56.9%), and this percentage increased to 70% at week 172.²⁴

Lebwohl et al²³ in a Post Hoc Analysis of Four Phase 3 Clinical Trials (UltIMMa-1, UltIMMa-2, IMMvent, and IMMhance) agreed with the LiMMItless study; patients treated with risankizumab during the study period experienced the longest duration of DLQI 0/1: 215.7 days (59% over one year) followed by patients receiving adalimumab, adalimumab/risankizumab, 159.1 days (44% over one year) and ustekinumab, 144.3 days (40% over one year). The patients who received PBO/risankizumab maintained the DLQI 0/1 for less time, 90.5 days (25% over one year).

Even small differences in PASI can be significant when assessing the implications for patients’ quality of life. In a Czech cohort of patients with moderate-severe psoriasis treated with RZB at week 16, patients with a PASI 100 response achieved greater reductions in DLQI compared with those who achieved a PASI 90 response (15.9 points vs 11.8 p<0.033).^27,34

In addition, the DLQI deteriorates more rapidly than the PASI when treatment is discontinued (49.7% versus 36.4%) based on predictive models.²⁰

Regarding the RZB dose, the DLQI 0/1 response rate is very good with both RZB 75 mg and 150 mg, both being much higher than the placebo (62.1% and 58.2% versus 5.2%, respectively). However, when the placebo group of patients was re-randomized to receive risankizumab 75 mg and 150 mg, the DLQI 0/1 response rates increased from week 16 to week 52 to 66.7% and 81.5%, respectively.²⁶

On the other hand, the impact of RZB on special areas, such as the genitals, has also been studied. Sotiriou et al³⁰ compared the efficacy and safety of risankizumab vs ixekizumab in this area, demonstrating a reduction in DLQI from baseline to week 24 of 91.8% and 92.1%, respectively, obtaining similar rates for PGA-G, falling to 0.3 and 0.4, respectively.

Limitations

The lack of SCOPUS database search and practical limitations when assessing the risk of bias in non-randomized studies.

In conclusion, risankizumab has shown not only to have very relevant data on effectiveness and safety, but all of this is associated with an improvement in quality of life related to health and psychological well-being measured on generic and specific quality of life scales, both in pivotal trials, ad hoc analysis, and data in real clinical practice.