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

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.

Psoriatic Arthritis Clinical Data

HUMIRA showed improved signs and symptoms of psoriatic arthritis, along with physical function in clinical trials

Help patients understand the connection between psoriasis and psoriatic arthritis

An estimated 7.4 million adult patients in the US have psoriasis.2 Up to 30% of psoriasis patients may develop psoriatic arthritis3,4

Approximately 1 out of 3 patients with psoriasis can develop PsA3,4

In one study, 40% of patients are misclassified and are being treated only for skin symptoms.4

The severity of skin symptoms and arthritis generally do not correlate5

Learn the correlation between Ps and PsA skin symptoms

BSA=Body Surface Area

70% to 80% of patients with PsA have psoriasis before joint disease manifests6

  • On average, joint disease appears about 10 years after the first sign of skin disease6,7

PsA may cause irreversible joint damage over time

PsA has been found to be erosive and deforming in 40% to 60% of patients and may become progressive within the first year of diagnosis5†

Normal distal interphalangeal (DIP) in PsA patients Normal distal interphalangeal (DIP) in PsA patients Normal distal
interphalangeal (DIP)
joint
Picture of mild soft-tissue swelling, narrowing of the joint space, and erosions in PsA patients Picture of mild soft-tissue swelling, narrowing of the joint space, and erosions in PsA patients Mild soft-tissue swelling,
narrowing of the joint
space, and erosions
Greater loss of bone and early resorption picture in the joints of psoriatic arthritis patients Greater loss of bone and early resorption picture in the joints of psoriatic arthritis patients Greater loss of bone and
early resorption
Picture of joint with more-advanced changes, including further loss of bone, with tapering appearance in PsA patients Picture of joint with more-advanced changes, including further loss of bone, with tapering appearance in PsA patients More-advanced changes,
including further loss of
bone, with tapering and a
“pencil-in-cup”
appearance
  • Approximately 50% of patients with PsA may develop structural damage5
  • AAD guidelines state that the course of PsA is variable and unpredictable, ranging from mild and nondestructive to a severe, debilitating, erosive arthropathy5

In patients with active psoriatic arthritis (PsA), HUMIRA goes beyond improving symptoms of PsA to inhibit joint damage progression and improve physical function1,5

ADEPT evaluated the efficacy and safety of HUMIRA in patients with active PsA over 48 weeks1,8,9

ADEPT was a 24-week, randomized, double-blind, placebo-controlled study of 313 adults with moderately to severely active PsA. Upon study completion, an open-label extension study was undertaken.

†Not all patients' disease is this severe. Joint damage occurs over time.

The American Academy of Dermatology (AAD) guidelines state5:

  • Because PsA can be a very severe disease with significant functional impairment, early diagnosis is critical
  • Left untreated, some patients with PsA may develop persistent inflammation with progressive joint damage, leading to physical limitations

—Gottlieb et al. J Am Acad Dermatol. 2008

ADEPT Study Design Details

ADEPT: A randomized, controlled trial of patients with moderate to severe active psoriatic arthritis (PsA)8,9

A 24-week, double-blind study followed by an open-label extension (OLE) phase with HUMIRA

ADEPT study design details of patients with moderate to severely active PsA

a315 patients were initially randomized; however, 2 patients did not receive study drug
EOW=every other week

A 24-week, randomized, double-blind placebo controlled trial of HUMIRA in adult patients with moderately to severely active PsA (≥3 swollen joints and ≥3 tender or painful joints) who had an inadequate response to NSAIDs.

Patients must have active psoriatic skin lesions or a documented history of psoriasis.

Primary endpoints were ACR 20 response at Week 12 and change in modified total Sharp score (mTSS) for HUMIRA-treated patients at Week 48 vs placebo at Week 24.

After Week 12, patients who failed to have at least a 20% decrease in both swollen and tender joint counts on 2 consecutive visits could receive rescue therapy with corticosteroids or DMARDs.

Safety in PsA

Safety data from clinical trial in PsA

HUMIRA treatment resulted in significant inhibition of structural joint damage progression1

HUMIRA-treated patients had significantly less joint damage progression vs placebo1

HUMIRA treatment mean change from baseline for patients with PsA

aFor HUMIRA-treated patients who did not have an mTSS at Week 48, mTSS was imputed by linear extrapolation using the baseline and Week 24 scores.9
bP<0.001 for the difference between HUMIRA at Week 48 vs placebo at Week 24 (primary analysis)
mTSS=modified total Sharp score

‡mTSS measures erosions and joint space narrowing, as well as radiographic changes specific to PsA patients, including DIP joints, with a maximum score of 570.9,10

Radiographs were taken at baseline, Week 24, and Week 48.

Approximately 9 out of 10 HUMIRA-treated patients had no radiographic progression§ at 24 and 48 weeks9

Patients with no radiographic progression§ at Weeks 24 and 489

Week 24

Patients with no radiographic progression at Weeks 24

HUMIRA

Radiographic progression at 24 weeks in placebo treated patients

Placebo

  • HUMIRA (n=144)
  • Placebo (n=152)

Week 48||

Patients with no radiographic progression at Weeks 48

HUMIRA

  • HUMIRA (n=133)

§No radiographic progression defined as change in mTSS of ≤0.5 from baseline
||HUMIRA patients with no radiographic progression in the OLE were treated with HUMIRA EOW in the RCT.
SD=standard deviation

At Week 24, 91% of HUMIRA-treated patients (n=144) had no radiographic progression§ vs 71% of placebo-treated patients (n=152).9
Nearly 9 out of 10 (87%) HUMIRA-treated patients (n=133) had no radiographic progression§,|| after 48 weeks.9

OLE limitations

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

HUMIRA demonstrated significantly greater improvement in signs and symptoms of PsA vs placebo at 12 and 24 weeks1,8

ADEPT ACR response rates at Weeks 12 and 241,8

Patients (%)

  • 100
  • 80
  • 60
  • 40
  • 20
  • 0
58a 36a 20a 14 4 1
  • ACR 20
  • ACR 50
  • ACR 70

Co-primary endpoint

Weeks 12

Patients (%)

  • 100
  • 80
  • 60
  • 40
  • 20
  • 0
57a 39a 23a 15 6 1
  • ACR 20
  • ACR 50
  • ACR 70

Weeks 24

HUMIRA vs placebo-treated patients

  • HUMIRA 40 mg EOW (n=151)
  • Placebo EOW (n=162)

aP<0.001 for HUMIRA vs placebo-treated patients

ACR=American College of Rheumatology; EOW=every other week; NRI=National Research Institute

The ACR response analysis is of the intention-to-treat (ITT) population, using NRI methodology. Patients who withdrew, had missing data, or received rescue therapy were counted as nonresponders.8

Among patients with PsA who received HUMIRA, the clinical responses were apparent in some patients at the time of first visit (2 weeks) and were maintained up to 88 weeks in the ongoing open-label study.1

HUMIRA significantly improved physical function1

HAQ-DI (Health Assessment Questionnaire Disability Index) measured the patient's ability to perform the following: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity over the past week. The 8 category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled). Improvement is measured in this trial by a mean percent decrease from baseline§ of HAQ-DI score.

HUMIRA treated patients showed greater improvement from baseline in the total HAQ-DI score vs placebo at 24 weeks1

HAQ-DI is a health assessment questionnaire that measures the patient’s ability to perform the following1,11§:

Patent's ability to dress/groom is one of many items measured by the HAQ-DI health assessment questionnaire
Dress/groom
Patient's ability to arise is one of many items measured by the HAQ-DI health assessment questionnaire
Arise
Patient's ability to eat is one of many items measured in the HAQ-DI health assessment questionnaire
Eat
Patient's ability to walk is an item measured in the HAQ-DI health assessment questionnaire
Walk
Ability to reach is one of several items measured in the HAQ-DI health assessment questionnaire
Reach
Patient's ability to grip is one of several items measured in the HAQ-DI health assessment questionnaire
Grip
Patient's ability to maintain hygiene is one of several items measured in the HAQ-DI health assessment questionnaire
Maintain
hygiene
Patient's ability to maintain daily activity over the past week is one of several items measured in the HAQ-DI health assessment questionnaire
Maintain daily
activity over the
past week
At 24 Weeks
HUMIRA (n=151)Placebo (n=162)
0.4
0.9
No disability
Baseline
Completely Disabled

§Improvement is measured in this trial by a mean percent decrease from baseline of HAQ-DI scores. The 8 category scores are averaged into an overall HAQ-DI score on a scale from 0 (no disability) to 3 (completely disabled).

Dosing for PsA

Just a single loading dose
for new starts or retreatment1

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. Rachakonda TD, Schupp CW, Armstrong AW. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;70(3):512-516. 3. Gladman DD. Epidemiology: psoriatic arthritis. In: Gordon KB, Ruderman EM, eds. Psoriasis and Psoriatic Arthritis: An Integrated Approach. Berlin Heidelberg: Springer-Verlag; 2005:57-65. 4. Mease PJ, Gladman DD, Papp KA, et al. Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics. J Am Acad Dermatol. 2013;69(5):729-735. 5. Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis. Section 2: psoriatic arthritis: overview and guidelines of care for treatment with an emphasis on the biologics. J Am Acad Dermatol. 2008;58(5):851-864. 6. Gladman DD, Antoni C, Mease P, Clegg DO, Nash P. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005;64(suppl 2):ii14-ii17. 7. Bruce IN, Ho PYP. Clinical features of psoriatic arthritis. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. Rheumatology. 6th ed. Philadelphia, PA: Mosby Elsevier; 2015:989-997. 8. Mease PJ, Gladman DD, Ritchlin CT, et al. 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. 9. Gladman DD, Mease PJ, Ritchlin CT, et al. Adalimumab for long-term treatment of psoriatic arthritis: forty-eight week data from the adalimumab effectiveness in psoriatic arthritis trial. Arthritis Rheum. 2007;56(2):476-488. 10. van der Heijde D, Sharp J, Wassenberg S, Gladman DD. Psoriatic arthritis imaging: a review of scoring methods. Ann Rheum Dis. 2005;64(suppl2):ii61-ii64. 11. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum. 1980;23(2):137-145.

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