Tremfya, known generically as guselkumab, is a prescription biologic medicine utilized for the treatment of several autoimmune conditions, including plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis in specific patient populations. Its therapeutic action is centered on targeting interleukin-23 (IL-23), a critical signaling protein, or cytokine, that plays a pivotal role in driving and sustaining inflammation characteristic of autoimmune diseases. When IL-23 is overexpressed or its regulation is disrupted, it leads to the abnormal and persistent activation of immune cells.
Understanding Tremfya's Mechanism of Action
The primary mechanism of action (MOA) for Tremfya involves its selective binding to the p19 subunit of interleukin-23 (IL-23). By specifically targeting this subunit, Tremfya effectively interrupts the IL-23 signaling pathway. IL-23 is a cytokine secreted by activated monocyte/macrophages and dendritic cells, recognized as a key driver of immune-mediated diseases such as active psoriatic arthritis.
IL-23 and Its Role in Inflammation
Interleukin-23 is a naturally occurring cytokine integral to normal inflammatory and immune responses. However, in conditions like psoriasis and psoriatic arthritis, IL-23 becomes dysregulated. It contributes to the overactivity of the immune system, which can lead to the attack of healthy tissues and cells, resulting in inflammation. This overactivity also causes an excessive proliferation of skin cells, leading to the formation of plaques, which are characteristic of psoriasis.
Psoriasis and Psoriatic Arthritis
- Plaque Psoriasis: Tremfya is FDA-approved for treating moderate to severe plaque psoriasis, the most common form of the condition. In plaque psoriasis, an overactive immune system prompts the body to produce too many skin cells, causing itchy, red or darker, sometimes white and scaly patches known as plaques. Tremfya may be considered for plaque psoriasis treatment when systemic therapy or phototherapy is appropriate.
- Psoriatic Arthritis (PsA): This chronic, immune-mediated inflammatory disease affects joints, entheses (where bones, tendons, and ligaments meet), and can involve dactylitis (swollen digits) and axial disease, alongside skin lesions typical of plaque psoriasis. In psoriatic arthritis, the immune system attacks healthy tissues, causing joint pain and inflammation. It commonly affects individuals between 30 and 50 years of age but can occur at any age. Studies indicate that up to 30% of individuals with plaque psoriasis also develop PsA.
Ulcerative Colitis and Crohn's Disease
- Ulcerative Colitis (UC): Tremfya is indicated for adults with moderately to severely active ulcerative colitis. It is prescribed to help achieve and maintain remission, a state with few or no symptoms. UC is an inflammatory bowel disease (IBD) affecting the colon and rectum, believed to stem from immune system overactivity. Inflammation and, in severe cases, ulcers can develop in these areas, leading to symptoms like blood in stool, diarrhea, abdominal pain, and weight loss. Tremfya is typically administered alone or with non-biologics for UC.
- Crohn's Disease: Similar to UC, Crohn's disease is a type of IBD. However, it can affect the entire digestive tract, from the stomach to the intestines and colon. Tremfya is also FDA-approved for the treatment of Crohn's disease.
Clinical Efficacy and Onset of Action
Clinical trials have demonstrated the effectiveness of Tremfya in treating various conditions. For plaque psoriasis, patients often experienced a reduction in symptoms within approximately 12 to 16 weeks. In clinical trials for psoriatic arthritis, over half of the participants showed a decrease in symptoms after 16 weeks of treatment. For ulcerative colitis, more than half of the patients treated with Tremfya experienced symptom reduction after 12 weeks, with some achieving remission.
The Phase 3b APEX study presented new data showing that Tremfya continued to reduce both the signs and symptoms of active psoriatic arthritis and inhibit the progression of structural joint damage at 48 weeks. At Week 24, Tremfya demonstrated a significantly greater ability to inhibit joint structural damage compared to placebo, with results consistent for patients receiving Tremfya every four or eight weeks. This inhibition of structural joint damage was sustained through Week 48. For patients who switched from placebo to Tremfya at Week 24, the rate of radiographic progression was substantially reduced.
Dr. Christopher Ritchlin, an investigator for the APEX study, noted that "Psoriatic arthritis is a chronic condition where joint damage can begin early and progress quickly if left untreated. The APEX study results show that guselkumab can inhibit this process, even once it has begun, making it a valuable treatment option for both initiating treatment early and for patients who already show signs of joint damage."
Tremfya also showed continued clinically meaningful improvement in American College of Rheumatology response criteria (ACR50) rates. The data from the APEX study were consistent with Tremfya's well-established safety profile, with no new safety signals identified.
Dosing and Administration
Tremfya is administered as a subcutaneous injection. The initial dosing regimen typically involves two injections given 4 weeks apart (induction treatment). For maintenance treatment, injections are administered every 4 or 8 weeks, depending on the specific condition being treated and the prescribed dose. Patients are instructed on how to perform self-injections at home. Tremfya should appear clear to light yellow and should not be used if it appears cloudy or contains particles. It should not be injected into an active psoriasis lesion.
The recommended dose of Tremfya is 100 mg administered subcutaneously at week 0, week 4, and every 8 weeks thereafter for plaque psoriasis. The medication may be administered by a healthcare professional, or a patient may self-inject after receiving proper training. Patients should be evaluated for tuberculosis (TB) infection prior to initiating treatment with Tremfya.
Preparation for injection involves allowing the prefilled syringe to reach room temperature for about 30 minutes without removing the needle cap. The recommended injection sites include the front of the thighs, the lower abdomen (at least an inch away from the belly button), or the outer area of the upper arm if administered by another person. Each injector or syringe is for single use only.
Safety Information and Potential Side Effects
Tremfya is a prescription medicine that may cause serious side effects, including serious allergic reactions. Symptoms of a severe allergic reaction can include fainting, swelling of the face or throat, difficulty breathing, hives, and itching. Patients should seek immediate medical help if these occur.
Infections: Tremfya can lower the immune system's ability to fight infections, increasing the risk of developing them. Healthcare providers will screen for infections, including tuberculosis (TB), before starting treatment and may treat active or latent TB. Signs of infection include fever, chills, muscle aches, cough, skin sores, diarrhea, shortness of breath, or blood in phlegm.
Liver Problems: Blood tests to monitor liver function are conducted before and during treatment, especially for those with Crohn's disease or ulcerative colitis. Treatment may be stopped if liver problems develop. Symptoms include unexplained rash, vomiting, fatigue, yellowing of the skin or eyes, nausea, abdominal pain, loss of appetite, and dark urine.
Other Potential Side Effects: The most common side effects reported in clinical trials include upper respiratory infections, headache, injection site reactions, joint pain, diarrhea, gastroenteritis, fungal skin infections, and herpes simplex infections.
It is not known if Tremfya will harm an unborn baby or pass into breast milk. Pregnant or breastfeeding individuals should discuss these risks with their healthcare provider. Patients should avoid receiving "live" vaccines while using Tremfya.
Other medications may interact with guselkumab. Patients should inform their healthcare provider about all medications they are taking, including over-the-counter drugs, vitamins, and herbal products.
Tremfya vs. Other Biologics
Tremfya (guselkumab) is an IL-23 blocker. Other biologics used for similar conditions include Stelara (ustekinumab), which targets IL-12 and IL-23, and TNF blockers like Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab). IL-17A receptor antagonists like Siliq (brodalumab) and IL-17A antagonists such as Taltz (ixekizumab) and Cosentyx (secukinumab) are also used. Otezla (apremilast), a PDE-4 inhibitor, is an oral medication. Tremfya's administration schedule of every 4 or 8 weeks for maintenance may offer an advantage in terms of adherence compared to some other biologics.
| Medication | Mechanism | Administration | Doses Year 1* | Doses Year 2* |
|---|---|---|---|---|
| Tremfya (guselkumab) | IL-23 blocker | SQ | 8 | 6 |
| Stelara (ustekinumab) | IL-12 and 23 antagonist | SQ | 4 | 4 |
| Enbrel (etanercept) | TNF blocker | SQ | 52 | 52 |
| Humira (adalimumab) | TNF blocker | SQ | 26 | 26 |
| Remicade (infliximab) | TNF blocker | IV | 8 | 6 |
| Siliq (brodalumab) | IL-17A receptor antagonist | SQ | 26 | 26 |
| Taltz (ixekizumab) | IL-17A antagonist | SQ | 18 | 13 |
| Cosentyx (secukinumab) | IL-17A antagonist | SQ | 17 | 13 |
| Otezla (apremilast) | PDE-4 inhibitor | Oral | 730 | 730 |
* Number of doses is an approximate calculation based on product labeling. Actual number of doses may vary.