8,000+ patients
treated in clinical studies.1
Rheumatology
Moderate to Severe
Rheumatoid Arthritis
Active
Psoriatic Arthritis
Active
Ankylosing Spondylitis
Moderate to Severe
Juvenile Idiopathic Arthritis
Non-Infectious
Intermediate, Posterior and Panuveitis
Dermatology
Moderate to Severe
Chronic Plaque Psoriasis
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
Moderate to Severe
Pediatric Ulcerative Colitis
Ophthalmology
Non-Infectious
Intermediate, Posterior and Panuveitis
US-MULT-210551
For the treatment of moderate to severe hidradenitis suppurativa (HS) in patients 12 years of age and older
Safety data in HS
Clinical trial experience across 10 immune-mediated diseases1-3
20+ years
of clinical trial experience
beginning with rheumatoid
arthritis in 1997.4
3 years
Up to 3 years of safety data in HS,
including open-label extension.3
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.5
No new safety signals in adults
The safety profile of HS was consistent with the safety profile of HUMIRA overall.1,5
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.1
Select safety profile from clinical trials across 3 dermatology indications1,6-13
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.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 randomized, double-blind, placebo-controlled clinical trials in adult patients with moderate to severe HS receiving HUMIRA 40 mg weekly (after initial doses). Primary endpoint: HiSCR at week 12 (Period A), defined as ≥50% reduction from baseline in abscess and inflammatory nodule count, with no increase in abscess and draining-fistula count.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), 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
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 570.11
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
No new safety signals were identified in the OLE period3,15
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/100 PYs) | n (%) | Events (Events/100 PYs) |
| 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 it 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
Well-studied global safety data2*
Evaluated long‑term safety data from HUMIRA global clinical trials including randomized controlled, open‑label, and long‑term extension studies
Nearly 18 years
of safety data
In 28,939† adult patients
receiving HUMIRA in select clinical trials*
From 74 global clinical trials*†
Serious adverse events of interest across 8 adult indications for HUMIRA*†
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.
†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.
INDICATIONS1
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.
Helpful Links
INDICATION(S) and IMPORTANT SAFETY INFORMATION FOR HUMIRA (adalimumab)1
INDICATION(S)1
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.
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.
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: 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.
Crohn’s Disease: HUMIRA is indicated for the treatment of moderately to severely active Crohn’s disease in adults and pediatric patients 6 years of age and older.
Ulcerative Colitis: HUMIRA is indicated for the treatment of moderately to severely active ulcerative colitis in adults and pediatric patients 5 years of age and older.
Limitations of Use:
The effectiveness of HUMIRA has not been established in patients who have lost response to or were intolerant to TNF blockers.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.
Please see Full Prescribing Information.
US-HUM-210183
References: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc. 2. Burmester, GR, Gordon, KB, Rosenbaum JT, Long-term safety of adalimumab in 29,967 adult patients from global clinical trials across multiple indications: an updated analysis. Adv Ther. 2020;37:364–380. 3. Zouboulis CC, Okun MM, Prens EP, et al. Long-term adalimumab efficacy in patients with moderate-to-severe hidradenitis suppurativa/acne inversa: 3-year results of phase 3 open-label extension study. J Am Acad Dermatol. 2019;80(1):60-69.e2. 4. 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(12):1863-1869. 5. Ryan C, Sobell JM, Leonardi CL, et al. Safety of adalimumab dosed every week and every other week: focus on patients with hidradenitis suppurativa or psoriasis. Am J Clin Dermatol. 2018;19(3):437-447. 6. Data on file, ABVRRTI61732. 7. Mease PJ, Ory P, Sharp JT, et al. Adalimumab for long-term treatment of psoriatic arthritis: 2-year data from the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT). Ann Rheum Dis. 2009;68(5):702-709. 8. Data on file, ABVRRTI61791. 9. Menter A, Tyring SK, Gordon K, et al. Adalimumab therapy for moderate to severe psoriasis: a randomized, controlled phase Ill trial. J Am Acad Dermatol. 2008;58(1):106-115. 10. Saurat JH, Stingl G, Dubertret L, et al; for CHAMPION Study Investigators. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol. 2008;158(3):558-566. 11. 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. 12. Mease PJ, Gladman DD, Ritchlin CT, et al; for Adalimumab Effectiveness in Psoriatic Arthritis Study Group. 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. 13. 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. 14. Gordon K, Papp K, Poulin Y, Gu Y, Rozzo S, Sasso EH. Long-term efficacy and safety of adalimumab in patients with moderate to severe psoriasis treated continuously over 3 years: results from an open-label extension study for patients from REVEAL. J Am Acad Dermatol. 2012;66(2):241-251. 15. Data on file, ABVRRTI66161. 16. Data on file, ABVRRTI61790. 17. Kimball AB, Okun MM, Williams DA, et al. Two phase 3 trials of adalimumab for hidradenitis suppurativa. N Engl J Med. 2016;375(5)(suppl):1-27. 18. Data on file, ABVRRTI61787.
REVEAL was a randomized, double-blind, placebo-controlled study of 1212 patients with chronic plaque psoriasis and ≥10% BSA involvement, PASI score ≥12, and PGA of at least moderate disease severity. Patients had a clinical diagnosis of psoriasis for at least 6 months and stable disease for at least 2 months before screening. Evaluations were performed over 3 treatment periods totaling 52 weeks. For the first 16 weeks (Period A), patients received either HUMIRA (n=814), at an initial dose of 80 mg SC at week 0 followed by 40 mg EOW SC starting at week 1, or placebo (n=398).
In Period B, patients who achieved at least a PASI 75 response at week 16 received open-label HUMIRA 40 mg EOW for 17 weeks. In Period C, patients who maintained at least a PASI 75 response at week 33 and were originally randomized to HUMIRA in Period A were re-randomized to receive HUMIRA 40 mg EOW or placebo for an additional 19 weeks. Primary efficacy endpoints at week 16 were proportion of patients achieving a PASI 75 response relative to baseline and proportion of patients achieving a PGA score of clear or minimal disease.
US-HUMD-200130
ADEPT STUDY DESIGN1,7,11,12
EOW=every other week
a315 patients were initially randomized; however, 2 patients did not receive study drug.12
- A 24-week, randomized, double-blind, placebo-controlled trial of HUMIRA in adult patients with moderately to severely active psoriatic arthritis (PsA) (≥3 swollen joints and ≥3 tender joints) who had an inadequate response to NSAIDs.11,12
- Patients must have active psoriatic skin lesions or a documented history of psoriasis.12
- Co-primary endpoints were American College of Rheumatology (ACR) 20 response at week 12 and mean change from baseline in modified total Sharp score (mTSS) for HUMIRA-treated patients at week 48 vs placebo patients at week 24.1,12
- Select secondary endpoints include ACR20 at week 24, ACR50/70 at weeks 12 and 24, and HAQ-DI score at week 12 and 24.12
- 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.12
- Patients who completed the original 24-week, double-blind ADEPT study (n=289) were eligible for open-label treatment through week 144, for which over 98% (n=285) elected to enroll.7,11
US-HUMD-200130
PIONEER I and II STUDY DESIGNS1,3,13,16
The first and only completed Phase 3 trials in HS
- Enrolled patients had a total abscess and inflammatory nodule (AN) count of ≥3 with lesions in ≥2 anatomic areas, one of which was Hurley Stage II or III.
- Primary efficacy endpoint was Hidradenitis Suppurativa Clinical Response (HiSCR) at week 12.
- Period B explored the safety and efficacy of different maintenance regimens (continuous HUMIRA EW, reduction to HUMIRA EOW, or treatment withdrawal) over 24 weeks.
aStratified by baseline Hurley Stage II vs III (PIONEER I & II) and baseline concomitant antibiotic use (PIONEER II).
b160 mg week 0; 80 mg week 2; 40 mg from week 4.
cRe-randomization at entry to Period B, stratified by week 12 HiSCR status and baseline Hurley Stage II vs III.
d160 mg week 12; 80 mg week 14; 40 mg weekly from week 16.
*Weeks of efficacy and patient-reported outcomes analysis.
†Loss of response=defined as a loss of ≥50% in improvement in AN count achieved from baseline to week 12.
‡Worsening or absence of improvement=an AN count ≥ the baseline AN count at 2 consecutive visits (excluding week 12) occurring at least 14 days apart.
US-HUMD-200257
REVEAL was a randomized, double-blind, placebo-controlled study of 1212 patients with chronic plaque psoriasis and ≥10% BSA involvement, PASI score ≥12, and PGA of at least moderate disease severity. Patients had a clinical diagnosis of psoriasis for at least 6 months and stable disease for at least 2 months before screening. Evaluations were performed over 3 treatment periods totaling 52 weeks. For the first 16 weeks (Period A), patients received either HUMIRA (n=814), at an initial dose of 80 mg SC at week 0 followed by 40 mg EOW SC starting at week 1, or placebo (n=398).
In Period B, patients who achieved at least a PASI 75 response at week 16 received open-label HUMIRA 40 mg EOW for 17 weeks. In Period C, patients who maintained at least a PASI 75 response at week 33 and were originally randomized to HUMIRA in Period A were re-randomized to receive HUMIRA 40 mg EOW or placebo for an additional 19 weeks. Co-primary efficacy endpoints at week 16 were proportion of patients achieving a PASI 75 response relative to baseline and proportion of patients achieving a PGA score of clear or minimal disease.
Eligible adult patients had moderate to severe plaque psoriasis (defined as ≥10% BSA and PASI ≥10).
- Patients were to have plaque psoriasis for at least 1 year and stable plaque psoriasis for at least 2 months
- Patients were candidates for systemic therapy or phototherapy
- All patients were naïve to anti-TNF therapy and MTX
- Concomitant psoriasis therapies were not permitted during the study, with the exception of shampoos free of corticosteroids, bland emollients, and low-potency topical corticosteroids for the palms, soles, face, inframammary areas, and groin only, provided they were not used within 24 hours of a study visit
aPatients were randomized to receive HUMIRA (80 mg followed by 40 mg EOW beginning 1 week later) or placebo in a 2:1 ratio.
Co-primary efficacy endpoints were proportion of patients achieving PASI 75 relative to baseline and proportion of patients achieving a PGA of clear or minimal by week 16.
US-HUMD-200130
REVEAL was a randomized, double-blind, placebo-controlled study of 1212 patients with chronic plaque psoriasis and ≥10% BSA involvement, PASI score ≥12, and PGA of at least moderate disease severity. Patients had a clinical diagnosis of psoriasis for at least 6 months and stable disease for at least 2 months before screening. Evaluations were performed over 3 treatment periods totaling 52 weeks. For the first 16 weeks (Period A), patients received either HUMIRA (n=814), at an initial dose of 80 mg SC at week 0 followed by 40 mg EOW SC starting at week 1, or placebo (n=398).8,9
In Period B, patients who achieved at least a PASI 75 response at week 16 received open-label HUMIRA 40 mg EOW for 17 weeks. In Period C, patients who maintained at least a PASI 75 response at week 33 and were originally randomized to HUMIRA in Period A were re-randomized to receive HUMIRA 40 mg EOW or placebo for an additional 19 weeks. Primary efficacy endpoints at week 16 were proportion of patients achieving a PASI 75 response relative to baseline and proportion of patients achieving a PGA score of clear or minimal disease.
US-HUMD-190337
EOW=every other week
a315 patients were initially randomized; however, 2 patients did not receive study drug.11
- A 24-week, randomized, double-blind, placebo-controlled trial of HUMIRA in adult patients with moderately to severely active psoriatic arthritis (PsA) (≥3 swollen joints and ≥3 tender joints) who had an inadequate response to NSAIDs.10,11
- Patients must have active psoriatic skin lesions or a documented history of psoriasis.11
- Co-primary endpoints were American College of Rheumatology (ACR) 20 response at week 12 and mean change from baseline in modified total Sharp score (mTSS) for HUMIRA-treated patients at week 48 vs placebo patients at week 24.1,11
- Select secondary endpoints include ACR20 at week 24, ACR50/70 at weeks 12 and 24, and HAQ-DI at week 12 and 24.11
- 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.11
- Patients who completed the original 24-week, double-blind ADEPT study (n=289) were eligible for open-label treatment through week 144, for which over 98% (n=285) elected to enroll.6,10
US-HUMD-190337
ADEPT STUDY DESIGN1-3,5
EOW=every other week
a315 patients were initially randomized; however, 2 patients did not receive study drug.3
- A 24-week, randomized, double-blind, placebo-controlled trial of HUMIRA in adult patients with moderately to severely active psoriatic arthritis (PsA) (≥3 swollen joints and ≥3 tender joints) who had an inadequate response to NSAIDs.2,3
- Patients must have active psoriatic skin lesions or a documented history of psoriasis.3
- Co-primary endpoints were American College of Rheumatology (ACR) 20 response at week 12 and mean change from baseline in modified total Sharp score (mTSS) for HUMIRA-treated patients at week 48 vs placebo patients at week 24.1,3
- Select secondary endpoints include ACR20 at week 24, ACR50/70 at weeks 12 and 24, and HAQ-DI score at week 12 and 24.3
- 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.3
- Select additional endpoints include: ACR components at week 2 and pain data at weeks 2 and 24.1,6
- Patients who completed the original 24-week, double-blind ADEPT study (n=289) were eligible for open-label treatment through week 144, for which over 98% (n=285) elected to enroll.2,5
US-HUMD-200130
PIONEER I and II STUDY DESIGNS1,12,14,15
The first and only completed Phase 3 trials in HS
- Enrolled patients had a total abscess and inflammatory nodule (AN) count of ≥3 with lesions in ≥2 anatomic areas, one of which was Hurley Stage II or III.
- Primary efficacy endpoint was Hidradenitis Suppurativa Clinical Response (HiSCR) at week 12.
- Period B explored the safety and efficacy of different maintenance regimens (continuous HUMIRA EW, reduction to HUMIRA EOW, or treatment withdrawal) over 24 weeks.
PIONEER I control=placebo PIONEER II control=placebo +/- antibiotic
aStratified by baseline Hurley Stage II vs III (PIONEER I & II) and baseline concomitant antibiotic use (PIONEER II).
b160 mg week 0; 80 mg week 2; 40 mg from week 4.
cRe-randomization at entry to Period B, stratified by week 12 HiSCR status and baseline Hurley Stage II vs III.
d160 mg week 12; 80 mg week 14; 40 mg weekly from week 16.
*Weeks of efficacy and patient-reported outcomes analysis.
†Loss of response=defined as a loss of ≥50% in improvement in AN count achieved from baseline to week 12.
‡Worsening or absence of improvement=an AN count ≥ the baseline AN count at 2 consecutive visits (excluding week 12) occurring at least 14 days apart.
US-HUMD-190337
HUMIRA demonstrated significant improvements from baseline in ACR components of disease activity (P<0.001)1
| HUMIRAa 40 mg EOW (n=151) | Placebo EOW (n=162) | |||
|---|---|---|---|---|
| Parameter: median | Baseline | 24 Weeks | Baseline | 24 Weeks |
| Tender joint countb | 20.0 | 5.0 | 23.0 | 17.0 |
| Swollen joint countc | 11.0 | 3.0 | 11.0 | 9.0 |
| Physician global assessmentd | 55.0 | 16.0 | 53.0 | 49.0 |
| Patient global assessmentd | 48.0 | 20.0 | 49.5 | 49.0 |
| Paind | 54.0 | 20.0 | 49.0 | 49.0 |
| Disability index (HAQ)e | 1.0 | 0.4 | 1.0 | 0.9 |
| CRP (mg/dL)f | 0.8 | 0.2 | 0.8 | 0.7 |
aP<0.001 for HUMIRA vs placebo; comparisons based on mean changes.
bScale 0-78.
cScale 0-76.
dVisual analog scale; 0=best, 100=worst.
eDisability Index of the Health Assessment Questionnaire (HAQ-DI); 0=best, 3=worst; measures the patient’s ability to perform the following: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity.
fNormal range: 0-0.287 mg/dL.
US-HUMD-200130
HUMIRA demonstrated significant improvements from baseline in every ACR component (P<0.001)1
| HUMIRA 40 mg EOW (n=151) | Placebo EOW (n=162) | |||
|---|---|---|---|---|
| Parameter: median | Baseline | 24 Weeks | Baseline | 24 Weeks |
| Number of tender joints | 20.0 | 5.0 | 23.0 | 17.0 |
| Number of swollen joints | 11.0 | 3.0 | 11.0 | 9.0 |
| Physician global assessment | 55.0 | 16.0 | 53.0 | 49.0 |
| Patient global assessment | 48.0 | 20.0 | 49.5 | 49.0 |
| Pain | 54.0 | 20.0 | 49.0 | 49.0 |
| Disability index (HAQ) | 1.0 | 0.4 | 1.0 | 0.9 |
| CRP (mg/dL) | 0.8 | 0.2 | 0.8 | 0.7 |
aP<0.001 for HUMIRA vs placebo; comparisons based on mean changes.
bScale 0-78.
cScale 0-76.
dVisual analog scale; 0=best, 100=worst.
eDisability Index of the Health Assessment Questionnaire (HAQ-DI); 0=best, 3=worst; measures the patient’s ability to perform the following: dress/groom, arise, eat, walk, reach, grip, maintain hygiene, and maintain daily activity.
fNormal range: 0-0.287 mg/dL.
US-HUMD-200130
PIONEER I and II STUDY DESIGNS—88 PATIENTS STUDIED IN OLE1-4
88 patients who were studied in OLE received continuous HUMIRA weekly throughout the trial period (periods A and B) and throughout the OLE.
- Enrolled patients had a total abscess and inflammatory nodule (AN) count of ≥3 with lesions in ≥2 anatomic areas, one of which was Hurley Stage II or III.
- Primary efficacy endpoint was Hidradenitis Suppurativa Clinical Response (HiSCR) at week 12.
- Period B explored the safety and efficacy of different maintenance regimens (continuous HUMIRA EW, reduction to HUMIRA EOW, or treatment withdrawal) over 24 weeks.
PIONEER I control=placebo PIONEER II control=placebo +/- antibiotic
aStratified by baseline Hurley Stage II vs III (PIONEER I & II) and baseline concomitant antibiotic use (PIONEER II).
b160 mg week 0; 80 mg week 2; 40 mg from week 4.
cRe-randomization at entry to Period B, stratified by week 12 HiSCR status and baseline Hurley Stage II vs III.
d160 mg week 12; 80 mg week 14; 40 mg weekly from week 16.
*Weeks of efficacy and patient-reported outcomes analysis.
†Loss of response=defined as a loss of ≥50% in improvement in AN count achieved from baseline to week 12.
‡Worsening or absence of improvement=an AN count ≥ the baseline AN count at 2 consecutive visits (excluding week 12) occurring at least 14 days apart.
US-HUMD-200052
ADEPT STUDY DESIGN1-4
EOW=every other week
a315 patients were initially randomized; however, 2 patients did not receive study drug.2
- A 24-week, randomized, double-blind, placebo-controlled trial of HUMIRA in adult patients with moderately to severely active psoriatic arthritis (PsA) (≥3 swollen joints and ≥3 tender joints) who had an inadequate response to NSAIDs.2,4
- Patients must have active psoriatic skin lesions or a documented history of psoriasis.2
- Co-primary endpoints were American College of Rheumatology (ACR) 20 response at week 12 and mean change from baseline in modified total Sharp score (mTSS) for HUMIRA-treated patients at week 48 vs placebo patients at week 24.1,2
- Select secondary endpoints include ACR20 at week 24, ACR 50/70 at weeks 12 and 24, and HAQ-DI score at week 12 and 24.2
- 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.2
- Patients who completed the original 24-week, double-blind ADEPT study (n=289) were eligible for open-label treatment through week 144, for which over 98% (n=285) elected to enroll.3,4
US-HUMD-200257
PIONEER I and II STUDY DESIGNS1,3-5
- Enrolled patients had a total abscess and inflammatory nodule (AN) count of ≥3 with lesions in ≥2 anatomic areas, one of which was Hurley Stage II or III.
- Primary efficacy endpoint was Hidradenitis Suppurativa Clinical Response (HiSCR) at week 12.
- Period B explored the safety and efficacy of different maintenance regimens (continuous HUMIRA EW, reduction to HUMIRA EOW, or treatment withdrawal) over 24 weeks.
PIONEER I control=placebo PIONEER II control=placebo +/- antibiotic
aStratified by baseline Hurley Stage II vs III (PIONEER I & II) and baseline concomitant antibiotic use (PIONEER II).
b160 mg week 0; 80 mg week 2; 40 mg from week 4.
cRe-randomization at entry to Period B, stratified by week 12 HiSCR status and baseline Hurley Stage II vs III.
d160 mg week 12; 80 mg week 14; 40 mg weekly from week 16.
*Weeks of efficacy and patient-reported outcomes analysis.
†Loss of response=defined as a loss of ≥ 50% in improvement in AN count achieved from baseline to week 12.
‡Worsening or absence of improvement=an AN count ≥ the baseline AN count at 2 consecutive visits (excluding week 12) occurring at least 14 days apart.
SELECT BASELINE PATIENT CHARACTERISTICS3,6
SELECT BASELINE DISEASE CHARACTERISTICS3,6,7
SELECT BASELINE LESION TYPE3,6,7
Baseline characteristics identified as different between PIONEER I and PIONEER II are:
- baseline weight
- baseline lesion count
These differences in baseline characteristics may in part account for the observed differences in magnitude between the 2 studies.
eControl=placebo.
fControl=placebo ± antibiotic.
gNumber of patients unless otherwise indicated EW.
hRace was self-reported.
iln PIONEER I, the “other” category included Asian (4 patients, 1.3%), American Indian or Alaskan native (2 patients, 0.7%), multiple races (1 patient, 0.3%), and other (4 patients,1.3%). In PIONEER II, the “other” category included Asian (10 patients, 3.1%), American Indian or Alaskan native (1 patient, 0.3%), Native Hawaiian or other Pacific Islander (1 patient, 0.3%), multiple races (3 patients, 0.9%), and other (9 patients, 2.8%).
jData reflect actual assessments, not the Hurley Stage stratification factor. A patient's overall Hurley Stage was documented as the highest stage across all affected anatomical regions. Stage I is defined as localized formation of single or multiple abscesses, without sinus tracts or scarring; Stage II as recurrent abscesses (single or multiple), with sinus tract formation and scarring; and Stage Ill as multiple abscesses, with extensive, interconnected sinus tracts and scarring.
kData missing for PIONEER II, HUMIRA EW (n=1).
lHigher values indicate a higher level of systemic inflammation.
US-HUMD-190337
PIONEER I and II STUDY DESIGNS1,3,5,6
- Enrolled patients had a total abscess and inflammatory nodule (AN) count of ≥3 with lesions in ≥2 anatomic areas, one of which was Hurley Stage II or III.
- Primary efficacy endpoint was Hidradenitis Suppurativa Clinical Response (HiSCR) at week 12.
- Period B explored the safety and efficacy of different maintenance regimens (continuous HUMIRA EW, reduction to HUMIRA EOW, or treatment withdrawal) over 24 weeks.
PIONEER I control=placebo PIONEER II control=placebo +/- antibiotic
aStratified by baseline Hurley Stage II vs III (PIONEER I & II) and baseline concomitant antibiotic use (PIONEER II).
b160 mg week 0; 80 mg week 2; 40 mg from week 4.
cRe-randomization at entry to Period B, stratified by week 12 HiSCR status and baseline Hurley Stage II vs III.
d160 mg week 12; 80 mg week 14; 40 mg weekly from week 16.
*Weeks of efficacy and patient-reported outcomes analysis.
†Loss of response=defined as a loss of ≥50% in improvement in AN count achieved from baseline to week 12.
‡Worsening or absence of improvement=an AN count ≥ the baseline AN count at 2 consecutive visits (excluding week 12) occurring at least 14 days apart.
SELECT BASELINE PATIENT CHARACTERISTICS3,4
SELECT BASELINE DISEASE CHARACTERISTICS3,4,7
SELECT BASELINE LESION TYPE3,4,7
Baseline characteristics identified as different between PIONEER I and PIONEER II are3:
- Baseline weight
- Baseline lesion count
These differences in baseline characteristics may in part account for the observed differences in magnitude between the 2 studies.
eControl=placebo.
fControl=placebo ± antibiotic.
gNumber of patients unless otherwise indicated EW.
hRace was self-reported.
iln PIONEER I, the “other” category included Asian (4 patients, 1.3%), American Indian or Alaskan native (2 patients, 0.7%), multiple races (1 patient, 0.3%), and other (4 patients,1.3%). In PIONEER II, the “other” category included Asian (10 patients, 3.1%), American Indian or Alaskan native (1 patient, 0.3%), Native Hawaiian or other Pacific Islander (1 patient, 0.3%), multiple races (3 patients, 0.9%), and other (9 patients, 2.8%).
jData reflect actual assessments, not the Hurley Stage stratification factor. A patient's overall Hurley Stage was documented as the highest stage across all affected anatomical regions. Stage I is defined as localized formation of single or multiple abscesses, without sinus tracts or scarring; Stage II as recurrent abscesses (single or multiple), with sinus tract formation and scarring; and Stage Ill as multiple abscesses, with extensive, interconnected sinus tracts and scarring.
kData missing for PIONEER II, HUMIRA EW (n=1).
lHigher values indicate a higher level of systemic inflammation.
US-HUMD-200052
PIONEER I and II STUDY DESIGNS1,3,13,16
The first and only completed Phase 3 trials in HS.
- Enrolled patients had a total abscess and inflammatory nodule (AN) count of ≥3 with lesions in ≥2 anatomic areas, one of which was Hurley Stage II or III.
- Primary efficacy endpoint was Hidradenitis Suppurativa Clinical Response (HiSCR) at week 12.
- Period B explored the safety and efficacy of different maintenance regimens (continuous HUMIRA EW, reduction to HUMIRA EOW, or treatment withdrawal) over 24 weeks.
SELECT BASELINE PATIENT CHARACTERISTICS13,17
SELECT BASELINE DISEASE CHARACTERISTICS13,17,18
SELECT BASELINE LESION TYPE13,17,18
Baseline characteristics identified as different between PIONEER I and PIONEER II are13:
- baseline weight
- baseline lesion count
These differences in baseline characteristics may in part account for the observed differences in magnitude between the 2 studies.
eControl=placebo.
fControl=placebo ± antibiotic.
gNumber of patients unless otherwise indicated EW.
hRace was self-reported.
iln PIONEER I, the “other” category included Asian (4 patients, 1.3%), American Indian or Alaskan native (2 patients, 0.7%), multiple races (1 patient, 0.3%), and other (4 patients,1.3%). In PIONEER II, the “other” category included Asian (10 patients, 3.1%), American Indian or Alaskan native (1 patient, 0.3%), Native Hawaiian or other Pacific Islander (1 patient, 0.3%), multiple races (3 patients, 0.9%), and other (9 patients, 2.8%).
jData reflect actual assessments, not the Hurley Stage stratification factor. A patient's overall Hurley Stage was documented as the highest stage across all affected anatomical regions. Stage I is defined as localized formation of single or multiple abscesses, without sinus tracts or scarring; Stage II as recurrent abscesses (single or multiple), with sinus tract formation and scarring; and Stage Ill as multiple abscesses, with extensive, interconnected sinus tracts and scarring.
kData missing for PIONEER II, HUMIRA EW (n=1).
lHigher values indicate a higher level of systemic inflammation.
US-HUMD-200257
PIONEER I and II STUDY DESIGNS—88 PATIENTS STUDIED IN OLE1,3,13,16
88 patients who were studied in OLE received continuous HUMIRA weekly throughout the trial period (periods A and B) and throughout the OLE.
- Enrolled patients had a total abscess and inflammatory nodule (AN) count of ≥3 with lesions in ≥2 anatomic areas, one of which was Hurley Stage II or III.
- Primary efficacy endpoint was Hidradenitis Suppurativa Clinical Response (HiSCR) at week 12.
- Period B explored the safety and efficacy of different maintenance regimens (continuous HUMIRA EW, reduction to HUMIRA EOW, or treatment withdrawal) over 24 weeks.
PIONEER I control=placebo PIONEER II control=placebo +/- antibiotic
aStratified by baseline Hurley Stage II vs III (PIONEER I & II) and baseline concomitant antibiotic use (PIONEER II).
160 mg week 0; 80 mg week 2; 40 mg from week 4.
bRe-randomization at entry to Period B, stratified by week 12 HiSCR status and baseline Hurley Stage II vs III.
c160 mg week 12; 80 mg week 14; 40 mg weekly from week 16.
dWeeks of efficacy and patient-reported outcomes analysis.
†Loss of response=defined as a loss of ≥50% in improvement in AN count achieved from baseline to week 12.
‡Worsening or absence of improvement=an AN count ≥ the baseline AN count at 2 consecutive visits (excluding week 12) occurring at least 14 days apart.
US-HUMD-200130
Safety data from randomized control and OLE periods in PIONEER I and II3,8,13,15
Adverse reaction rate observed in clinical trials and open-label extension (OLE) studies may not predict the rates observed in a broader HS patient population in clinical practice.
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.
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.
Adverse reaction rate observed in clinical trials and OLE studies may not predict the rates observed in a broader HS patient population in clinical practice.
*Safety data for PIONEER I, Period B not shown as there is no comparable control group.
†Study design dosing: HUMIRA EW/HUMIRA EW.
‡Study design dosing: HUMIRA EW/HUMIRA EW/HUMIRA EW.
§Other than lymphoma, HSTCL, leukemia, NMSC or melanoma.
US-HUMD-200130
ADEPT Study Design1-4
EOW=every other week
a315 patients were initially randomized; however, 2 patients did not receive study drug.2
A 24-week, randomized, double-blind, placebo-controlled trial of HUMIRA in adult patients with moderately to severely active psoriatic arthritis (PsA) (≥3 swollen joints and ≥3 tender joints) who had an inadequate response to NSAIDs.2,4
Patients must have active psoriatic skin lesions or a documented history of psoriasis.2
Co-primary endpoints were American College of Rheumatology (ACR) 20 response at Week 12 and mean change from baseline in modified total Sharp score (mTSS) for HUMIRA-treated patients at Week 48 vs placebo patients at Week 24.1,2
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.2
Select additional endpoints include ACR20 response rates at week 2, VAS pain scores at Week 2 and 24, and change from baseline in individual ACR components by visit.2
Select secondary endpoints include ACR20 at Week 24, ACR 50/70 at Weeks 12 and 24, HAQ-DI score at Weeks 12 and 24, and PASI 75 at Week 24.2
Patients who completed the original 24-week double-blind ADEPT study (n=289) were eligible for open-label treatment through Week 144, for which over 98% (n=285) elected to enroll.3,4
US-HUMD-200130
REVEAL STUDY DESIGN1,2,5
REVEAL was a randomized, double-blind, placebo-controlled study of 1212 patients with chronic plaque psoriasis and ≥10% BSA involvement, PASI score ≥12, and PGA of at least moderate disease severity. Patients had a clinical diagnosis of psoriasis for at least 6 months and stable disease for at least 2 months before screening. Evaluations were performed over 3 treatment periods totaling 52 weeks. For the first 16 weeks (Period A), patients received either HUMIRA (n=814), at an initial dose of 80 mg SC at week 0 followed by 40 mg EOW SC starting at week 1, or placebo (n=398).
In Period B, patients who achieved at least a PASI 75 response at week 16 received open-label HUMIRA 40 mg EOW for 17 weeks. In Period C, patients who maintained at least a PASI 75 response at week 33 and were originally randomized to HUMIRA in Period A were re-randomized to receive HUMIRA 40 mg EOW or placebo for an additional 19 weeks. Primary efficacy endpoints at week 16 were proportion of patients achieving a PASI 75 response relative to baseline and proportion of patients achieving a PGA score of clear or minimal disease.
US-HUMD-190337
Fingernail Psoriasis Study Design1,2,9,13
A Phase 3, randomized, double-blind study evaluated adult subjects with moderate to severe fingernail psoriasis who also had moderate to severe chronic plaque psoriasis.1,2
BSA=body surface area; EOW=every other week; mNAPSI=modified Nail Psoriasis Severity Index;
PGA-F=Physician’s Global Assessment of Fingernail Psoriasis; PGA-S=Physician’s Global Assessment of Skin Psoriasis.
Key inclusion criteria were adult subjects with2:
- Moderate to severe chronic plaque psoriasis with disease duration of at least 6 months and psoriasis in at least one fingernail
- Fingernail involvement ≥ moderate as measured by 5-point PGA-F scale
- mNAPSI score of target fingernail ≥8
- BSA ≥10%, or ≥5% BSA with a total mNAPSI score for all fingernails ≥20
Primary endpoint was proportion of subjects achieving PGA-F of 0 (clear) or 1 (minimal) and at least 2-grade improvement from baseline at Week 26.
Key secondary endpoint was proportion of subjects achieving ≥75% improvement from baseline in mNAPSI (mNAPSI 75) at Week 26.
US-HUMD-200257