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

Ankylosing Spondylitis: HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.

ATLAS: A pivotal trial (N=315) in patients with active AS1,2

ATLAS was a 24-week, multicenter, randomized, double-blind, placebo-controlled study of 315 patients with active AS who had an inadequate response or intolerance to 1 or more nonsteroidal anti-inflammatory drugs (NSAIDs). Patients were randomized to receive HUMIRA 40 mg every other week (EOW), (n=208) or placebo (n=107).

The co-primary endpoints were 1) ASAS 20 response (≥20% improvement according to the Assessment in Ankylosing Spondylitis International Working Group criteria) at Week 12 for HUMIRA compared to placebo EOW; and 2) change in modified Stoke AS Spine Score (mSASSS) from baseline to Week 104 for the HUMIRA cohort (n=307) compared to the Outcome in AS International Study (OASIS) cohort, a historical control cohort of TNF-antagonist naïve patients (n=169).2,3 Select secondary endpoints were ASAS20 at Week 24, MASES, and ASQoL.2

At Week 24, patients completing the placebo-controlled, double-blind portion of the trial were eligible for enrollment in the open-label extension (OLE).4

Study Design Details

ATLAS: A pivotal trial in AS1,2

The ATLAS study design for patients with AS.

EOW=every other week.
aPatients who did not achieve an ASAS20 response at Weeks 12, 16, or 20 were considered for open-label HUMIRA.4

Patients who did not achieve an ASAS20 response could switch to open-label HUMIRA (“early escape” protocol) at Weeks 12, 16, and 20; 69.2% (74/107) of placebo patients and 38.9% (81/208) of HUMIRA patients entered the early escape protocol.

Active AS was defined as fulfillment of at least 2 of the following: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4; total back pain score ≥4 (VAS 0-10 cm); morning stiffness lasting ≥1 hour.2

ATLAS: Demographics and clinical characteristics comparable between groups2

ASAS=Assessment in Ankylosing Spondylitis International Working Group; BASFI=Bath Ankylosing Spondylitis Functional Index; BASDAI=Bath Ankylosing Spondylitis Disease Activity Index; BASMI=Bath Ankylosing Spondylitis Metrology Index; MASES=Maastricht Ankylosing Spondylitis Enthesitis Score.

HUMIRA: help improve measures of disease activity for patients with active AS

HUMIRA significantly improved all 4 ASAS20 criteria measuring signs and symptoms2

Co-primary endpoint: Percentage of ASAS20 response at Week 12

  • ASAS20 response at Week 12: 58% of HUMIRA-treated patients (n=208) demonstrated ASAS20 response vs 21% of placebo-treated patients (n=107) (P<0.001 HUMIRA vs placebo)1
HUMIRA ASAS20 data for AS patients.

BASFI=Bath Ankylosing Spondylitis Functional Index.
aLast observation carried forward (LOCF) analysis of intent-to-treat population. If a patient received early-escape open-label adalimumab prior to Week 24, the last observation prior to early-escape open-label adalimumab was carried forward.

Co-primary endpoint: Change in mSASSS at Week 104

  • Mean change in mSASSS from baseline to 2 years: the results were not significantly different between the HUMIRA (n=307) and OASIS (n=169) cohorts (0.8 and 0.9, respectively; P=0.771)3

Additional data in AS

Change in measure of enthesitis

Change in measure of enthesitis for patients with AS.

aMaastricht Ankylosing Spondylitis Enthesitis Score (MASES). Evaluates 13 tendon insertion points for pain (total score, 0-13).
dLast observation carried forward (LOCF) analysis of the intent-to-treat population.

Ankylosing Spondylitis Quality of Life (ASQoL) questionnaire results

Ankylosing Spondylitis quality of life questionnaire results.

aAnkylosing Spondylitis Quality of Life (ASQoL). Comprised of 18 statements to be filled in by the patient. Each statement on the ASQoL is given a score of "1" or "0." All item scores are summed to give a total score or index. Scores range from 0 (good quality of life) to 18 (poor quality of life).

ATLAS open-label extension (OLE) in AS: results observed through 2 years

Assessment of signs and symptoms at Years 1 and 2

Signs and symptoms at years 1 and 2 for AS patients.

aObserved analysis by duration of exposure to HUMIRA 40 mg EOW using last observation prior to the first dose of adalimumab at baseline.

ASAS20 component data at 2 years

ASAS20 Component data at 2 years with HUMIRA for AS patients.

aThe majority of patients treated with placebo for the first 24 weeks of the ATLAS study did not have 2 years of exposure to adalimumab at the time of the analysis.
bAll values are the mean (SD). For observed and last observation carried forward (LOCF) analyses, the baseline value is the last observation before the first dose of adalimumab.

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.



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. van der Heijde D, Kivitz A, Schiff MH, et al; for ATLAS Study Group. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006;54(7):2136-2146. 3. van der Heijde D, Salonen D, Weissman B, et al. Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Ther. 2009;11(4):R127. 4. van der Heijde D, Schiff MH, Sieper J, et al; for ATLAS Study Group. Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-term results from the ATLAS trial. Ann Rheum Dis. 2009;68(6):922-929. 5. Data on file, AbbVie Inc.

1641190-1516827


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.