Tremfya Meets Main Study Goals in Patients With Axial Involvement
Johnson & Johnson has announced topline results from the Phase 4 STAR study evaluating Tremfya (guselkumab) in adults with active psoriatic arthritis (PsA) and axial involvement.
The study met its primary endpoint and major secondary endpoints.
The results showed improvements in axial symptoms and a reduction in inflammation measured by magnetic resonance imaging (MRI).
STAR is designed specifically for patients with psoriatic arthritis who have inflammation affecting the spine and sacroiliac joints.
Johnson & Johnson said STAR is the first dedicated randomized, double-blind, placebo-controlled study to prospectively evaluate an interleukin-23 (IL-23) inhibitor in patients with axial involvement confirmed by MRI.
Detailed efficacy and safety results, including the MRI findings, will be presented at an upcoming scientific congress.
What Is Axial Psoriatic Arthritis?
Psoriatic arthritis is a chronic inflammatory disease that can affect the joints, skin and nails.
In some patients, the disease also affects the spine and the sacroiliac joints, which connect the lower spine to the pelvis.
This is known as axial involvement or axial PsA.
Axial PsA can cause inflammatory back pain, stiffness, fatigue and reduced mobility.
Patients may also experience the other symptoms commonly associated with PsA, including joint swelling, skin psoriasis and nail changes.
Axial Involvement Can Affect a Significant Number of Patients
The frequency of axial involvement can vary depending on how long a person has had psoriatic arthritis.
According to Johnson & Johnson, axial involvement may affect approximately 5% to 28% of patients with early PsA.
Among people with longer-standing disease, axial involvement may affect approximately 25% to 70% of patients.
Patients with axial involvement can have a poorer quality of life compared with people who have PsA without this type of disease involvement.
STAR Study Evaluated Biologic-Naïve Patients
The STAR study enrolled adults with active PsA and axial involvement who had not previously received biologic treatment.
Participants had objective evidence of inflammation in the axial skeleton confirmed through centrally reviewed MRI scans.
They also had elevated C-reactive protein (CRP), a marker that can indicate inflammation.
Participants had previously received non-biologic disease-modifying antirheumatic drugs (DMARDs), apremilast and/or nonsteroidal anti-inflammatory drugs (NSAIDs).
The study enrolled 411 participants worldwide.
Tremfya Met the Primary Endpoint
The primary endpoint evaluated changes in the Bath Ankylosing Spondylitis Disease Activity Index, or BASDAI, at Week 24 compared with baseline.
BASDAI is a patient-reported measure that looks at several aspects of disease activity.
It includes spinal pain, stiffness, fatigue, joint symptoms and areas of tenderness.
Johnson & Johnson reported that Tremfya produced a statistically significant improvement in BASDAI compared with placebo at Week 24.
This means patients receiving Tremfya reported greater improvement in the symptoms measured by the assessment than those receiving placebo.
Tremfya Also Improved Axial Symptoms
The study also met major secondary endpoints.
One of these evaluated axial symptoms using the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein, known as ASDAS-CRP.
Tremfya showed a significant reduction in axial disease activity compared with placebo.
The study also evaluated inflammation in the sacroiliac joints using MRI.
Johnson & Johnson reported that Tremfya significantly reduced objective MRI-measured inflammation in these joints.
The MRI findings are important because they provide an imaging-based measure of inflammation in addition to patient-reported symptoms.
MRI Adds an Objective Measure of Disease Activity
One of the notable features of the STAR study is its use of MRI to confirm axial inflammation before patients entered the study.
MRI can show inflammation in areas such as the sacroiliac joints that may not always be fully captured through symptoms alone.
Philip J. Mease, M.D., director of rheumatology research at Providence Swedish Medical Center and clinical professor at the University of Washington School of Medicine, said the study provides a more objective assessment of inflammation alongside clinical outcomes.
Detailed MRI results will be presented at a future scientific meeting.
STAR Was Designed Specifically for Axial PsA
Axial involvement in PsA remains an area where clinical research is still developing.
Although axial PsA shares some features with axial spondyloarthritis, researchers increasingly recognize axial involvement as a specific domain of psoriatic arthritis.
There are currently no universally accepted classification criteria specifically for axial PsA.
There have also been relatively few prospective clinical trials designed specifically for patients with PsA and confirmed axial involvement.
The STAR study was designed to address this gap by prospectively enrolling patients with MRI-confirmed axial inflammation.
The Study Included a Placebo-Controlled Period
STAR is a multicenter, randomized, double-blind, placebo-controlled Phase 4 study.
The trial includes a 24-week placebo-controlled treatment period followed by a 24-week active treatment period.
The primary assessment was conducted at Week 24.
Researchers also evaluated other aspects of the disease, including axial symptoms, MRI inflammation, physical function, peripheral musculoskeletal symptoms, skin disease and safety.
Tremfya Safety Profile Remained Consistent
Johnson & Johnson said the overall safety profile observed in the STAR study was consistent with the established safety profile of Tremfya in psoriatic arthritis.
The company reported that no new safety signals were identified.
More detailed safety findings will be presented along with the complete efficacy and MRI data at an upcoming scientific congress.
Tremfya Targets the IL-23 Pathway
Tremfya is an IL-23 inhibitor.
IL-23 is a cytokine, or signaling protein, involved in immune system activity and inflammation.
It is produced by certain immune cells, including activated monocytes, macrophages and dendritic cells.
Excessive immune activity involving IL-23 has been linked to inflammatory diseases such as psoriatic arthritis.
Tremfya is designed to block IL-23.
Johnson & Johnson also describes Tremfya as a dual-acting antibody that binds to CD64, a receptor found on cells that produce IL-23.
The company notes that the CD64-related findings are based on in vitro studies and that the clinical significance of this binding is not known.
Tremfya Has Multiple Approved Uses
Tremfya is already approved in the United States for several inflammatory diseases.
It is approved for adults and children aged 6 years and older who weigh at least 40 kg with moderate-to-severe plaque psoriasis who may benefit from systemic therapy or phototherapy.
It is also approved for adults and children aged 6 years and older who weigh at least 40 kg with active psoriatic arthritis.
In addition, Tremfya is approved in adults with moderately to severely active ulcerative colitis and Crohn's disease.
The medicine is also approved in Europe, Canada, Japan and other countries for several of these inflammatory conditions.
Johnson & Johnson Recently Expanded Tremfya's PsA Label
Johnson & Johnson recently received U.S. Food and Drug Administration approval for a label expansion covering the inhibition of progression of structural joint damage in adults with active psoriatic arthritis.
The company said this makes Tremfya the only IL-23 inhibitor proven to help stop further joint damage.
The STAR results add additional clinical evidence focused specifically on axial involvement in PsA.
What the STAR Results Could Mean for Axial PsA
Axial involvement remains an area where patients and physicians have limited disease-specific clinical evidence.
The STAR study provides data from a prospective trial designed specifically around this patient population.
The combination of patient-reported symptom measures, disease activity assessments and MRI evaluation allows researchers to examine both how patients feel and how inflammation appears on imaging.
Whether these findings change treatment approaches will depend on the full dataset and how the results are evaluated by the medical community.
What Happens Next for Tremfya?
Johnson & Johnson plans to present detailed efficacy and safety results from the STAR study at an upcoming scientific congress.
The full presentation is expected to include additional information about MRI findings and other clinical outcomes.
The company will continue to evaluate the data as it builds the evidence base for Tremfya across different manifestations of psoriatic arthritis.
Tremfya is manufactured by Janssen Biotech, Inc., and Johnson & Johnson maintains exclusive worldwide marketing rights to the medicine.
