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

Hidradenitis Suppurativa: HUMIRA is indicated for the treatment of adult patients with moderate to severe hidradenitis suppurativa.

Two pivotal studies evaluated HUMIRA for Hidradenitis Suppurativa Clinical Response (HiSCR) at Week 121,4

PIONEER I and II represent the first and only completed Phase III trials in hidradenitis suppurativa (HS)

PIONEER I (N=307) and PIONEER II (N=326) were 36-week studies comparing HUMIRA 40 mg every week with control in patients with moderate to severe HS defined by Hurley Stages II and III who were intolerant, had a contraindication, or inadequate response to systemic antibiotic therapy. Primary endpoint was the proportion of patients achieving HiSCR at 12 weeks. HiSCR was defined as at least a 50% reduction in the total abscess and inflammatory nodule count with no increase in abscess count and no increase in draining fistula count relative to baseline. During Period B (Week 12 to Week 35), patients who received HUMIRA were re-randomized to HUMIRA 40 mg every week, HUMIRA 40 mg every other week, or control. Control patients were assigned to either HUMIRA 40 mg every week (PIONEER I) or control (PIONEER II).1,2

Study Design Details and Baseline Characteristics

Two pivotal studies evaluated HUMIRA for Hidradenitis Suppurativa Clinical Response (HiSCR) at week 12 (primary endpoint)1,2

The pivotal trials studied HUMIRA with and without concomitant antibiotics1,2

PIONEER I & II clinical trial evaluated HUMIRA for clinical response at Week 12 (primary endpoint).
  • In PIONEER I, control group given placebo (n=154) during Period A was then given HUMIRA 40 mg EW for Period B. In PIONEER II, control group given placebo +/- antibiotic (n=163) during Period A continued the same regimen in Period B.2

EOW=every other week; EW=every week; OLE=open-label extension.

See the PIONEER trial clinical data for patients with significant disease severity.

AN=abscess and inflammatory nodule; EW=every week; hs-CRP=high-sensitivity C-reactive protein; SD=standard deviation.
aControl=placebo.
bControl=placebo ± antibiotic.
cNumber of patients unless otherwise indicated EW.
dRace was self-reported.
eIncludes for PIONEER I: Asian (n=4; 1.3%), American Indian/Alaska Native (n=2; 0.7%), multiracial (n=1; 0.3%), other (n=4; 1.3%), For PIONEER II: Asian (n=10; 3.1%), American Indian/Alaska Native (n=1; 0.3%), Native Hawaiian or other Pacific Islander (n=1; 0.3%), multiracial (n=3; 0.9%) other (n=9; 2.8%).
fBased on actual Hurley Stage assessments, not on the Hurley stratification factor. A patient’s overall Hurley Stage was determined by the worse Hurley Stage across all affected anatomic regions.
gData missing for PIONEER II, HUMIRA EW (n=1).

Baseline characteristics identified as different between PIONEER I and PIONEER II2

  • Baseline weight
  • Baseline lesion count

Differences in baseline characteristics may in part account for the observed difference in magnitude between the 2 studies.

Assessing HiSCR: A measure of clinical response in this debilitating disease

HiSCR requires counting abscesses and inflammatory nodules (ANs) and draining fistulas before and after an intervention, making it applicable in both research and clinical practice.3

HiSCR requires1,2:

  • At least a 50% reduction in the total AN* count relative to baseline
  • No increase in abscess count AND
  • No increase in draining fistula count
Assessment of clinical response in a theoretical PIONEER trial patient.

*AN=abscess and inflammatory nodule.

HUMIRA offered clinically meaningful improvement for patients with moderate to severe HS

See how HUMIRA helped a greater proportion of patients with moderate to severe HS achieve HiSCR at week 12 vs. placebo.

aFor PIONEER I, control=placebo; for PIONEER II, control=placebo ± antibiotic.
bP=0.003 vs control.
cP<0.001 vs control.

PIONEER I: Significantly greater proportion of HUMIRA patients achieved HiSCR vs control patients
PIONEER II: >2x as many patients treated with HUMIRA achieved HiSCR vs control patients

Flare in patients withdrawn from HUMIRA1
22% of patients who were withdrawn from HUMIRA experienced flare of HS during Period B following the primary efficacy time point in both studies. Flare was defined as ≥25% increase from baseline in abscesses and inflammatory nodule counts and with a minimum of 2 additional lesions.

Patients who were withdrawn from therapy received HUMIRA in Period A and were rerandomized to control in Period B (PIONEER I: n=49, PIONEER II: n=51).

What clinically meaningful improvement may look like for your patients with moderate to severe HS

Before and after illustration of moderate to severe HS in the armpit.

Baseline prior to treatment

Before and after illustration of moderate to severe HS in the armpit.

HiSCR achieved at Week 12

Move slider to see baseline and Week 12

Computerized illustrations of 50% reduction in abscesses and nodules at 3 months. Individual results may vary.

Before and after illustration of moderate to severe HS in the breast of women.

Baseline prior to treatment

Before and after illustration of moderate to severe HS in the breast of women.

HiSCR achieved at Week 12

Move slider to see baseline and Week 12

Computerized illustrations of 50% reduction in abscesses and nodules at 3 months. Individual results may vary.

Before and after illustration of moderate to severe HS near the groin.

Baseline prior to treatment

Before and after illustration of moderate to severe HS near the groin.

HiSCR achieved at Week 12

Move slider to see baseline and Week 12

Computerized illustrations of 50% reduction in abscesses and nodules at 3 months. Individual results may vary.

Move slider to see baseline and Week 12

Computerized illustrations of 50% reduction in abscesses and nodules at 3 months. Individual results may vary.

IMPORTANT SAFETY INFORMATION for HUMIRA (adalimumab)1

SERIOUS INFECTIONS

Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Discontinue HUMIRA if a patient develops a serious infection or sepsis.

Reported infections include:

  • Active tuberculosis (TB), including reactivation of latent TB. Patients with TB have frequently presented with disseminated or extrapulmonary disease. Test patients for latent TB before HUMIRA use and during therapy. Initiate treatment for latent TB prior to HUMIRA use.
  • Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized, disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Consider empiric anti-fungal therapy in patients at risk for invasive fungal infections who develop severe systemic illness.
  • Bacterial, viral, and other infections due to opportunistic pathogens, including Legionella and Listeria.

Carefully consider the risks and benefits of treatment with HUMIRA prior to initiating therapy in patients: 1. with chronic or recurrent infection, 2. who have been exposed to TB, 3. with a history of opportunistic infection, 4. who resided in or traveled in regions where mycoses are endemic, 5. with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

  • Do not start HUMIRA during an active infection, including localized infections.
  • Patients older than 65 years, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants may be at greater risk of infection.
  • If an infection develops, monitor carefully and initiate appropriate therapy.
  • Drug interactions with biologic products: A higher rate of serious infections has been observed in RA patients treated with rituximab who received subsequent treatment with a TNF blocker. An increased risk of serious infections has been seen with the combination of TNF blockers with anakinra or abatacept, with no demonstrated added benefit in patients with RA. Concomitant administration of HUMIRA with other biologic DMARDs (e.g., anakinra or abatacept) or other TNF blockers is not recommended based on the possible increased risk for infections and other potential pharmacological interactions.
MALIGNANCY

Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including HUMIRA. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including HUMIRA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.

  • Consider the risks and benefits of HUMIRA treatment prior to initiating or continuing therapy in a patient with known malignancy.
  • In clinical trials, more cases of malignancies were observed among HUMIRA-treated patients compared to control patients.
  • Non-melanoma skin cancer (NMSC) was reported during clinical trials for HUMIRA-treated patients. Examine all patients, particularly those with a history of prolonged immunosuppressant or PUVA therapy, for the presence of NMSC prior to and during treatment with HUMIRA.
  • In HUMIRA clinical trials, there was an approximate 3-fold higher rate of lymphoma than expected in the general U.S. population. Patients with chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at higher risk of lymphoma than the general population, even in the absence of TNF blockers.
  • Postmarketing cases of acute and chronic leukemia were reported with TNF blocker use. Approximately half of the postmarketing cases of malignancies in children, adolescents, and young adults receiving TNF blockers were lymphomas; other cases included rare malignancies associated with immunosuppression and malignancies not usually observed in children and adolescents.
HYPERSENSITIVITY
  • Anaphylaxis and angioneurotic edema have been reported following HUMIRA administration. If a serious allergic reaction occurs, stop HUMIRA and institute appropriate therapy.
HEPATITIS B VIRUS REACTIVATION
  • Use of TNF blockers, including HUMIRA, may increase the risk of reactivation of hepatitis B virus (HBV) in patients who are chronic carriers. Some cases have been fatal.
  • Evaluate patients at risk for HBV infection for prior evidence of HBV infection before initiating TNF blocker therapy.
  • Exercise caution in patients who are carriers of HBV and monitor them during and after HUMIRA treatment.
  • Discontinue HUMIRA and begin antiviral therapy in patients who develop HBV reactivation. Exercise caution when resuming HUMIRA after HBV treatment.
NEUROLOGIC REACTIONS
  • TNF blockers, including HUMIRA, have been associated with rare cases of new onset or exacerbation of central nervous system and peripheral demyelinating diseases, including multiple sclerosis, optic neuritis, and Guillain-Barré syndrome.
  • Exercise caution when considering HUMIRA for patients with these disorders; discontinuation of HUMIRA should be considered if any of these disorders develop.
  • There is a known association between intermediate uveitis and central demyelinating disorders.
HEMATOLOGIC REACTIONS
  • Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia has been infrequently reported with HUMIRA.
  • Consider stopping HUMIRA if significant hematologic abnormalities occur.
CONGESTIVE HEART FAILURE
  • Worsening and new onset congestive heart failure (CHF) has been reported with TNF blockers. Cases of worsening CHF have been observed with HUMIRA; exercise caution and monitor carefully.
AUTOIMMUNITY
  • Treatment with HUMIRA may result in the formation of autoantibodies and, rarely, in development of a lupus-like syndrome. Discontinue treatment if symptoms of a lupus-like syndrome develop.
IMMUNIZATIONS
  • Patients on HUMIRA should not receive live vaccines.
  • Pediatric patients, if possible, should be brought up to date with all immunizations before initiating HUMIRA therapy.
  • Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the in utero exposed infant. The safety of administering live or live-attenuated vaccines in infants exposed to HUMIRA in utero is unknown. Risks and benefits should be considered prior to vaccinating (live or live-attenuated) exposed infants.
ADVERSE REACTIONS
  • The most common adverse reactions in HUMIRA clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.

INDICATIONS1
  • Rheumatoid Arthritis: HUMIRA is indicated, alone or in combination with methotrexate or other non-biologic DMARDs, for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis.
  • Juvenile Idiopathic Arthritis: HUMIRA is indicated, alone or in combination with methotrexate, for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.
  • Psoriatic Arthritis: HUMIRA is indicated, alone or in combination with non-biologic DMARDs, for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis.
  • Ankylosing Spondylitis: HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.
  • Adult Crohn’s Disease: HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy, and reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.
  • Pediatric Crohn’s Disease: HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active Crohn’s disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate.
  • Ulcerative Colitis: HUMIRA is indicated for inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine, or 6-mercaptopurine. The effectiveness of HUMIRA has not been established in patients who have lost response to or were intolerant to anti-TNF agents.
  • Plaque Psoriasis: HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
  • Hidradenitis Suppurativa: HUMIRA is indicated for the treatment of adult patients with moderate to severe hidradenitis suppurativa.
  • Uveitis: HUMIRA is indicated for the treatment of non-infectious intermediate, posterior and panuveitis in adult patients.

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

1641190-1880520

Legal Notices/Privacy Policy. ©2015 AbbVie Inc. North Chicago, IL 60064. If you have any questions about AbbVie's HUMIRAPro.com website that have not been answered click here. This website and the information contained herein is intended for use by US physicians only and is provided for informational purposes only.

References: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc. 2. Kimball AB, Okun MM, Williams DA, et al. Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa. N Engl J Med. 2016;375(5):422-434. 3. Kimball AB, Jemec GBE, Yang M, et al. Assessing the validity, responsiveness and meaningfulness of the Hidradenitis Suppurativa Clinical Response (HiSCR) as the clinical endpoint for hidradenitis suppurativa treatment. Br J Dermatol. 2014;171(6):1434-1442. 4. Data on file ABVRRTI61790.

1641190-1855782


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

THIS IS WORTH POINTING OUT.

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




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Indication1

Plaque Psoriasis: HUMIRA (adalimumab) is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.

Safety Considerations1

Serious Infections

Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Malignancies

Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including HUMIRA.

Other Serious Adverse Reactions

Patients treated with HUMIRA also may be at risk for other serious adverse reactions, including anaphylaxis, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, and a lupus-like syndrome.