What Is Guselkumab?
Guselkumab is an FDA-approved medication for the treatment of psoriatic disease, including psoriasis and psoriatic arthritis, as well as moderate-to-severe plaque psoriasis. Known by the brand name Tremfya, it is an IL-23 p19 subunit antagonist. This means it works by selectively blocking interleukin-23 (IL-23), a protein involved in inflammation. By binding to IL-23 with high affinity and potency, guselkumab helps to neutralize this inflammatory signal, potentially enriching its presence in inflamed tissues.
In addition to its approved uses, guselkumab is currently being investigated in clinical trials for other conditions. These include inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, as well as other inflammatory skin conditions like hidradenitis suppurativa and pityriasis rubra pilaris. Researchers are also exploring its potential for non-alcoholic fatty liver disease and alcoholic liver disease.
Uses and Conditions Under Study
Guselkumab is primarily studied for immune-mediated inflammatory conditions, particularly those affecting the skin and joints. It is FDA-approved for various forms of psoriasis and psoriatic arthritis.
- Psoriatic Conditions: Guselkumab is extensively studied for psoriasis, with 22 trials focusing on this condition. This includes specific forms like psoriasis vulgaris (4 trials) and plaque psoriasis (4 trials). It is also investigated for psoriatic arthritis, a related condition causing joint pain and swelling, with a total of 15 trials. Guselkumab may help by targeting the IL-23 pathway, which is implicated in the inflammation seen in these conditions. Studies also explore its use for new-onset guttate psoriasis and scalp psoriasis.
- Inflammatory Bowel Diseases (IBD): Guselkumab is being evaluated for Crohn's disease (10 trials) and ulcerative colitis (5 trials). These are chronic inflammatory conditions of the digestive tract. The drug's ability to modulate the immune response by blocking IL-23 may offer a therapeutic benefit for patients with these conditions.
- Other Inflammatory Skin Conditions: Research is underway for hidradenitis suppurativa (3 trials), a chronic skin condition characterized by painful lumps and abscesses. Guselkumab is also being explored for pityriasis rubra pilaris, a rare inflammatory skin disease. The mechanism of blocking IL-23 is thought to be relevant given the inflammatory nature of these disorders.
- Liver Conditions: Guselkumab is being studied for its potential effects on non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease. While approved for psoriatic arthritis, its use for liver conditions is investigational, with researchers exploring if its anti-inflammatory properties can impact liver inflammation.
- Healthy Participants: 7 trials involving healthy individuals are conducted to understand the drug's safety, how it moves through the body, and how it interacts with other medications.
Dosing
Guselkumab is administered as an injection, either intravenously (IV) or subcutaneously (SC). Clinical trials have explored various dosing regimens and strengths for different conditions.
For induction, some studies have used guselkumab 400 mg intravenously at week 0, week 4, and week 8. Other induction regimens include 200 mg intravenously every 4 weeks for 3 doses. Following an induction phase, maintenance dosing typically involves subcutaneous injections.
Common subcutaneous maintenance doses studied include 200 mg every 4 weeks, or 100 mg every 8 weeks. Other strengths under investigation include 30 mg, 70 mg, and 100 mg administered at different intervals, such as every 4 weeks or every 8 weeks. These varied dosing strategies are being evaluated to optimize treatment outcomes for conditions like psoriasis, psoriatic arthritis, and inflammatory bowel diseases.
Side Effects
In clinical trials, the most commonly reported side effect for patients taking Guselkumab was nasopharyngitis (common cold). Across 17 trials involving over 10,000 patients, 12.0% of those on Guselkumab experienced nasopharyngitis, compared to 10.3% of patients on placebo.
Other common side effects reported in Guselkumab clinical trials, compared to placebo, include:
- Upper respiratory tract infection: 8.7% of patients on Guselkumab experienced this, compared to 6.7% on placebo.
- Increased alanine aminotransferase (a liver enzyme): 5.2% of patients on Guselkumab, compared to 3.0% on placebo.
- Headache: 4.8% of patients on Guselkumab, compared to 4.1% on placebo.
- Arthralgia (joint pain): 4.8% of patients on Guselkumab, compared to 3.8% on placebo.
- Abdominal pain: 3.6% of patients on Guselkumab, compared to 2.5% on placebo.
- Bronchitis: 2.9% of patients on Guselkumab, compared to 2.5% on placebo.
Clinical Trial Results
Plaque Psoriasis
In a study (NCT02203032) comparing Guselkumab to ustekinumab in patients with moderate to severe plaque psoriasis who had an inadequate response to ustekinumab, Guselkumab showed greater improvement. From Week 28 through Week 40, patients on Guselkumab achieved a 90% improvement in Psoriasis Area and Severity Index (PASI 90) response during an average of 2.2 visits, compared to 1.1 visits for those on ustekinumab. At Week 28, 31.1% of Guselkumab patients achieved an Investigator's Global Assessment (IGA) score of cleared or minimal with at least a 2-grade improvement, versus 14.3% of ustekinumab patients.
Two large studies (NCT02207231 and NCT02207244) evaluated Guselkumab for moderate to severe plaque psoriasis. At Week 16, Guselkumab significantly improved quality of life, reducing the Dermatology Life Quality Index (DLQI) score by an average of 11.2 units, compared to a reduction of 0.6 to 2.6 units for placebo. Guselkumab also led to clearer skin, with 85.1% of patients achieving an IGA score of cleared or minimal at Week 16, compared to 6.9% to 8.5% on placebo. A PASI 90 response was achieved by 73.3% of Guselkumab patients at Week 16, versus 2.4% to 2.9% on placebo. When compared to adalimumab at Week 24, 80.2% of Guselkumab patients achieved PASI 90, compared to 47.9% of adalimumab patients. Long-term data from these studies showed that approximately 84% of patients maintained a PASI 90 response at Week 252 with continuous Guselkumab treatment.
Psoriatic Arthritis
In a study (NCT02319759) of patients with active psoriatic arthritis, Guselkumab demonstrated significant improvements. At Week 24, 58.0% of patients on Guselkumab achieved an American College of Rheumatology (ACR) 20 response, a measure of disease improvement, compared to 18.4% on placebo. Physical function also improved, with Guselkumab patients showing a mean reduction of 0.42 units in the Health Assessment Questionnaire-Disability Index (HAQ-DI) score at Week 24, versus a 0.06 unit reduction for placebo. For patients with dactylitis (inflammation of fingers or toes) at baseline, 100% of Guselkumab patients achieved a median percent change from baseline in dactylitis scores at Week 24, indicating complete resolution, compared to 33.3% on placebo. Similarly, for enthesitis (inflammation where tendons or ligaments attach to bone), 100% of Guselkumab patients achieved a median percent change from baseline in Leeds Enthesitis Index (LEI) scores at Week 24, compared to 33.3% on placebo.
Palmoplantar Pustulosis
A study (NCT02641730) in participants with palmoplantar pustulosis showed that Guselkumab improved disease severity. At Week 16, Guselkumab 100 mg reduced the Palmoplantar Pustulosis Area and Severity Index (PPPASI) total score by an average of 15.08 units, compared to a 7.79 unit reduction for placebo. For the Palmoplantar Severity Index (PPSI) total score, Guselkumab 100 mg led to a mean reduction of 3.9 units, versus a 2.0 unit reduction for placebo. At Week 16, 57.4% of patients on Guselkumab 100 mg achieved at least a 50% improvement in PPPASI (PPPASI-50 response), compared to 34.0% on placebo. Additionally, 35.2% of patients receiving Guselkumab 100 mg achieved a Physician's Global Assessment (PGA) score of cleared or almost cleared at Week 16, compared to 5.7% on placebo.
Currently Recruiting Trials
For individuals interested in contributing to medical research, there are currently 24 clinical trials recruiting participants to further investigate guselkumab. These studies are exploring its potential across a range of inflammatory conditions, seeking to understand its efficacy and safety in diverse patient populations.
One ongoing Phase 4 study, NCT06916390, sponsored by Universitaire Ziekenhuizen KU Leuven, is investigating guselkumab's effectiveness, both alone and with dietary intervention, for patients with Pouchitis, aiming to enroll 20 participants. Another study, NCT07444060, compares guselkumab to ustekinumab in 100 participants with moderate-to-severe Crohn's disease (CD) and obstructive symptoms of intestinal stenosis. The SHIFT-IBD Study (NCT07245394) is evaluating guselkumab for 200 people with active Inflammatory Bowel Disease (IBD), including Crohn's disease and ulcerative colitis, who previously used ustekinumab.
The efficacy and safety of guselkumab with JAK inhibitors in patients with difficult-to-treat IBD is being assessed in NCT07487311, targeting 80 participants. A Phase 4 study, NCT07310095, is evaluating guselkumab in 78 Chinese participants with Crohn's disease who no longer respond to ustekinumab. The UPGRADE study (NCT07246460) is an observational study of 90 adults with Crohn's disease, assessing guselkumab response using ultrasound and proteomics. For psoriasis, NCT07430319 is evaluating real-life dosing interval adjustments for 100 participants.
In psoriatic arthritis (PsA), a Phase 4 study (NCT07141004) is evaluating guselkumab's safety and efficacy in 100 Indian participants who had an inadequate response to standard therapies. NCT06586281 is examining shared mechanisms between Nonalcoholic fatty liver disease (NAFLD) and PsA severity in 20 patients receiving guselkumab. A Phase 2 study (NCT06651489) is investigating guselkumab for 10 participants with Hailey-Hailey disease, a debilitating genetic skin disorder. Another Phase 2 study (NCT06563323) is assessing guselkumab in 17 adults with pyoderma gangrenosum.
For psoriasis vulgaris, NCT06398106 is comparing proactive therapeutic drug monitoring (TDM) versus standard dosing of biologics in 210 participants. A long-term extension study (NCT06663332) is evaluating the long-term safety of guselkumab in 196 pediatric participants with ulcerative colitis, Crohn's disease, or juvenile psoriatic arthritis. A study (NCT07532486) is comparing high-dose and extended-interval guselkumab versus standard-dose in 400 Chinese participants with moderate-to-severe plaque psoriasis. The potential role of guselkumab in modulating pain perception and related gene pathways in psoriatic arthritis is explored in NCT06974474 with 26 participants.
NCT06408935 is evaluating guselkumab's efficacy in achieving transmural healing in 112 Crohn's disease patients. An observational study, VOICE-Early Response (NCT06249555), is exploring the time course of response to vedolizumab and IL-23 antagonists, including guselkumab, in 300 Crohn's disease participants. A Phase 3 study (NCT05923073) is evaluating guselkumab's clinical and endoscopic efficacy in 120 pediatric participants with moderately to severely active Crohn's disease. NCT05669833 compares guselkumab to golimumab in 63 PsA patients who had an inadequate response to a TNF inhibitor. The immune spatial features of guselkumab's cutaneous response in scalp psoriasis lesions are being examined in NCT05858632 with 10 participants.
Further studies include NCT05503875, which aims to immunoclassify psoriasis for precision medicine with 100 participants, and NCT05535738, a Phase 2/3 study with 45 participants using a contact dermatitis model to study skin inflammation. The multi-center PAMPA study (NCT05004727) is a Phase 4 trial of guselkumab in 176 high-risk psoriasis patients. Finally, the OTIS Autoimmune Diseases in Pregnancy Project (NCT02103361) is monitoring 200 planned and unplanned pregnancies exposed to medications like guselkumab, following infants for one year after birth.
Where to Participate
Guselkumab clinical trials have a broad geographic reach, with studies conducted across 52 sites in 44 cities and 24 states. The top locations for participation include:
- New York, New York (5 sites)
- Atlanta, Georgia (3 sites)
- Boston, Massachusetts (2 sites)
- Fort Worth, Texas (2 sites)
- Indianapolis, Indiana (2 sites)
- Salt Lake City, Utah (2 sites)
- Worcester, Massachusetts (2 sites)
- Philadelphia, Pennsylvania (2 sites)
- Portland, Oregon (2 sites)
- San Francisco, California (2 sites)
Eligibility for these studies is generally inclusive, welcoming participants of all genders aged between 2 and 99 years. Healthy volunteers are also invited to participate in some studies, and children are eligible for specific trials.
Development Timeline
The journey of guselkumab in clinical research began on May 31, 2013, with the latest trial anticipated to conclude by April 16, 2026. Since its inception, a total of 91 clinical trials have been initiated, enrolling over 22,868 participants to date. Janssen Research & Development, LLC has been a primary driver of this research, sponsoring 42 of these studies.
Initial investigations into guselkumab focused on conditions such as IBS-C and hyperphosphatemia. Over time, the research pipeline significantly expanded to explore its potential in a wider array of inflammatory and autoimmune diseases. This expansion included conditions like Crohn's Disease, Ulcerative Colitis, Psoriasis Vulgaris, and Psoriatic Arthritis, which now represent major areas of study.
The development has progressed through all phases of clinical research, with 30 trials reaching Phase 3, 15 in Phase 4, and 14 in Phase 2. This systematic progression through early-phase studies to later-stage efficacy and post-market evaluations demonstrates a comprehensive approach to understanding guselkumab's therapeutic profile across various indications.