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.
Adult Crohn’s Disease: HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy, and reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.
Pediatric Crohn’s Disease: HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active Crohn’s disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate.
Ulcerative Colitis: HUMIRA is indicated for inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine, or 6-mercaptopurine. The effectiveness of HUMIRA has not been established in patients who have lost response to or were intolerant to anti-TNF agents.
Plaque Psoriasis: HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow-up visits with a physician.
Hidradenitis Suppurativa: HUMIRA is indicated for the treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older.
Uveitis: HUMIRA is indicated for the treatment of non-infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older.
Please see Full Prescribing Information.
US-HUM-181930
References: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc.
REVEAL STUDY DESIGN1,2,8
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.
CHAMPION STUDY DESIGN1,3
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-190337
REVEAL STUDY DESIGN1,8,13
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.
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ADEPT STUDY DESIGN1,6,10,11
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
- 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.4,5
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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.
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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 |
| Number of tender jointsb | 20.0 | 5.0 | 23.0 | 17.0 |
| Number of swollen jointsc | 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.
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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.
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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-190337
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, ACR50/70 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-190337
PIONEER I and II STUDY DESIGNS1-4
- 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 CHARACTERISTICS2,5
SELECT BASELINE DISEASE CHARACTERISTICS2,5,6
SELECT BASELINE LESION TYPE2,5,6
Baseline characteristics identified as different between PIONEER I and PIONEER II are2:
- 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
- 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.
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PIONEER I and II STUDY DESIGNS1,4,6,7
- 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 CHARACTERISTICS4,5
SELECT BASELINE DISEASE CHARACTERISTICS4,5,8
SELECT BASELINE LESION TYPE4,5,8
Baseline characteristics identified as different between PIONEER I and PIONEER II are2:
- 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.
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Path of Continuous EW Population for PIONEER I and II Integrated Analysis of Flare Occurrence (n=99*)1-4,6,7,9
Patients treated with HUMIRA (adalimumab) received continuous HUMIRA 40 mg weekly over 36 weeks
- HUMIRA
40 mg EW
- Flare defined as ≥25% increase in AN count and an absolute increase of ≥2 relative to baseline.1-3
- Included 11 ADAew/ew patients who escaped period B early due to loss of response or worsening or absence of improvement and continued ADAew treatment in the OLE.9
PIONEER I control=placebo PIONEER II control=placebo +/- antibiotic
LOR: Loss of response
WOAI: Worsening or absence of improvement
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.
*ADAew/ew population, defined as patients randomized to ADAew in Period A and re-randomized to ADAew in Period B (including patients who escaped Period B early) due to loss of response or worsening or absence of improvement and continued ADAew treatment in the OLE.
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PIONEER I and II STUDY DESIGNS1,2,13,15
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.
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.
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PIONEER I and II STUDY DESIGNS—88 PATIENTS STUDIED IN OLE1,2,13,15
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
Stratified 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.
Re-randomization at entry to Period B, stratified by week 12 HiSCR status and baseline Hurley Stage II vs III.
160 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.
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Safety data from randomized control and OLE periods in PIONEER I and II2,8,13,16
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.
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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.
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