Guselkumab (GUS) is a subcutaneously administered monoclonal antibody that targets interleukin (IL) 23.1 It is being investigated in a Phase 2 study to treat rheumatoid arthritis (RA) and moderate to severe plaque psoriasis (PsA).
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On June 11, 2015, at the 2015 meeting of the European League Against Rheumatism (EULAR) in Rome, Italy, researchers presented an evaluation of the safety and efficacy of treating patients with active RA (n=274) with guselkumab or ustekinumab, despite methotrexate (MTX) treatment. This randomized, multicenter, double-blind, placebo-controlled, parallel-group study involved patients with six or more tender joints (TJC) and six swollen joints (SJC) with a CRP of at least 0.80 mg/dL.2 Randomized patients received placebo; ustekinumab (UST) 90 mg on Weeks 0, 4 and then every eight weeks; UST 90 mg on Weeks 0, 4 and then every 12 weeks; GUS 200 mg on Weeks 0, 4 and then every eight weeks; or GUS 50 mg on Weeks 0, 4 and then every eight weeks. MTX doses ranged from 10–25 mg weekly and had to be stable for a minimum of 12 weeks prior to randomization. Prednisone 10 mg daily or less, and non-steroidal anti-inflammatory agents were permitted.
Placebo-treated patients at Week 12 were given UST 90 mg on Weeks 16, 20 and 28 if they did not have at least a 10% improvement in both TJC and SJC. The number of patients obtaining an ACR20 was not significantly different between the groups.
Some differences were noted in secondary endpoints. More than one treatment-emergent adverse event (TEAE) occurred at Week 48 for 46% of placebo-treated patients, 50% of combined UST-treated patients and 43% of combined GUS-treated patients. There were also two cases of malignancy, squamous cell lung cancer in one UST 90 mg every 12-weeks-treated patient, and breast cancer in one GUS 200 mg every eight-weeks-treated patient. ACR20 efficacy at Week 28 was not seen in GUS- or UST-treated patients with active RA.
Minor improvements were seen in some secondary endpoints. These results show that IL-12 and/or IL-23 inhibition lack sign and symptom alleviation in patients with active RA. GUS is currently in Phase 3 clinical trials for the treatment of moderate to severe plaque psoriasis in both the U.S. and European Union.
In one Phase 3 study presented at the 2015 meeting of the European League Against Rheumatism (EULAR), researchers randomized 596 patients to receive either etanercept (ETN) or an etanercept biosimilar (SB4) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate (MTX) therapy.3 Patients received SB4 50 mg (n=299) or ETN 50 mg (n=297) administered subcutaneously weekly for 52 weeks. Demographics were similar between the two treatment groups.
The primary endpoint (ACR20) at Week 24 was similar between the two treatment groups: 78% for SB4 and 80% for ETN. ACR50 responses at Week 24 were 47% and 42% for SB4 and ETN, respectively. ACR70 responses were 26% and 23%, respectively.
The safety profile of SB4 was similar to ETN. At least one TEAE occurred in 55% of SB4-treated patients and 58% of ETN-treated patients. Serious infections occurred in 1.3% of ETN-treated patients (n=4) and 0.3% of SB4-treated patients (n=1). Injection site reactions were also more common in ETN-treated patients (17% v. 4%). SB4 showed similar clinical efficacy and safety compared with ETN.
There were no statistically significant differences between the three biologics. In addition, there were fewer adverse events with the etanercept biosimilar than with adalimumab & infliximab.
In a separate descriptive, cross-sectional study, Santos-Moreno et al evaluated the effectiveness of an etanercept biosimilar (Etanar) to adalimumab and infliximab in patients with longstanding RA in a real-life setting.4 Patients who visited a rheumatologist at least six times in the prior two years were included.
Patients were divided into two groups: a remission/low disease activity (LDA) group and a moderate to severe disease activity group (SDA). Determining the percentage of SDA patients who reached LDA or remission was the study’s goal. Clinical follow-up evaluated the DAS28 at different points within the study. The average patient age was 59 (±10 years) with a disease duration of 11 years; 158 patients were included; 61 received adalimumab; 62 received etanercept biosimilar; and 35 received infliximab.
At Month 24, there was a statistically significant increase in the percentage of patients in remission and a statistically significant decrease in the percentage of patients with SDA. For all three biologics, the DAS28 was 3.6 at baseline and 2.6 at Month 24. There were no statistically significant differences between the three biologics. In addition, there were fewer adverse events with the etanercept biosimilar than with adalimumab and infliximab.
Additionally, the therapeutic equivalence of BOW015 (infliximab biosimilar) was evaluated in reference to infliximab (rIFX, Remicade) in 189 subjects with active RA in a randomized, 54-week, double-blind, active-comparator Phase 3 study.5 The objectives were to determine whether BOW015 had equivalent efficacy in suppressing disease activity (DAS28-CRP) and physical function (HAQ-DI) when combined with patients’ stable doses of MTX (10–20 mg/week).
Patients received either BOW015 or rIFX as 3 mg/kg intravenously (IV) every eight weeks—at Weeks 0, 2, 6 and 14. Patients then received open-label BOW015 through Week 54. At Week 16, clinically significant improvements from baseline were noted for both scores in both treatment groups. Significant reductions in DAS and disability were maintained throughout the study’s open-label phase to Week 54.
Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
- Johnson & Johnson. News release: Anti-interleukin-23 monoclonal antibody guselkumab shows significant efficacy in treatment of moderate to severe plaque psoriasis. 24 March 2014.
- Smolen J, Agarwal SK, Llivanova E, et al. A Phase 2 study evaluating the efficacy and safety of subcutaneously administered ustekinumab and guselkumab in patients with active rheumatoid arthritis despite treatment with methotrexate. Ann Rheum Dis. 2015;74(Suppl2):76–77. doi: 10.1136/annrheumdis-2015-eular.3989.
- Vencovský J, Sylwestrzak A, Leszczyński P, et al. A phase 3 randomized, double-blind clinical study comparing sb4, an etanercept biosimilar, with etanercept reference product (Enbrel®) in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy (24-week results). Ann Rheum Dis. June 2015;74(Suppl2):467. Abstract FRI0128. doi: 10.1136/annrheumdis-2015-eular.1220.
- Santos-Moreno P, Saavedra-Martinez G, Villarreal L, et al. Etanar—A etanercept biosimilar is as effective as adalimumab and infliximab in a cohort of real-life of patients with rheumatoid arthritis. Ann Rheum Dis. June 2015;74(Suppl2):789. Abstract SAT0360. doi: 10.1136/annrheumdis-2015-eular.2508.
- 5Kay J, Chopra A, Lassen C, Shneyer L, Wyand M. BOW015, a biosimilar infliximab: Disease activity and disability outcomes from a phase 3 active comparator study in patients with active rheumatoid arthritis on stable methotrexate doses. Ann Rheum Dis. June 2015;74(Suppl2):462. Abstract FRI0117. doi: 10.1136/annrheumdis-2015-eular.4973.