A first-line biologic treatment that provides...
DURABLE REMISSION
through 56 weeks1
Week 4
CLASSIC‑I
Bio-naïve rapid remission*
in HUMIRA vs control1,2
36% vs 12%
24%
Treatment
Difference
GAIN
Bio-experienced patient remission
in HUMIRA vs control1,3
21% vs 7%
14%
Treatment
Difference
Weeks 26 & 56
CHARM
Durable remission
in HUMIRA
vs control1,4
40% vs 17%
23%
Treatment
Difference
36% vs 12%
24%
Treatment
Difference
Remission at Weeks 26 and 56 in
bio‑naïve and bio‑experienced patients4
Remission at Week 56 by disease duration5,6
Year 4
OLE remission data7
The use of HUMIRA in
CD beyond 1 year has
not been evaluated in
controlled clinical
studies.1
CLASSIC-I Study Design Intro: 4-week, randomized, double-blind, placebo‑controlled study in 299 adults who have had an inadequate response† to conventional therapy. Patients were randomized to one of four treatment arms (± concomitant therapy). Primary endpoint: percentage of patients achieving induction of clinical remission in the 2 higher doses vs control at Week 4.1,2
GAIN Study Design Intro: 4-week, randomized, double‑blind, placebo‑controlled study in 325 adults. Patients were randomized to receive HUMIRA or control (placebo), both ± concomitant conventional therapy. Primary endpoint: percentage of patients achieving induction of clinical remission at Week 4.1,3
CHARM Study Design Intro: 56-week, randomized controlled study in 854 adults. All patients received open-label HUMIRA 80 mg at Week 0 and 40 mg at Week 2. The 499 patients with CR-70 response at Week 4 were randomized to one of three treatment arms (± concomitant conventional therapy) and were included in the analysis. Co-primary endpoints: Clinical remission (Week 26, Week 56) for each HUMIRA group vs control in the 499 patients with CR-70 response at Week 4.1,4
OLE Study Design Intro: This subanalysis includes patients from the CHARM trial who were randomized responders, remained blinded on
HUMIRA 40 mg EOW therapy for the duration of the trial, and entered (n=75) and remained on HUMIRA 40 mg EOW in the OLE.7
EOW=every other week; OLE=open-label extension
*Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score <150 points.
†Clinical response (CR-70; symptom improvement) was defined as a reduction of ≥70 points from baseline CDAI score.
Rapid Remission & response at Week 4
Week 4
Clinical remission* and response† were achieved as early as 4 weeks in CD patients1,2
Remission for Total Population at Week 4 (Primary Endpoint) – All Patients Were Bio‑naïve1,2
- HUMIRA 160 mg/80 mg (n=76)
- Control (n=74)
Response for Total Population at
Week 4 (Secondary Endpoint) – All Patients Were Bio‑naïve1,2
- HUMIRA 160 mg/80 mg (n=76)
- Control (n=74)
aP<0.001, HUMIRA vs control.
bP<0.01, HUMIRA vs control.
*Clinical remission was defined as a Crohn’s Disease Activity Index (CDAI) score <150 points.
†Clinical response (CR-70; symptom improvement) was defined as a reduction of ≥70 points from baseline CDAI score.
Durable Remission & Response at Week 56
Weeks 26 & 56
HUMIRA delivered remission* and response1,†
Remission for Total Population at Weeks 26 and 56 (Co-primary Endpoints)1,4
~50% of Patients Were Bio-naïve and ~50% of Patients Were Bio-experienced
Double-blind, placebo-controlled period
EOW=every other week
aP<0.001, HUMIRA vs control.
Among patients not in response by Week 12, continued therapy did not result in significantly more responses.1
Subgroup Analysis Methodology: The subgroup analysis is of the modified intention-to-treat study population (all randomized patients who received ≥1 dose
of study drug and achieved CR-70 at Week 4) achieving clinical remission (decrease in CDAI score to <150) at Weeks 26 and 56, stratified by prior anti-TNF
exposure and using non-responder imputation for missing data. Patients who discontinued double-blind treatment were classified as not in clinical remission.6
CDAI=Crohn’s Disease Activity Index; EOW=every other week
bP<0.05, HUMIRA vs control.
*Clinical remission was defined as a CDAI score <150 points.
†Clinical response (CR-70; symptom improvement) was defined as a reduction of ≥70 points from baseline CDAI score.
~50% of Patients Were Bio-naïve and ~50% of Patients Were Bio-experienced
Statistical Considerations: Post-hoc analyses are not powered or tested to demonstrate a statistically significant difference in treatment effect; no statistical inferences can be made due to the exploratory nature of the analysis.
Post-hoc Analysis Methodology: This post-hoc analysis was performed on patients in the modified intention‑to‑treat population (all randomized patients who received ≥1 dose of study drug and achieved CR-70 at Week 4) of CHARM who were divided into groups by disease duration: <2 years (n=48), 2 to <5 years (n=62), and ≥5 years (n=232). Clinical remission rates within each group for HUMIRA were compared with control at Week 56.5
EOW=every other week
*Clinical remission was defined as a Crohn’s Disease Activity Index score of <150 points.
Durable response* was achieved at Weeks 26 and 561,4
Response for Total Population at Weeks 26 and 56 (Prespecified Secondary Endpoints)1,4
~50% of Patients Were Bio-naïve and ~50% of Patients Were Bio-experienced
Double-blind, placebo-controlled period
EOW=every other week
aP<0.001, HUMIRA vs control.
*Clinical response (CR-70; symptom improvement) was defined as a reduction of ≥70 points from baseline Crohn’s Disease Activity Index score.
Year 4
Long-term Remission*
Remission Through 4 Years (56-Week RCT + 156-Week OLE)
Among patients not in response† by Week 12, continued therapy did not result in significantly more responses.1
CHARM RCT (56 weeks)
CHARM OLE Observed Analysis (156 weeks)
- % of patients in remission (HUMIRA 40 mg EOW)
The use of HUMIRA in CD beyond 1 year has not been evaluated in controlled clinical studies.1
- OLE populations generally consist of treatment responders, as patients who are unable to tolerate the drug or who do not respond to the drug drop out.
- Patients who dropped out of the OLE trial or who were missing Crohn’s Disease Activity Index (CDAI) scores were not included in the analysis at each time point.7
OLE Study Design Intro: This subanalysis includes patients from the CHARM trial who were randomized responders, remained blinded on HUMIRA
40 mg EOW therapy for the duration of the trial, and entered (n=75) and remained on HUMIRA 40 mg EOW in the OLE.7
EOW=every other week; OLE=open-label extension; RCT=randomized controlled trial
*Clinical remission was defined as a CDAI score <150 points.
†Clinical response (CR-70; symptom improvement) was defined as a reduction of ≥70 points from baseline CDAI score.
INDICATION1
Adult Crohn’s Disease (CD): HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn’s disease who have had an inadequate response to conventional therapy. HUMIRA is indicated for reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.
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 (RA): HUMIRA is indicated, alone or in combination with methotrexate or other non‑biologic DMARDs, for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis.
Juvenile Idiopathic Arthritis (JIA): HUMIRA is indicated, alone or in combination with methotrexate, for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis in patients 2 years of age and older.
Psoriatic Arthritis (PsA): HUMIRA is indicated, alone or in combination with non‑biologic DMARDs, for reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with active psoriatic arthritis.
Ankylosing Spondylitis (AS): HUMIRA is indicated for reducing signs and symptoms in adult patients with active ankylosing spondylitis.
Adult Crohn's Disease (CD): HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active Crohn's disease who have had an inadequate response to conventional therapy, and reducing signs and symptoms and inducing clinical remission in these patients if they have also lost response to or are intolerant to infliximab.
Pediatric Crohn's Disease: HUMIRA is indicated for reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients 6 years of age and older with moderately to severely active Crohn's disease who have had an inadequate response to corticosteroids or immunomodulators such as azathioprine, 6‑mercaptopurine, or methotrexate.
Ulcerative Colitis (UC): HUMIRA is indicated for inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine, or 6‑mercaptopurine. The effectiveness of HUMIRA has not been established in patients who have lost response to or were intolerant to anti‑TNF agents.
Plaque Psoriasis (Ps): HUMIRA is indicated for the treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy, and when other systemic therapies are medically less appropriate. HUMIRA should only be administered to patients who will be closely monitored and have regular follow‑up visits with a physician.
Hidradenitis Suppurativa (HS): HUMIRA is indicated for the treatment of moderate to severe hidradenitis suppurativa in patients 12 years of age and older.
Uveitis: HUMIRA is indicated for the treatment of non‑infectious intermediate, posterior, and panuveitis in adults and pediatric patients 2 years of age and older.
Please see full Prescribing Information.
References: 1.HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc. 2. Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn’s disease: the CLASSIC-I trial. Gastroenterology. 2006;130(2):323-333. 3. Sandborn WJ, Rutgeerts P, Enns R, et al. Adalimumab induction therapy for Crohn’s disease previously treated with infliximab: a randomized trial. Ann Intern Med. 2007;146(12):829–838. 4. Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132(1):52-65. 5. Data on File REF-43165. 6. Schreiber S, Reinisch W, Colombel JF, et al. Subgroup analysis of the placebo‑controlled CHARM trial: increased remission rates through 3 years for adalimumab‑treated patients with early Crohn’s disease. J Crohns Colitis. 2013;7(3):213-221. 7. Data on File ABVRRTI63406.
Study Designs
CHARM Study Design1,4
DURATION: 56‑week, randomized, double‑blind, placebo‑controlled, multicenter study
PATIENTS: 854 adult patients with moderately to severely active Crohn's disease defined by a Crohn's Disease Activity Index (CDAI) score of 220–450 points
CONCOMITANT THERAPIES: All patients may have received concomitant conventional therapies that included 5‑aminosalicylates, immunomodulators, corticosteroids, and Crohn's‑related antibiotics
DOSING: All patients received open‑label HUMIRA 80 mg at Week 0 and 40 mg at Week 2
- Patients who achieved clinical response* (CR‑70) at Week 4 were randomized to control (placebo), HUMIRA 40 mg EOW, or
HUMIRA 40 mg weekly, all ± concomitant therapy
Approved maintenance dose:
HUMIRA 40 mg EOW
CO-PRIMARY ENDPOINTS: Clinical remission† (Week 26, Week 56) for each HUMIRA group vs control in the 499 patients with CR‑70 response at Week 4 after open‑label induction therapy
CHARM OLE Study Design7
This subanalysis evaluated clinical remission† to 156 weeks in patients who received
HUMIRA 40 mg EOW throughout the open‑label extension (OLE) of the CHARM study. Patients who dropped out of the trial or who were missing CDAI scores were not included in the analysis at each time point.
EOW=every other week
aThis subanalysis includes patients from the CHARM trial who were randomized responders, remained blinded on
HUMIRA 40 mg EOW therapy for the duration of the trial, and entered (n=75) and remained on HUMIRA 40 mg EOW in the OLE.
bA flare was defined as an increase in CDAI of ≥70 points and a CDAI above 220 when compared to Week 4 of the preceding randomized, controlled trial. Nonresponse was defined as a decrease of <70 points compared to the baseline visit in the preceding randomized, controlled trial.
*Clinical response (CR-70; symptom improvement) was defined as a reduction of ≥70 points from baseline CDAI score.
†Clinical remission was defined as a CDAI score <150 points.
US-HUMG-190451
GAIN Study1,3
Remission* at Week 4 (Primary Endpoint)1,3
Response† at Week 4 (Secondary Endpoint)1,3
Study Design Intro: 4‑week, randomized, double‑blind, placebo‑controlled study in 325 adults with moderately to severely active Crohn’s disease who lost response to, or intolerant to, infliximab. Patients were randomized to receive HUMIRA or control (placebo), both ± concomitant conventional therapy. Primary endpoint: percentage of patients achieving induction of clinical remission at Week 4.1,3
aP<0.001, HUMIRA vs control.
bP<0.01, HUMIRA vs control.
*Clinical remission was defined as a Crohn's Disease Activity Index (CDAI) score <150 points.
†Clinical response (CR-70; symptom improvement) was defined as a reduction of ≥70 points from baseline CDAI score.
GAIN Study Design1,3
Duration: 4‑week, randomized, double‑blind, placebo‑controlled, multicenter study
Patients: 325 adults with moderately to severely active Crohn's disease (defined by a Crohn’s Disease Activity Index (CDAI) score of 220–450 points) who lost response to, or were intolerant to, infliximab
Concomitant Therapies: All patients may have received concomitant stable doses of conventional therapies that included 5‑aminosalicylates, immunomodulators, corticosteroids, and Crohn's‑related antibiotics
Dosing: Patients were randomized to receive 160 mg at Week 0 and 80 mg at Week 2, or control (placebo), both ± concomitant therapy and followed through Week 4
Primary Endpoint: Percentage of patients achieving induction of clinical remission* in HUMIRA‑treated patients vs control at Week 4
Secondary Endpoint: Percentage of patients achieving clinical response† (CR‑70) at Week 4
*Clinical remission was defined as a CDAI score <150 points.
†Clinical response (CR‑70; symptom improvement) was defined as a reduction of ≥70 points from baseline CDAI score.
US-HUMG-190451