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 largest
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.
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.
Dr. Casey Chapman and fellow experts discuss HUMIRA’s known safety profile in CD from clinical trials and additional safety data from real‑world clinical practice.
Did you enjoy this video? See Data Hunter Dr. Casey Chapman talk with fellow experts about CD efficacy
No new
safety signals
requiring label changes were reported
Up to 6 years
of follow up
– safety profile confirmed
in largest prospective study
in routine clinical practice
>5000 patients
followed totalling 16,680 PYs
of HUMIRA exposure
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:
Safety profile consistent with known safety profile from global clinical trials and across approved indications7
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
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
Reported infections include:
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
Reported infections include:
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
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
PI=prescribing information; RA=rheumatoid arthritis; TNF=tumor necrosis factor
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.
The use of HUMIRA in CD beyond 1 year has not been evaluated in controlled clinical studies.1
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.
The use of HUMIRA in CD beyond 1 year has not been evaluated in controlled clinical studies.1
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.
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
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
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.
Drs. Miguel Regueiro, Asher Kornbluth, Casey Chapman, and Bincy Abraham take a deeper look at clinical trial and real-world HUMIRA safety data
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.
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:
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.
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.
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.