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

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.

IMAgINE 1, the largest double-blind study to date of an anti-TNF agent in children with moderate to severe CD2

IMAgINE 1 was a randomized, double-blind, 52-week clinical study of 2 dose levels of HUMIRA in moderately to severely active pediatric CD in patients (PCDAI score >30) who had over the previous 2-year period an inadequate response or intolerance to corticosteroids or an immunomodulator. Patients who previously had loss of response or intolerance to infliximab were allowed to enter the trial.1,2

Patients received open-label induction therapy at a dose based on their body weight (≥40 kg and <40 kg). Patients weighing ≥40 kg received 160 mg at Week 0 and 80 mg at Week 2. Patients weighing <40 kg received 80 mg at Week 0 and 40 mg at Week 2. At Week 4, patients within each body weight category (≥40 kg and <40 kg) were randomized 1:1 to one of the two maintenance dose regimens (high dose and low dose). The high dose was 40 mg every other week for patients weighing ≥40 kg and 20 mg every other week for patients weighing <40 kg. The low dose was 20 mg every other week for patients weighing ≥40 kg and 10 mg for patients weighing <40 kg.1

Primary endpoint was the percentage of patients achieving clinical remission at Week 26 comparing High Maintenance Dose vs Low Maintenance Dose.2

44% of patients in the IMAgINE 1 study had previously lost response or were intolerant to a TNF blocker; 56% were anti-TNF naïve2

IMAgINE 1 did not have a placebo control arm1,2

Study Design Details

IMAgINE 1: Study Design and Selected Baseline Characteristics1,2

IMAgINE 1: Study Design and Selected Baseline Characteristics for patients with pediatric CD.

Week 41,2

Randomly assigned (1:1) to double-blind HUMIRA High Maintenance Dose or HUMIRA Low Maintenance Dose. Stratified according to:

  • Week-4 clinical response* status
  • Prior exposure to infliximab

Week 261,2

Primary endpoint: Proportion of patients in clinical remission comparing High Maintenance Dose vs Low Maintenance Dose.

DOSING1:

OL Induction: Based on weight at baseline

  • ≥40 kg: HUMIRA 160 mg at Week 0 and HUMIRA 80 mg at Week 2
  • <40 kg HUMIRA 80 mg at Week 0 and HUMIRA 40 mg at Week 2

Double-blind Maintenance: Randomized to 1 of 2 maintenance dose regimens; dose in each regimen was based on Week 4 body weight

  • High Maintenance Dose: Week 4:

20 mg EOW for patients weighing <40 kg and

40 mg EOW for patients weighing ≥40 kg

  • Low Maintenance Dose: Week 4:

10 mg EOW for patients weighing <40 kg and

20 mg EOW for patients weighing ≥40 kg

At Week 12, patients who experienced a disease flare or who were nonresponders§ were allowed to dose-escalate (ie, switch from blinded every other week dosing to blinded every week dosing). Every week dosing is not the recommended maintenance dosing regimen.

PRIMARY ENDPOINT: Primary endpoint was proportion of patients achieving clinical remission at Week 26 comparing High Maintenance Dose vs Low Maintenance Dose.1,2

SECONDARY ENDPOINTS: Ranked secondary endpoints comparing High Maintenance Dose vs Low Maintenance Dose include2:

  • Clinical remission at Week 52
  • Clinical response at Week 26
  • Clinical response at Week 52

CONCOMITANT TREATMENTS: Stable doses of concomitant therapies permitted throughout the study were corticosteroids, immunomodulators, aminosalicylates, CD-related antibiotics, and growth hormone.1,2

ANALYSIS: Intent-to-treat (ITT) population using nonresponder imputation. All randomized patients receiving at least 1 dose of double-blind study medication were included in the analysis. Patients who discontinued the study, switched to weekly dosing, or did not have the relevant PCDAI score were considered not to have achieved clinical remission or response.1,2

IMAgINE 1: Selected baseline characteristics for double-blind maintenance population (N=188)2

  • Anti-TNF use
    • 56% anti-TNF naïve
    • 44% previously lost response or were intolerant to a TNF blocker
  • Moderately to severely active CD: PCDAI score >30 at baseline
    • PCDAI scores range from 0-100
  • CD diagnosis made at least 12 weeks prior to trial screening and confirmed by endoscopy or radiologic evaluation
  • Ages 6 to 17, Mean age 13.6
  • Disease duration: Mean 3 years
  • Concomitant medications at baseline
    • CorticosteroidsII: 38%
    • Immunomodulators: 62%
    • Aminosalicylates#: 36%
    • Antibiotics#: 8%

IMAgINE 1: Study population at Week 41

  • OL Induction result: Of the 188 patients who entered the double-blind maintenance phase at Week 4, 28% (52/188) of patients were in clinical remission (defined as PCDAI score ≤10)
    • During the 4-week OL induction phase, the most common adverse reactions were injection site pain (6%) and injection site reaction (5%)

PCDAI=Pediatric Crohn's Disease Activity Index; EOW=every other week
*Clinical response was defined as a decrease in PCDAI score of ≥15 points from baseline.
Clinical remission was defined as PCDAI score of ≤10.
Increase in PCDAI score of ≥15 from Week 4 and absolute PCDAI score of >30.
§Did not achieve a decrease in PCDAI score of ≥15 from baseline for 2 consecutive visits at least 2 weeks apart.
IICorticosteroids could be tapered after Week 4 in patients who experienced clinical response (PCDAI score decrease of ≥15 points compared with baseline).
Immunomodulator therapy could be discontinued at or after Week 26 for patients meeting the clinical response criterion and could not be reinstated.
#Other CD-specific concomitant medications were to be maintained at a constant dose throughout the study.

Recommended regimen is the High Maintenance Dose1

Clinical remission* and response rates were numerically higher in the High Maintenance Dose group compared with the Low Maintenance Dose group, and those differences were either not statistically significant or exploratory.1,2

WEEK 26: Remission and response1,2

IMAgINE 1: Percentage of patients who achieved clinical remission at Week 26 in the high maintenance dose (39%) compared to the low maintenance dose (28%).

Low Maintenance Dose: 28% (n=95)

  • Low Maintenance Dose was based on Week-4 weight (<40 kg=10 mg, ≥40 kg=20 mg); every other week
IMAgINE 1: Percentage of patients who achieved clinical response at Week 26 in the high maintenance dose (59%) compared to the low maintenance dose (48%).

Low Maintenance Dose: 48% (n=95)

  • Low Maintenance Dose was based on Week-4 weight (<40 kg=10 mg, ≥40 kg=20 mg); every other week

Week 52: Remission and response1,2

IMAgINE 1: Percentage of patients who achieved clinical remission at Week 52 in the high maintenance dose (33%) compared to the low maintenance dose (23%).

Low Maintenance Dose: 23% (n=95)

  • Low Maintenance Dose was based on Week-4 weight (<40 kg=10 mg, ≥40 kg=20 mg); every other week
IMAgINE 1: Percentage of patients who achieved clinical response at Week 52 in the high maintenance dose (42%) compared to the low maintenance dose (28%).

Low Maintenance Dose: 28% (n=95)

  • Low Maintenance Dose was based on Week-4 weight (<40 kg=10 mg, ≥40 kg=20 mg); every other week

Adverse events in IMAgINE 1 study population (n=192)1

  • 67% of children experienced an infection including upper respiratory tract infection and nasopharyngitis
  • 5% of children experienced a serious infection (these included viral infection, device-related sepsis [catheter], gastroenteritis, H1N1 influenza, and disseminated histoplasmosis)
  • Allergic reactions were observed in 5% of patients. All of them were non-serious and primarily localized reactions

Risk of HSTCL1

Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of fatal lymphoma, have been reported in patients treated with TNF blockers, including HUMIRA. The majority of cases were in adolescent and young adult males with inflammatory bowel disease who had received concomitant or prior treatment with azathioprine or 6-mercaptopurine.

*Clinical remission was defined as PCDAI score of ≤10.
Clinical response was defined as a decrease from baseline in the PCDAI score of ≥15 points.
Prior to entering maintenance phase, patients received open-label induction dose 160 mg at Week 0 and 80 mg at Week 2 for patients weighing ≥40 kg at baseline; or 80 mg at Week 0 and 40 mg at Week 2 for patients weighing <40 kg at baseline.
PCDAI=Pediatric Crohn's Disease Activity Index

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. Hyams JS, Griffiths A, Markowitz J, et al. Safety and efficacy of adalimumab for moderate to severe Crohn’s disease in children. Gastroenterology. 2012;143(2):365-374.

1641190-1516827


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

THIS IS WORTH POINTING OUT.

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




  DOWNLOAD PRESCRIBING INFORMATION
VIEW PRESS RELEASE »

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.