Rheumatology Drug Updates: Efficacy & Safety of Guselkumab, Plus FX006 for Knee OA

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Guselkumab Improves Active Psoriatic Arthritis

New research has revealed that patients with active psoriatic arthritis (PsA) and ≥3% body area of plaque psoriasis benefit from treatment with a human monoclonal antibody known as guselkumab (GUS). GUS is specific for the p19 subunit of interleukin 23 (IL-23). Patients in the Phase 2 clinical trial experienced significant improvement in joint symptoms, physical function, psoriasis, enthesitis, dactylitis and quality of life. Specifically, more than half (58%) of the patients treated with GUS experienced at least a 20% improvement in ACR signs and symptoms of disease (ACR20) at Week 24 compared with 18.4% of placebo-treated patients—the study’s primary endpoint (P<0.001).¹

“It is encouraging to see how well patients responded to guselkumab with respect to improvements in signs and symptoms of psoriatic arthritis as early as Week 4 and to see the improvements in health-related quality of life outcomes, such as measures of physical and mental health,” says senior author Atul Deodhar, MD, a rheumatologist at Oregon Health & Science University in Portland, in an email to The Rheumatologist.

Participants in the double-blind, placebo-controlled multicenter study received standard-of-care therapy for PsA, including tumor necrosis factor alpha (TNFα) inhibitors. Despite standard treatment, the participants had at least 3% of their body surface area covered with plaques. The investigators randomized patients (2:1) to receive either 100 mg GUS subcutaneously or placebo at Weeks 0, 4 and every eight weeks thereafter through Week 44. Only four placebo-treated patients (8.2%) and nine GUS-treated patients (9.0%) had previously received TNFα inhibitors.

If patients from either group had less than a 5% improvement from baseline in both tender joint counts and swollen joints at Week 16, they were given the option of early escape to open-label ustekinumab. At Week 24, the remaining placebo patients crossed over to receive 100 mg GUS subcutaneously, given at Week 28 and every eight weeks thereafter through Week 44. The protocol was similar to that used with the initial randomization group.

“We learn something new with each of the studies using targeted biologic therapies,” explains Dr. Deodhar. “We were already aware that therapies that target IL-12 + IL-23 [ustekinumab] and those that target IL-17A were effective in treating psoriatic arthritis, but we did not know if specifically targeting IL-23 would demonstrate the same (or better) efficacy in the signs and symptoms of arthritis, enthesitis and dactylitis. Guselkumab is the first biologic therapy that specifically targets IL-23 that has been studied in PsA.” The results confirm that IL-23 plays a key role in the immunopathogenesis of psoriatic arthritis.

The study’s secondary endpoints were a 75% reduction in the Psoriasis Area and Severity Index (PASI75) and ACR50 responses, as well as change from baseline in Health Assessment Questionnaire Disability Index (HAQ-DI), improvement in enthesitis (Leeds Enthesitis Index) and dactylitis score (a 0–3 scoring system) at Week 24, as well as ACR20 response at Week 16. At Week 24, GUS treatment led to significantly greater improvements in dactylitis, enthesitis and health-related quality of life as measured by the Short Form Health Survey (SF-36 physical and mental component summary scores) compared with placebo-treated patients. In addition, at Week 24, minimal disease activity was attained by a higher percentage of GUS-treated patients compared with placebo-treated patients (23% vs. 2%; P=0.001). “It is difficult to compare guselkumab with other existing therapies for PsA, since no head-to-head studies have been done,” says Dr. Deodhar. “However, the improvements seen with guselkumab in the various manifestations of psoriatic arthritis and patient-reported outcomes are very promising.”

GUS was well tolerated with no unexpected safety findings. Both the treatment and control groups had comparable numbers of adverse events through Week 24 (placebo: 33%; GUS: 36.0%). The most common adverse event was infection, which occurred in 20% of placebo-treated patients and 17% of GUS-treated patients.

FX006 Promising for Knee OA

A new drug application has been submitted to the FDA for FX006 (Zilretta), a long-acting steroid injection for knee OA.2 The treatment combines triamcinolone acetonide (TCA) in a polymer to provide longer lasting pain relief.

In a Phase 3 trial, patients who received FX006 reported about half of the pain level on average compared with placebo-treated patients through 12 weeks.² This study was a Phase 3, randomized, double-blind, placebo-controlled, active-comparator trial. Efficacy was assessed in 484 patients at four-week intervals over 24 weeks. The primary trial endpoint was pain reduction assessed by the weekly mean of the average pain score for active comparator compared with placebo, which was achieved by FX006 (P<0.0001).

‘It is encouraging to see how well patients responded to guselkumab with respect to improvements in signs & symptoms of psoriatic arthritis as early as Week 4.’ —Dr. Deodhar

The treatment also achieved statistically significant improvements in WOMAC A (pain), B (stiffness) and C (function) at Weeks 4, 8 and 12 compared with placebo and immediate-release TCA (P<0.05). Efficacy by Knee Injury and Osteoarthritis Outcome Score quality of life at four-week intervals over 24 weeks was also achieved by FX006.

Adverse events were mild and balanced across treatment and placebo study arms. No serious adverse events occurred.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

Acknowledgment: Thanks to Lara C. Pullen, PhD, a medical writer based in the Chicago area, for her assistance in writing the Efficacy & Safety of Guselkumab section of this column.

References

1. Deodhar AA, Gottlieb AB, Boehncke WH, et al. Efficacy and safety results of guselkumab, an anti-IL23 monoclonal antibody, in patients with active psoriatic arthritis over 24 weeks: A phase 2a, randomized, double-blind, placebo-controlled study [abstract]. Arthritis Rheumatol. 2016;68(suppl 10).
2. Stendahl M. Fast-growing Burlington biotech Flexion files for approval of lead drug. Boston Business Journal. 2016 Dec 12.