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

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 moderate to severe hidradenitis suppurativa in patients 12 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.

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.

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.

Uveitis: HUMIRA is indicated for the treatment of non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older.

HUMIRA Safety Data: Global Data, along with Ps, PsA, HS Safety Data

Long-term safety across 6 indications in global clinical trials2

Serious adverse events of interest across 6 indications

Methodology

  • Evaluated nearly 12 years of long-term safety data in 23,458 patients from 71 HUMIRA global clinical trials including randomized, controlled, open-label and long-term extension studies2
  • Assessed serious adverse events (SAEs) of interest2
  • Because clinical trials are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not predict the rates observed in a broader patient population in clinical practice1
Rheumatoid
Arthritis
(RA)
Psoriatic
Arthritis
(PSA)
Ankylosing
Spondylitis
(AS)
Rates displayed as events per 100 patient-years (PYs)
As of November 6, 2010
Serious Adverse
Events of Interest
23,942.6 PYa
N=14109
997.5 PYa
N=837
1985.6 PYa
N=1684
Serious Infections 4.6 2.8 1.4
Active tuberculosis 0.3 0.2 0
Opportunistic infections <:0.1 0 0
Malignanciesb 0.9 0.2 0.2
Lymphoma 0.1 0.2 <0.1
Serious non-melanoma
skin cancer
0.2 0.1 0.3
Melanoma <0.1 0 <0.1
Demyelinating disorder <0.1 0 <0.1
Lupus-like syndrome <0.1 0 0.1
Congestive heart failure 0.2 0 0.1
New onset/
worsening psoriasis
<0.1 0.1 <0.1
Any AE leading to death 0.8 0.3 <0.1
Adult
Crohn’s
Disease
(CD)
Chronic
Plaque
Psoriasis
(Ps)
Juvenile
Idiopathic
Arthritis
(JIA)
Rates displayed as events per 100 patient-years (PYs)
As of November 6, 2010
Serious Adverse
Events of Interest
4138.0 PYa
N=3606
5061.8 PYa
N=3010
604.9 PYa
N=212
Serious Infections 6.7 1.7 2.0
Active tuberculosis <0.1 0.1 0
Opportunistic infections <0.1 0 0
Malignanciesb 0.5 0.6 0
Lymphoma <0.1 <0.1 0
Serious non-melanoma
skin cancer
<0.1 0.1 0
Melanoma 0 0.2 0
Demyelinating disorder 0.1 0 0
Lupus-like syndrome <0.1 0 0
Congestive heart failure 0 <0.1 0
New onset/
worsening psoriasis
<0.1 <0.1 0
Any AE leading to death 0.1 0.2 0
Rheumatoid
Arthritis
(RA)
Psoriatic
Arthritis
(PSA)
Ankylosing
Spondylitis
(AS)
Adult
Crohn’s
Disease
(CD)
Chronic
Plaque
Psoriasis
(Ps)
Juvenile
Idiopathic
Arthritis
(JIA)
Rates displayed as events per 100 patient-years (PYs)
As of November 6, 2010
Serious Adverse
Events of Interest
23,942.6 PYa
N=14109
997.5 PYa
N=837
1985.6 PYa
N=1684
4138.0 PYa
N=3606
5061.8 PYa
N=3010
604.9 PYa
N=212
Serious Infections 4.6 2.8 1.4 6.7 1.7 2.0
Active tuberculosis 0.3 0.2 0 <0.1 0.1 0
Opportunistic infections <0.1 0 0 <0.1 0 0
Malignanciesb 0.9 0.2 0.2 0.5 0.6 0
Lymphoma 0.1 0.2 <0.1 <0.1 <0.1 0
Serious non-melanoma
skin cancer
0.2 0.1 0.3 <0.1 0.1 0
Melanoma <0.1 0 <0.1 0 0.2 0
Demyelinating disorder <0.1 0 <0.1 0.1 0 0
Lupus-like syndrome <0.1 0 0.1 <0.1 0 0
Congestive heart failure 0.2 0 0.1 0 <0.1 0
New onset/
worsening psoriasis
<0.1 0.1 <0.1 <0.1 <0.1 0
Any AE leading to death 0.8 0.3 <0.1 0.1 0.2 0

aData were derived from global clinical trials of HUMIRA, including randomized controlled and open-label trials and long-term extension studies—36 in RA, 4 in PsA, 4 in AS, 13 in Ps, 3 in JIA, and 11 in CD.
bMalignancies excluding lymphoma and non-melanoma skin cancer and malignancies not considered serious by investigators.

Juvenile Idiopathic Arthritis (JIA) Clinical Trials

In general, the adverse reactions in HUMIRA-treated JIA patients were similar in frequency and type to those seen in adult patients. In Study JIA-I, 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. In Study JIA-II, serious infections were observed in 9% of patients receiving HUMIRA in the study and included dental caries, rotavirus gastroenteritis, and varicella.1

The risks and benefits of HUMIRA should be carefully considered prior to initiating therapy

Risk of 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.
  • Discontinue HUMIRA if a patient develops a serious infection or sepsis.
  • Test patients for latent TB before HUMIRA use and during therapy. Initiate treatment for latent TB prior to HUMIRA use.
  • 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.

Postmarketing Reports of Pediatric Malignancy

  • Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF-blockers, including HUMIRA

Postmarketing Reports of Hepatosplenic T-cell Lymphoma (HSTCL)

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

Patients treated with HUMIRA may be at risk for other serious adverse reactions including:

  • Malignancies – More cases were observed among HUMIRA-treated adult patients than in controls. Lymphoma, non-melanoma skin cancer (NMSC), acute and chronic leukemia, and others have been reported. Examine all patients for the presence of NMSC prior to and during treatment.
  • Hypersensitivity – Anaphylaxis or serious allergic reactions may occur. If a serious allergic reaction occurs, stop HUMIRA and begin appropriate therapy.
  • Hepatitis B virus (HBV) reactivation – Risk of reactivation may increase in patients who are chronic carriers. Monitor HBV carriers during and after treatment with HUMIRA. If reactivation occurs, stop HUMIRA and begin appropriate therapy.
  • Demyelinating disease – Exacerbation or new onset central nervous system or peripheral demyelinating disease may occur. Exercise caution when considering HUMIRA for patients with these disorders.
  • Cytopenias, pancytopenia – Consider stopping HUMIRA in patients with significant hematologic abnormalities.
  • Heart failure – Worsening or new onset congestive heart failure (CHF) may occur. Exercise caution in patients with CHF and monitor them carefully.
  • Lupus-like syndrome – Development of autoantibodies and lupus-like syndrome. Stop HUMIRA if syndrome develops.

Well-studied safety profile in clinical trials and clinical practice for moderate to severe chronic plaque psoriasis (Ps)

Safety of HUMIRA across indications1

The safety assessed in the HUMIRA full Prescribing Information includes patients treated with HUMIRA for various immune-mediated diseases (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, plaque psoriasis, ulcerative colitis, uveitis, and hidradenitis suppurativa).

Adverse events (AEs) of interest for HUMIRA from the full Prescribing Information1
These rates are from the controlled portion of 39 HUMIRA trials in adult patients:
HUMIRA (n=7973) Control (n=4848)
Serious infectious AEs 4.3 Events/100 PYs 2.9 Events/100 PYs
Non-melanoma
skin cancer (NMSC)
0.8 Events/100 PYs 0.2 Events/100 PYs
Malignancies (excluding NMSC) 0.7 Events/100 PYs 0.7 Events/100 PYs
These rates are from 52 global HUMIRA controlled and uncontrolled clinical trials:
HUMIRA (n=24605)
Tuberculosis 0.20 Events/100 PYs
Serious opportunistic infections 0.05 Events/100 PYs
Lymphomaa 0.11 Events/100 PYs
Adverse events (AEs) of interest for HUMIRA from the full Prescribing Information1
These rates are from the controlled portion of 39 HUMIRA trials in adult patients:
HUMIRA (n=7973) Control (n=4848)
Serious infectious AEs 4.3 Events/100 PYs 2.9 Events/100 PYs
Non-melanoma skin cancer (NMSC) 0.8 Events/100 PYs 0.2 Events/100 PYs
Malignancies (excluding NMSC) 0.7 Events/100 PYs 0.7 Events/100 PYs
These rates are from 52 global HUMIRA controlled and uncontrolled clinical trials:
HUMIRA (n=24605)
Tuberculosis 0.20 Events/100 PYs
Serious opportunistic infections 0.05 Events/100 PYs
Lymphomaa 0.11 Events/100 PYs

aThe observed rate of lymphomas is approximately 0.11/100 PYs in clinical trials of HUMIRA-treated patients. This is approximately 3-fold higher than expected in the general population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to severalfold) than the general population for the development of lymphoma, even in the absence of TNF blockers.
PYs=patient-years

Safety of HUMIRA in moderate to severe chronic plaque psoriasis across 13 trials3

Study objective: To assess the safety profile from 5 clinical trials, ranging from 12 weeks to 5 years, of patients with moderate to severe chronic plaque psoriasis. This analysis included patients who started HUMIRA 40 mg EOW beginning 1 week after an 80-mg initial dose or started on placebo treatment and switched to HUMIRA 40 mg EOW.

Adverse events (AEs) of interest in the
EOW population3
June 2007
N 1403
Exposure (PYs) 1883.5
Mean exposure per patient (mo) 16.1
Adverse event Events Incidence
(events/100 PYs)
Any AE 5220 277.1
Infectious AE 1613 85.6
Serious AE 119 6.32
Serious infectious AE 25 1.33
Malignancies (excluding NMSC) 10 0.53
NMSC 14 0.74
Lymphoma 0 0
Fatal AE 1 0.05
Opportunistic infections (excluding TB) 5 0.27
TB 4 0.21
Congestive heart failure 1 0.05
Allergic reaction 6 0.32
Demyelinating disease 1 0.05
Lupus-like syndrome 0 0
April 2010
N 1403
Exposure (PYs) 2854.1
Mean exposure per patient (mo) 24.4
Adverse event Events Incidence
(events/100 PYs)
Any AE 7036 246.5
Infectious AE 2133 74.7
Serious AE 196 6.87
Serious infectious AE 39 1.37
Malignancies (excluding NMSC) 17 0.60
NMSC 21 0.74
Lymphoma 0 0
Fatal AE 4 0.14
Opportunistic infections (excluding TB) 7 0.25
TB 5 0.18
Congestive heart failure 6a 0.21
Allergic reaction 15b 0.53
Demyelinating disease 1 0.04
Lupus-like syndrome 0 0
Adverse events (AEs) of interest in the EOW population3
June 2007 April 2010
N 1403 1403
Exposure (PYs) 1883.5 2854.1
Mean exposure per patient (mo) 16.1 24.4
Adverse event Events Incidence
(events/100 PYs)
Events Incidence
(events/100 PYs)
Any AE 5220 277.1 7036 246.5
Infectious AE 1613 85.6 2133 74.7
Serious AE 119 6.32 196 6.87
Serious infectious AE 25 1.33 39 1.37
Malignancies (excluding NMSC) 10 0.53 17 0.60
NMSC 14 0.74 21 0.74
Lymphoma 0 0 0 0
Fatal AE 1 0.05 4 0.14
Opportunistic infections (excluding TB) 5 0.27 7 0.25
TB 4 0.21 5 0.18
Congestive heart failure 1 0.05 6a 0.21
Allergic reaction 6 0.32 15b 0.53
Demyelinating disease 1 0.05 1 0.04
Lupus-like syndrome 0 0 0 0

aSearch criteria for the MedDRA Preferred Term “congestive heart failure” were expanded after June 2007 and prior to April 2010 to include events with a clear diagnosis or indication of congestive heart failure reported (ie, symptoms indicated as secondary to congestive heart failure or action taken pertinent to the diagnosis of congestive heart failure).
bSearch criteria for the MedDRA Preferred Term “allergic reaction” were expanded after June 2007 and prior to April 2010 to include events developed in association with the injection of adalimumab and not caused by another agent/drug.
EOW=every other week; NMSC=non-melanoma skin cancer; PYs=patient-years; TB=tuberculosis

HUMIRA dosing in moderate to severe chronic plaque psoriasis1

The recommended dosage of HUMIRA for adult patients with moderate to severe chronic plaque psoriasis is an initial dose of 80 mg subcutaneously (SC) followed by 40 mg SC given every other week starting 1 week after the initial dose. The use of HUMIRA in plaque psoriasis beyond 1 year has not been evaluated in controlled clinical studies.

Safety data from the REVEAL Clinical Trial in Moderate to Severe Chronic Plaque Ps4

REVEAL adverse event rates (events/patient years) at 52 weeks in the all HUMIRA group4
Adverse event AII-HUMIRA groupa (540.5 PYs)
Event Event/PY
Any AE 2157 3.99
Serious AE 33 0.06
Serious Infectious AE 12 0.02
Infectious AE 650 1.20
AE leading to withdrawal 42 0.08
AE of interest
Tuberculosis 1 0.002
Opportunistic infections excluding tuberculosis 1 0.002
Congestive heart failure 1 0.002
Allergic reaction 1 0.002
Injection-site reaction 92 0.170
Malignancies, excluding NMSC and lymphoma 2 0.004
NMSC 7 0.013
Lymphoma 0 0
Lupus-like syndrome 0 0
Demyelinating disorder 0 0
REVEAL adverse event rates (events/patient years) at 52 weeks in the all HUMIRA group4
Adverse event AII-HUMIRA groupa (540.5 PYs)
Event Event/PY
Any AE 2157 3.99
Serious AE 33 0.06
Serious Infectious AE 12 0.02
Infectious AE 650 1.20
AE leading to withdrawal 42 0.08
AE of interest
Tuberculosis 1 0.002
Opportunistic infections excluding tuberculosis 1 0.002
Congestive heart failure 1 0.002
Allergic reaction 1 0.002
Injection-site reaction 92 0.170
Malignancies, excluding NMSC and lymphoma 2 0.004
NMSC 7 0.013
Lymphoma 0 0
Lupus-like syndrome 0 0
Demyelinating disorder 0 0

aAll patients receiving at least 1 dose of adalimumab during the 52 weeks of study; includes safety data up to 70 days after last dose.
AE=adverse event; NMSC=non-melanoma skin cancer; PYs=patient-years

Adverse reaction rates observed in clinical trials may not predict the rates observed in a broader patient population in clinical practice. This is because clinical trials are conducted under controlled conditions (i.e., employing exclusion criteria such as co-morbid conditions and use of select concomitant medications, frequent monitoring of patients, etc).1

Additionally, adverse reaction rates observed in open-label extension studies may not predict the rates observed in a broader patient population, as patients who experience significant adverse events may be more likely to discontinue.

REVEAL: RCT and OLE serious adverse event rates5

Adverse reaction rates observed in clinical trials and OLE studies may not predict the rates observed in a broader patient population in clinical practice.

Serious infection rates over 3 years (events per 100 patient-years [PYs])5
RCTPeriod A(weeks 0-16)
RCTPeriod C(weeks 33-52)
OverallRCT(52 weeks)
OverallRCT + OLE(weeks 0-160)
HUMIRA2.8(n=814)
PYs=250.2
HUMIRA1.1(n=250)
PYs=90.9
HUMIRA2.2(n=840)
PYs=540.5
HUMIRA1.4(n=1047)
PYs=2748.5
placebo3.3(n=398)
PYs=120.7
placebo2.4(n=240)
PYs=82.2
Serious infection rates over 3 years (events per 100 patient-years [PYs])5
RCTPeriod A(weeks 0-16)
HUMIRA2.8(n=814)
PYs=250.2
placebo3.3(n=398)
PYs=120.7
RCTPeriod C(weeks 33-52)
HUMIRA1.1(n=250)
PYs=90.9
placebo2.4(n=240)
PYs=82.2
OverallRCT(52 weeks)
HUMIRA2.2(n=840)
PYs=540.5
OverallRCT + OLE(weeks 0-160)
HUMIRA1.4(n=1047)
PYs=2748.5

OLE=open-label extension; RCT=randomized controlled trial

Risk of Serious Infection1

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.
Carefully consider the risks and benefits of treatment with HUMIRA prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with HUMIRA.

  • Do not start HUMIRA in patients with 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
Malignancy* rates over 3 years (events per 100 PYs)5
RCTPeriod A(weeks 0-16)
RCTPeriod C(weeks 33-52)
OverallRCT(52 weeks)
OverallRCT + OLE(weeks 0-160)
HUMIRA0.8(n=814)
PYs=250.2
HUMIRA0(n=250)
PYs=90.9
HUMIRA0.4(n=840)
PYs=540.5
HUMIRA0.7(n=1047)
PYs=2748.5
placebo0.8(n=398)
PYs=120.7
placebo0(n=240)
PYs=82.2
Malignancy* rates over 3 years (events per 100 PYs)5
RCTPeriod A(weeks 0-16)
HUMIRA0.8(n=814)
PYs=250.2
placebo0.8(n=398)
PYs=120.7
RCTPeriod C(weeks 33-52)
HUMIRA0(n=250)
PYs=90.9
placebo0(n=240)
PYs=82.2
OverallRCT(52 weeks)
HUMIRA0.4(n=840)
PYs=540.5
OverallRCT + OLE(weeks 0-160)
HUMIRA0.7(n=1047)
PYs=2748.5

*Excluding non-melanoma skin cancer and lymphoma
OLE=open-label extension; PYs=patient years; RCT=randomized controlled trial

Risk of Malignancy1

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.

  • More cases of malignancies were observed among HUMIRA-treated patients compared to control patients in clinical trials
  • Consider the risks and benefits of HUMIRA treatment prior to initiating or continuing therapy in patients with a known malignancy
  • Examine all patients, especially patients with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment, for the presence of non-melanoma skin cancer (NMSC) prior to and during treatment with HUMIRA.
Active tuberculosis (TB) rates over 3 years (events per 100 PYs)5
RCTPeriod A(weeks 0-16)
RCTPeriod C(weeks 33-52)
OverallRCT(52 weeks)
OverallRCT + OLE(weeks 0-160)
HUMIRA0(n=814)
PYs=250.2
HUMIRA0(n=250)
PYs=90.9
HUMIRA0.2(n=840)
PYs=540.5
HUMIRA0.1(n=1047)
PYs=2748.5
placebo0(n=398)
PYs=120.7
placebo1.2(n=240)
PYs=82.2
Active tuberculosis (TB) rates over 3 years (events per 100 PYs)5
RCTPeriod A(weeks 0-16)
HUMIRA0(n=814)
PYs=250.2
placebo0(n=398)
PYs=120.7
RCTPeriod C(weeks 33-52)
HUMIRA0(n=250)
PYs=90.9
placebo1.2(n=240)
PYs=82.2
OverallRCT(52 weeks)
HUMIRA0.2(n=840)
PYs=540.5
OverallRCT + OLE(weeks 0-160)
HUMIRA0.1(n=1047)
PYs=2748.5

OLE=open-label extension; PYs=patient years; RCT=randomized controlled trial

Risk of Tuberculosis1

Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death, including:

  • 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
  • Monitor patients closely for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the development of TB in patients who tested negative for latent TB infection prior to initiating therapy
Lymphoma rates over 3 years (events per 100 PYs)5
RCTPeriod A(weeks 0-16)
RCTPeriod C(weeks 33-52)
OverallRCT(52 weeks)
OverallRCT + OLE(weeks 0-160)
HUMIRA0(n=814)
PYs=250.2
HUMIRA0(n=250)
PYs=90.9
HUMIRA0(n=840)
PYs=540.5
HUMIRA0(n=1047)
PYs=2748.5
placebo0(n=398)
PYs=120.7
placebo0(n=240)
PYs=82.2
Lymphoma rates over 3 years (events per 100 PYs)5
RCTPeriod A(weeks 0-16)
HUMIRA0(n=814)
PYs=250.2
placebo0(n=398)
PYs=120.7
RCTPeriod C(weeks 33-52)
HUMIRA0(n=250)
PYs=90.9
placebo0(n=240)
PYs=82.2
OverallRCT(52 weeks)
HUMIRA0(n=840)
PYs=540.5
OverallRCT + OLE(weeks 0-160)
HUMIRA0(n=1047)
PYs=2748.5

OLE=open-label extension; PYs=patient years; RCT=randomized controlled trial

Risk of Lymphoma1

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which HUMIRA is a member.
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have occurred in adolescent and young adults with inflammatory bowel disease treated with TNF blockers including HUMIRA.
The rate of lymphoma in controlled and uncontrolled clinical trials of HUMIRA in patients with RA, PsA, AS, CD, UC, and Ps was approximately 3-fold higher than expected in the general population.

ESPRIT: Seven-Year interim results from a safety registry of HUMIRA in moderate to severe chronic plaque psoriasis6,7

ESPRIT is an ongoing, 10-year-long postmarketing safety monitoring commitment to regulatory agencies for HUMIRA in the treatment of moderate to severe chronic plaque psoriasis

  • Data were collected from September 2008 through November 2015

6051 adult patients with moderate to severe chronic plaque psoriasis were enrolled and dosed with HUMIRA as recommended in the local product label

  • 83.4% of patients were registered in the US or Canada
  • 2557 of these patients had received their initial dose of HUMIRA ≤4 weeks prior to registry start
ESPRIT Registry: Enrollment of patients analyzed in all-Rx group given ≥1 dose of HUMIRA (N=6051) in the registry

ESPRIT patients may resemble those in your practice

Baseline demographics and characteristics6
All-treated population
N=6051
New-prescription population
N=2557
Sex n (%) n (%)
Male 3489 (57.7) 1380 (54.0)
Female 2562 (42.3) 1177 (46.0)
Racea n (%) n (%)
White 5268 (87.3) 2223 (87.1)
Black 178 (2.9) 65 (2.5)
Asian 259 (4.3) 106 (4.2)
Otherb 331 (5.5) 159 (6.2)
Disease Characteristics
Psoriatic arthritis c 867 (34.0)d
Family history of psoriasis c 1067 (41.9)e
Median (range) Median (range)
Age (years) 47.0 (18-94) 46.0 (18-91)
Weight (kg) 87.0 (41-252) n=5927 86.0 (41-218) n=2497
BMI (kg/m)2 29.4 (16-77) n=5909 29.4 (16-70) n=2492
Duration of psoriasisf (years) c 13.4 (0-68) n=2548
Baseline demographics and characteristics6
All-treated population
N=6051
New-prescription population
N=2557
Sex n (%) n (%)
Male 3489 (57.7) 1380 (54.0)
Female 2562 (42.3) 1177 (46.0)
Racea n (%) n (%)
White 5268 (87.3) 2223 (87.1)
Black 178 (2.9) 65 (2.5)
Asian 259 (4.3) 106 (4.2)
Otherb 331 (5.5) 159 (6.2)
Disease Characteristics
Psoriatic arthritis c 867 (34.0)d
Family history of psoriasis c 1067 (41.9)e
Median (range) Median (range)
Age (years) 47.0 (18-94) 46.0 (18-91)
Weight (kg) 87.0 (41-252) n=5927 86.0 (41-218) n=2497
BMI (kg/m)2 29.4 (16-77) n=5909 29.4 (16-70) n=2492
Duration of psoriasisf (years) c 13.4 (0-68) n=2548

aMissing data: All-Rx: n=15; New-Rx: n=4.
bIncludes American Indian/Alaska Native (all-treated, 0.3%; new-prescription, 0.3%), native Hawaiian or other Pacific Islander (all-treated, 0.7%; new-prescription, 1.0%), multiple races (all-treated, 0.4%; new-prescription, 0.5%), other (all-treated, 4.2%; new-prescription, 4.5%).
cNot analyzed because not all data were captured in the registry database.
dMissing data: New-Rx: n=7.
eMissing data: New-Rx: n=9.
fCalculated from start of registry.
All-Rx=all-treated patient population; BMI=body mass index; New-Rx=new prescription patient population

See loading and maintenance dosing schedules for  HUMIRA (adalimumab)
Dosing for Ps

Just a single loading dose
for new starts or retreatment1

See loading and maintenance
dosing schedule

Study Limitations8

  • Observational data are subject to outcome-reporting bias and bias related to rules attributing safety events to HUMIRA despite exposure to other therapies
  • At entry into the registry, some patients were HUMIRA-naïve
  • For patients with long-term HUMIRA treatment before registry enrollment, the total exposure-adjusted incidence rate of TEAEs may be underestimated
  • The AEs of interest may result from differences in demographics and clinical characteristics that are not accounted for in the analysis and remain unadjusted, influencing rates of AEs of interest

ESPRIT safety registry at 7 years: to date, no new safety signals have been observed in this ongoing registry6,7

Incidence rates of TEAEs of interest in patients with different durations of exposure to HUMIRA and in all patients taking HUMIRA6,7

Subgroups of patients with different durations of total exposure to HUMIRA, events (E/100 PYs)6,7
≤1 year of total
exposurea
>1 to 3 years of
total exposure
>3 to 5 years of
total exposure
>5 to 7 years of
total exposure
>7 years of
total exposureb
Overall All-Rx
N=1235
PY=588.7
N=1260
PY=2359.7
N=1285
PY=5132.4
N=1517
PY=9195.5
N=754
PY=6383.8
N=6051
PY=23660.1
TEAE leading to discontinuation of adalimumab 143 (24.3) 134 (5.7) 85 (1.7) 39 (0.4) 8 (0.1) 409 (1.7)
Any serious TEAE 125 (21.2) 197 (8.3) 232 (4.5) 290 (3.2) 191 (3.0) 1035 (4.4)
Any serious infection 40 (6.8) 52 (2.2) 53 (1.0) 58 (0.6) 44 (0.7) 247 (1.0)
Malignancyc 19 (3.2) 35 (1.5) 43 (0.8) 83 (0.9) 67 (1.0) 247 (1.0)
Non-melanoma
skin cancer
6 (1.0) 11 (0.5) 16 (0.3) 60 (0.7) 53 (0.8) 146 (0.6)
Lymphoma 0 0 3 (<0.1) 2 (<0.1) 0 5 (<0.1)
TEAE leading to
death
8 (1.4) 12 (0.5) 7 (0.1) 2 (<0.1) 2 (<0.1) 31 (0.1)
Active tuberculosis 2 (0.3) 2 (<0.1) 2 (<0.1) 0 0 6 (<0.1)
Opportunistic infection, otherd 0 1 (<0.1) 1 (<0.1) 1 (<0.1) 0 3 (<0.1)
Congestive heart
failure
2 (0.3) 0 5 (<0.1) 3 (<0.1) 1 (<0.1) 11 (<0.1)
Subgroups of patients with different durations of total exposure to HUMIRA, events (E/100 PYs)6,7
≤1 year of total
exposurea
>1 to 3 years of
total exposure
>3 to 5 years of
total exposure
N=1235
PY=588.7
N=1260
PY=2359.7
N=1285
PY=5132.4
TEAE leading to discontinuation of adalimumab 143 (24.3) 134 (5.7) 85 (1.7)
Any serious TEAE 125 (21.2) 197 (8.3) 232 (4.5)
Any serious infection 40 (6.8) 52 (2.2) 53 (1.0)
Malignancyc 19 (3.2) 35 (1.5) 43 (0.8)
Non-melanoma
skin cancer
6 (1.0) 11 (0.5) 16 (0.3)
Lymphoma 0 0 3 (<0.1)
TEAE leading to
death
8 (1.4) 12 (0.5) 7 (0.1)
Active tuberculosis 2 (0.3) 2 (<0.1) 2 (<0.1)
Opportunistic infection, otherd 0 1 (<0.1) 1 (<0.1)
Congestive heart
failure
2 (0.3) 0 5 (<0.1)
>5 to 7 years of
total exposure
>7 years of
total exposureb
Overall All-Rx
N=1517
PY=9195.5
N=754
PY=6383.8
N=6051
PY=23660.1
TEAE leading to discontinuation of adalimumab 39 (0.4) 8 (0.1) 409 (1.7)
Any serious TEAE 290 (3.2) 191 (3.0) 1035 (4.4)
Any serious infection 58 (0.6) 44 (0.7) 247 (1.0)
Malignancyc 83 (0.9) 67 (1.0) 247 (1.0)
Non-melanoma
skin cancer
60 (0.7) 53 (0.8) 146 (0.6)
Lymphoma 2 (<0.1) 0 5 (<0.1)
TEAE leading to
death
2 (<0.1) 2 (<0.1) 31 (0.1)
Active tuberculosis 0 0 6 (<0.1)
Opportunistic infection, otherd 1 (<0.1) 0 3 (<0.1)
Congestive heart
failure
3 (<0.1) 1 (<0.1) 11 (<0.1)

All treatment-emergent adverse events (All-TEAEs) were events occurring from the date of initial (first ever) HUMIRA dose through 70 days after the date of last HUMIRA dose in the registry, excluding AEs occurring during TIs.
aIntolerance to initial ADA therapy and subsequent discontinuations most likely occurred during the first year ADA and a majority of these events were summarized as TEAEs within the ≤1 yr subgroup.
bThe higher incidence of All-TEAEs in the subgroup with highest overall exposure to HUMIRA (>7 years), which includes a majority of rollover patients from feeder studies, is likely due to closer AE documentation in feeder studies compared with registry AE collection and retroactive collection of AEs for patients who initiated HUMIRA therapy outside of an AbbVie clinical trial before the registry.
cThere were no cases of hepatosplenic T-cell lymphoma (HSTCL) or leukemia.
dExcluding oral candidiasis and tuberculosis.
Some patients were exposed to adalimumab up to 6 years before entering the registry.

SAFETY IN THE FINGERNAIL PSORIASIS TRIAL ADDS TO HUMIRA’S WELL-STUDIED PROFILE2,9

No new safety signals identified10

Study subjects reported adverse events (Period A)9

Overview of number and percentage of subjects with treatment-ermergent adverse events

Adverse Events Humira EOW (N=109) Placebo (N=108)
N % N %
Any AE 62 56.9 60 55.6
Any SAE 8 7.3 5 4.6
Any AE leading to discontinuation of study drug 6 5.5 3 2.8
Any severe AE 5 4.6 6 5.6
Any AE with reasonable possibility of being related to study druga 29 26.6 22 20.4
Any SAE with reasonable possibility of being related to study druga 5 4.6 2 1.9
Any infection 32 29.4 30 27.8
Any serious infection 4 3.7 2 1.9
Any opportunistic infection (excluding oral candidiasis and TB) 0 0 0 0
Any TB (active or latent) 0 0 0 0
Any lymphoma 0 0 0 0
Any NMSC 0 0 0 0
Any malignancy (excluding lymphoma, HSTCL, leukemia, NMSC, and melanoma) 0 0 0 0
Any demyelinating disorder 0 0 0 0
Any AE leading to death 0 0 0 0
Deaths 0 0 0 0

Study subjects reported adverse events (Period A)9

Overview of number and percentage of subjects with treatment-ermergent adverse events

Adverse
Events
Humira EOW (N=109)
N %
Any AE 62 56.9
Any SAE 8 7.3
Any AE leading to discontinuation of study drug 6 5.5
Any severe AE 5 4.6
Any AE with reasonable possibility of being related to study druga 29 26.6
Any SAE with reasonable possibility of being related to study druga 5 4.6
Any infection 32 29.4
Any serious infection 4 3.7
Any opportunistic infection (excluding oral candidiasis and TB) 0 0
Any TB (active or latent) 0 0
Any lymphoma 0 0
Any NMSC 0 0
Any malignancy (excluding lymphoma, HSTCL, leukemia, NMSC, and melanoma) 0 0
Any demyelinating disorder 0 0
Any AE leading to death 0 0
Deaths 0 0
Placebo (N=108)
N %
Any AE 60 55.6
Any SAE 5 4.6
Any AE leading to discontinuation of study drug 3 2.8
Any severe AE 6 5.6
Any AE with reasonable possibility of being related to study druga 22 20.4
Any SAE with reasonable possibility of being related to study druga 2 1.9
Any infection 30 27.8
Any serious infection 2 1.9
Any opportunistic infection (excluding oral candidiasis and TB) 0 0
Any TB (active or latent) 0 0
Any lymphoma 0 0
Any NMSC 0 0
Any malignancy (excluding lymphoma, HSTCL, leukemia, NMSC, and melanoma) 0 0
Any demyelinating disorder 0 0
Any AE leading to death 0 0
Deaths 0 0

aAs assessed by the Investigator.
AE=adverse event; EOW=every other week; HSTCL=hepatosplenic T-celll lymphoma; NMSC=non-melanoma skin cancer; SAE=serious adverse event; TB=tuberculosis

HUMIRA (adalimumab) preferred/first-line formulary access
Preferred/First-line*
Formulary Access

In 2018, over 97% of National Commercial
and Medicare Part D patients
have access to HUMIRA® (adalimumab) as a
preferred, first-line targeted
immunomodulator (TIM) on
formulary11

*Preferred/Step 1/First-line means the product is listed on the preferred branded formulary and non-preferred products require a higher out-of-pocket cost or a step edit.

A targeted immunomodulator is a pharmacologic agent that modifies the immune response by targeting certain mediators or select cell surface markers on immune cells.

HUMIRA safety data in psoriatic arthritis (PsA)

Safety data from the ADEPT clinical trial in PsA12

Most common adverse events (AEs) through Week 2412,a
HUMIRA 40 mg EOW
(n=151)
Placebo
(n=162)
Upper respiratory
tract infection NOS
19 (12.6%) 24 (14.8%)
Nasopharyngitis 15 (9.9%) 15 (9.3%)
Injection-site
reaction NOS
10 (6.6%) 5 (3.1%)
Headache NOS 9 (6.0%) 14 (8.6%)
Hypertension NOS 8 (5.3%) 5 (3.1%)
Psoriatic arthropathy
aggravated
5 (3.3%) 11 (6.8%)
Arthralgia 3 (2.0%) 9 (5.6%)
Psoriasis aggravated 3 (2.0%) 10 (6.2%)
Diarrhea NOS 3 (2.0%) 9 (5.6%)
Most common adverse events (AEs) through Week 2412,a
HUMIRA 40 mg EOW
(n=151)
Placebo
(n=162)
Upper respiratory tract infection NOS 19 (12.6%) 24 (14.8%)
Nasopharyngitis 15 (9.9%) 15 (9.3%)
Injection-site reaction NOS 10 (6.6%) 5 (3.1%)
Headache NOS 9 (6.0%) 14 (8.6%)
Hypertension NOS 8 (5.3%) 5 (3.1%)
Psoriatic arthropathy aggravated 5 (3.3%) 11 (6.8%)
Arthralgia 3 (2.0%) 9 (5.6%)
Psoriasis aggravated 3 (2.0%) 10 (6.2%)
Diarrhea NOS 3 (2.0%) 9 (5.6%)

aAdverse events experienced by ≥5% of patients in either study arm
NOS=not otherwise specified

Most common adverse reactions1:

  • The most common adverse reactions in HUMIRA clinical trials (incidence >10%) were: infections (eg, upper respiratory, sinusitis), injection site reactions, headache, and rash.
HUMIRA (adalimumab) preferred/first-line formulary access
Preferred/First-line*
Formulary Access

In 2018, over 97% of National Commercial
and Medicare Part D patients
have access to HUMIRA® (adalimumab) as a
preferred, first-line targeted
immunomodulator (TIM) on
formulary11

*Preferred/Step 1/First-line means the product is listed on the preferred branded formulary and non-preferred products require a higher out-of-pocket cost or a step edit.

A targeted immunomodulator is a pharmacologic agent that modifies the immune response by targeting certain mediators or select cell surface markers on immune cells.

HUMIRA safety in moderate to severe hidradenitis suppurativa (HS)

The safety profile in adult HS patients with weekly dosing was consistent with the known safety profile of HUMIRA.1

PIONEER I: Overview of
treatment-emergent adverse
events per 100 patient-years
(PYs) in adults during Period A13
Control (N=152) (PYs=34.6)
Events (E/100PY)
Any AE 232 (670.5)
Any SAE 7 (20.2)
Any AE leading
to discontinuation
of study drug
3 (8.7)
Any severe AE 14 (40.5)
Any AE at least
possibly related
to study druga
66 (190.8)
Any SAE at least
possibly related
to study druga
4 (11.6)
Any infection 55 (159.0)
Any serious
infection
0 0
Any opportunistic
infection (excluding
oral candidiasis
and TB)
0 0
Any TB (active
or latent)
0 0
Any lymphoma 0 0
Any NMSC 0 0
Any malignancy
(excluding lymphoma,
HSTCL, leukemia,
NMSC, and
melanoma)
1 (2.9)
Any demyelinating
disorder
0 0
Any AE leading
to death
0 0
Deaths 0 0
HUMIRA EW (N=153) (PYs=34.9)
Events (E/100PY)
Any AE 190 (544.4)
Any SAE 3 (8.6)
Any AE leading
to discontinuation
of study drug
1 (2.9)
Any severe AE 14 (40.1)
Any AE at least
possibly related
to study druga
65 (186.2)
Any SAE at least
possibly related
to study druga
2 (5.7)
Any infection 43 (123.2)
Any serious infection 1 (2.9)
Any opportunistic
infection (excluding
oral candidiasis
and TB)
0 0
Any TB (active
or latent)
0 0
Any lymphoma 0 0
Any NMSC 0 0
Any malignancy
(excluding lymphoma,
HSTCL, leukemia,
NMSC, and
melanoma)
0 0
Any demyelinating
disorder
0 0
Any AE leading
to death
0 0
Deaths 0 0
PIONEER I: Overview of treatment-emergent adverse events per 100 patient-years (PYs) in adults during Period A13
Control (N=152) (PYs=34.6) HUMIRA EW (N=153) (PYs=34.9)
Events (E/100PY) Events (E/100PY)
Any AE 232 (670.5) 190 (544.4)
Any SAE 7 (20.2) 3 (8.6)
Any AE leading to discontinuation of study drug 3 (8.7) 1 (2.9)
Any severe AE 14 (40.5) 14 (40.1)
Any AE at least possibly related to study druga 66 (190.8) 65 (186.2)
Any SAE at least possibly related to study druga 4 (11.6) 2 (5.7)
Any infection 55 (159.0) 43 (123.2)
Any serious infection 0 0 1 (2.9)
Any opportunistic infection (excluding oral candidiasis and TB) 0 0 0 0
Any TB (active or latent) 0 0 0 0
Any lymphoma 0 0 0 0
Any NMSC 0 0 0 0
Any malignancy (excluding lymphoma, HSTCL, leukemia, NMSC, and melanoma) 1 (2.9) 0 0
Any demyelinating disorder 0 0 0 0
Any AE leading to death 0 0 0 0
Deaths 0 0 0 0

Control=placebo.
Only Period A safety shown, as control patients were re-randomized to HUMIRA in Period B.

PIONEER II: Overview of
treatment-emergent adverse
events per 100 patient-years
(PYs) in adults during Periods A and B13
Control (N=163) (PYs=73.4)
Events (E/100PY)
Any AE 477 (649.9)
Any SAE 22 (30.0)
Any AE leading
to discontinuation
of study drug
13 (17.7)
Any severe AE 31 (42.2)
Any AE at least
possibly related
to study druga
138 (188.0)
Any SAE at least
possibly related
to study druga
0 0
Any infection 126 (171.7)
Any serious
infection
4 (5.4)
Any opportunistic
infection (excluding
oral candidiasis
and TB)
0 0
Any TB (active
or latent)
0 0
Any lymphoma 0 0
Any NMSC 0 0
Any malignancy
(excluding lymphoma,
HSTCL, leukemia,
NMSC, and
melanoma)
0 0
Any demyelinating
disorder
0 0
Any AE leading
to death
0 0
Deaths 0 0
HUMIRA EW/EWb (N=163) (PYs=57.3)
Events (E/100PY)
Any AE 419 (731.2)
Any SAE 8 (14.0)
Any AE leading
to discontinuation
of study drug
5 (8.7)
Any severe AE 21 (36.6)
Any AE at least
possibly related
to study druga
149 (260.0)
Any SAE at least
possibly related
to study druga
5 (8.7)
Any infection 100 (174.5)
Any serious infection 2 (3.5)
Any opportunistic
infection (excluding
oral candidiasis
and TB)
0 0
Any TB (active
or latent)
0 0
Any lymphoma 0 0
Any NMSC 0 0
Any malignancy
(excluding lymphoma,
HSTCL, leukemia,
NMSC, and
melanoma)
0 0
Any demyelinating
disorder
0 0
Any AE leading
to death
0 0
Deaths 0 0
PIONEER II: Overview of treatment-emergent adverse events per 100 patient-years (PYs) in adults during Periods A and B13
Control (N=163) (PYs=73.4) HUMIRA EW/EW (N=163) (PYs=57.3)
Events (E/100PY) Events (E/100PY)
Any AE 477 (649.9) 419 (731.2)
Any SAE 22 (30.0) 8 (14.0)
Any AE leading to discontinuation of study drug 13 (17.7) 5 (8.7)
Any severe AE 31 (42.2) 21 (36.6)
Any AE at least possibly related to study druga 138 (188.0) 149 (260.0)
Any SAE at least possibly related to study druga 0 0 5 (8.7)
Any infection 126 (171.7) 100 (174.5)
Any serious infection 4 (5.4) 2 (3.5)
Any opportunistic infection (excluding oral candidiasis and TB) 0 0 0 0
Any TB (active or latent) 0 0 0 0
Any lymphoma 0 0 0 0
Any NMSC 0 0 0 0
Any malignancy (excluding lymphoma, HSTCL, leukemia, NMSC, and melanoma) 0 0 0 0
Any demyelinating disorder 0 0 0 0
Any AE leading to death 0 0 0 0
Deaths 0 0 0 0

Control=placebo ± antibiotic.
Treatment-emergent adverse event is defined as any adverse event with an onset date on or after the first dose of study drug in Period A and prior to the first dose of Period B or up to 70 days after the last dose of study drug if the patient discontinued prematurely from Period A.

Events with unknown severity were counted as severe. Events with an unknown relationship to study drug were counted as drug related.

Adverse reaction rates observed in clinical trials may not predict the rates observed in a broader patient population in clinical practice. This is because clinical trials are conducted under controlled conditions (eg, employing exclusion criteria such as co-morbid conditions and use of select concomitant medications, frequent monitoring of patients, etc).

HUMIRA has been studied in adults with HS in 3 controlled studies and 1 open-label extension study, and the safety profile for adult patients with HS treated with HUMIRA weekly dosing was consistent with the known safety profile of HUMIRA.

Anticipated Safety in Adolescents

Safety of the recommended HUMIRA dose in the adolescent HS population is anticipated to be consistent with the known safety profile of HUMIRA based on a cross-indication safety profile of HUMIRA in both adults and pediatric patients at similar or higher exposure determined through pharmacokinetic modeling.

aAs assessed by investigator.
bAccording to AE analysis conventions, AEs that occurred for patients who were on HUMIRA in Period A and withdrawn to control in Period B are counted up to 70 days from the last EW dose.
AEs=adverse events; E/100PY=events per 100 patient-years; EW=every week; HSTCL=hepatosplenic T-cell lymphoma; NMSC=non-melanoma skin cancer; PYs=patient-years.

See loading and maintenance dosing schedules for  HUMIRA (adalimumab)
Dosing in HS

Clinically meaningful results
with a weekly dosing regimen
in adults1

See loading and maintenance
dosing schedule

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 moderate to severe hidradenitis suppurativa in patients 12 years of age and older.
  • Uveitis: HUMIRA is indicated for the treatment of non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older.

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

US-HUM-181930

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References: 1. HUMIRA Injection [package insert]. North Chicago IL: AbbVie Inc. 2. Burmester GR, Panaccione R, Gordon KB, McIIraith M, Lacerda AP. Adalimumab: long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn’s disease. Ann Rheum Dis. 2013;72(4):517-524. 3. Leonardi C, Papp K, Strober B, et al. The long-term safety of adalimumab treatment in moderate to severe psoriasis: a comprehensive analysis of all adalimumab exposure in all clinical trials. Am J Clin Dermatol. 2011;12(5):321-337. 4. Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase III trial. J Am Acad Dermatol. 2008;58(1):106-115. 5. Data on File ABVRRTI61732. 6. Kerdel F, Menter A, Wu JJ, et al. Seven-year interim results from the ESPRIT 10-year postmarketing surveillance registry of adalimumab for moderate to severe psoriasis. Poster presented at: European Academy of Dermatology and Venereology Conference; September 28 to October 2, 2016. Vienna, Austria. 7. Wu JJ, Thaçi D, Abramovits W, et al. Treatment emergent cardiovascular events, serious infections, and malignancies from the ESPRIT 10-year postmarketing surveillance registry of adalimumab for moderate to severe psoriasis: a 7-year interim safety analysis. Poster presented at: European Academy of Dermatology and Venereology Conference; September 28 to October 2, 2016. Vienna, Austria. 8. Menter A, Thaçi D, Papp KA, et al. Five-year analysis from the ESPRIT 10-year postmarketing surveillance registry of adalimumab for moderate to severe psoriasis. J Am Acad Dermatol. 2015;73(3):410-419. E6. 9. Data on File ABVRRTI64116. 10. Elewski BE, Rich PA, Okun MM, et al. Adalimumab for nail psoriasis: efficacy and safety from the first 26 weeks of a phase-3, randomized, placebo-controlled trial. Poster presented at: 5th Congress of the Psoriasis International Network (Psoriasis 2016); July 7-9; Paris, France. Poster P131. 11. Data on File, AbbVie Inc. Source: Payer-reported lives. October 2017. 12. Mease PJ, Gladman DD, Ritchlin CT, et al; for Adalimumab Effectiveness in Psoriatic Arthritis Trial Study Group. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005;52(10):3279-3289. 13. Data on File ABVRRTI61791.

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