Adalimumab is a human monoclonal antibody used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and Crohn's disease by blocking tumor necrosis factor-alpha (TNF-α). It was discovered in 1993 and approved by the FDA in 2008. Adalimumab works by binding to TNF-α molecules in the blood and tissues to block their interaction with cell surface receptors and lyse TNF-expressing cells, reducing inflammation. Clinical trials demonstrated its efficacy in treating psoriasis and other conditions. While common side effects include pain, nausea and fatigue, it poses risks like severe infections and cancer with long term use.

1. ADALIMUMAB

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
Severe 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.

14. Overdose
• still unclear
• does not show toxic effects in clinical trials

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