Humira

HUMIRA is a tumor necrosis factor (TNF) blocker indicated 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
  . 
  (
  1.1
  )
   
  
  
• Reducing signs and symptoms of
  moderately to severely active polyarticular
  juvenile idiopathic arthritis
   in patients 2 years of age and older.
  (
  1.2
  )
  
  
  
• Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in adult patients with
  active
  psoriatic arthritis
  .
  (
  1.3
  )
  
  
  
• Reducing signs and symptoms in adult patients with
  active
  ankylosing spondylitis
  . 
  (
  1.4
  )
  
  
  
• Treatment of
  moderately
  to severely active Crohn’s disease
  in adults and pediatric patients 6 years of age and older.
  (
  1.5
  )
  
  
  
• Treatment of
  moderately
  to severely active ulcerative colitis
  in adults and pediatric patients 5 years of age and older. 
  (
  1.6
  )
  
  
  
  Limitations of Use:
   Effectiveness has not been established in patients who have lost response to or were intolerant to TNF blockers.
  
  
• 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.
  (
  1.7
  )
  
  
  
• Treatment of
  moderate to severe hidradenitis suppurativa
  in patients 12 years of age and older.
  (
  1.8
  )
  
  
  
• Treatment of
  non-infectious intermediate, posterior, and panuveitis
  in adults and pediatric patients 2 years of age and older.
  (
  1.9
  )

• Administer by subcutaneous injection

• Adults:
  40 mg every other week.
  
  • Some patients with RA not receiving methotrexate may benefit from increasing the dosage to 40 mg every week or 80 mg every other week.

• Adults:
  160 mg on Day 1 (given in one day or split over two consecutive days); 80 mg on Day 15; and 40 mg every other week starting on Day 29.
  
  
• Pediatric Patients
   
  6 Years of Age and Older
  :

• Adults:
  160 mg on Day 1 (given in one day or split over two consecutive days), 80 mg on Day 15 and 40 mg every other week starting on Day 29. Discontinue in patients without evidence of clinical remission by eight weeks (Day 57).
  
  
• Pediatric Patients
   
  5 Years of Age and Older
  :

• Adults
  : 80 mg initial dose, followed by 40 mg every other week starting one week after initial dose.

• Adults:
  
  
  ○ Day 1: 160 mg (given in one day or split over two consecutive days)
  
  ○ Day 15: 80 mg 
  
  ○ Day 29 and subsequent doses: 40 mg every week or 80 mg every other week
  
  
• Adolescents 12 years of age and older:

HUMIRA is a clear and colorless solution available as:

• Pen
  (HUMIRA Pen)
  
  Injection: 80 mg/0.8 mL in a single-dose pen.
  
  Injection: 40 mg/0.8 mL in a single-dose pen.
  
  Injection: 40 mg/0.4 mL in a single-dose pen.

• Prefilled Syringe
  
  
  Injection: 80 mg/0.8 mL in a single-dose prefilled glass syringe.
  
  Injection: 40 mg/0.8 mL in a single-dose prefilled glass syringe.
  
  Injection: 40 mg/0.4 mL in a single-dose prefilled glass syringe.
  
  Injection: 20 mg/0.4 mL in a single-dose prefilled glass syringe.
  
  Injection: 20 mg/0.2 mL in a single-dose prefilled glass syringe.
  
  Injection: 10 mg/0.2 mL in a single-dose prefilled glass syringe.
  
  Injection: 10 mg/0.1 mL in a single-dose prefilled glass syringe.

• Single-Dose Institutional Use Vial
  
  
  Injection: 40 mg/0.8 mL in a single-dose, glass vial for institutional use only.

Available studies with use of adalimumab during pregnancy do not reliably establish an association between adalimumab and major birth defects. Clinical data are available from the Organization of Teratology Information Specialists (OTIS)/MotherToBaby HUMIRA Pregnancy Registry in pregnant women with rheumatoid arthritis (RA) or Crohn’s disease (CD). Registry results showed a rate of 10% for major birth defects with first trimester use of adalimumab in pregnant women with RA or CD and a rate of 7.5% for major birth defects in the disease-matched comparison cohort. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects

Adalimumab is actively transferred across the placenta during the third trimester of pregnancy and may affect immune response in the

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Published data suggest that the risk of adverse pregnancy outcomes in women with RA or inflammatory bowel disease (IBD) is associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

Monoclonal antibodies are increasingly transported across the placenta as pregnancy progresses, with the largest amount transferred during the third trimester

A prospective cohort pregnancy exposure registry conducted by OTIS/MotherToBaby in the U.S. and Canada between 2004 and 2016 compared the risk of major birth defects in live-born infants of 221 women (69 RA, 152 CD) treated with adalimumab during the first trimester and 106 women (74 RA, 32 CD) not treated with adalimumab.

The proportion of major birth defects among live-born infants in the adalimumab-treated and untreated cohorts was 10% (8.7% RA, 10.5% CD) and 7.5% (6.8% RA, 9.4% CD), respectively. The lack of pattern of major birth defects is reassuring and differences between exposure groups may have impacted the occurrence of birth defects. This study cannot reliably establish whether there is an association between adalimumab and major birth defects because of methodological limitations of the registry, including small sample size, the voluntary nature of the study, and the non-randomized design.

In an independent clinical study conducted in ten pregnant women with IBD treated with HUMIRA, adalimumab concentrations were measured in maternal serum as well as in cord blood (n=10) and infant serum (n=8) on the day of birth. The last dose of HUMIRA was given between 1 and 56 days prior to delivery. Adalimumab concentrations were 0.16-19.7 µg/mL in cord blood, 4.28-17.7 µg/mL in infant serum, and 0-16.1 µg/mL in maternal serum. In all but one case, the cord blood concentration of adalimumab was higher than the maternal serum concentration, suggesting adalimumab actively crosses the placenta. In addition, one infant had serum concentrations at each of the following: 6 weeks (1.94 µg/mL), 7 weeks (1.31 µg/mL), 8 weeks (0.93 µg/mL), and 11 weeks (0.53 µg/mL), suggesting adalimumab can be detected in the serum of infants exposed

In an embryo-fetal perinatal development study, pregnant cynomolgus monkeys received adalimumab from gestation days 20 to 97 at doses that produced exposures up to 373 times that achieved with the MRHD without methotrexate (on an AUC basis with maternal IV doses up to 100 mg/kg/week). Adalimumab did not elicit harm to the fetuses or malformations.