For pediatric patients with moderate to severe Crohn’s disease (CD)
US-MULT-230356
US-MULT-230356
For pediatric patients with moderate to severe Crohn’s disease (CD)
Study Design Intro: A multicenter, 4-week, open-label induction followed by 52-week, double-blind, randomized, maintenance study of 2 dose levels of HUMIRA in moderate to severe pediatric CD in patients (PCDAI score >30) who had, over the previous 2-year period, an inadequate response to or intolerance to corticosteroids or an immunomodulator. Patients who previously had loss of response to or intolerance to infliximab were allowed entry to trial. 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
The endpoint was a comparison of the High Maintenance Dose vs. the Low Maintenance Dose. Only the High Maintenance Dose results are depicted.1,2
Clinical remission at Week 4 was an exploratory endpoint and was 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.
Adverse events in IMAgINE 1 study population (n=192)1
*Clinical remission was defined as PCDAI score of ≤10.
PCDAI=Pediatric Crohn’s Disease Activity Index; TNF=tumor necrosis factor
*Clinical remission was defined as Pediatric Crohn's Disease Activity Index (PCDAI) score of ≤10.
†Bio‑naïve and bio‑experienced refers to patients that were infliximab‑naïve and infliximab‑experienced.
These data were 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 analyses.
The endpoint was a comparison of the High Maintenance Dose vs. the Low Maintenance Dose. Only the High Maintenance Dose results are depicted.2
*Clinical response was defined as a decrease in PCDAI score of ≥15 points from baseline.
†Bio-naïve and bio-experienced refers to patients that were infliximab-naïve and infliximab-experienced.
| Adverse Event | N=93, % (n) | PYs=54.1, Events (E/100 PYs) |
| Any AE | 92.5% (86) | 507 (937.2) |
| Severe AE | 20.4% (19) | 27 (49.9) |
| Serious AEb | 23.7% (22) | 24 (44.4) |
| Leading to discontinuation of study drug | 16.1% (15) | 20 (37.0) |
| Infectious AE | 60.2% (56) | 98 (181.1) |
| Serious infectionsc | 5.4% (5) | 5 (9.2) |
| Opportunistic infections, excluding TB | 1.1% (1) | 1 (1.8) |
| Any malignancies | 0 | 0 |
| Injection site reactions | 9.7% (9) | 25 (46.2) |
| Hepatic-related AE | 4.3% (4) | 5 (9.2) |
| Allergic reactions | 6.5% (6) | 8 (14.8) |
| Hematologic-related AE | 9.7% (9) | 11 (20.3) |
aPatients may have received concomitant conventional therapies.
bSerious AEs were defined as fatal or immediately life-threatening; required inpatient hospitalization or prolonged existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly; spontaneous or elective abortion; or required medical or surgical intervention to prevent a serious outcome.
cAbdominal abscess, histoplasmosis disseminated, gastroenteritis, anal abscess, H1N1 influenza.
*Treatment-emergent AEs were any AEs with an onset date on or after the first double-blind dose and up to 70 days after the last dose of study drug or up to the first dose of weekly blinded adalimumab.
Crohn's Disease (CD): 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.
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:
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.
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.
HYPERSENSITIVITY
HEPATITIS B VIRUS REACTIVATION
NEUROLOGIC REACTIONS
HEMATOLOGIC REACTIONS
CONGESTIVE HEART FAILURE
AUTOIMMUNITY
IMMUNIZATIONS
ADVERSE REACTIONS
Please see Full Prescribing Information.
US-HUM-210183
References:
IMAgINE 1: A multicenter, 4-week, open-label induction followed by 52-week, double-blind, randomized, maintenance study of 2 dose levels of HUMIRA in moderate to severe pediatric CD in patients (PCDAI score >30) who had, over the previous 2-year period, an inadequate response to or intolerance to corticosteroids or an immunomodulator. Patients who previously had loss of response to or intolerance to infliximab were allowed entry to trial.1,2
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
At Week 12, patients who experienced a disease flare‡ or who were nonresponders§ were allowed to dose-escalate (i.e., switch from blinded EOW dosing to blinded every week dosing). Every week dosing is not the recommended maintenance dosing regimen.1
PRIMARY ENDPOINT: Primary endpoint was clinical remission† at Week 26 comparing High Maintenance Dose vs Low Maintenance Dose.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: Intention-to-treat (ITT) population using nonresponder imputation was used. 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: Selected baseline characteristics for double-blind maintenance population (N=188)1,2
IMAgINE 1: Study population at Week 41
*Clinical response was defined as a decrease in PCDAI score of ≥15 points from baseline.1
†Clinical remission was defined as PCDAI score of ≤10.1
‡Increase in PCDAI score of ≥15 from Week 4 and absolute PCDAI score of >30.1,2
§Did not achieve a decrease in PCDAI score of ≥15 points from baseline for 2 consecutive visits at least 2 weeks apart.1,2
IICorticosteroids could be tapered after Week 4 in patients who experienced clinical response (PCDAI score decrease of ≥15 points compared with baseline).2
¶Immunomodulator therapy could be discontinued at or after Week 26 for patients meeting the clinical response criterion and could not be reinstated.2
#Other CD-specific concomitant medications were to be maintained at a constant dose throughout the study.2
EOW=every other week; OL=open-label; PCDAI=Pediatric Crohn’s Disease Activity Index; TNF=tumor necrosis factor
The primary endpoint was clinical remission* at Week 26 comparing High Maintenance Dose vs Low Maintenance Dose.2
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.
Ranked secondary endpoints comparing High Maintenance Dose vs Low Maintenance Dose include2:
The High Maintenance Dose was based on Week 4 weight (<40 kg=20 mg, ≥40 kg=40 mg); EOW
The Low Maintenance Dose was based on Week 4 weight (<40 kg=10 mg, ≥40 kg=20 mg); EOW
Remission
Week 26: High Maintenance Dose: 39% (n=93) vs Low Maintenance Dose: 28% (n=95)‡
Week 52: High Maintenance Dose: 33% (n=93) vs Low Maintenance Dose: 23% (n=95)‡
Response
Week 26: High Maintenance Dose: 59% (n=93) vs Low Maintenance Dose: 48% (n=95)‡
Week 52: High Maintenance Dose: 42% (n=93) vs Low Maintenance Dose: 28% (n=95)‡
*Clinical remission was defined as Pediatric Crohn’s Disease Activity Index (PCDAI) score of ≤10.
†Clinical response was defined as a decrease in PCDAI score of ≥15 points from baseline.
‡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.
US-HUM-210672
US-HUM-210672
HUMIRA has >90% preferred national commercial and Medicare Part D formulary coverage under the pharmacy benefit as of January 20231*
*Preferred means HUMIRA is on a preferred tier or otherwise has preferred status on the plan’s formulary.
Coverage requirements and benefit designs vary by payer and may change over time. Please consult with payers directly for the most current reimbursement policies.
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Learn more about how to help your patients access HUMIRA
1. Data on file, AbbVie Inc., January 2023.
US-HUM-220513
