Serious Infections: Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Malignancies: Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including HUMIRA.
Other Serious Adverse Reactions: Patients treated with HUMIRA also may be at risk for other serious adverse reactions, including anaphylaxis, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, and a lupus-like syndrome.
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.
IMAgINE 1 was a randomized, double-blind, 52-week clinical study of 2 dose levels of HUMIRA in moderately to severely active pediatric CD in patients (PCDAI score >30) who had over the previous 2-year period an inadequate response or intolerance to corticosteroids or an immunomodulator. Patients who previously had loss of response or intolerance to infliximab were allowed to enter the trial.1,2
Patients received open-label induction therapy at a dose based on their body weight (≥40 kg and <40 kg). Patients weighing ≥40 kg received 160 mg at Week 0 and 80 mg at Week 2. Patients weighing <40 kg received 80 mg at Week 0 and 40 mg at Week 2. At Week 4, patients within each body weight category (≥40 kg and <40 kg) were randomized 1:1 to one of the two maintenance dose regimens (high dose and low dose). The high dose was 40 mg every other week for patients weighing ≥40 kg and 20 mg every other week for patients weighing <40 kg. The low dose was 20 mg every other week for patients weighing ≥40 kg and 10 mg for patients weighing <40 kg.1
Primary endpoint was the percentage of patients achieving clinical remission at Week 26 comparing High Maintenance Dose vs Low Maintenance Dose.2
44% of patients in the IMAgINE 1 study had previously lost response or were intolerant to a TNF blocker; 56% were anti-TNF naïve2
IMAgINE 1 did not have a placebo control arm1,2
Randomly assigned (1:1) to double-blind HUMIRA High Maintenance Dose or HUMIRA Low Maintenance Dose. Stratified according to:
Primary endpoint: Proportion of patients in clinical remission comparing High Maintenance Dose vs Low Maintenance Dose.†
OL Induction: Based on weight at baseline
Double-blind Maintenance: Randomized to 1 of 2 maintenance dose regimens; dose in each regimen was based on Week 4 body weight
20 mg EOW for patients weighing <40 kg and
40 mg EOW for patients weighing ≥40 kg
10 mg EOW for patients weighing <40 kg and
20 mg EOW for patients weighing ≥40 kg
At Week 12, patients who experienced a disease flare‡ or who were nonresponders§ were allowed to dose-escalate (ie, switch from blinded every other week dosing to blinded every week dosing). Every week dosing is not the recommended maintenance dosing regimen.
PRIMARY ENDPOINT: Primary endpoint was proportion of patients achieving clinical remission at Week 26 comparing High Maintenance Dose vs Low Maintenance Dose.1,2
SECONDARY ENDPOINTS: Ranked secondary endpoints comparing High Maintenance Dose vs Low Maintenance Dose include2:
CONCOMITANT TREATMENTS: Stable doses of concomitant therapies permitted throughout the study were corticosteroids, immunomodulators, aminosalicylates, CD-related antibiotics, and growth hormone.1,2
ANALYSIS: Intent-to-treat (ITT) population using nonresponder imputation. All randomized patients receiving at least 1 dose of double-blind study medication were included in the analysis. Patients who discontinued the study, switched to weekly dosing, or did not have the relevant PCDAI score were considered not to have achieved clinical remission or response.1,2
IMAgINE 1: Study population at Week 41
PCDAI=Pediatric Crohn's Disease Activity Index; EOW=every other week
*Clinical response was defined as a decrease in PCDAI score of ≥15 points from baseline.
†Clinical remission was defined as PCDAI score of ≤10.
‡Increase in PCDAI score of ≥15 from Week 4 and absolute PCDAI score of >30.
§Did not achieve a decrease in PCDAI score of ≥15 from baseline for 2 consecutive visits at least 2 weeks apart.
IICorticosteroids could be tapered after Week 4 in patients who experienced clinical response (PCDAI score decrease of ≥15 points compared with baseline).
¶Immunomodulator therapy could be discontinued at or after Week 26 for patients meeting the clinical response criterion and could not be reinstated.
#Other CD-specific concomitant medications were to be maintained at a constant dose throughout the study.
Clinical remission* and response† rates were numerically higher in the High Maintenance Dose group compared with the Low Maintenance Dose group, and those differences were either not statistically significant or exploratory.1,2
Adverse events in IMAgINE 1 study population (n=192)1
Risk of HSTCL1
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of fatal lymphoma, have been reported in patients treated with TNF blockers, including HUMIRA. The majority of cases were in adolescent and young adult males with inflammatory bowel disease who had received concomitant or prior treatment with azathioprine or 6-mercaptopurine.
*Clinical remission was defined as PCDAI score of ≤10.
†Clinical response was defined as a decrease from baseline in the PCDAI score of ≥15 points.
‡Prior to entering maintenance phase, patients received open-label induction dose 160 mg at Week 0 and 80 mg at Week 2 for patients weighing ≥40 kg at baseline; or 80 mg at Week 0 and 40 mg at Week 2 for patients weighing <40 kg at baseline.
PCDAI=Pediatric Crohn's Disease Activity Index
Patients treated with HUMIRA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.
Discontinue HUMIRA if a patient develops a serious infection or sepsis.
Reported infections include:
Carefully consider the risks and benefits of treatment with HUMIRA prior to initiating therapy in patients: 1. with chronic or recurrent infection, 2. who have been exposed to TB, 3. with a history of opportunistic infection, 4. who resided in or traveled in regions where mycoses are endemic, 5. with underlying conditions that may predispose them to infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with HUMIRA, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, including HUMIRA. Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma, have been reported in patients treated with TNF blockers, including HUMIRA. These cases have had a very aggressive disease course and have been fatal. The majority of reported TNF blocker cases have occurred in patients with Crohn’s disease or ulcerative colitis and the majority were in adolescent and young adult males. Almost all of these patients had received treatment with azathioprine or 6-mercaptopurine concomitantly with a TNF blocker at or prior to diagnosis. It is uncertain whether the occurrence of HSTCL is related to use of a TNF blocker or a TNF blocker in combination with these other immunosuppressants.
For full Prescribing Information, visit rxabbvie.com/pdf/humira.pdf
References: 1. HUMIRA Injection [package insert]. North Chicago, IL: AbbVie Inc. 2. Hyams JS, Griffiths A, Markowitz J, et al. Safety and efficacy of adalimumab for moderate to severe Crohn’s disease in children. Gastroenterology. 2012;143(2):365-374.