Safety Considerations1

Serious Infections: Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death.These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Malignancies: Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including HUMIRA.

Other Serious Adverse Reactions: Patients treated with HUMIRA also may be at risk for other serious adverse reactions, including anaphylaxis, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, and a lupus-like syndrome.

Indications1

Juvenile Idiopathic Arthritis: HUMIRA is indicated, alone or in combination with methotrexate, for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.

HUMIRA efficacy in moderate to severe polyarticular Juvenile Idiopathic Arthritis (JIA)

DE038: A pivotal trial in patients (ages 4 to 17) with moderate to severe polyarticular JIA1,2

DE038 was a randomized, double-blind, stratified, placebo-controlled, multicenter, medication-withdrawal study with a 16-week, open-label, lead-in phase; a 32-week, double-blind, medication-withdrawal phase; and an open-label extension phase. Patients 4 to 17 years of age (N=171) with active polyarticular JIA who had not responded adequately to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), analgesics, corticosteroids, or disease-modifying antirheumatic drugs (DMARDs) underwent stratification into 2 groups according to methotrexate (MTX) use (HUMIRA + MTX: n=85; HUMIRA alone: n=86). Both groups received 24 mg of HUMIRA per square meter body surface area (BSA) subcutaneously every other week (EOW) for 16 weeks, up to a maximum dose of 40 mg EOW.

At Week 16, patients with an ACR Pedi 30 response underwent randomization to receive subcutaneous injections of either HUMIRA or placebo EOW in a 32-week, double-blind treatment phase. Patients who enrolled in the double-blind phase were eligible to receive open-label treatment with HUMIRA in an extension phase of the study. Patients remained on stable doses of NSAIDs and/or prednisone.

Primary efficacy endpoint was disease flare in the non-MTX patient population during the double-blind phase (Weeks 16 to 48).1,2 Disease flare was defined as (a) Worsening of ≥30% from baseline in ≥3 of 6 Pediatric ACR core criteria; (b) ≥2 active joints; and (c) Improvement of >30% in no more than 1 criterion. Select secondary endpoints were ACR Pedi 30, 50, and 70 levels of response and median time to onset of disease flare during the double-blind phase.2,3

Study Design Details

DE038: A pivotal study in patients (ages 4 to 17) with moderate to severe polyarticular JIA1,2

Patients 4 to 17 years of age with polyarticular JIA were stratified into 2 groups, according to MTX use. Patients demonstrating a Pediatric ACR30 response at the end of the open-label lead-in phase were randomized into the double-blind phase for 32 weeks, or until disease flare, and then entered the OLE phase.2

The design details of DEO38, a study in patients with moderate to severe polyarticular JIA.

MTX=methotrexate.
aPatients remained on stable doses of NSAIDs and/or prednisone.1
bBody surface area (BSA) dose: HUMIRA 24 mg/m2 every other week (EOW) up to a maximum dose of 40 mg/m2 EOW.2
cFixed dose (FD): HUMIRA 20 mg EOW if <30 kg; HUMIRA 40 mg EOW if ≥30 kg.2

DE038: Patient demographics comparable across study arms

DMARDs=disease-modifying antirheumatic drugs; MTX=methotrexate; RF=rheumatoid factor.
aAll values are means except values for C-reactive protein, which are medians.
bA 100-mm visual analog scale (VAS) was used in which higher scores indicated more active disease.
cA 100-mm VAS was used in which higher scores indicated more severe pain.
dScores range from 0 (best) to 3 (worst).
eThe normal median value is less than 0.287 mg/dL.

HUMIRA demonstrated efficacy in patients (ages 4 to 17) with polyarticular JIA

Significantly fewer HUMIRA-treated patients experienced disease flare

Results were seen both with and without MTX vs MTX and placebo, respectively, in moderate to severe polyarticular JIA

See disease flare data for HUMIRA treated patients with moderate to severe polyarticular JIA.

Disease flare=worsening of ≥30% from baseline in ≥3 of 6 pediatric ACR core criteria, ≥2 active joints, and an improvement of >30% in no more than 1 of 6 criteria.1 Pediatric ACR Core Criteria=physician's global assessment of disease activity, patient’s or parent’s global assessment of overall well-being, the number of joints with active arthritis (joints with swelling not caused by deformity or joints without swelling with limitation of passive motion accompanied by pain, tenderness, or both), number of joints with limitation of passive motion, physical function (Childhood HAQ-DI) and laboratory assessment of inflammation (eg, CRP).4

HUMIRA-treated patients experienced longer median time to disease flare vs placebo3

See disease flare data for HUMIRA treated patients with moderate to severe polyarticular JIA.

Disease flare=worsening of ≥30% from baseline in ≥3 of 6 pediatric ACR core criteria, ≥2 active joints, and an improvement of >30% in no more than 1 of 6 criteria.1 Pediatric ACR Core Criteria=physician global assessment of disease activity, patient’s or parent’s global assessment of overall well-being, the number of joints with active arthritis (joints with swelling not caused by deformity or joints without swelling with limitation of passive motion accompanied by pain, tenderness, or both), number of joints with limitation of passive motion, physical function (Childhood HAQ-DI) and laboratory assessment of inflammation (eg, CRP).4

Significantly more patients experienced symptom improvement with HUMIRA + MTX vs placebo + MTX2

ACR Pedi responses in patients with moderate to severe polyarticular JIA.

ACR Pedi 30, 50, and 70 responses are defined as improvements of at least 30%, 50%, and 70%, respectively, in ≥3 of 6
Pediatric Core Criteria, with worsening of >30% in no more than 1 criterion.2
NRI analysis=nonresponder imputation (NRI) of the intent-to-treat population; a patient who flared according to protocol definition was declared a nonresponder regardless of final pediatric ACR response.

Greater ACR Pedi response rates were sustained through 48 weeks with HUMIRA + MTX vs placebo + MTX2,3

HUMIRA + MTX treatment resulted in significantly greater and sustained ACR Pedi 70 response rates vs placebo + MTX in moderate to severe polyarticular JIA2,3

ACR pedi response rates in moderate to severe polyarticular JIA patients through 48 weeks.

NRI analysis=nonresponder imputation (NRI) of the intent-to-treat population; a patient who flared according to protocol definition was declared a nonresponder regardless of final pediatric ACR response.

Immunization considerations—It is recommended that JIA patients, if possible, be brought up to date with all immunizations in agreement with current immunization guidelines prior to initiating HUMIRA therapy. Patients on HUMIRA may receive concurrent vaccinations, except for live vaccines.1

Safety From DE038 Clinical Trial —In general, the adverse reactions in the HUMIRA-treated pediatric patients in DE038 were similar in frequency and type to those seen in adult patients. Serious infections were observed in 4% of patients within approximately 2 years of initiation of treatment with HUMIRA and included cases of herpes simplex, pneumonia, urinary tract infection, pharyngitis, and herpes zoster. Reported severe adverse reactions, some that differ from adults, include neutropenia, streptococcal pharyngitis, increased aminotransferases, herpes zoster, myositis, metrorrhagia, and appendicitis.1 Postmarketing cases of malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF blockers, including HUMIRA.

DE038: 2-year open-label extension (OLE)1,2

OLE limitations: As with any long-term open-label extension, there are several limitations with the OLE portion of this study. For example, there is the potential for enrichment of long-term data in the remaining patient population, as those who remain in the study generally fare better than those who discontinue.

DE038 OLE: ACR Pedi response rates were maintained for up to 2 years in the OLE phase in patients who received HUMIRA throughout the study2

ACR pedi response rates in moderate to severe polyarticular JIA patients through 2 years.

LOCF analysis=last observation carried forward: analysis of intent-to-treat population.
Patient response during the first 104 weeks of the OLE phase regardless of whether HUMIRA was dosed according to BSA or body weight.



IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)1

SERIOUS INFECTIONS

Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Discontinue HUMIRA if a patient develops a serious infection or sepsis.

Reported infections include:

  • Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before HUMIRA use and during therapy. Initiate treatment for latent TB prior to HUMIRA use.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

Carefully consider the risks and benefits of treatment with HUMIRA prior to initiating therapy in patients: 1. with chronic or recurrent infection, 2. who have been exposed to TB, 3. with a history of opportunistic infection, 4. who resided in or traveled in regions where mycoses are endemic, 5. with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

  • Do not start HUMIRA during an active infection, including localized infections.
  • Patients older than 65 years, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection.
  • If an infection develops, monitor carefully and initiate appropriate therapy.
  • Drug interactions with biologic products: A higher rate of serious infections has been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker. An increased risk of serious infections has been seen with the combination of TNF blockers with anakinra or abatacept, with no demonstrated added benefit in patients with RA. Concomitant administration of HUMIRA with other biologic DMARDs (e.g., anakinra or abatacept) or other TNF blockers is not recommended based on the possible increased risk for infections and other potential pharmacological interactions.
MALIGNANCY

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including HUMIRA. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including HUMIRA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.

  • Consider the risks and benefits of HUMIRA treatment prior to initiating or continuing therapy in a patient with known malignancy.
  • In clinical trials, more cases of malignancies were observed among HUMIRA-treated patients compared to control patients.
  • Non-melanoma skin cancer (NMSC) was reported during clinical trials for HUMIRA-treated patients. Examine all patients, particularly those with a history of prolonged immunosuppressant or PUVA therapy, for the presence of NMSC prior to and during treatment with HUMIRA.
  • In HUMIRA clinical trials, there was an approximate 3-fold higher rate of lymphoma than expected in the general U.S. population. Patients with chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk of lymphoma than the general population, even in the absence of TNF blockers.
  • Postmarketing cases of acute and chronic leukemia were reported with TNF blocker use. Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving TNF blockers were lymphomas; other cases included rare malignancies associated with immunosuppression and malignancies not usually observed in children and adolescents.
HYPERSENSITIVITY
  • Anaphylaxis and angioneurotic edema have been reported following HUMIRA administration. If a serious allergic reaction occurs, stop HUMIRA and institute appropriate therapy.
HEPATITIS B VIRUS REACTIVATION
  • Use of TNF blockers, including HUMIRA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases have been fatal.
  • Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy.
  • Exercise caution in patients who are carriers of HBV and monitor them during and after HUMIRA treatment.
  • Discontinue HUMIRA and begin antiviral therapy in patients who develop HBV reactivation. Exercise caution when resuming HUMIRA after HBV treatment.
NEUROLOGIC REACTIONS
  • TNF blockers, including HUMIRA, have been associated with rare cases of new onset or exacerbation of central nervous system and peripheral demyelinating diseases, including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome.
  • Exercise caution when considering HUMIRA for patients with these disorders; discontinuation of HUMIRA should be considered if any of these disorders develop.
  • There is a known association between intermediate uveitis and central demyelinating disorders.
HEMATOLOGIC REACTIONS
  • Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia has been infrequently reported with HUMIRA.
  • Consider stopping HUMIRA if significant hematologic abnormalities occur.
CONGESTIVE HEART FAILURE
  • Worsening and new onset congestive heart failure (CHF) has been reported with TNF blockers. Cases of worsening CHF have been observed with HUMIRA; exercise caution and monitor carefully.
AUTOIMMUNITY
  • Treatment with HUMIRA may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.
IMMUNIZATIONS
  • Patients on HUMIRA should not receive live vaccines.
  • Pediatric patients, if possible, should be brought up to date with all immunizations before initiating HUMIRA therapy.
  • Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. The safety of administering live or live-attenuated vaccines in infants exposed to HUMIRA in utero is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants.
ADVERSE REACTIONS
  • The most common adverse reactions in HUMIRA clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.

INDICATIONS1
  • Rheumatoid Arthritis: HUMIRA is indicated, alone or in combination with methotrexate or other non-biologic DMARDs, 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.
  • Juvenile Idiopathic Arthritis: HUMIRA is indicated, alone or in combination with methotrexate, for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.
  • Psoriatic Arthritis: HUMIRA is indicated, alone or in combination with non-biologic DMARDs, for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis.
  • Ankylosing Spondylitis: HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.
  • Adult Crohn’s Disease: HUMIRA 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, and 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: HUMIRA 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: HUMIRA 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. The effectiveness of HUMIRA has not been established in patients who have lost response to or were intolerant to anti-TNF agents.
  • Plaque Psoriasis: HUMIRA 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. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
  • Hidradenitis Suppurativa: HUMIRA is indicated for the treatment of adult patients with moderate to severe hidradenitis suppurativa.
  • Uveitis: HUMIRA is indicated for the treatment of non-infectious intermediate, posterior and panuveitis in adult patients.

For full Prescribing Information, visit rxabbvie.com/pdf/humira.pdf

1641190-1880520

Legal Notices/Privacy Policy. ©2015 AbbVie Inc. North Chicago, IL 60064. If you have any questions about AbbVie's HUMIRAPro.com website that have not been answered click here. This website and the information contained herein is intended for use by US physicians only and is provided for informational purposes only.

References: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc. 2. Lovell DJ, Ruperto N, Goodman S, et al. Adalimumab with or without methotrexate in juvenile rheumatoid arthritis. N Engl J Med. 2008;359(8):810-820. 3. Data on file, AbbVie Inc. 4. Ravelli A, Martini A. Juvenile idiopathic arthritis. Lancet. 2007;369(9563):767-778.

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Important Safety Information New HUMIRA (adalimumab) data for treating moderate to severe fingernail psoriasis.

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There's a treatment for moderate to severe chronic plaque psoriasis with new data for moderate to severe fingernail psoriasis.




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Indication1

Plaque Psoriasis: HUMIRA (adalimumab) 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. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

Safety Considerations1

Serious Infections

Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Malignancies

Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including HUMIRA.

Other Serious Adverse Reactions

Patients treated with HUMIRA also may be at risk for other serious adverse reactions, including anaphylaxis, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, and a lupus-like syndrome.