New long-term data on guselkumab published

Phase III data on the IL23p19 inhibitor guselkumab demonstrate complete resolution of skin symptoms and positive joint effects in adult patients with active psoriatic arthritis (PsoA) lasting over two years.

Data from the DISCOVER-2 study(box) show that the reductions in skin and joint symptoms previously demonstrated with guselkumab (Tremfya®) over durations of 24 and 52 weeks, respectively, were maintained over a 112-week period in adults with active psoriatic arthritis (PsoA) [1–3]. The safety profile also proved to be constant over this period. These are the first and, to date, only long-term results from a phase III study of the treatment of PsoA with a selective IL23 inhibitor, examining the effects on radiographic progression over a two-year period, Janssen Pharmaceutical Companies of Johnson & Johnson informs [14]. Radiographic progression is measured by assessing erosions and narrowing of the joint space in the hands and feet [12]. Further, the data confirmed that the robust efficacy of guselkumab already present at week 24 on physical function, physical aspects of health-related quality of life, and enthesitis and dactylitis persisted through week 100. [1–8].

Study results in week 100

Complete healing of skin symptoms: of patients with clinically significant skin symptoms* at baseline, 53% of those treated with guselkumab every eight weeks (q8w) achieved complete healing of skin symptoms (Psoriasis Area Severity Index [PASI] 100; non-responder imputation [NRI]) [1,2].

* body surface area affected by psoriasis of ≥3% and as an IGA score of at least 2 at study entry [15].

Improvement in joint symptoms: Among randomized patients, 74% in the guselkumab q8w 100 mg-treated group achieved at least a 20% improvement in response according to American College of Rheumatology (ACR 20)** (NRI)*** criteria [2].

** An ACR 20/50/70 response is defined as improvement in terms of number of tender and swollen joints from baseline by at least 20/50/70% and in three of the following five criteria by at least 20/50/70% from baseline: patient general assessment, physician general assessment, functional capacity measurement, pain score on a visual analog scale, and erythrocyte sedimentation rate or C-reactive protein. [17].

*** ACR response rates at week 100 were determined post-hoc by NRI, i.e., patients who withdrew from the study between weeks 24 and 100 were considered non-responders.

Radiological Progression: In patients treated with guselkumab q8w, rates of radiological progression of joint damage were low between week 52 and week 100 (0.46) and further reduced compared with results from weeks 0 to 52 (0.99; q8w) [1,2].

Duration: robust response rates in joint and skin symptoms and mean improvements in outcomes from respective baselines persisted over two years, and approximately 90% of randomized patients receiving guselkumab continued this treatment up to and including week 100 [1,2].

Safety: no new safety signals were identified in the safety analysis conducted up to and including week 112 [1,2]. The safety profile of guselkumab in patients with active PsoA over two years was comparable to the safety profile at six months and at one year, and was generally consistent with the safety profile of guselkumab in patients with moderate-to-severe plaque PsO [10,11]. There were 6.1 serious adverse events and 2.2 serious infections per 100 patient-years of treatment with guselkumab q8w. None of the patients treated with guselkumab developed anaphylactic reaction/serum sickness or active tuberculosis.

In addition, results showed that 55% of patients treated with guselkumab q8w achieved at least 50% improvement in ACR response (NRI) [2]. Among those with clinically significant plaque PsO at baseline, 55% of patients treated with guselkumab q8w achieved freedom from skin appearance with an Investigator Global Assessment (IGA) score of 0 (NRI) [2].

Literature:

McInnes I, et al: Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19-Subunit of Interleukin-23, Through 2 Years: Results from a Phase 3, Randomized, Double-blind, Placebo-controlled Study Conducted in Biologic-naïve Patients with Active Psoriatic Arthritis. Presented at the 2021 Innovations in Dermatology: Virtual Spring Conference; March 16-20 (ABSTRACT).
McInnes IB, et al: Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19-Subunit of Interleukin-23, Through 2 Years: Results from a Phase 3, Randomized, Double-blind, Placebo-controlled Study Conducted in Biologic-naïve Patients with Active Psoriatic Arthritis. Presented at the Innovations in Dermatology: Virtual Spring Conference; March 16-20, 2021 (POSTER).
Deodhar A, et al: Guselkumab in patients with active psoriatic arthritis who were biologic-naive or had previously received TNFα inhibitor treatment (DISCOVER-1): a double-blind, randomised, placebo-controlled phase 3 trial. The Lancet 2020; 395(10230): 1115-1125.
Mease P, et al. Guselkumab in biologic-naive patients with active psoriatic arthritis (DISCOVER-2): a double-blind, randomised, placebo-controlled phase 3 trial. The Lancet 2020; 395(10230): 1126-1136.
Helliwell P, et al: Efficacy of Guselkumab, a Monoclonal Antibody that Specifically Binds to the p19 Subunit of IL-23, on Endpoints Related to Axial Involvement in Patients with Active PsA with Imaging-Confirmed Sacroiliitis: Week-24 Results from Two Phase 3, Randomized, Double-blind, Placebo-controlled Studies. Presented at the 2020 EULAR E-Congress June 3-6.
Mease P, et al: Efficacy of Guselkumab, a Monoclonal Antibody that Specifically Binds to the p19 Subunit of IL-23, on Axial-Related Endpoints in Patients with Active PsA with Imaging-Confirmed Sacroiliitis: Week-52 Results from Two Phase 3, Randomized, Double-blind, Placebo-controlled Studies. Abstract 898117. Presented at ACR Convergence 2020 November 5-9.
Ritchlin C, et al: Guselkumab, an inhibitor of the IL-23p19 subunit, provides sustained improvement in signs and symptoms of active psoriatic arthritis: 1 year results of a phase III randomised study of patients who were biologic-naïve or TNFα inhibitor-experienced. RMD Open 2020;7(1):e001457.
McInnes I, et al. Efficacy and Safety of Guselkumab, an Interleukin-23p19-Specific Monoclonal Antibody, Through 1 Year in Biologic-naïve Psoriatic Arthritis Patients. Arthritis & Rheumatology. Oct 11 2020 doi: 10.1002/art.41553. Epub ahead of print.
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Griffiths CEM, et al: Continuous treatment with guselkumab maintains clinical responses through 4 years in patients with moderate-to-severe psoriasis: results from VOYAGE 1. Journal of Dermatological Treatment 2020, 1-9. https://doi.org/10.1080/09546634.2020.1782817
Reich, K, et al: Maintenance of Response Through up to 4 Years of Continuous Guselkumab Treatment of Psoriasis in the VOYAGE 2 Phase 3 Study. American Journal of Clinical Dermatology 2020, 21(6), 881-890.
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“New Phase III data on the first-in-class inhibitor TREMFYA® (guselkumab) show complete resolution of skin symptoms and positive joint effects in adult patients with active psoriatic arthritis (PsoA) over two years,” Janssen Switzerland, Zug, Switzerland, March 25, 2021.
Clinicaltrials.gov. A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis (DISCOVER-2). Identifier: NCT03158285. www.clinicaltrials.gov/ct2/show/NCT03158285. Accessed March 2021.
Clinicaltrialsregister.eu. A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Subjects with Active Psoriatic Arthritis. Identifier 2016-001224-63. Available at: www.clinicaltrialsregister.eu/ctr-search/trial/2016-001224-63/ES. Accessed March 2021.
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