Active

Psoriatic Arthritis

Active

Ankylosing Spondylitis

Moderate to Severe

Juvenile Idiopathic Arthritis

Non-Infectious

Intermediate, Posterior and Panuveitis

Active

Psoriatic Arthritis

Moderate to Severe

Hidradenitis Suppurativa

Gastroenterology

Moderate to Severe

Crohn's Disease

Moderate to Severe

Pediatric Crohn's Disease

Moderate to Severe

Ulcerative Colitis

Ophthalmology

Non-Infectious

Intermediate, Posterior and Panuveitis

The largest safety database ever published in the anti-tnf category The largest safety database ever published in the anti-tnf category The largest safety database ever published in the anti-tnf category

20+

Years of clinical trial
experience

starting in
rheumatoid arthritis3

>100

Global clinical trials with
46,000+ patients
across 10
US‑approved immune‑mediated
indications4

#1

Prescribed biologic
in bio‑naïve
patients
with CD5,*

>1,000,000

Patients currently treated
worldwide across all indications6,†

Pyramid, the longest
prospective adult CD registry
assessing
the safety of HUMIRA
in routine clinical practice7

TNF=tumor necrosis factor

*A bio-naïve CD patient has not had a biologic drug claim for CD in the preceding 3 years.

As of June 2018.

Global Safety Data

Serious adverse events (AEs) of interest across 8 adult indications8,a

 
 
 
Serious infections
Tuberculosis
  • Active
  • Latent
Opportunistic infectionc
Demyelinating disorder
Lupus-like syndrome
Congestive heart failure
Ps new onset/worsening
Malignancyd
Lymphoma
NMSC
Melanoma
Sarcoidosis
Any AE leading to death
Rheumatoid
arthritis
(RA)
Ankylosing
spondylitis
(AS)
Psoriatic
arthritis
(PsA)
Plaque
psoriasis
(Ps)
Hidradenitis
suppurativa
(HS)
Crohn's
disease
(CD)
Ulcerative
colitis
(UC)
Uveitisb
(UV)
< SWIPE
37,106 PYs
N=15,512
2,120 PYs
N=2,026
998 PYs
N=837
5,479 PYs
N=3,732
1,198 PYs
N=733
4,359 PYs
N=3,896
3,407 PYs
N=1,739
1,151 PYs
N=464
3.9
1.8
2.8
1.8
2.8
6.9
3.5
4.1
0.2
0.1
0.2
0.2
0
0.2
<0.1
0.4
0.2
0.1
0.2
0.2
0
0.1
<0.1
0.2
<0.1
0
0
0
0
<0.1
0
0.3
<0.1
0
0
0
0
<0.1
<0.1
0.4
<0.1
<0.1
0
0
0
0.1
<0.1
0.3
<0.1
<0.1
0
0
0
<0.1
<0.1
<0.1
0.2
<0.1
0
0.1
0.2
0
<0.1
<0.1
<0.1
<0.1
0.1
<0.1
<0.1
<0.1
<0.1
0
0.7
0.2
0.2
0.5
0.5
0.4
0.6
0.7
0.1
<0.1
0.2
<0.1
<0.1
<0.1
<0.1
<0.1
0.2
0.2
0.1
0.1
<0.1
<0.1
<0.1
0.2
<0.1
<0.1
0
0.2
0
0
<0.1
0
<0.1
<0.1
0
0
0
0
0
<0.1
0.6
<0.1
0.3
0.2
0.5
0.1
0.1
0.6

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 practice.

Rates displayed as events per 100 PYs as of December 31, 2016

aData derived from global clinical trials of HUMIRA, including randomized controlled, open-label, and long-term extension studies (33 in RA, 5 in AS, 3 in PsA, 13 in Ps, 3 in HS, 11 in CD, 4 in UC, and 2 in UV).
bNon-infectious (NI) Intermediate, Posterior, and Panuveitis.
cExcludes oral candidiasis and tuberculosis.
dExcludes lymphoma, hepatosplenic T-cell lymphoma, leukemia, NMSC, and melanoma.

AE=adverse event; NMSC=non-melanoma skin cancer; PYs=patient‑years

Patients treated with HUMIRA may be at risk for other serious adverse reactions including:1

Hypersensitivity

Anaphylaxis and angioneurotic edema have been reported. 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; discontinuation of HUMIRA should be considered if any of these disorders develop.

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.

Pyramid Registry

PYRAMID: The longest postmarketing registry assessing HUMIRA safety in routine clinical practice7

No new
safety signals

requiring label changes were reported

Up to 6 years
of follow up

– safety profile confirmed
in longest prospective study
in routine clinical practice

>5000 patients

followed totalling 16,680 PYs
of HUMIRA exposure

Registry Treatment-Emergent Adverse Events (AEs)7

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.

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.

Summary of registry treatment-emergent AEs
Adverse Events HUMIRA
N=5025 (n) PYs=16680.4,
Events
(E/100 PY)
Any AE 47.6% (2392) 6124 (36.7)
Serious AE 36.9% (1853) 4129 (24.8)
Serious AE at least possibly related to HUMIRAa 8.4% (422) 627 (3.8)
AE leading to HUMIRA discontinuation 11.9% (596) 766 (4.6)
AE leading to death 0.9% (43) 52 (0.3)
Any infection 17.0% (855) 1333 (8.0)
Serious infection 11.1% (556) 792 (4.7)
Opportunistic infection
(excluding oral candidiasis and TB)
0.4% (19) 21 (0.1)
Active TB 0.2% (10) 10 (<0.1)
Latent TB 0.1% (7) 7 (<0.1)
Any malignancy 2.3% (116) 134 (0.8)
NMSC 0.7% (36) 49 (0.3)
Lymphoma 0.2% (10) 10 (0.06)
Melanoma 0.2% (11) 12 (<0.1)
Leukemia <0.1% (3) 3 (<0.1)
Malignancy other than lymphoma, leukemia,
NMSC, or melanoma
1.2% (60) 60 (0.4)
Injection site reaction 0.2% (12) 22 (0.1)
Demyelinating disorder 0.2% (8) 8 (<0.1)

NMSC=non-melanoma skin cancer; PYs=patient-years; TB=tuberculosis

aAs assessed by investigator.

Data Limitations:

  • Observational data are subject to outcome‑reporting bias and the bias related to rules attributing safety events to HUMIRA despite exposure to other therapies and results should be cautiously interpreted.

Safety profile consistent with known safety profile from global clinical trials and across approved indications7

  • Rate of infections consistent with previously reported infection rates in clinical trials of HUMIRA and other anti‑TNF agents
  • Malignancy and lymphoma rates did not exceed estimated rates based upon the general population
  • Malignancy rates in HUMIRA-treated patients consistent with previously reported malignancy rates in clinical trials of HUMIRA for multiple indications and similar rates were observed for anti-TNF agents
  • No increase in the relative risk of non-melanoma skin cancer or other malignancies in patients receiving HUMIRA monotherapy. In contrast, patients treated with HUMIRA plus immunomodulator had significantly increased risks of malignancies compared with the general population

Study Design Intro: PYRAMID was a multi-center, uncontrolled, observational registry of 5025 (16680.4 PYs) adult patients with moderately to severely active CD treated with HUMIRA in a routine clinical practice setting. Patients were newly prescribed or currently receiving HUMIRA according to local product labels and were followed for up to 6 years. The mean HUMIRA exposure was over 3 years. The primary goal was to rule out a doubling of the risk of lymphoma in patients treated with HUMIRA from an estimated background lymphoma rate in the general population adjusted for thiopurine use.7

PYs=patient-years; TNF=tumor necrosis factor

Safety Profile in CD

Safety evaluated in >3600 adult patients with CD2

Serious Adverse Event (AE) Rate in Moderate to Severe CD for:2

6.7 events per 100 patient-years (PYs) of HUMIRA exposure

= 1 patient-year (PY)

= 1 event of serious infection

4138.0 PYs; N=3606

Data as of November 6, 2010

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

PI=prescribing information

Understanding PYs

One event per 100 PYs means that 1 event occurred in a population of 100 clinical trial patients on therapy for 1 year.

Safety Considerations1

  • Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other 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.

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 with chronic or recurrent infection. Monitor all patients for the development of signs and symptoms of infection during and after treatment with HUMIRA, including development of TB during treatment, even if initial latent TB test is negative.

PI=prescribing information

<0.1 event per 100 patient-years (PYs) of HUMIRA exposure

= 1 patient-year (PY)

= 1 event of active TB

4138.0 PYs; N=3606

Data as of November 6, 2010

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

PI=prescribing information

Understanding PYs

One event per 100 PYs means that 1 event occurred in a population of 100 clinical trial patients on therapy for 1 year.

Safety Considerations1

  • Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death, including tuberculosis (TB), bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections due to other 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.

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.
  • Carefully consider the risks and benefits of treatment with HUMIRA prior to initiating therapy in patients with chronic or recurrent infection. Monitor all patients for the development of signs and symptoms of infection during and after treatment with HUMIRA, including development of TB during treatment, even if initial latent TB test is negative.

PI=prescribing information

0.5 event per 100 patient-years (PYs) of HUMIRA exposure

= 1 patient-year (PY)

= 1 event of malignancya

4138.0 PYs; N=3606

Data as of November 6, 2010

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

PI=prescribing information; RA=rheumatoid arthritis; TNF=tumor necrosis factor

aMalignancies excluding lymphoma and non-melanoma skin cancer and malignancies not considered serious by investigators.

Understanding PYs

One event per 100 PYs means that 1 event occurred in a population of 100 clinical trial patients on therapy for 1 year.

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.

Safety Considerations1

  • In the controlled portions of clinical trials of all the TNF blockers (including HUMIRA) in adults, more cases of lymphoma or malignancies, respectively, have been observed when treated with TNF blockers compared to control.
  • 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 several fold) than the general population for the development of lymphoma, even in the absence of TNF blockers.

PI=prescribing information; RA=rheumatoid arthritis; TNF=tumor necrosis factor

aMalignancies excluding lymphoma and non-melanoma skin cancer and malignancies not considered serious by investigators.

<0.1 event per 100 patient-years (PYs) of HUMIRA exposure

= 1 patient-year (PY)

= 1 event of lymphoma

4138.0 PYs; N=3606

Data as of November 6, 2010

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

PI=prescribing information; RA=rheumatoid arthritis; TNF=tumor necrosis factor

Understanding PYs

One event per 100 PYs means that 1 event occurred in a population of 100 clinical trial patients on therapy for 1 year.

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.

Safety Considerations1

  • In the controlled portions of clinical trials of all the TNF blockers (including HUMIRA) in adults, more cases of lymphoma or malignancies, respectively, have been observed when treated with TNF blockers compared to control.
  • 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 several fold) than the general population for the development of lymphoma, even in the absence of TNF blockers.

PI=prescribing information; RA=rheumatoid arthritis; TNF=tumor necrosis factor

Long-Term Safety

Understanding HUMIRA safety through 5 years of data

Rates (events per 100 PYs) of treatment‑emergent adverse events (AEs)a of interest in 9 controlled and uncontrolled moderate to severe adult CD studies for:9,10,b

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.

The use of HUMIRA in CD beyond 1 year has not been evaluated in controlled clinical studies.1

  • OLE populations generally consist of treatment responders, as patients who are unable to tolerate the drug or who do not respond to the drug drop out.

CHARM Study Design Intro: 56-week, randomized controlled study in 854 adults. All patients received open-label HUMIRA 80 mg at Week 0 and 40 mg at Week 2. The 499 patients with CR-70 response at Week 4 were randomized to one of three treatment arms (± concomitant conventional therapy) and were included in the analysis.1,11

EOW=every other week; OLE=open-label extension; PYs=patient-years; RCT=randomized controlled trial

aTreatment-emergent AE is defined as any adverse event with an onset date on or after the first HUMIRA dose and up to 70 days after the last dose of HUMIRA.
bExcluding Japanese studies.
cData as of December 31, 2014.
dNine pooled controlled and uncontrolled studies.
eControl=placebo ± concomitant therapy.

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.

The use of HUMIRA in CD beyond 1 year has not been evaluated in controlled clinical studies.1

  • OLE populations generally consist of treatment responders, as patients who are unable to tolerate the drug or who do not respond to the drug drop out.

CHARM Study Design Intro: 56-week, randomized controlled study in 854 adults. All patients received open-label HUMIRA 80 mg at Week 0 and 40 mg at Week 2. The 499 patients with CR-70 response at Week 4 were randomized to one of three treatment arms (± concomitant conventional therapy) and were included in the analysis.1,11

EOW=every other week; OLE=open-label extension; PYs=patient-years; RCT=randomized controlled trial

aTreatment-emergent AE is defined as any adverse event with an onset date on or after the first HUMIRA dose and up to 70 days after the last dose of HUMIRA.
bExcluding Japanese studies.
cData as of December 31, 2014.
dNine pooled controlled and uncontrolled studies.
eControl=placebo ± concomitant therapy.

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.

  • Consider the risks and benefits of HUMIRA treatment prior to initiating or continuing therapy in patients with a known malignancy.
  • More cases of malignancies were observed among HUMIRA-treated patients compared to control patients in clinical trials.

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.

The use of HUMIRA in CD beyond 1 year has not been evaluated in controlled clinical studies.1

  • OLE populations generally consist of treatment responders, as patients who are unable to tolerate the drug or who do not respond to the drug drop out.

CHARM Study Design Intro: 56-week, randomized controlled study in 854 adults. All patients received open-label HUMIRA 80 mg at Week 0 and 40 mg at Week 2. The 499 patients with CR-70 response at Week 4 were randomized to one of three treatment arms (± concomitant conventional therapy) and were included in the analysis.1,11

EOW=every other week; OLE=open-label extension; PYs=patient-years; RCT=randomized controlled trial

aTreatment-emergent AE is defined as any adverse event with an onset date on or after the first HUMIRA dose and up to 70 days after the last dose of HUMIRA.
bExcluding Japanese studies.
cIncludes any malignancy AE.
dData as of December 31, 2014.
eNine pooled controlled and uncontrolled studies.
fExcluding non-melanoma skin cancer and lymphoma.
gControl=placebo ± concomitant therapy.

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 was approximately 3-fold higher than expected in the general population.

Patients with chronic inflammatory diseases, particularly those with highly active disease, are at a higher risk for the development of lymphoma.

The use of HUMIRA in CD beyond 1 year has not been evaluated in controlled clinical studies.1

  • OLE populations generally consist of treatment responders, as patients who are unable to tolerate the drug or who do not respond to the drug drop out.

CHARM Study Design Intro: 56-week, randomized controlled study in 854 adults. All patients received open-label HUMIRA 80 mg at Week 0 and 40 mg at Week 2. The 499 patients with CR-70 response at Week 4 were randomized to one of three treatment arms (± concomitant conventional therapy) and were included in the analysis.1,11

EOW=every other week; OLE=open-label extension; PYs=patient-years; RCT=randomized controlled trial

aTreatment-emergent AE is defined as any adverse event with an onset date on or after the first HUMIRA dose and up to 70 days after the last dose of HUMIRA.
bExcluding Japanese studies.
cData as of December 31, 2014.
dNine pooled controlled and uncontrolled studies.
eControl=placebo ± concomitant therapy.

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INDICATION1

Adult Crohn’s Disease (CD): 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. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

IMPORTANT SAFETY INFORMATION1

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 (RA): 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 (JIA): 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 (PsA): 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 (AS): HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.

Adult Crohn's Disease (CD): 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 (UC): 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 (Ps): 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 (HS): 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.

Please see full Prescribing Information.

References: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc. 2. Burmester GR, Panaccione R, Gordon KB, et al. 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. Burmester GR, Mease P, Dijkmans BAC, et al. Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases. Ann Rheum Dis. 2009;68:1863–1869. 4. Data on File ABVRRTI62537. 5. Data on File, AbbVie Inc. Symphony Health, PatientSource®, September 2017–August 2018. 6. Data on File, AbbVie Inc. IMS NPA and IMS NSP cumulative data as of June 2018. 7. D’Haens GD, Reinisch W, Pannaccione R, et al. Lymphoma risk and overall safety profile of adalimumab in patients with Crohn’s disease with up to 6 years of follow-up in the Pyramid Registry. Am J Gastroenterol. 2018;113:872–882. 8. Burmester GR, Panaccione R, Gordon KB, et al. Long-term safety of adalimumab (HUMIRA) in adult patients from global clinical trials across multiple indications: an updated analysis in 29,987 patients representing 56,951 patient-years. Poster presented at: American College of Rheumatology Annual Meeting; November 3-8, 2017; San Diego, CA. Poster 2481. 9. Data on File ABVRRTI61915. 10. Data on File ABVRRTI61912. 11. Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132(1):52–65.

Indications1

Adult Crohn’s Disease (CD): 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. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

Important Safety Information1

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.

Important Safety Information
and Indications1

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

Indications1

Adult Crohn’s Disease (CD): 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. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

Important Safety Information1

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.

Important Safety Information
and Indications1

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

INDICATION1

Adult Crohn's Disease (CD): 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. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.

IMPORTANT SAFETY INFORMATION1

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 (RA): 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 (JIA): 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 (PsA): 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 (AS): HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.

Adult Crohn's Disease (CD): 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 (UC): 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 (Ps): 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 (HS): 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.

Please see full Prescribing Information.

Reference: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc.