Real-world evidence for comprehensive evaluation of guselkumab in the treatment of psoriasis

Abstract

Diamant Thaçi

While randomized controlled trials (RCTs) remain the gold standard of evidence-based medicine, real-world evidence (RWE) is becoming increasingly important.¹ Despite potential challenges with data sources, such as missing/limited data and the lack of patient randomization, RWE is considered more relatable to daily clinical practice and aids investigation of long-term effectiveness and treatment safety.¹ This is particularly relevant for chronic conditions like moderate-to-severe psoriasis, which usually requires long-term treatment and is associated with numerous comorbidities.

Guselkumab, a human monoclonal antibody that inhibits interleukin-23, was approved for the treatment of moderate-to-severe psoriasis in 2017. This supplemental issue of JEADV discusses guselkumab RWE as an important evidence source to complement RCTs in psoriasis, presenting five non-interventional studies (PERSIST,² G-EPOSS,³ GULLIVER,⁴ SPRING⁵ and a study by Tskhvarashvili et al.⁶) comprising >1400 guselkumab-treated patients across five European countries.^2-6 Together, they describe effectiveness, health-related quality of life (HRQoL) and safety outcomes with guselkumab treatment, as well as drug persistence, in a real-world setting.

The limitations of RWE noted above emphasize the importance of conducting non-interventional studies with robust methodology. PERSIST, G-EPOSS and GULLIVER were prospective, multicentre, observational studies conducted in Germany^{2, 3} and Italy.⁴ They had predefined patient eligibility criteria and study endpoints, and their population sizes were planned using rigorous statistical methodology. SPRING and the Tskhvarashvili et al. study were multicentre, retrospective studies conducted in Spain⁵ and Finland/Sweden,⁶ respectively, with defined patient eligibility criteria. Tskhvarashvili et al. conducted sensitivity analyses to account for biases in drug availability, changing treatment practices and uncertainty in drug discontinuation dates.⁶

Although RCTs typically provide rigorous evaluation of a drug's efficacy and safety profile, the controlled conditions and stringent patient eligibility criteria may limit the generalizability of the results obtained.¹ For example, patients enrolled in the guselkumab RCTs VOYAGE 1 and 2 were required to have a baseline Psoriasis Area and Severity Index (PASI) ≥ 12;^{7, 8} as such, baseline PASI was lower in the guselkumab non-interventional studies.^2-5 Additionally, patients typically have received fewer biologics prior to enrolment in RCTs, compared with RWE studies, which can impact clinical responses.⁹ Furthermore, patients in routine practice often have a greater disease burden due to comorbidities or are more refractory to treatment than those enrolled in RCTs.^{2, 5, 10} Overall, patients in RWE studies are more representative of the general patient population.^{9, 10}

While RCTs generally investigate key efficacy and safety outcomes to achieve regulatory approval, RWE offers the opportunity to investigate non-traditional outcomes with a focus on specific populations or bodily locations. G-EPOSS evaluated the effect of guselkumab on sexual impairment and perceived stigmatization—factors that substantially impact patients with psoriasis yet are rarely investigated.³ Similarly, GULLIVER focused on patients with facial and/or genital psoriasis, who are under-represented in RCTs.⁴ Treatment of these conditions represents a substantial unmet and clinically relevant medical need.^{3, 4}

The data in this supplement further our understanding of the effectiveness of guselkumab for moderate-to-severe psoriasis in routine clinical practice. SPRING and PERSIST reported sustained improvements in both PASI and Dermatology Life Quality Index (DLQI) to Weeks 52⁵ and 104² with guselkumab treatment, and similar findings have also been reported in other RWE studies.^11-13 Moreover, skin improvements were reported in special locations, including the facial⁴ and/or anogenital regions^2-4 and nails.^{2, 3} Sexual impairment and perceived stigmatization improved from baseline to Week 28 in G-EPOSS, highlighting the impact that effective treatment can have beyond physical symptoms.³ Additionally, G-EPOSS identified that Question 9 of the commonly used DLQI may be a valuable indicator (to the treating physician) of sexual impairment and anogenital psoriasis.³ Finally, by investigating drug persistence as a proxy for treatment effectiveness and tolerability, Tskhvarashvili et al. reported that 90% of patients continued guselkumab treatment for ≥1 year,⁶ consistent with SPRING⁵ and PERSIST² and other RWE studies of guselkumab.^{11, 14-16} The safety profile of guselkumab was evaluated across the study populations; no new safety signals were observed.^2-5

Consistent with previous RWE studies,^{11, 14} greater improvements in skin^{2, 3} and HRQoL² were reported with guselkumab treatment in biologic-naïve than biologic-experienced patients, indicating that early treatment initiation may be beneficial. However, in clinical practice, patients often receive guselkumab after inadequate response/intolerance to other conventional systemic and biologic therapies.^{2, 5}

In conclusion, the studies in this supplement demonstrate the value of well-conducted RWE, validating findings from guselkumab RCTs and extending their relevance to a population reflective of clinical practice, including biologic-experienced patients, patients with comorbidities and patients with psoriasis in sensitive locations. As psoriasis is a chronic condition requiring long-term treatment, the data highlight a place for RWE in evaluating the long-term effectiveness and tolerability of treatments using patient-relevant outcomes, which may ultimately inform treatment guidelines.

This paper was funded by Johnson & Johnson Innovative Medicine.

Diamant Thaci is an advisor, speaker or consultant for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Galderma, Janssen, Kyowa Kirin, L'Oréal, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, Sanofi/Genzyme and UCB.

Procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional or regional) and with the Helsinki Declaration of 1975, as revised in 1983.

This editorial adheres to the ICMJE recommendations for patient privacy.