Tremfya Becomes First IL-23 Inhibitor to Show Spinal Pain and Stiffness Benefit in Axial Psoriatic Arthritis
核心洞察
Johnson & Johnson's Tremfya (guselkumab) met the primary endpoint of the Phase 4 STAR study in adults with active psoriatic arthritis (搜索) and MRI-confirmed axial involvement.
At week 24, guselkumab produced greater improvement than placebo on the Bath Ankylosing Spondylitis Disease Activity Index, a measure including spinal pain and stiffness.
The trial is the first dedicated study to prospectively evaluate an IL-23 (搜索) inhibitor specifically in MRI-confirmed axial psoriatic arthritis (搜索), enrolling 411 biologic-naive adults worldwide.
Johnson & Johnson reported that TREMFYA (guselkumab) met the primary endpoint of the Phase 4 STAR study, becoming the first and only IL-23 (搜索) inhibitor to show significant improvement in spinal pain and stiffness in adults with active psoriatic arthritis (搜索) (PsA) and axial involvement. The company said the drug demonstrated greater improvement than placebo at Week 24 on a disease activity measure that includes spinal pain and stiffness.
STAR Study Design and Endpoints
STAR (NCT04929210) is a Phase 4, multicenter, randomized, double-blind, placebo-controlled study evaluating TREMFYA in biologic-naive adults with active PsA and axial involvement. Eligible participants had active PsA with objective evidence of axial inflammation confirmed by centrally read MRI and elevated C-reactive protein despite previous treatment with non-biologic disease-modifying antirheumatic drugs (DMARDs), apremilast and/or nonsteroidal anti-inflammatory drugs (NSAIDs).
The study enrolled 411 participants worldwide and includes a 24-week placebo-controlled treatment period followed by a 24-week active treatment period. The primary endpoint evaluated change from baseline in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at Week 24. BASDAI is a validated patient-reported outcome originally developed to measure disease activity on a 0 to 10 scale in ankylosing spondylitis, now referred to as radiographic axial spondyloarthritis.
Secondary endpoints include additional assessments of axial symptoms, MRI inflammation, physical function, peripheral musculoskeletal manifestations, skin disease and safety. The trial also met major secondary endpoints, showing improvements in axial symptoms and a reduction in inflammation of the sacroiliac joints measured using MRI.
"Clinical data continue to expand the evidence base for TREMFYA effectiveness across multiple domains of psoriatic arthritis (搜索)," said Philip J. Mease, M.D., MACR, FRCP, Director of Rheumatology Research at the Providence Swedish Medical Center and Clinical Professor at the University of Washington School of Medicine in Seattle. "What makes the STAR study particularly noteworthy is that, for the first time in a prospective, randomized, double-blinded, placebo-controlled PsA study, it evaluates MRI assessments for inclusion and provides a rigorous and objective measure of improvements in inflammation alongside clinical outcomes in axial PsA. Together, these findings contribute to a more comprehensive understanding of disease activity and treatment effects."
Dr. Mease is a paid consultant for Johnson & Johnson and has not been compensated for any media work.
Safety and Ongoing Evaluation
Johnson & Johnson said the safety profile observed in STAR was consistent with TREMFYA's established profile in psoriatic arthritis (搜索), with no new safety signals identified. Detailed efficacy and safety results, including the MRI findings, have not yet been presented and are expected at an upcoming scientific congress. The STAR trial remains ongoing, with the clinical study record showing an end date in April 2027 as the company continues longer-term evaluation of guselkumab in axial psoriatic arthritis (搜索).
An Unmet Need in Axial PsA
Axial involvement is a clinical domain of PsA in which inflammation affects the spine and sacroiliac joints, the joints connecting the lower spine to the pelvis. It can cause back pain, morning stiffness, fatigue, impaired mobility and reduced physical function, and is associated with poorer quality of life than PsA without axial involvement. Axial involvement may affect approximately 5 to 28 percent of patients with early PsA and 25 to 70 percent of those with longer-standing disease.
Despite advances in treating PsA, axial involvement remains an area of significant unmet need. There are currently no universally accepted classification criteria specific to axial PsA, and very few prospective clinical trials have been dedicated specifically to this patient population. While axial involvement shares some clinical features with axial spondyloarthritis, it is increasingly recognized as a distinct domain of psoriatic arthritis (搜索).
TREMFYA's Mechanism and Regulatory Position
TREMFYA is the first and only fully-human, dual-acting monoclonal antibody approved to treat PsA that blocks IL-23 (搜索) while also binding to CD64 (搜索), a receptor on cells that produce IL-23. IL-23 is a cytokine secreted by activated monocyte/macrophages and dendritic cells that is known to be a driver of immune-mediated diseases including active psoriatic arthritis (搜索). Findings for the dual-acting mechanism are based on in vitro studies demonstrating that guselkumab binds to CD64, which is expressed on the surface of IL-23 producing cells in an inflammatory monocyte model; the clinical significance of this finding is not known.
Johnson & Johnson recently received FDA approval of a label expansion for the inhibition of progression of structural joint damage in adults with active PsA, making TREMFYA the only IL-23 (搜索) inhibitor proven to help stop further joint damage.
TREMFYA is approved in the U.S. for adults and children six years and older weighing at least 40 kg with moderate to severe plaque psoriasis, and for the same age and weight group with active psoriatic arthritis (搜索). It is also approved for adults with moderately to severely active ulcerative colitis and adults with moderately to severely active Crohn's disease. The drug is approved in Europe, Canada, Japan and a number of other countries for moderate-to-severe plaque psoriasis, active psoriatic arthritis, moderate-to-severe Crohn's disease and moderate-to-severe ulcerative colitis in adults. Janssen Biotech, Inc. is the manufacturer, and Johnson & Johnson maintains exclusive worldwide marketing rights to TREMFYA.
TREMFYA is available as 100 mg/mL and 200 mg/2mL for subcutaneous injection and as a 200 mg/20 mL (10 mg/mL) single dose vial for intravenous infusion. The most common side effects include respiratory tract infections, headache, injection site reactions, arthralgia, diarrhea, gastroenteritis, fungal skin infections, herpes simplex infections, stomach pain, bronchitis, fatigue, pyrexia and skin rash. TREMFYA may lower the ability of the immune system to fight infections and may increase infection risk, including tuberculosis.