What to Know About Inflectra (Infliximab-Dyyb)

Inflectra (infliximab-dyyb) is a biosimilar to Remicade (infliximab). This medication is given intravenously (through a vein) as a treatment for a variety of inflammatory conditions, including rheumatoid arthritis, plaque psoriasis, and Crohn's disease.

A biosimilar drug is "highly similar" to a biologic drug. Inflectra, like Remicade, blocks the action of an immune-system cell called tumor necrosis factor (TNF). This class of drugs is called TNF antagonists, anti-TNF drugs, or TNF blockers.

Inflectra was the first Remicade biosimilar to be approved. The FDA has since approved several others: Renflexis (infliximab-abda), Ixifi (infliximab-qbtx), and Avsola (infliximab-axxq). (To distinguish between the different products, these have been given a new brand name,in addition to a suffix containing four consonants to the end of each generic name.)

Uses

Inflectra is FDA-approved for treating several diseases and conditions.

• Rheumatoid arthritis, moderately to severely active: In combination with the drug methotrexate, Inflectra reduces signs and symptoms, inhibits the progression of joint damage, and improves physical function.
• Ankylosing spondylitis, active: Reduces signs and symptoms
• Psoriatic arthritis, active: Reduces signs and symptoms, inhibits the progression of structural damage, and improves physical function
• Plaque psoriasis (adults): Treats chronic, severe cases in candidates for systemic therapy, and when other systemic therapies are less medically appropriate
• Crohn's disease, moderately to severely active (adults, children over 6): Reduces signs and symptoms, induces and maintains clinical remission in those who've had an inadequate response to conventional treatment.
• Fistulating disease Crohn's disease (adults): Reduces the number of draining fistulas and maintains fistula closure
• Ulcerative colitis, moderately to severely active (adults): Reduces signs and symptoms, induces and maintains clinical remission and mucosal healing, and eliminates corticosteroid use in those who've had an inadequate response to conventional therapy

Clinicians may prescribe Inflectra for off-label use (without FDA approval) in other autoimmune and inflammatory conditions.

Before Taking

Before prescribing Inflectra or another TNF blocker, your doctor may perform tests to gauge your level of disease activity. This may include checking standard markers of inflammation, such as the erythrocyte sedimentation rate (ESR or sed rate) or C-reactive protein (CRP). It may also contain disease-specific tests such as the Vectra DA blood test for rheumatoid arthritis disease activity.

Inflectra is sometimes given as a first-line treatment (the first one you try) but is more often a second-line treatment given only after other treatments have failed. Much of this depends on what it's prescribed for.

For rheumatoid arthritis, Inflectra plus methotrexate may be used as a first-line treatment. Inflectra may also be a second-line treatment after methotrexate alone or methotrexate plus another TNF blocker have failed.

For ankylosing spondylitis, psoriatic arthritis, and some cases of plaque psoriasis, it may be used as a first-line treatment or as a replacement for another TNF blocker that hasn't been successful.

Inflectra is considered only as a second-line treatment for:

• Some cases of plaque psoriasis
• Crohn's disease
• Ulcerative colitis

Precautions and Contraindications

Inflectra is not appropriate for everyone and must be used with caution in certain individuals.

Pregnant and Breastfeeding Women

Little is known about how taking Inflectra while pregnant or breastfeeding may affect your baby. However, infliximab products have been found to cross the placenta.

In babies whose mothers took the drug, it has been found in their blood up to six months later. This could increase a child's risk of serious and even fatal infections.

Breastfeeding is not recommended for women taking Inflectra.

Children

Inflectra and other infliximab products have not been studied for children under 6. Children this age and older being prescribed Inflectra should be brought up-to-date on their vaccinations before starting this drug.

However, if an infant was exposed to Inflectra or infliximab in utero, there should be at least a six-month waiting period after birth before any live vaccine (e.g., BCG and rotavirus) is given because of the increased risk of infection. Your pediatrician should be able to guide you as to what vaccines are and aren't safe for your child.

Comorbities/Risk Factors

Inflectra should not be administered during an active infection of any kind. If you've ever had a hepatitis B infection, Inflectra may put you at risk for reactivation. Your doctor should test you for hepatitis B before you start taking this drug and monitor you closely if you test positive.

Doses of Inflectra larger than 5 milligrams (mg) per kilogram (kg) of body weight should not be given to people with moderate-to-severe heart failure. Inflectra can worsen heart failure symptoms.

Inflectra may exacerbate demyelinating diseases such as multiple sclerosis. Your doctor is unlikely to prescribe Inflectra if you have a demyelinating disease.

The risks/benefits of using Inflectra should be assessed in patients with certain factors related to cancer in their medical history.

Allergies

Don't take Inflectra if you're allergic to infliximab, murine (rodent) proteins, or any of its inactive ingredients:

• Sucrose
• Polysorbate 80
• Sodium dihydrogen phosphate monohydrate
• Di-Sodium hydrogen phosphate dihydrate

Biologics are produced using living organisms or parts of living organisms. The U.S. Food and Drug Administration says biosimilar drugs must have "no clinically meaningful differences" from the original biologic. However, inactive ingredients may be different.

Other Biosimilars for Systemic Inflammation

Several biosimilars are on the market for treating diseases that involve systemic inflammation.

Humira, Enbrel, and their biosimilars are classified as TNF blockers. MabThera and its biosimilars alter the immune system's level of B-cells, which (like TNF) are a part of your body's inflammatory response.

Dosage and Schedule

You'll go to a doctor's office, hospital, or infusion center to be given intravenous (IV) infusions of Inflectra. The dosage and infusion schedule will depend on your diagnosis. Expect the infusion to take at least two hours.

*If treatment results for rheumatoid arthritis aren't adequate at this dosage, your doctor may adjust it up to 10mg/kg or may shorten the time between infusions. However, these adjustments may increase your risk of side effects.

Modifications

If you have a mild-to-moderate reaction during an infusion, the process may be slowed down or suspended for a while. Depending on the nature of your reaction, you may be treated with acetaminophen, antihistamines, and/or corticosteroids. If you then continue to have a reaction, your infusion will be discontinued.

If you have an allergic reaction, you'll need to go off of Inflectra right away. Facilities that do infusions should have the appropriate staffing and medication to deal with a severe allergic reaction such as anaphylaxis.

Side Effects

Unwanted side effects are possible with any medication. If you have side effects that are severe or don't diminish over time, let your doctor know about it.

Common

The most common adverse reactions, based on clinical trials of infliximab products, include:

• Infections (upper respiratory, sinusitis, and pharyngitis)
• Infusion-related reactions (shortness of breath, flushing, headache, rash)
• Headache
• Abdominal pain

Severe

Rare but serious reactions that can occur during the infusion include:

• Anaphylaxis
• Convulsions
• Erythematous rash
• Low blood pressure (hypotension)

The infusion facility should be equipped to deal with these reactions.

Warnings and Interactions

Certain drugs don't interact well when they're combined. While you're taking Inflectra, you should avoid:

• Kineret (anakinra)
• Orencia (abatacept)
• Actemra (tocilizumab)
• Other biologic drugs

Certain other warnings have been established to both ensure the safe use of Inflectra and to guide cessation, if necessary. Your doctor should monitor you for the following complications while you're taking Inflectra.

If you need to go off of the drug, get advice from your doctor on how to do so safely.

Infections

Inflectra poses a risk of invasive fungal infections. If you develop a systemic illness while using Inflectra and you live in a region where fungal conditions are endemic, an anti-fungal therapy should be considered.

If an infection develops while using Inflectra, it should be monitored carefully and if it becomes serious, Inflectra should be stopped.

Opportunistic infections (infections that occur more severely or frequently in those with weakened immune systems) have been reported in patients treated with TNF blockers. Also, reactivation of tuberculosis or new tuberculosis infections have occurred with the use of infliximab products.

Malignancies

The incidence of malignancies, including lymphoma, has been found to be greater in patients treated with TNF blockers than in controls. Any signs of cancer should be investigated with this in mind.

Hepatotoxicity

Rare severe hepatic reactions can occur. Some may be potentially fatal or require liver transplantation. With the development of jaundice or significantly elevated liver enzymes, Inflectra should be stopped.

Heart Failure

New-onset heart failure may occur with the use of Inflectra. If this happens to you, talk to your doctor about options for stopping Inflectra and finding another treatment.

Cytopenias

There may be a reduction in the number of blood cells with use of Inflectra. Patients should seek medical attention if symptoms of any type of cytopenia develop. These include anemia, thrombocytopenia, leukopenia, and pancytopenia.

Hypersensitivity

Serious infusion reactions may develop, including anaphylaxis or serum sickness-like reactions.

Lupus-Like Syndrome

A syndrome associated with lupus-like symptoms can develop with use of Inflectra. The drug should be stopped if the syndrome develops.

Black Box Warnings

Inflectra carries black box warnings, the FDA's most serious warning, with regard to:

• Increased risk of serious infection
• Increased risk of lymphoma
• Importance of testing for latent tuberculosis prior to starting the drug