2. Introduction
• human monoclonal antibody against TNF-alpha
• C6428H9912N1694O1987S46
• organic chemical
• produced by recombinant DNA technology using mammalian cell
expression system
• Adalimumab is used for treatment of rheumatoid arthritis, psoriatic
arthritis, ankylosing spondylitis and Crohn’s disease
• immune system mediated diseases
3. History
• 1993 - BASF bioresearch and Cambridge Antibody
• 3rd TNF inhibitor approved in United States
• fully human monoclonal
• initially discovered using CAT’s phage display technology and being
named as D2E7
• BASF bioresearch Corporation – create
• Abbott Laboratories – further manufacturing and marketing
4. • 2008 - Food and Drug Administration (FDA) approved adalimumab as
treatment of arthritis and Crohn’s disease
• 2012 - FDA approved for treatment of ulcerative colitis
• 2014 - generic drugs of adalimumab has been launched by other
companies
5. • sold under the trade name, Humira
• rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis,
plaque psoriasis, Crohn’s disease
• tumor necrosis factor-alpha (TNF- α) blocker
6. How it works?
• directly binding to TNF- α molecules in the blood and diseased tissue
• blocks its interaction with the p55 and p75 cell surface TNF receptors
• lyses surface TNF expressing cells in vitro
• does not bind or inactivate lymphotoxin (TNF-beta)
• Excess production of TNF-alpha - rapid growth of skin cells and
damages to joint tissue
• Adalimumab helps to stop the inflammatory cycle of psoriatic disease
and prevent from causing the inflammation that result in psoriasis
plaques.
7. Prescription, Pharmacodynamics,
Pharmacokinetics
• prescribed by either itself or in combination with methotrexate
• given after other medications has failed in treatment
• safe to take it with topical treatments or pain relievers
• Adult – decrease acute inflammation, C-reactive protein (CRP),
erythrocyte sedimentation rate (ESR), and serum cytokines (IL-6)
• maximized with the maximum serum concentration
• Tmax were 4.7 ± 1.6 µg/mL and 131 ± 56 hours
• linear over the dose range of 0.5 to 10.0 mg/kg following a single
intravenous dose
8. efficacy of adalimumab
• phase II randomized placebo-controlled trial evaluate 147 patients
with psoriasis that at least 5% of their (BSA) infected and minimum 10
(PASI)
• Patient had achieved the primary endpoint of PASI 75 or better as
compared to 4% of the patients who received placebo.
• phase II trial is to compare the efficacy of adalimumab to
methotrexate (MTX) and placebo.
9. • phase III trials were performed to directly compare the therapeutic
efficacy, safety and tolerability and to provide greater body of data
• 80patients given adalimumab, 36% patients given methotrexate and
19% patients given placebo achieving a PASI 75 response rate at a
given time
• (PGA) score :73% in adalimumab, 30% in methotrexate and 11% in
placebo
• second phase III trials was to examine the short- and long-term
efficacy of adalimumab as monotherapy against placebo
• treatment with 40mg adalimumab every other week
• efficacy of adalimumab is sustainable.
10. • high dose in phase II - Adverse reaction of pain with injection
• headache, nausea, elevated triglycerides, cough, sinus congestion,
and fatigue
• no increase of serious adverse events in phase III trials
• recommended dose of 40 mg every other week, and the higher dose
of 40 mg weekly, either alone or in combination with methotrexate or
other DMARDs
• short- and long-term safety, tolerability and substantial efficacy
11. Risk
• developing severe and even fatal infections
• Tuberculosis may be caused by a new infection or by reactivation of a
previous infection
• tumor necrosis factor (TNF) blocker - develop Lymphoma and other
types of cancer such as hepatosplenic T-cell lymphoma (HSTCL)
• attempt a TB skin test before taking Adalimumab
• positive result should begin treatment for TB
• negative result should also be monitored for signs of TB while using
adalimumab
12. Precautions
• Should not drive - dizziness or vision changes
• avoid contact with people who have colds or infections
• should not do any activities that may cause bruising or injury
• should not breastfeed
13. Side Effects
Common side effect
• back pain, headache, redness or swelling at injection site
• mild stomach pain, nausea or runny nose
Server side effect
• rash, itching, difficulty in breathing, swelling of lips or tongue, blood
in urine, burning, numbness, chest pain, fainting, blistered, peeling
skin, swelling of ankles, diarrhoea or vomit.
15. Challenges
• target specific drugs
• specialized drug for individual
• competition of new generic drugs
• Amgen for patenting rights
16. Conclusion
• fully human monoclonal anti-TNF antibody drug
• treat inflammation and chronic skin condition
• Efficacy of adalimumab is sustainable
• side effect isn’t life threatening
• No high toxic effect
• taken by itself of accompanied by some other drug
