Guselkumab

Guselkumab (Tremfya) is a biological prescription medicine used to treat the inflammatory autoimmune conditions plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis in certain patients. Guselkumab helps reduce inflammation, pain, swelling, and skin, joint, and gastrointestinal symptoms.

Guselkumab works by binding to the p19 subunit of interleukin-23 (IL-23) and blocking it from attaching to its receptor. IL-23 is a naturally occurring small protein called a cytokine, which plays a role in your normal inflammatory and immune responses. By blocking IL-23, guselkumab reduces the release of the chemokines and cytokines that cause inflammation. Guselkumab is a biological medicine from the drug class known as interleukin inhibitors, and it is also called a human immunoglobulin G1 lambda (IgG1 lambda) monoclonal antibody.

Guselkumab can be self-administered as an injection under the skin (subcutaneous injection) using prefilled syringes or pens, or it may be given as an infusion by a healthcare professional, depending on your condition and stage of treatment. Guselkumab is given every 4 to 8 weeks as maintenance treatment, after the initial doses.

Guselkumab brand name is Tremfya by Janssen Biotech. It received FDA approval in 2017. It comes as a prefilled syringe, a prefilled pen (Tremfya Pen), and a One-Press injector for injection under the skin, and as a single-dose vial for infusion into a vein.

No biosimilars of guselkumab have been approved. Biosimilars are highly similar versions of a biological medicine that are designed to work in the same way as the original, but they are not identical.

Guselkumab is an FDA-approved prescription medicine indicated to treat:

• Plaque psoriasis in adults and children 6 years of age and older who weigh at least 40 kg, with moderate-to-severe disease, and who may benefit from injections or pills (systemic therapy) or phototherapy (treatment using ultraviolet or UV light)
• Psoriatic arthritis in adults and children 6 years of age and older who weigh at least 40 kg, with active disease. It helps provide symptom control and significantly slows the progression of structural joint damage.
• Ulcerative colitis in adults with moderately to severely active disease
• Crohn's disease in adults with moderately to severely active disease

The safety and effectiveness of guselkumab have been established in children 6 years of age and older who weigh at least 40 kg for plaque psoriasis and psoriatic arthritis. They have not been established in children for ulcerative colitis or Crohn's disease, or in children under 6 years of age.

Guselkumab's mechanism of action (MOA) is to bind selectively to the p19 subunit of interleukin-23 (IL-23), a naturally occurring cytokine (protein). Cytokines are substances released by cells of the immune system that influence other cells and play a key role in promoting inflammation and immune responses in chronic immune-mediated diseases.

By blocking the effects of IL-23, guselkumab helps regulate the immune system and control inflammation, so that symptoms of these conditions improve. Guselkumab is an interleukin-23 antagonist.

Plaque psoriasis. In two pivotal trials (PsO1 and PsO2), 84 to 85 percent of adults reached clear or almost clear skin (an IGA score of 0 or 1) at Week 16, compared with 7 to 8 percent on placebo, and 70 to 73 percent achieved a PASI 90 response, compared with 2 to 3 percent on placebo.

Psoriatic arthritis. Across three trials (PsA1, PsA2, and PsA3), ACR20 response at Week 24 ranged from 52 to 68 percent with guselkumab, compared with 22 to 47 percent on placebo. In trial PsA3, guselkumab produced a statistically significant reduction in the progression of structural joint damage (measured by the modified van der Heijde-Sharp score) compared with placebo.

Ulcerative colitis. In the intravenous induction trial (UC1), 23 percent of adults reached clinical remission at Week 12, compared with 8 percent on placebo, and in the subcutaneous induction trial (UC4), 26 percent reached remission at Week 12, compared with 7 percent. In the maintenance trial (UC2), 45 to 50 percent were in clinical remission at Week 44, compared with 19 percent on placebo.

Crohn's disease. In the intravenous induction trials (CD1 and CD2), about 47 percent of adults reached clinical remission at Week 12, compared with 15 to 20 percent on placebo. In the subcutaneous induction trial (CD3), 56 percent reached remission at Week 12, compared with 22 percent on placebo, and 59 to 65 percent were in remission at Week 48, compared with 17 percent.

These results are from the Tremfya prescribing information.

Guselkumab subcutaneous injection is used for the initial (induction) doses and the maintenance doses for all four conditions. Patients with Crohn's disease or ulcerative colitis may be given the option of receiving their induction doses as an intravenous infusion in a healthcare facility by a healthcare provider, or as a subcutaneous injection.

This medicine should be used under the guidance and supervision of a healthcare professional. A subcutaneous injection may be given by a healthcare professional, a patient, or a caregiver after proper training on correct injection technique. Use guselkumab exactly as your healthcare provider tells you to, and follow the detailed Instructions for Use that come with the medicine.

Prepare for your injection

• Remove the prefilled syringe or One-Press injector carton from the refrigerator and, keeping it in the carton, let it sit on a flat surface at room temperature for at least 30 minutes before use. Do not warm it any other way.
• Check the expiration date (EXP) on the back panel of the carton, and do not use the device if the date has passed.
• Do not inject guselkumab if the perforations on the carton are broken. Call your healthcare provider or pharmacist for a refill.

Choose and clean an injection site

• Use the front of the thighs (recommended) or the lower stomach area (lower abdomen), except for a 2-inch area around the navel. The back of the upper arms can be used only if someone else is giving you the injection.
• Do not inject into skin that is tender, bruised, red, hard, thick, scaly, or affected by psoriasis.
• Wash your hands well with soap and warm water, wipe the site with an alcohol swab, and allow it to dry. Do not touch, fan, or blow on the site after cleaning it.

Inspect the liquid

The liquid in the viewing window should be clear to slightly yellow and may contain tiny white or clear particles, and you may see one or more air bubbles, which is normal. Do not inject if the liquid is cloudy or discolored or has large particles. Call your healthcare provider or pharmacist for a refill.

Inject with the prefilled syringe

• Hold the syringe by the body and pull the needle cover straight off. It is normal to see a drop of liquid. Inject within 5 minutes of removing the cover. Do not put the cover back on, and do not touch the needle or let it touch any surface. Do not use a syringe that has been dropped.
• Place your thumb, index, and middle fingers directly under the finger flange. Do not touch the plunger or the area above the flange, as this may activate the needle safety device.
• Pinch enough skin at the site to inject under the skin and not into muscle, position the syringe at about a 45-degree angle, and insert the needle with a quick, dart-like motion.
• Release the pinch, grasp the body of the syringe, and press the plunger all the way down until it stops. When you release the plunger, the safety guard covers the needle and lifts it from your skin.

Inject with the One-Press injector

• Twist and pull off the bottom cap and keep your hands away from the needle guard. Inject within 5 minutes of removing the cap. Do not put the cap back on, and do not use an injector that has been dropped after the cap is removed.
• Position the injector straight onto the skin at about a 90-degree angle, then push the handle straight down at a comfortable speed. The medicine injects as you push. Do not lift the injector during the injection, or the needle guard will lock and the full dose will not be delivered.
• The injection is complete when the handle is pushed all the way down, you hear a click, and the teal body is no longer visible. Lift straight up; the yellow band shows the needle guard is locked.

After your injection

• Put the used syringe or injector in an FDA-cleared sharps disposal container right away. Do not throw it in household trash, and do not recycle the sharps container.
• There may be a small amount of blood or liquid at the site. Hold pressure with a cotton ball or gauze pad until any bleeding stops, and do not rub the site. Cover it with a bandage if needed.

Allergies

You should not use guselkumab if you are allergic to it, to polysorbate 80, or to any of the other inactive ingredients in this medicine.

Tuberculosis

Before starting guselkumab, tell your doctor if you have ever had tuberculosis (TB), if anyone in your household has TB, or if you have recently traveled somewhere TB is common. Your doctor will test you for TB before you begin treatment and will treat latent TB first if needed. Also tell your doctor if you have an active or chronic infection, or if you have recently received or are scheduled to receive a vaccine.

Vaccines

Make sure you are current on all vaccines before you start treatment with guselkumab. Avoid the use of live vaccines while being treated with this medicine.

Hepatotoxicity

When you are treated for Crohn's disease or ulcerative colitis, your liver enzymes and bilirubin will be checked before treatment, for at least the first 16 weeks, and periodically after that. Treatment will be paused if a liver problem is suspected until it is ruled out.

Pregnancy

It is not known whether guselkumab will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant. If you are pregnant, your name may be listed on a pregnancy registry called MotherToBaby to track the effects of guselkumab on the baby. You can enroll by visiting mothertobaby.org/ongoing-study/tremfya-guselkumab, by calling 1-877-311-8972, or by emailing [email protected].

Breastfeeding

It is not known whether guselkumab passes into breast milk or whether it could affect the nursing baby. Tell your doctor if you are breastfeeding.

Common guselkumab side effects

The most common side effects of guselkumab include:

• Infections (23%)
• Upper respiratory tract infection (14.3%)
• Headache (4.6%)
• Injection site reaction, including pain, itching, swelling, redness, or bruising where the medicine was injected (4.5%)
• Joint pain (2.7%)
• Elevated liver enzymes (2.6%)
• Diarrhea (1.6%)
• Gastroenteritis, inflammation of the stomach and intestines causing pain, vomiting, and diarrhea (1.3%)
• Fungal skin infections (1.1%)
• Herpes simplex infections (1.1%)

These common side effects occurred in 1 percent or more of plaque psoriasis patients treated with guselkumab for 16 weeks in clinical trials PsO1 and PsO2.

Serious side effects and warnings

Hypersensitivity reactions. Get emergency medical help if you have signs of an allergic reaction to guselkumab: hives, rash, itching; chest tightness, difficulty breathing; feeling light-headed; or swelling of your face, lips, tongue, or throat.

Infections. This medicine can weaken (suppress) your immune system, and you may get an infection more easily. Call your doctor at once if you have signs of infection, such as:

• fever, chills, body aches, night sweats
• weight loss, feeling very tired
• cough (may contain blood or mucus), shortness of breath
• pain or burning when you urinate
• severe diarrhea or stomach cramps
• skin redness, tingling, blisters, oozing, or sores that look different from psoriasis

Tuberculosis (TB). Guselkumab may increase your risk of infections, including reactivation of tuberculosis (TB). Your doctor will check you for TB before you start treatment and will watch for signs of active TB during and after treatment. Tell your doctor right away if you have symptoms of TB, such as a cough that does not go away, coughing up blood or mucus, chest pain, unexplained fever, night sweats, or weight loss.

Liver problems (hepatotoxicity). Drug-induced liver injury has been reported with guselkumab. When treating Crohn’s disease or ulcerative colitis, your doctor will check your liver with blood tests before and during treatment and may pause treatment if a liver problem is suspected. For plaque psoriasis or psoriatic arthritis, if clinically indicated, they will evaluate liver enzymes and bilirubin at baseline, and periodically thereafter according to routine patient management. Tell your doctor right away if you have symptoms of a liver problem, such as an unexplained rash, nausea, vomiting, stomach (abdominal) pain, tiredness, loss of appetite, yellowing of the skin or the whites of your eyes, or dark urine.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Plaque psoriasis and psoriatic arthritis (adults and children 6 years and older, at least 40 kg): 100 mg by subcutaneous injection at Week 0, Week 4, and every 8 weeks thereafter. For psoriatic arthritis, guselkumab may be used alone or with a conventional disease-modifying antirheumatic drug (cDMARD) such as methotrexate.

Ulcerative colitis or Crohn's disease (adults), induction: 200 mg by intravenous infusion over at least 1 hour at Week 0, Week 4, and Week 8, or 400 mg by subcutaneous injection at Week 0, Week 4, and Week 8. For the 400mg dose, administer two 200 mg prefilled pens or prefilled syringes to achieve the full 400 mg dose.

Ulcerative colitis or Crohn's disease (adults), maintenance: 100 mg by subcutaneous injection at Week 16 and every 8 weeks thereafter, or 200 mg by subcutaneous injection at Week 12 and every 4 weeks thereafter.

For the full schedule, see the detailed guselkumab dosage information.

Guselkumab formulations

Guselkumab (Tremfya) injections for subcutaneous use are available as a 100 mg/mL One-Press injector, a 100 mg/mL and a 200 mg/2 mL prefilled pen (Tremfya Pen), and a 100 mg/mL and a 200 mg/2 mL (100 mg/mL) prefilled syringe. For intravenous infusion, guselkumab is available as a 200 mg/20 mL (10 mg/mL) single-dose vial.

What happens if I miss a dose?

If you miss a dose, inject it as soon as you remember, then take your next dose at the regular scheduled time. Call your healthcare provider if you are not sure what to do.

What happens if I overdose?

If you inject more guselkumab than prescribed, call your healthcare provider right away.

Other drugs may interact with guselkumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

CYP450 substrates. When starting guselkumab in patients who are taking a CYP450 substrate, particularly one with a narrow therapeutic index, the healthcare provider will monitor the therapeutic effect or drug concentration and consider a dosage adjustment as needed.

Live vaccines. Live vaccines should be avoided during treatment with guselkumab. This is an immune-related precaution rather than a drug interaction, so see the Vaccines section under Before taking guselkumab for details.

This list is not all-inclusive, and other medicines may interact with guselkumab.

Healthcare professionals and patients often use the guselkumab package insert (Tremfya) for more detailed information about this medicine. The package insert contains more comprehensive information on indications and usage, dosage and administration, clinical pharmacology, clinical studies, drug interactions, and more. It is sometimes called the prescribing information (PI) or FDA label. This is not all the information you need for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

The guselkumab J code is J1628. J codes are used for medicines that are not taken by mouth, including injections, inhalations, and chemotherapies, and they support accurate, consistent coding for billing and reimbursement. Your physician will need the guselkumab J code when filling out forms for your treatment.

• Store guselkumab in the refrigerator at 36 F to 46 F (2 C to 8 C).
• Do not freeze the prefilled syringe or One-Press injector.
• Do not shake the prefilled syringe or One-Press injector.
• Keep the device in the original carton to protect it from light and physical damage.
• Keep guselkumab and all medicines out of the reach of children.

How should I dispose of the used prefilled syringe or One-Press injector?

If you do not have an FDA-cleared sharps disposal container, you may use a household container that is made of heavy-duty plastic, can be closed with a tight-fitting puncture-resistant lid, is upright and stable during use, is leak-resistant, and is properly labeled to warn of hazardous waste inside. When the container is almost full, follow your community guidelines for disposal, and note that there may be state or local laws about how to throw away used needles and syringes. For more information, including guidance for your state, go to the FDA website at fda.gov/safesharpsdisposal.

Active ingredient: guselkumab

Inactive ingredients. Single-dose prefilled syringe, One-Press injector, and prefilled pen (Tremfya Pen) for subcutaneous use: L-histidine, L-histidine monohydrochloride monohydrate, polysorbate 80, sucrose, and water for injection. Single-dose vial for intravenous infusion: EDTA disodium dihydrate, L-histidine, L-histidine monohydrochloride monohydrate, L-methionine, polysorbate 80, sucrose, and water for injection. Guselkumab is not made with natural rubber latex.

Guselkumab is manufactured under the brand name Tremfya by Janssen Biotech, Inc., Horsham, PA 19044, US.