• Studies confirm improvement achieved and maintained through one year of active treatment with similar scores for patients switching from placebo to guselkumab
  • Guselkumab is the first and only U.S. FDA-approved selective anti-IL-23 therapy for active psoriatic arthritis and the only therapy for psoriatic arthritis to have improvement in fatigue as measured by FACIT-F in the product label.

Data from two Phase 3 clinical trials, DISCOVER-1 and DISCOVER-2 showed that guselkumab  (TREMFYA) improved fatigue in adult patients with active psoriatic arthritis (PsA) and maintained response through 52 weeks of active treatment, as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Scale.1,a Guselkumab improved fatigue during the placebo-controlled periods of both studies at week 24, and through one year of active treatment. In both studies, guselkumab had positive effect on fatigue, in addition to other clinical outcomes, including ACR20 response.b,1 Guselkumab is FDA-approved for administration as a 100 mg subcutaneous (SC) injection every eight weeks (q8w), following two starter doses at weeks 0 and 4.2

Data assessing fatigue outcomes of the studies will be presented as a poster presentation (Abstract #0347) on Friday, November 6 from 9:00 – 11:00 a.m. EST during ACR Convergence 2020, the American College of Rheumatology (ACR) virtual annual meeting.1

Fatigue is considered one of the three most important symptoms by patients with active PsA, and moderate to severe fatigue occurs in up to 50 percent of these patients.3-6 Fatigue is defined as an overwhelming, sustained sense of exhaustion and decreased capacity for physical and mental work.7 It includes a range of experiences, from tiredness to exhaustion, which can interfere with normal daily function and reduce health-related quality of life. Fatigue is ranked high by patients regarding impact on life and priority for improvement.6

“Fatigue associated with psoriatic arthritis can have a serious impact on patients’ health-related quality of life and can lead to social isolation and loss of employment,”8 said Proton Rahman,i M.D., Professor of Medicine, Rheumatology, Memorial University in Newfoundland, Canada and presenting author of the study. “These findings from the DISCOVER-1 and DISCOVER-2 studies showing an improvement in fatigue a full year into treatment with guselkumab add to the previously presented 52-week data demonstrating an improvement in joint and skin symptoms. Considered together, the data are encouraging for active psoriatic arthritis patients who struggle with multiple symptoms.” In both DISCOVER-1 and DISCOVER-2 clinical trials:1

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  • The FACIT-Fatigue Scale, a validated patient-reported outcomes instrument, was used to assess fatigue and its impact on daily activities and function over the prior 7 days. Scale scores range from 0 to 52, with the higher score denoting less fatigue. A change of ≥4 points is considered clinically meaningful.9
  • At baseline in both studies, the mean FACIT-Fatigue scores were 30.4 (10.4) and 29.7 (9.7), respectively, indicating that patients with active PsA experienced fatigue worse than the general population [43.6 (9.4)].
  • At week 24 in both studies, treatment with guselkumab led to greater improvements in FACIT-Fatigue scores compared with placebo, as early as week 16 in DISCOVER-1 and week 8 in DISCOVER-2, with 54%-63% of guselkumab patients achieving clinically meaningful improvement (≥4 points) in FACIT-Fatigue compared with 35%-46% of placebo patients (unadjusted p≤0.003).9
    • FACIT-Fatigue least squares (LS) mean changes from baseline were 5.6 and 5.8 for q8w and every four weeks (q4w), respectively, compared with 2.2 for placebo in DISCOVER-1, and 7.6 and 7.1 for q8w and q4w, respectively, compared with 3.6 for placebo in DISCOVER-2.
  • After crossing over to guselkumab q4w at week 24, patients who had previously been on placebo achieved FACIT-Fatigue scores comparable to those of guselkumab patients through week 52 (mean change from baseline of 6.6 vs. 6.9, respectively, in DISCOVER-1, and 7.5 vs. 7.7, respectively, in DISCOVER-2).
  • At 52 weeks, 61%-70% of both guselkumab patients and those who crossed over from placebo to guselkumab after 24 weeks achieved a clinically meaningful improvement in FACIT-Fatigue score.

In both studies, guselkumab was well-tolerated through study completion, and adverse events (AEs) were generally consistent with previous studies of guselkumab and current prescribing information.2  Serious AEs and serious infections occurred in 4 percent and 1 percent of guselkumab -treated patients, respectively, in both DISCOVER-1 and DISCOVER-2.10,11

Guselkumab was approved in July 2020 by the U.S. FDA for adult patients with active PsA, a chronic progressive disease characterized by painful joints and skin inflammation,2,12 and is the first and only therapy approved for active PsA to have improvement in fatigue as measured by FACIT-F in the product label. The approval was based on results from two pivotal Phase 3 clinical trials, DISCOVER-1 and DISCOVER-2, which evaluated the efficacy and safety of guselkumab administered by SC injection in adults with active PsA compared to placebo, and showed that a significant percentage of patients treated with guselkumab reached the studies’ primary endpoint of ACR20 at 24 weeks.13,14 Recently announced data showed that guselkumab demonstrated improvements in multiple clinical outcomes including joint symptoms, skin symptoms, soft tissue inflammation, physical function, axial-related disease,15,16 and reduction in radiographic progression at week 52.10,11

 

References:

  1. Rahman P, et al. In Two Phase-3 Trials, Guselkumab Reduced Fatigue over 52 Weeks in Patients with Psoriatic Arthritis and Demonstrated Independent Treatment Effects on Fatigue After Adjustment for Clinical Response (ACR20). Abstract: 898351. Presented at ACR Convergence 2020 November 5-9.
  2. Food and Drug Administration TREMFYA (guselkumab) injection Full Prescribing Information. http://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TREMFYA-pi.pdf
  3. Husted JA, Tom BD, Farewell VT, Gladman DD: Longitudinal analysis of fatigue in psoriatic arthritis. J Rheumatol 2010, 37(9):1878-1884.
  4. Husted JA, Tom BD, Schentag CT, Farewell VT, Gladman DD: Occurrence and correlates of fatigue in psoriatic arthritis. Ann Rheum Dis 2009, 68(10):1553-1558.
  5. Tobin AM, Sadlier M, Collins P, Rogers S, FitzGerald O, Kirby B: Fatigue as a symptom in psoriasis and psoriatic arthritis: an observational study. Br J Dermatol 2017, 176(3):827-828.
  6. Gudu T, Etcheto A, de Wit M, Heiberg T, Maccarone M, Balanescu A, Balint PV, Niedermayer DS, Canete JD, Helliwell P et al: Fatigue in psoriatic arthritis – a cross-sectional study of 246 patients from 13 countries. Joint Bone Spine 2016, 83(4):439-443.
  7. Nursing Care Plan and Diagnosis, Fatigue [https://www.registerednursern.com/nursing-care-plan-and-diagnosis-fatigue/].
  8. Krajewska-Włodarczyk M, Owczarczyk-Saczonek A, Placek W. Fatigue – an underestimated symptom in psoriatic arthritis. Reumatologia/Rheumatology. 2017;55(3):125-130. doi:10.5114/reum.2017.68911.
  9. Cella D, Wilson H, Shalhoub H, Revicki DA, Cappelleri JC, Bushmakin AG, Kudlacz E, Hsu MA: Content validity and psychometric evaluation of Functional Assessment of Chronic Illness Therapy-Fatigue in patients with psoriatic arthritis. J Patient Rep Outcomes 2019, 3(1):30.
  10. Ritchlin, C, et al. Guselkumab, an IL-23 Inhibitor That Specifically Binds to the IL23p19-Subunit, for Active Psoriatic Arthritis: One Year Results of a Phase 3, Randomized, Double-blind, Placebo-controlled Study of Patients who Were Biologic-Naïve or TNFα Inhibitor-Experienced. SAT0397. Presented at the 2020 EULAR E-Congress June 3—6.
  11. McInnes, I, et al. Efficacy and Safety of Guselkumab, a Monoclonal Antibody Specific to the p19-Subunit of Interleukin-23, Through Week 52 of a Phase 3, Randomized, Double-blind, Placebo-controlled Study Conducted in Biologic-naïve Patients with Active Psoriatic Arthritis. SAT0402. Presented at the 2020 EULAR E-Congress June 3—6.
  12. National Psoriasis Foundation. About Psoriatic Arthritis. Available at: https://www.psoriasis.org/about-psoriatic-arthritis. Accessed May 2020.
  13. 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, Randomized, Placebo-controlled Phase 3 Trial. The Lancet 2020 395:1115–1125.
  14. Mease PJ, et al. Guselkumab in Biologic-naive Patients with Active Psoriatic Arthritis (DISCOVER-2): A Double-blind, Randomized, Placebo-controlled Phase 3 Trial. The Lancet 2020; 395:1126–1136.
  15. 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.
  16. 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.
  17. Acaster S, et al. Qualitative and quantitative validation of the FACIT-fatigue scale in iron deficiency anemia Health Qual Life Outcomes. 2015; 13: 60. Published online 2015 May 17.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434873/, Accessed Oct.2020
  18. Felson D, The ACR20 and defining a threshold for response in rheumatic diseases: too much of a good thing, Arthritis Res Ther. 2014; 16(1): 101. Published online 2014 Jan 3., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3978644/, Accessed Oct. 2020
  19. Clinicaltrials.gov. A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis Including Those Previously Treated With Biologic Anti-Tumor Necrosis Factor (TNF) Alpha Agent(s) (DISCOVER-1). Identifier: NCT03162796. Available at: https://clinicaltrials.gov/ct2/show/NCT03162796. Accessed May 2020.
  20. Clinicaltrials.gov. A Study Evaluating the Efficacy and Safety of Guselkumab Administered Subcutaneously in Participants With Active Psoriatic Arthritis (DISCOVER-2). Identifier: NCT03158285. Available at: https://clinicaltrials.gov/ct2/show/NCT03158285. Accessed May 2020.
  21. Belasco J, Wei N. Psoriatic Arthritis: What is Happening at the Joint?. Rheumatol Ther. 2019;6(3):305-315. doi:10.1007/s40744-019-0159-1.
  22. National Psoriasis Foundation. Statistics. Available at: https://www.psoriasis.org/content/statistics Accessed May 2020.
  23. European Medicines Agency. TREMFYA Summary of Product Characteristics. 2019. Available at: www.medicines.org.uk/emc/medicine/34321. Accessed September 2020.
  24. Benson JM, et al. Discovery and Mechanism of Ustekinumab. MAbs 2011 3:535.