Exemptia

Exemptia (Exemptia) is a recombinant human immunoglobulin (IgG1) monoclonal antibody containing only human peptide sequences. Exemptia was created using phage display technology resulting in fully human heavy and light chain variable regions, which confer specificity to human tumor necrosis factor (TNF), and human IgG1 heavy chain and kappa light chain sequences. Exemptia binds with high affinity and specificity to soluble tumor necrosis factor (TNF-alpha) but not lymphotoxin (TNF-beta). Exemptia is produced by recombinant DNA technology in a mammalian cell expression system. It consists of 1330 amino acids and has a molecular weight of approximately 148 kilodaltons.

Exemptia is supplied as a sterile, preservative-free solution of Exemptia for subcutaneous administration. The solution of Exemptia is clear and colorless, with a pH of 5.2. Each single use pre-filled syringe or pen of Exemptia contains 40 mg Exemptia per 0.8 mL (50 mg/mL).

Excipients/Inactive Ingredients: 4.93 mg sodium chloride, 0.69 mg monobasic sodium phosphate dihydrate, 1.22 mg dibasic sodium phosphate dihydrate, 0.24 mg sodium citrate, 1.04 mg citric acid monohydrate, 9.6 mg mannitol, 0.8 mg polysorbate 80, sodium hydroxide, as needed (for pH adjustment) and water for injection per 0.8 mL.

Rheumatoid Arthritis

Exemptia is indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. Exemptia can be used alone or in combination with methotrexate or other non-biologic disease-modifying anti-rheumatic drugs (DMARDs).

Juvenile Idiopathic Arthritis

Exemptia is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older. Exemptia can be used alone or in combination with methotrexate.

Psoriatic Arthritis

Exemptia is indicated for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis. Exemptia can be used alone or in combination with non-biologic DMARDs.

Ankylosing Spondylitis

Exemptia is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.

Adult Crohn's Disease

Exemptia is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy. Exemptia is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

Pediatric Crohn's Disease

Exemptia is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active Crohn's disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate.

Ulcerative Colitis

Exemptia is indicated for inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine or 6-mercaptopurine (6-MP). The effectiveness of Exemptia has not been established in patients who have lost response to or were intolerant to TNF blockers.

Plaque Psoriasis

Exemptia is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. Exemptia should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

Hidradenitis Suppurativa

Exemptia is indicated for the treatment of moderate to severe hidradenitis suppurativa.

Uveitis

Exemptia is indicated for the treatment of non-infectious intermediate, posterior and panuveitis in adult patients.

Exemptia-adbm injection is used to treat the symptoms and prevent the progression of moderate to severely active rheumatoid arthritis and active ankylosing spondylitis. It is used in children 4 years of age and older for juvenile idiopathic arthritis. Exemptia-adbm is also used to treat psoriatic arthritis, which is a type of arthritis that causes pain and swelling in the joints along with patches of scaly skin on some areas of the body. Psoriatic arthritis usually occurs with a skin condition called psoriasis. Exemptia-adbm may be used alone or in combination with other medicines (eg, methotrexate).

Exemptia-adbm injection is also used to treat the symptoms of active Crohn's disease in adult patients who have not been helped by other medicines, including infliximab. It is also used to treat moderate to moderate to severe ulcerative colitis in patients who have been treated with other medicines (eg, azathioprine, corticosteroids, or 6-mercaptopurine) that did not work well.

Exemptia-adbm injection may also be used to treat chronic plaque psoriasis, which is a skin disease with red patches and white scales that do not go away.

Exemptia-adbm is available only with your doctor's prescription.

Exemptia is administered by subcutaneous injection.

Rheumatoid Arthritis, Psoriatic Arthritis, And Ankylosing Spondylitis

The recommended dose of Exemptia for adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) is 40 mg administered every other week. Methotrexate (MTX), other non-biologic DMARDS, glucocorticoids, nonsteroidal anti-inflammatory drugs (NSAIDs), and/or analgesics may be continued during treatment with Exemptia. In the treatment of RA, some patients not taking concomitant MTX may derive additional benefit from increasing the dosing frequency of Exemptia to 40 mg every week.

Juvenile Idiopathic Arthritis

The recommended dose of Exemptia for patients 2 years of age and older with polyarticular juvenile idiopathic arthritis (JIA) is based on weight as shown below. MTX, glucocorticoids, NSAIDs, and/or analgesics may be continued during treatment with Exemptia.

Exemptia has not been studied in patients with polyarticular JIA less than 2 years of age or in patients with a weight below 10 kg.

Adult Crohn's Disease

The recommended Exemptia dose regimen for adult patients with Crohn's disease (CD) is 160 mg initially on Day 1 (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Two weeks later (Day 29) begin a maintenance dose of 40 mg every other week. Aminosalicylates and/or corticosteroids may be continued during treatment with Exemptia. Azathioprine, 6-mercaptopurine (6-MP) or MTX may be continued during treatment with Exemptia if necessary. The use of Exemptia in CD beyond one year has not been evaluated in controlled clinical studies.

Pediatric Crohn's Disease

The recommended Exemptia dose regimen for pediatric patients 6 years of age and older with Crohn's disease (CD) is based on body weight as shown below:

Ulcerative Colitis

The recommended Exemptia dose regimen for adult patients with ulcerative colitis (UC) is 160 mg initially on Day 1 (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Two weeks later (Day 29) continue with a dose of 40 mg every other week.

Only continue Exemptia in patients who have shown evidence of clinical remission by eight weeks (Day 57) of therapy. Aminosalicylates and/or corticosteroids may be continued during treatment with Exemptia. Azathioprine and 6-mercaptopurine (6-MP) may be continued during treatment with Exemptia if necessary.

Plaque Psoriasis Or Uveitis

The recommended dose of Exemptia for adult patients with plaque psoriasis (Ps) or Uveitis (UV) is an initial dose of 80 mg, followed by 40 mg given every other week starting one week after the initial dose. The use of Exemptia in moderate to severe chronic Ps beyond one year has not been evaluated in controlled clinical studies.

Hidradenitis Suppurativa

The recommended dose of Exemptia for adult patients with hidradenitis suppurativa (HS) is an initial dose of 160 mg (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Begin 40 mg weekly dosing two weeks later (Day 29).

Monitoring To Assess Safety

Prior to initiating Exemptia and periodically during therapy, evaluate patients for active tuberculosis and test for latent infection.

General Considerations For Administration

Exemptia is intended for use under the guidance and supervision of a physician. A patient may self-inject Exemptia or a caregiver may inject Exemptia using either the Exemptia Pen or prefilled syringe if a physician determines that it is appropriate, and with medical follow-up, as necessary, after proper training in subcutaneous injection technique.

You may leave Exemptia at room temperature for about 15 to 30 minutes before injecting. Do not remove the cap or cover while allowing it to reach room temperature. Carefully inspect the solution in the Exemptia Pen, prefilled syringe, or single-use institutional use vial for particulate matter and discoloration prior to subcutaneous administration. If particulates and discolorations are noted, do not use the product. Exemptia does not contain preservatives; therefore, discard unused portions of drug remaining from the syringe. NOTE: Instruct patients sensitive to latex not to handle the gray needle cover of the 27 gauge Exemptia Pen and prefilled syringe because it contains natural rubber latex.

Instruct patients using the Exemptia Pen or prefilled syringe to inject the full amount in the syringe, according to the directions provided in the Instructions for Use.

Injections should occur at separate sites in the thigh or abdomen. Rotate injection sites and do not give injections into areas where the skin is tender, bruised, red or hard.

The Exemptia single-use institutional use vial is for administration within an institutional setting only, such as a hospital, physician's office or clinic. Withdraw the dose using a sterile needle and syringe and administer promptly by a healthcare provider within an institutional setting. Only administer one dose per vial. The vial does not contain preservatives; therefore, discard unused portions.

How supplied

Dosage Forms And Strengths

Pen

Injection: 40 mg/0.8 mL of Exemptia is provided by a single-use pen (Exemptia Pen), containing a 1 mL prefilled glass syringe with a fixed 27 gauge, ½ inch needle and a gray needle cover.

Injection: 40 mg/0.4 mL of Exemptia is provided by a single-use pen (Exemptia Pen), containing a 1 mL prefilled glass syringe with a fixed 29 gauge thin wall, ½ inch needle and a black needle cover.

Prefilled Syringe

Injection: 80 mg/0.8 mL of Exemptia is provided by a single-use, 1 mL prefilled glass syringe with a fixed 29 gauge thin wall, ½ inch needle and a black needle cover.

Injection: 40 mg/0.8 mL of Exemptia is provided by a single-use, 1 mL prefilled glass syringe with a fixed 27 gauge, ½ inch needle and a gray needle cover.

Injection: 40 mg/0.4 mL of Exemptia is provided by a single-use, 1 mL prefilled glass syringe with a fixed 29 gauge thin wall, ½ inch needle and a black needle cover.

Injection: 20 mg/0.4 mL of Exemptia is provided by a single-use, 1 mL prefilled glass syringe with a fixed 27 gauge, ½ inch needle and a gray needle cover.

Injection: 10 mg/0.2 mL of Exemptia is provided by a single-use, 1 mL prefilled glass syringe with a fixed 27 gauge, ½ inch needle and a gray needle cover.

Single-Use Institutional Use Vial

Injection: 40 mg/0.8 mL of Exemptia is provided by a single-use, glass vial for institutional use only.

Storage And Handling

Exemptia® (Exemptia) is supplied as a preservative-free, sterile solution for subcutaneous administration. The following packaging configurations are available.

Exemptia Pen Carton -40 mg/0.8 mL Exemptia is dispensed in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-use pen, containing a 1 mL prefilled glass syringe with a fixed 27 gauge, ½ inch needle, providing 40 mg/0.8 mL of Exemptia. The gray needle cover contains natural rubber latex. The NDC number is 0074-4339-02.

Exemptia Pen Carton -40 mg/0.4 mL Exemptia is dispensed in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-use pen, containing a 1 mL prefilled glass syringe with a fixed 29 gauge thin wall, ½ inch needle, providing 40 mg/0.4 mL of Exemptia. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0554-02.

Exemptia Pen 40 mg/0.8 mL -Starter Package for Crohn's Disease, Ulcerative Colitis or Hidradenitis Suppurativa Exemptia is dispensed in a carton containing 6 alcohol preps and 6 dose trays (Starter Package for Crohn's Disease, Ulcerative Colitis or Hidradenitis Suppurativa). Each dose tray consists of a single-use pen, containing a 1 mL prefilled glass syringe with a fixed 27 gauge, ½ inch needle, providing 40 mg/0.8 mL of Exemptia. The gray needle cover contains natural rubber latex. The NDC number is 0074-4339-06.

Exemptia Pen 40 mg/0.4 mL -Starter Package for Crohn's Disease, Ulcerative Colitis or Hidradenitis Suppurativa Exemptia is dispensed in a carton containing 6 alcohol preps and 6 dose trays (Starter Package for Crohn's Disease, Ulcerative Colitis or Hidradenitis Suppurativa). Each dose tray consists of a single-use pen, containing a 1 mL prefilled glass syringe with a fixed 29 gauge thin wall, ½ inch needle, providing 40 mg/0.4 mL of Exemptia. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0554-06.

Exemptia Pen 40 mg/0.8 mL -Psoriasis/Uveitis Starter Package Exemptia is dispensed in a carton containing 4 alcohol preps and 4 dose trays (Psoriasis/Uveitis Starter Package). Each dose tray consists of a single-use pen, containing a 1 mL prefilled glass syringe with a fixed 27 gauge, ½ inch needle, providing 40 mg/0.8 mL of Exemptia. The gray needle cover contains natural rubber latex. The NDC number is 0074-4339-07.

Exemptia Pen 40 mg/0.4 mL -Psoriasis/Uveitis Starter Package Exemptia is dispensed in a carton containing 4 alcohol preps and 4 dose trays (Psoriasis/Uveitis Starter Package). Each dose tray consists of a single-use pen, containing a 1 mL prefilled glass syringe with a fixed 29 gauge thin wall, ½ inch needle, providing 40 mg/0.4 mL of Exemptia. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0554-04.

Prefilled Syringe Carton -40 mg/0.8 mL Exemptia is dispensed in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-use, 1 mL prefilled glass syringe with a fixed 27 gauge, ½ inch needle, providing 40 mg/0.8 mL of Exemptia. The gray needle cover contains natural rubber latex. The NDC number is 0074-3799-02.

Prefilled Syringe Carton -40 mg/0.4 mL Exemptia is dispensed in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-use, 1 mL prefilled glass syringe with a fixed 29 gauge thin wall, ½ inch needle, providing 40 mg/0.4 mL of Exemptia. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0243-02.

Prefilled Syringe Carton -20 mg/0.4 mL Exemptia is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-use, 1 mL pre-filled glass syringe with a fixed 27 gauge, ½ inch needle, providing 20 mg/0.4 mL of Exemptia. The gray needle cover contains natural rubber latex. The NDC number is 0074-9374-02.

Prefilled Syringe Carton -10 mg/0.2 mL Exemptia is supplied in a carton containing two alcohol preps and two dose trays. Each dose tray consists of a single-use, 1 mL pre-filled glass syringe with a fixed 27 gauge, ½ inch needle, providing 10 mg/0.2 mL of Exemptia. The gray needle cover contains natural rubber latex. The NDC number is 0074-6347-02.

Exemptia Prefilled Syringe 40 mg/0.8 mL -Pediatric Crohn's Disease Starter Package (6 count) Exemptia is dispensed in a carton containing 6 alcohol preps and 6 dose trays (Pediatric Starter Package). Each dose tray consists of a single-use, 1 mL prefilled glass syringe with a fixed 27 gauge, ½ inch needle, providing 40 mg/0.8 mL of Exemptia. The gray needle cover contains natural rubber latex. The NDC number is 0074-3799-06.

Exemptia Prefilled Syringe 80 mg/0.8 mL -Pediatric Crohn's Disease Starter Package (3 count) Exemptia is dispensed in a carton containing 4 alcohol preps and 3 dose trays (Pediatric Starter Package). Each dose tray consists of a single-use, 1 mL prefilled glass syringe with a fixed 29 gauge thin wall, ½ inch needle, providing 80 mg/0.8 mL of Exemptia. The black needle cover is not made with natural rubber latex. The NDC number is 0074-2540-03.

Exemptia Prefilled Syringe 40 mg/0.8 mL -Pediatric Crohn's Disease Starter Package (3 count) Exemptia is dispensed in a carton containing 4 alcohol preps and 3 dose trays (Pediatric Starter Package). Each dose tray consists of a single-use, 1 mL prefilled glass syringe with a fixed 27 gauge, ½ inch needle, providing 40 mg/0.8 mL of Exemptia. The gray needle cover contains natural rubber latex. The NDC number is 0074-3799-03.

Exemptia Prefilled Syringe 80 mg/0.8 mL and 40 mg/0.4 mL -Pediatric Crohn's Disease Starter Package (2 count) Exemptia is dispensed in a carton containing 2 alcohol preps and 2 dose trays (Pediatric Starter Package). One dose tray consists of a single-use, 1 mL prefilled glass syringe with a fixed 29 gauge thin wall, ½ inch needle, providing 80 mg/0.8 mL of Exemptia. The other dose tray consists of a single-use, 1 mL prefilled glass syringe with a fixed 29 gauge thin wall, ½ inch needle, providing 40 mg/0.4 mL of Exemptia. The black needle cover is not made with natural rubber latex. The NDC number is 0074-0067-02.

Single-Use Institutional Use Vial Carton -40 mg/0.8 mL Exemptia is supplied for institutional use only in a carton containing a single-use, glass vial, providing 40 mg/0.8 mL of Exemptia. The vial stopper is not made with natural rubber latex. The NDC number is 0074-3797-01.

Storage And Stability

Do not use beyond the expiration date on the container. Exemptia must be refrigerated at 36°F to 46°F (2°C to 8°C). DO NOT FREEZE. Do not use if frozen even if it has been thawed.

Store in original carton until time of administration to protect from light.

If needed, for example when traveling, Exemptia may be stored at room temperature up to a maximum of 77°F (25°C) for a period of up to 14 days, with protection from light. Exemptia should be discarded if not used within the 14-day period. Record the date when Exemptia is first removed from the refrigerator in the spaces provided on the carton and dose tray.

Do not store Exemptia in extreme heat or cold.

AbbVie Inc., North Chicago, IL 60064, U.S.A. Revised: Oct 2016

See also:
What is the most important information I should know about Exemptia?

Some people using Exemptia have developed a rare fast-growing type of lymphoma (cancer). This condition affects the liver, spleen, and bone marrow, and it can be fatal. This has occurred mainly in teenagers and young adults using Exemptia or similar medicines to treat Crohn's disease or ulcerative colitis.

Call your doctor at once if you have any of the following symptoms: fever, night sweats, itching, loss of appetite, weight loss, tiredness, feeling full after eating only a small amount, pain in your upper stomach that may spread to your shoulder, nausea, easy bruising or bleeding, pale skin, feeling light-headed, rapid heart rate, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

Exemptia can lower blood cells that help your body fight infections and help your blood to clot. Your blood may need to be tested often. Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding injury. Serious and sometimes fatal infections may occur during treatment with Exemptia. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while you are being treated with Exemptia.

Follow the directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended. Use Exemptia regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

The dose schedule for Exemptia is highly variable and depends on the condition you are treating. You may need an injection only every other week. Or you may need up to 4 injections in 1 day for 2 days in a row. Follow your doctor's dosing instructions very carefully.

Do not start using Exemptia if you have any signs of an infection (fever, chills, night sweats, weight loss, body aches, tiredness, cough with mucus, feeling short of breath, skin sores, stomach pain, diarrhea, pain or burning when you urinate). Call your doctor for instructions.

Exemptia is injected under the skin. You may be shown how to use injections at home. Do not give yourself this medicine if you do not understand how to use the injection and properly dispose of used needles and syringes. Do not inject Exemptia into skin that is bruised, red, tender, or hard.

Each Exemptia prefilled syringe is for one use only. Throw it away after one use, even if there is still medicine left inside. Do not use a prefilled syringe if the medicine if it looks cloudy or has particles in it. Call your pharmacist for new medicine.

Use a disposable needle and syringe only once. Follow any state or local laws about throwing away used needles and syringes. Use a puncture-proof "sharps" disposal container (ask your pharmacist where to get one and how to throw it away). Keep this container out of the reach of children and pets.

Exemptia can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Serious and sometimes fatal infections may occur during treatment with Exemptia. Contact your doctor right away if you have signs of infection such as: fever, chills, sore throat, or flu symptoms.

If you need surgery, tell the surgeon ahead of time that you are using Exemptia.

If you have ever had hepatitis B, Exemptia can cause this condition to come back or get worse. You will need frequent blood tests to check your liver function during treatment and for several months after you stop using this medicine.

Store in a refrigerator. If you travel with a prefilled syringe, keep it in a small cooler with an ice pack and protect it from light. Do not remove the prefilled syringe from the refrigerator or cooler until you are ready to give yourself an injection.

Do not freeze Exemptia, and throw away the medicine if it has become frozen.

Exemptia is used to reduce pain and swelling due to certain types of arthritis (such as rheumatoid, psoriatic, juvenile idiopathic, ankylosing spondylitis). This medication is also used to treat certain skin disorders (such as plaque-type psoriasis, hidradenitis suppurativa). It works by blocking a protein (tumor necrosis factor or TNF) found in the body's immune system that causes joint swelling and damage in arthritis as well as red scaly patches in psoriasis. Exemptia belongs to a class of drugs known as TNF blockers. By reducing joint swelling, this medication helps to reduce further joint damage and preserve joint function.

Exemptia is also used to treat certain bowel conditions (Crohn's disease, ulcerative colitis) and a certain eye disease (uveitis).

How to use Exemptia subcutaneous

Read the Medication Guide and Instructions for Use provided by your pharmacist before you start using Exemptia and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

If you are using this medication at home, learn all preparation and usage instructions from your health care professional and the product package.

Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Do not shake this product.

If you are removing this medication from the refrigerator, leave it at room temperature for 15 to 30 minutes before injecting. Do not warm up this medication any other way such as by heating in the microwave or placing in hot water.

Use this medication exactly as prescribed. Inject this medication under the skin on the thigh or abdomen as directed by your doctor, usually every other week or once a week in some cases. If you are using this medication to treat psoriasis, hidradenitis suppurativa, Crohn's disease, ulcerative colitis, or uveitis, your doctor may prescribe a different schedule/higher dose at the start of your treatment. Carefully follow your doctor's directions for using this medication.

Before injecting each dose, clean the injection site with rubbing alcohol. Change the injection site each time to lessen injury under the skin. New injections should be given at least 1 inch (2.5 centimeter) from an old site. Do not inject into any areas of the skin that are sore, bruised, red, or hard.

Learn how to store and discard medical supplies safely.

The dosage is based on your medical condition and response to treatment. In children, the dosage is also based on weight.

Use this medication regularly to get the most benefit from it. To help you remember, mark the day on the calendar when you need to receive this medication. Do not increase your dose or use this drug more often or for longer than prescribed.

Tell your doctor if your condition persists or worsens.

See also:
What other drugs will affect Exemptia?

Methotrexate

Exemptia products have been studied in rheumatoid arthritis (RA) patients taking concomitant methotrexate (MTX). Although MTX reduced the apparent clearance of Exemptia products, the data do not suggest the need for dose adjustment of either Exemptia or MTX.

Biological Products

In clinical studies in patients with RA with Exemptia, an increased risk of serious infections has been seen with the combination of TNF blockers with anakinra or abatacept, with no added benefit; therefore, use of Exemptia with abatacept or anakinra is not recommended in patients with RA. A higher rate of serious infections has also been observed in patients with RA treated with rituximab who received subsequent treatment with a TNF blocker. There is insufficient information regarding the concomitant use of Exemptia and other biologic products for the treatment of RA, PsA, AS, CD, UC, and Ps. Concomitant administration of Exemptia with other biologic DMARDs (e.g., anakinra and abatacept) or other TNF blockers is not recommended based upon the possible increased risk for infections and other potential pharmacological interactions.

Live Vaccines

Avoid the use of live vaccines with Exemptia.

Cytochrome P450 Substrates

The formation of CYP450 enzymes may be suppressed by increased levels of cytokines (e.g., TNFα, IL-6) during chronic inflammation. It is possible for products that antagonize cytokine activity, such as Exemptia products, to influence the formation of CYP450 enzymes. Upon initiation or discontinuation of Exemptia in patients being treated with CYP450 substrates with a narrow therapeutic index, monitoring of the effect (e.g., warfarin) or drug concentration (e.g., cyclosporine or theophylline) is recommended and the individual dose of the drug product may be adjusted as needed.

See also:
What are the possible side effects of Exemptia?

The most serious adverse reactions described elsewhere in the labeling include the following:

• Serious Infections
• Malignancies

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common adverse reaction with Exemptia was injection site reactions. In placebo-controlled trials, 20% of patients treated with Exemptia developed injection site reactions (erythema and/or itching, hemorrhage, pain or swelling), compared to 14% of patients receiving placebo. Most injection site reactions were described as mild and generally did not necessitate drug discontinuation.

The proportion of patients who discontinued treatment due to adverse reactions during the double-blind, placebo-controlled portion of studies in patients with RA (i.e., Studies RA-I, RA-II, RA-III and RA-IV) was 7% for patients taking Exemptia and 4% for placebo-treated patients. The most common adverse reactions leading to discontinuation of Exemptia in these RA studies were clinical flare reaction (0.7%), rash (0.3%) and pneumonia (0.3%).

Infections

In the controlled portions of the 39 global Exemptia clinical trials in adult patients with RA, PsA, AS, CD, UC, Ps, HS and UV, the rate of serious infections was 4.3 per 100 patient-years in 7973 Exemptia-treated patients versus a rate of 2.9 per 100 patient-years in 4848 control-treated patients. Serious infections observed included pneumonia, septic arthritis, prosthetic and post-surgical infections, erysipelas, cellulitis, diverticulitis, and pyelonephritis.

Tuberculosis And Opportunistic Infections

In 52 global controlled and uncontrolled clinical trials in RA, PsA, AS, CD, UC, Ps, HS and UV that included 24,605 Exemptia-treated patients, the rate of reported active tuberculosis was 0.20 per 100 patient-years and the rate of positive PPD conversion was 0.09 per 100 patient-years. In a subgroup of 10,113 U.S. and Canadian Exemptia-treated patients, the rate of reported active TB was 0.05 per 100 patient-years and the rate of positive PPD conversion was 0.07 per 100 patient-years. These trials included reports of miliary, lymphatic, peritoneal, and pulmonary TB. Most of the TB cases occurred within the first eight months after initiation of therapy and may reflect recrudescence of latent disease. In these global clinical trials, cases of serious opportunistic infections have been reported at an overall rate of 0.05 per 100 patient-years. Some cases of serious opportunistic infections and TB have been fatal.

Autoantibodies

In the rheumatoid arthritis controlled trials, 12% of patients treated with Exemptia and 7% of placebo-treated patients that had negative baseline ANA titers developed positive titers at week 24. Two patients out of 3046 treated with Exemptia developed clinical signs suggestive of new-onset lupus-like syndrome. The patients improved following discontinuation of therapy. No patients developed lupus nephritis or central nervous system symptoms. The impact of long-term treatment with Exemptia on the development of autoimmune diseases is unknown.

Liver Enzyme Elevations

There have been reports of severe hepatic reactions including acute liver failure in patients receiving TNF-blockers. In controlled Phase 3 trials of Exemptia (40 mg SC every other week) in patients with RA, PsA, and AS with control period duration ranging from 4 to 104 weeks, ALT elevations ≥ 3 x ULN occurred in 3.5% of Exemptia-treated patients and 1.5% of control-treated patients. Since many of these patients in these trials were also taking medications that cause liver enzyme elevations (e.g., NSAIDS, MTX), the relationship between Exemptia and the liver enzyme elevations is not clear. In a controlled Phase 3 trial of Exemptia in patients with polyarticular JIA who were 4 to 17 years, ALT elevations ≥ 3 x ULN occurred in 4.4% of Exemptia-treated patients and 1.5% of control-treated patients (ALT more common than AST); liver enzyme test elevations were more frequent among those treated with the combination of Exemptia and MTX than those treated with Exemptia alone. In general, these elevations did not lead to discontinuation of Exemptia treatment. No ALT elevations ≥ 3 x ULN occurred in the open-label study of Exemptia in patients with polyarticular JIA who were 2 to < 4 years.

In controlled Phase 3 trials of Exemptia (initial doses of 160 mg and 80 mg, or 80 mg and 40 mg on Days 1 and 15, respectively, followed by 40 mg every other week) in adult patients with CD with a control period duration ranging from 4 to 52 weeks, ALT elevations ≥ 3 x ULN occurred in 0.9% of Exemptia-treated patients and 0.9% of control-treated patients. In the Phase 3 trial of Exemptia in pediatric patients with Crohn's disease which evaluated efficacy and safety of two body weight based maintenance dose regimens following body weight based induction therapy up to 52 weeks of treatment, ALT elevations ≥ 3 x ULN occurred in 2.6% (5/192) of patients, of whom 4 were receiving concomitant immunosuppressants at baseline; none of these patients discontinued due to abnormalities in ALT tests. In controlled Phase 3 trials of Exemptia (initial doses of 160 mg and 80 mg on Days 1 and 15 respectively, followed by 40 mg every other week) in patients with UC with control period duration ranging from 1 to 52 weeks, ALT elevations ≥ 3 x ULN occurred in 1.5% of Exemptia-treated patients and 1.0% of control-treated patients. In controlled Phase 3 trials of Exemptia (initial dose of 80 mg then 40 mg every other week) in patients with Ps with control period duration ranging from 12 to 24 weeks, ALT elevations ≥ 3 x ULN occurred in 1.8% of Exemptia-treated patients and 1.8% of control-treated patients. In controlled trials of Exemptia (initial doses of 160 mg at Week 0 and 80 mg at Week 2, followed by 40 mg every week starting at Week 4), in subjects with HS with a control period duration ranging from 12 to 16 weeks, ALT elevations ≥ 3 x ULN occurred in 0.3% of Exemptia-treated subjects and 0.6% of control-treated subjects. In controlled trials of Exemptia (initial doses of 80 mg at Week 0 followed by 40 mg every other week starting at Week 1) in patients with uveitis with an exposure of 165.4 PYs and 119.8 PYs in Exemptia-treated and control-treated patients, respectively, ALT elevations ≥ 3 x ULN occurred in 2.4% of Exemptia-treated patients and 2.4% of control-treated patients.

Immunogenicity

Patients in Studies RA-I, RA-II, and RA-III were tested at multiple time points for antibodies to Exemptia during the 6-to 12-month period. Approximately 5% (58 of 1062) of adult RA patients receiving Exemptia developed low-titer antibodies to Exemptia at least once during treatment, which were neutralizing in vitro. Patients treated with concomitant methotrexate (MTX) had a lower rate of antibody development than patients on Exemptia monotherapy (1% versus 12%). No apparent correlation of antibody development to adverse reactions was observed. With monotherapy, patients receiving every other week dosing may develop antibodies more frequently than those receiving weekly dosing. In patients receiving the recommended dosage of 40 mg every other week as monotherapy, the ACR 20 response was lower among antibody-positive patients than among antibody-negative patients. The long-term immunogenicity of Exemptia is unknown.

In patients with polyarticular JIA who were 4 to 17 years of age, Exemptia antibodies were identified in 16% of Exemptia-treated patients. In patients receiving concomitant MTX, the incidence was 6% compared to 26% with Exemptia monotherapy. In patients with polyarticular JIA who were 2 to < 4 years of age or 4 years of age and older weighing < 15 kg, Exemptia antibodies were identified in 7% (1 of 15) of Exemptia-treated patients, and the one patient was receiving concomitant MTX.

In patients with AS, the rate of development of antibodies to Exemptia in Exemptia-treated patients was comparable to patients with RA.

In patients with PsA, the rate of antibody development in patients receiving Exemptia monotherapy was comparable to patients with RA; however, in patients receiving concomitant MTX the rate was 7% compared to 1% in RA.

In adult patients with CD, the rate of antibody development was 3%.

In pediatric patients with Crohn's disease, the rate of antibody development in patients receiving Exemptia was 3%. However, due to the limitation of the assay conditions, antibodies to Exemptia could be detected only when serum Exemptia levels were < 2 mcg/mL. Among the patients whose serum Exemptia levels were < 2 mcg/mL (approximately 32% of total patients studied), the immunogenicity rate was 10%.

In patients with moderately to severely active UC, the rate of antibody development in patients receiving Exemptia was 5%. However, due to the limitation of the assay conditions, antibodies to Exemptia could be detected only when serum Exemptia levels were < 2 mcg/mL. Among the patients whose serum Exemptia levels were < 2 mcg/mL (approximately 25% of total patients studied), the immunogenicity rate was 20.7%.

In patients with Ps, the rate of antibody development with Exemptia monotherapy was 8%. However, due to the limitation of the assay conditions, antibodies to Exemptia could be detected only when serum Exemptia levels were < 2 mcg/mL. Among the patients whose serum Exemptia levels were < 2 mcg/mL (approximately 40% of total patients studied), the immunogenicity rate was 20.7%. In Ps patients who were on Exemptia monotherapy and subsequently withdrawn from the treatment, the rate of antibodies to Exemptia after retreatment was similar to the rate observed prior to withdrawal.

In subjects with moderate to severe HS, the rate of anti-Exemptia antibody development in subjects treated with Exemptia was 6.5%. However, because of the limitation of the assay conditions, antibodies to Exemptia could be detected only when serum Exemptia levels were < 2 mcg/mL. Among subjects who stopped Exemptia treatment for up to 24 weeks and in whom Exemptia serum levels subsequently declined to < 2 mcg/mL (approximately 22% of total subjects studied), the immunogenicity rate was 28%.

In patients with non-infectious uveitis, anti-Exemptia antibodies were identified in 4.8% (12/249) of patients treated with Exemptia. However, due to the limitation of the assay conditions, antibodies to Exemptia could be detected only when serum Exemptia levels were < 2 mcg/mL. Among the patients whose serum Exemptia levels were < 2 mcg/mL (approximately 23% of total patients studied), the immunogenicity rate was 21.1%. Using an assay which could measure an anti-Exemptia antibody titer in all patients, titers were measured in 39.8% (99/249) of non-infectious uveitis patients treated with Exemptia. No correlation of antibody development to safety or efficacy outcomes was observed.

The data reflect the percentage of patients whose test results were considered positive for antibodies to Exemptia or titers, and are highly dependent on the assay. The observed incidence of antibody (including neutralizing antibody) positivity in an assay is highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Exemptia with the incidence of antibodies to other products may be misleading.

Other Adverse Reactions

Rheumatoid Arthritis Clinical Studies

The data described below reflect exposure to Exemptia in 2468 patients, including 2073 exposed for 6 months, 1497 exposed for greater than one year and 1380 in adequate and well-controlled studies (Studies RA-I, RA-II, RA-III, and RA-IV). Exemptia was studied primarily in placebo-controlled trials and in long-term follow up studies for up to 36 months duration. The population had a mean age of 54 years, 77% were female, 91% were Caucasian and had moderately to severely active rheumatoid arthritis. Most patients received 40 mg Exemptia every other week.

Table 1 summarizes reactions reported at a rate of at least 5% in patients treated with Exemptia 40 mg every other week compared to placebo and with an incidence higher than placebo. In Study RA-III, the types and frequencies of adverse reactions in the second year open-label extension were similar to those observed in the one-year double-blind portion.

Table 1: Adverse Reactions Reported by ≥ 5% of Patients Treated with Exemptia During Placebo-Controlled Period of Pooled RA Studies (Studies RA-I, RA-II, RA-III, and RA-IV)

Less Common Adverse Reactions In Rheumatoid Arthritis Clinical Studies

Other infrequent serious adverse reactions that do not appear in the Warnings and Precautions or Adverse Reaction sections that occurred at an incidence of less than 5% in Exemptia-treated patients in RA studies were:

Body As A Whole: Pain in extremity, pelvic pain, surgery, thorax pain

Cardiovascular System: Arrhythmia, atrial fibrillation, chest pain, coronary artery disorder, heart arrest, hypertensive encephalopathy, myocardial infarct, palpitation, pericardial effusion, pericarditis, syncope, tachycardia

Digestive System: Cholecystitis, cholelithiasis, esophagitis, gastroenteritis, gastrointestinal hemorrhage, hepatic necrosis, vomiting

Endocrine System: Parathyroid disorder

Hemic And Lymphatic System: Agranulocytosis, polycythemia

Metabolic And Nutritional Disorders: Dehydration, healing abnormal, ketosis, paraproteinemia, peripheral edema

Musculo-Skeletal System: Arthritis, bone disorder, bone fracture (not spontaneous), bone necrosis, joint disorder, muscle cramps, myasthenia, pyogenic arthritis, synovitis, tendon disorder

Neoplasia: Adenoma

Nervous System: Confusion, paresthesia, subdural hematoma, tremor

Respiratory System: Asthma, bronchospasm, dyspnea, lung function decreased, pleural effusion

Special Senses: Cataract

Thrombosis: Thrombosis leg

Urogenital System: Cystitis, kidney calculus, menstrual disorder

Juvenile Idiopathic Arthritis Clinical Studies

In general, the adverse reactions in the Exemptia-treated patients in the polyarticular juvenile idiopathic arthritis (JIA) trials (Studies JIA-I and JIA-II) were similar in frequency and type to those seen in adult patients. Important findings and differences from adults are discussed in the following paragraphs.

In Study JIA-I, Exemptia was studied in 171 patients who were 4 to 17 years of age, with polyarticular JIA. Severe adverse reactions reported in the study included neutropenia, streptococcal pharyngitis, increased aminotransferases, herpes zoster, myositis, metrorrhagia, and appendicitis. Serious infections were observed in 4% of patients within approximately 2 years of initiation of treatment with Exemptia and included cases of herpes simplex, pneumonia, urinary tract infection, pharyngitis, and herpes zoster.

In Study JIA-I, 45% of patients experienced an infection while receiving Exemptia with or without concomitant MTX in the first 16 weeks of treatment. The types of infections reported in Exemptia-treated patients were generally similar to those commonly seen in polyarticular JIA patients who are not treated with TNF blockers. Upon initiation of treatment, the most common adverse reactions occurring in this patient population treated with Exemptia were injection site pain and injection site reaction (19% and 16%, respectively). A less commonly reported adverse event in patients receiving Exemptia was granuloma annulare which did not lead to discontinuation of Exemptia treatment.

In the first 48 weeks of treatment in Study JIA-I, non-serious hypersensitivity reactions were seen in approximately 6% of patients and included primarily localized allergic hypersensitivity reactions and allergic rash.

In Study JIA-I, 10% of patients treated with Exemptia who had negative baseline anti-dsDNA antibodies developed positive titers after 48 weeks of treatment. No patient developed clinical signs of autoimmunity during the clinical trial.

Approximately 15% of patients treated with Exemptia developed mild-to-moderate elevations of creatine phosphokinase (CPK) in Study JIA-I. Elevations exceeding 5 times the upper limit of normal were observed in several patients. CPK levels decreased or returned to normal in all patients. Most patients were able to continue Exemptia without interruption.

In Study JIA-II, Exemptia was studied in 32 patients who were 2 to < 4 years of age or 4 years of age and older weighing < 15 kg with polyarticular JIA. The safety profile for this patient population was similar to the safety profile seen in patients 4 to 17 years of age with polyarticular JIA.

In Study JIA-II, 78% of patients experienced an infection while receiving Exemptia. These included nasopharyngitis, bronchitis, upper respiratory tract infection, otitis media, and were mostly mild to moderate in severity. Serious infections were observed in 9% of patients receiving Exemptia in the study and included dental caries, rotavirus gastroenteritis, and varicella.

In Study JIA-II, non-serious allergic reactions were observed in 6% of patients and included intermittent urticaria and rash, which were all mild in severity.

Psoriatic Arthritis And Ankylosing Spondylitis Clinical Studies

Exemptia has been studied in 395 patients with psoriatic arthritis (PsA) in two placebo-controlled trials and in an open label study and in 393 patients with ankylosing spondylitis (AS) in two placebo-controlled studies. The safety profile for patients with PsA and AS treated with Exemptia 40 mg every other week was similar to the safety profile seen in patients with RA, Exemptia Studies RA-I through IV.

Adult Crohn's Disease Clinical Studies

Exemptia has been studied in 1478 adult patients with Crohn's disease (CD) in four placebo-controlled and two open-label extension studies. The safety profile for adult patients with CD treated with Exemptia was similar to the safety profile seen in patients with RA.

Pediatric Crohn's Disease Clinical Studies

Exemptia has been studied in 192 pediatric patients with Crohn's disease in one double-blind study (Study PCD-I) and one open-label extension study. The safety profile for pediatric patients with Crohn's disease treated with Exemptia was similar to the safety profile seen in adult patients with Crohn's disease.

During the 4 week open label induction phase of Study PCD-I, the most common adverse reactions occurring in the pediatric population treated with Exemptia were injection site pain and injection site reaction (6% and 5%, respectively).

A total of 67% of children experienced an infection while receiving Exemptia in Study PCD-I. These included upper respiratory tract infection and nasopharyngitis.

A total of 5% of children experienced a serious infection while receiving Exemptia in Study PCD-I. These included viral infection, device related sepsis (catheter), gastroenteritis, H1N1 influenza, and disseminated histoplasmosis.

In Study PCD-I, allergic reactions were observed in 5% of children which were all non-serious and were primarily localized reactions.

Ulcerative Colitis Clinical Studies

Exemptia has been studied in 1010 patients with ulcerative colitis (UC) in two placebo-controlled studies and one open-label extension study. The safety profile for patients with UC treated with Exemptia was similar to the safety profile seen in patients with RA.

Plaque Psoriasis Clinical Studies

Exemptia has been studied in 1696 subjects with plaque psoriasis (Ps) in placebo-controlled and open-label extension studies. The safety profile for subjects with Ps treated with Exemptia was similar to the safety profile seen in subjects with RA with the following exceptions. In the placebo-controlled portions of the clinical trials in Ps subjects, Exemptia-treated subjects had a higher incidence of arthralgia when compared to controls (3% vs. 1%).

Hidradenitis Suppurativa Clinical Studies

Exemptia has been studied in 727 subjects with hidradenitis suppurativa (HS) in three placebo-controlled studies and one open-label extension study. The safety profile for subjects with HS treated with Exemptia weekly was consistent with the known safety profile of Exemptia.

Flare of HS, defined as ≥ 25% increase from baseline in abscesses and inflammatory nodule counts and with a minimum of 2 additional lesions, was documented in 22 (22%) of the 100 subjects who were withdrawn from Exemptia treatment following the primary efficacy timepoint in two studies.

Uveitis Clinical Studies

Exemptia has been studied in 464 patients with uveitis (UV) in placebo-controlled and open-label extension studies. The safety profile for patients with UV treated with Exemptia was similar to the safety profile seen in patients with RA.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Exemptia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Exemptia exposure.

Gastrointestinal disorders: Diverticulitis, large bowel perforations including perforations associated with diverticulitis and appendiceal perforations associated with appendicitis, pancreatitis

General disorders and administration site conditions: Pyrexia

Hepato-biliary disorders: Liver failure, hepatitis

Immune system disorders: Sarcoidosis

Neoplasms benign, malignant and unspecified (including cysts and polyps): Merkel Cell Carcinoma (neuroendocrine carcinoma of the skin)

Nervous system disorders: Demyelinating disorders (e.g., optic neuritis, Guillain-Barré syndrome), cerebrovascular accident

Respiratory disorders: Interstitial lung disease, including pulmonary fibrosis, pulmonary embolism

Skin reactions: Stevens Johnson Syndrome, cutaneous vasculitis, erythema multiforme, new or worsening psoriasis (all sub-types including pustular and palmoplantar), alopecia

Vascular disorders: Systemic vasculitis, deep vein thrombosis