For the treatment of moderate to severe hidradenitis suppurativa (HS) in patients 12 years of age and older
Safety data in HS
Well-studied safety profile in clinical trials in adults1-3
Clinical trial experience across 10 immune-mediated diseases1-5
8,000+ patients
treated in clinical studies.
20+ years
of clinical trial experience beginning with rheumatoid arthritis in 1997.
3 years
Up to 3 years of safety data in HS, including open-label extension.
Studied to compare weekly vs every-other-week dosing
Analysis of 15 trials for 5 HUMIRA indications showed no new safety risks or increased rates of select adverse events with weekly vs every-other-week dosing.
No new safety signals in adults
The safety profile of HS was consistent with the safety profile of HUMIRA overall.
Anticipated safety in adolescents
Safety of the recommended HUMIRA dose in the adolescent HS population is anticipated to be consistent with the known safety profile of HUMIRA based on a cross-indication safety profile of HUMIRA in both adults and pediatric patients at similar or higher exposure determined through pharmacokinetic modeling.
Clinical trial safety data
Select safety profile from clinical trials across 3 dermatology indications1,6-13
Serious AE |
Any AE leading to trial discontinuation |
Serious Infection |
Malignancya,b |
Lymphoma |
Active tuberculosis |
Ps
REVEAL
Adverse events (AE) of interest rates at week 16
(Events/100 PYs)
HUMIRA (N=814, PYs=250.2) |
Placebo (N=398, PYs= 120.7) |
|
|---|---|---|
Serious AE |
6.8 |
5.8 |
Any AE leading to trial discontinuation |
2.0 |
0.0 |
Serious Infection |
2.8 |
3.3 |
Malignancya,b |
0.8 |
0.8 |
Lymphoma |
0.0 |
0.0 |
Active tuberculosis |
0.0 |
0.0 |
REVEAL was a 52-week randomized, double-blind, placebo-controlled study of 1212 adult patients with moderate to severe chronic plaque psoriasis. CHAMPION was a 16-week randomized, double-blind, placebo-controlled study of 161 adult patients with moderate to severe plaque psoriasis.9,10
PsA
ADEPT
Adverse events (AE) of interest rates at week 24
(Events/100 PYs)
HUMIRA (N=151, PYs=66.8) |
Placebo (N=162, PYs= 71.1) | |
|---|---|---|
Serious AE |
7.5 |
15.5 |
Any AE leading to trial discontinuation |
9.0 |
8.4 |
Serious Infection |
1.5 |
1.4 |
Malignancya,b |
0.0 |
0.0 |
Lymphoma |
0.0 |
0.0 |
Active tuberculosis |
0.0 |
0.0 |
ADEPT was a 24-week, randomized, double-blind placebo-controlled study in 313 adult patients with active PsA who had an inadequate response to NSAIDs. Co-primary endpoints were ACR 20 response at week 12 and mean change from baseline in mTSS* for HUMIRA-treated patients at week 48 vs placebo at week 24.1,11,12
HS in adult patients
PIONEER I
Adverse events (AE) of interest rates at week 12 (Period A)
(Events/100 PYs)
HUMIRA (N=153, PYs=34.9) |
Placebo (N=152, PYs= 34.6) | |
|---|---|---|
Serious AE |
8.6 |
20.2 |
Any AE leading to trial discontinuation |
2.9 |
8.7 |
Serious Infection |
2.9 |
0.0 |
Malignancya,b |
0.0 |
2.9 |
Lymphoma |
0.0 |
0.0 |
Active tuberculosis |
0.0 |
0.0 |
PIONEER II
Adverse events (AE) of interest rates at week 36 (Periods A and B)
(Events/100 PYs)
HUMIRA (N=163, PYs=57.3) |
Placebo (N=163, PYs=73.4) | |
|---|---|---|
Serious AE |
14.0 |
30.0 |
Any AE leading to trial discontinuation |
8.7 |
17.7 |
Serious Infection |
3.5 |
5.4 |
Malignancya,b |
0.0 |
0.0 |
Lymphoma |
0.0 |
0.0 |
Active tuberculosis |
0.0 |
0.0 |
PIONEER I (N=307) and II (N=326) were 2 similarly designed clinical trials in adult patients with two double-blind, placebo-controlled periods. In Period A, patients were assigned to either HUMIRA 40 mg weekly after initial doses or placebo for 12 weeks. In Period B, patients were reassigned to HUMIRA weekly or EOW, or placebo for 24 weeks. Primary endpoint was HiSCR at week 12, defined as at least a 50% reduction from baseline in abscess and inflammatory nodule count, with no increase in abscess and draining-fistula counts.13
Adverse reaction rates observed in clinical trials may not predict the rates observed in a broader patient population in clinical practice.
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
Risk of Malignancy1
Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including HUMIRA.
- More cases of malignancies were observed among HUMIRA-treated patients compared to control patients in clinical trials
- Consider the risks and benefits of HUMIRA treatment prior to initiating or continuing therapy in patients with a known malignancy
- Examine all patients, especially patients with a medical history of prior prolonged immunosuppressant therapy or psoriasis patients with a history of PUVA treatment, for the presence of non-melanoma skin cancer (NMSC) prior to and during treatment with HUMIRA
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
Risk of Lymphoma1
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which HUMIRA is a member.
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have occurred in adolescent and young adults with inflammatory bowel disease treated with TNF blockers including HUMIRA.
The rate of lymphoma in controlled and uncontrolled clinical trials of HUMIRA in patients with RA, PsA, AS, CD, UC, and Ps was approximately 3-fold higher than expected in the general population.
Select global safety profile from clinical trials
Serious adverse events of interest for HUMIRA from the full Prescribing Information1
Results from 39 global, controlled portions of HUMIRA clinical trials in adult patients
| HUMIRA (n=7,973) Events/100 PYs |
Control (n=4,848) Events/100 PYs |
|
|---|---|---|
| Serious infections | 4.3 | 2.9 |
| Non-melanoma skin cancer (NMSC) | 0.8 | 0.2 |
| Malignancies (excluding NMSC) | 0.7 | 0.7 |
Results from 52 global, controlled and uncontrolled clinical trials
| HUMIRA (n=24,605) Events/100 PYs |
|
|---|---|
| Tuberculosis (active) | 0.20 |
| Serious opportunistic infections | 0.05 |
| Lymphomac | 0.11 |
cThe observed rate of lymphomas is approximately 0.11/100 PYs in clinical trials of HUMIRA-treated patients. This is approximately 3-fold higher than expected in the general population. Patients with RA and other chronic inflammatory diseases, particularly those with highly active disease and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) than the general population for the development of lymphoma, even in the absence of TNF blockers.1
The safety data assessed in the HUMIRA full Prescribing Information include adult patients treated with HUMIRA for various immune-mediated diseases including rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn’s disease (CD), ulcerative colitis (UC), plaque psoriasis (Ps), hidradenitis suppurativa (HS), and uveitis (UV).
*mTSS or modified Total Sharp Score measures erosions and joint space narrowing, as well as radiographic changes specific to PsA patients, including DIP joints, with a maximum score of 570.
aIn REVEAL and ADEPT, malignancies excluded lymphoma and non-melanoma skin cancer.
bIn PIONEER I and II, malignancies excluded hepatosplenic T-cell lymphoma, leukemia, lymphoma, non-melanoma skin cancer, and melanoma.
AE=adverse event; EW=every week; EOW=every other week;
HSTCL=hepatosplenic T-cell lymphoma; PYs=patient years
OLE safety data
No new safety signals were identified in the OLE period2,16
Select adverse events in the OLE period
| Continuous HUMIRA EW Populationa (Up to 168 Weeks, n=88, PYs=194.1) |
Continuous HUMIRA EW Populationb (Starting in Period A, B, or OLE, n=326, PYs=654.6) |
|||
|---|---|---|---|---|
| Adverse Event | n (%) | Events (Events/100PYs) | n (%) | Events (Events/100PYs) |
| Any serious AE | 12 (13.6) | 14 (7.2) | 58 (17.8) | 87 (13.3) |
| Any AE leading to discontinuation of study drug | 13 (14.8) | 15 (7.7) | 51 (15.6) | 62 (9.5) |
| Serious infection | 3 (3.4) | 3 (1.5) | 18 (5.5) | 20 (3.1) |
| Any TB (active or latent) | 2 (2.3) | 2 (1.0) | 8 (2.5) | 8 (1.2) |
| Any malignancy other than lymphoma, HSTCL, leukemia, NMSC, and melanoma | 0 | 0 | 3 (0.9) | 4 (0.6) |
| Any lymphoma | 0 | 0 | 0 | 0 |
Risk of Malignancy1
Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including HUMIRA.
- More cases of malignancies were observed among HUMIRA-treated patients compared to control patients in clinical trials
- Consider the risks and benefits of HUMIRA treatment prior to initiating or continuing therapy in patients with a known malignancy
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), which includes 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
OLE Limitations: As with any long-term OLE there are several limitations with the OLE portion of this study. For example, there is 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 has been studied for HS in 2 phase 3 controlled studies and 1 OLE study, and the safety profile for patients with HS treated with HUMIRA weekly dosing was consistent with the known safety profile of HUMIRA.
aStudy design dosing: HUMIRA EW/HUMIRA EW/HUMIRA EW.
bContinuous HUMIRA EW population consisted of those who were maintained on HUMIRA EW therapy once they started regardless of whether is was period A, B, or during the OLE (study design dosing: HUMIRA EW/EW/EW, CTRL/HUMIRA EW/HUMIRA EW, and Control/Control/HUMIRA EW populations).
AE=adverse event; EW=every week; EOW=every other week; OLE=open-label extension PYs=patient years; RCT=randomized controlled trial; TEAE=treatment-emergent adverse events
Global safety data
Well-studied global safety data across indications3*
Nearly 18 years
of safety data
In 28,959† patients
receiving HUMIRA in select clinical trials*
From 74 global
clinical trials*
Serious adverse events of interest in HUMIRA adult clinical trials
Adverse reaction rates observed in clinical trials may not predict the rates observed in a broader patient population in clinical practice.
The risks and benefits of HUMIRA should be carefully considered prior to initiating therapy.
Rates displayed as events per 100 patient-years (PYs) as of December 31, 2016
| Rheumatoid arthritis | Plaque psoriasis | Psoriatic arthritis | Hidradenitis suppurativa | Ankylosing spondylitis | Crohn’s disease | Ulcerative colitis | NI Uveitis | |
|---|---|---|---|---|---|---|---|---|
| SAEs of interest† | 37,106 PYs (n=15,512) |
5,479 PYs (n=3,732) |
998 PYs (n=837) |
1,198 PYs (n=733) |
2,120 PYs (n=2026) |
4,359 PYs (n=3,896) |
3,407 PYs (n=1,739) |
1,151 PYs (n=464) |
| Serious infection | 3.9 | 1.8 | 2.8 | 2.8 | 1.8 | 6.9 | 3.5 | 4.1 |
| Tuberculosis (TB) | 0.2 | 0.2 | 0.2 | 0 | 0.1 | 0.2 | <0.1 | 0.4 |
| Active TB | 0.2 | 0.2 | 0.2 | 0 | 0.1 | 0.1 | <0.1 | 0.2 |
| Latent TB | <0.1 | 0 | 0 | 0 | 0 | <0.1 | 0 | 0.3 |
| Opportunistic infection‡ | <0.1 | 0 | 0 | 0 | 0 | <0.1 | <0.1 | 0.4 |
| Malignancy§ | 0.7 | 0.5 | 0.2 | 0.5 | 0.2 | 0.4 | 0.6 | 0.7 |
| Lymphoma | 0.1 | <0.1 | 0.2 | <0.1 | <0.1 | <0.1 | <0.1 | <0.1 |
| NMSC | 0.2 | 0.1 | 0.1 | <0.1 | 0.2 | <0.1 | <0.1 | 0.2 |
| Melanoma | <0.1 | 0.2 | 0 | 0 | <0.1 | 0 | <0.1 | 0 |
| Sarcoidosis | <0.1 | 0 | 0 | 0 | <0.1 | 0 | 0 | <0.1 |
| Demyelinating disorder | <0.1 | 0 | 0 | 0 | <0.1 | 0.1 | <0.1 | 0.3 |
| Lupus-like syndrome | <0.1 | 0 | 0 | 0 | <0.1 | <0.1 | <0.1 | <0.1 |
| Congestive heart failure | 0.2 | 0.1 | 0 | 0.2 | <0.1 | 0 | <0.1 | <0.1 |
| New onset/worsening of Ps | <0.1 | <0.1 | 0.1 | <0.1 | <0.1 | <0.1 | <0.1 | 0 |
| Any AE leading to death | 0.6 | 0.2 | 0.3 | 0.5 | <0.1 | 0.1 | 0.1 | 0.6 |
* Total includes the 8 populations shown plus 20 patients with Behcet's disease (35.5 PYs).
†Data from 74 clinical trials and their 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 NI uveitis.
‡Excludes oral candidiasis and tuberculosis.
§Excludes lymphoma, hepatosplenic T-cell lymphoma, leukemia, non-melanoma skin cancer, and melanoma.
SAE=serious adverse events; NMSC=non-melanoma skin cancer; Ps=plaque psoriasis; PYs=patient years; TB=tuberculosis
Additional Safety Considerations1
RISK OF SERIOUS INFECTION1
Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Discontinue HUMIRA if a patient develops a serious infection or sepsis.
Test patients for latent TB before HUMIRA use and during therapy. Initiate treatment for latent TB prior to HUMIRA use.
Monitor patients closely for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
RISK OF MALIGNANCY1
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including HUMIRA.
Postmarketing cases of HSTCL, a rare type of fatal lymphoma, have been reported in patients treated with TNF blockers, including HUMIRA. The majority of these cases were in adolescent and young adult males with inflammatory bowel disease who had received concomitant or prior treatment with azathioprine or 6-mercaptopurine.
More cases were observed among HUMIRA-treated adult patients than in controls. Lymphoma, non-melanoma skin cancer (NMSC), acute and chronic leukemia, and others have been reported. Examine all patients for the presence of NMSC prior to and during treatment.
PATIENTS TREATED WITH HUMIRA MAY BE AT RISK FOR OTHER SERIOUS ADVERSE REACTIONS INCLUDING1:
HYPERSENSITIVITY
Anaphylaxis and angioneurotic edema have been reported. If a serious allergic reaction occurs, stop HUMIRA and begin appropriate therapy.
HEPATITIS B VIRUS REACTIVATION
Risk of reactivation may increase in patients who are chronic carriers. Some cases have been fatal. Monitor hepatitis B virus (HBV) carriers during and after treatment with HUMIRA. If reactivation occurs, stop HUMIRA and begin appropriate therapy.
NEUROLOGIC REACTIONS
Exacerbation or new onset central nervous system or peripheral demyelinating disease may occur, including multiple sclerosis, optic neuritis, and Guillain‑Barré syndrome. Exercise caution when considering HUMIRA for patients with these disorders. There is a known association between intermediate uveitis and central demyelinating disorders.
HEMATOLOGIC REACTIONS
Rare reports of pancytopenia, including aplastic anemia, have been reported. Consider stopping HUMIRA in patients with significant hematologic abnormalities.
CONGESTIVE HEART FAILURE
Worsening or new onset congestive heart failure (CHF) may occur. Exercise caution in patients with CHF and monitor them carefully.
AUTOIMMUNITY
Treatment with HUMIRA may result in formation of autoantibodies and, rarely, in development of lupus-like syndrome. Stop HUMIRA if symptoms of a lupus‑like syndrome develop.
INDICATIONS
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.
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.
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.
Hidradenitis Suppurativa: HUMIRA is indicated for the treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older.
Ankylosing Spondylitis: HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.
Adult Crohn's Disease: HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy, and reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.
Ulcerative Colitis: HUMIRA is indicated for inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine, or 6-mercaptopurine. The effectiveness of HUMIRA has not been established in patients who have lost response to or were intolerant to anti-TNF agents.
Uveitis: HUMIRA is indicated for the treatment of non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older.
