Infliximab (Remicade)

Remicade
● Active substance: Infliximab
● Developed by Junming Le and Jan Vilcek at the New York School of
Medicine.
Remicade
● Chimeric (human-murine) monoclonal antibody directed against tumor
necrosis factor alpha.
○ Approx. 30% murine variable region - confers antigen-binding specificity to human TNF-alpha
○ 70 % remaining - human IgG1 heavy chain constant region and a human kappa light chain
constant region
Remicade
● Approved on August, 1998 for acute treatment of moderate to severe Crohn’s
disease in patients who have had an inadequate response to conventional
therapy
○ Making Remicade as the first TNF-alpha inhibitor in the US
Biotech
Development genetics

● Infliximab monoclonal antibody is expressed using chimeric antibody genes

consisting of the variable region sequences cloned from the murine anti-TNF
alpha hybridoma A2, and human antibody constant region sequences
supplied by the plasmid expression vectors.
● Generation of murine anti-TNF alpha hybridoma - immunization of BALB/c
mice with purified recombinant human TNF alpha.
Biotech
Manufacture

● Infliximab is a recombinant antibody

● Produced and secreted from mouse myeloma cells (SP2/0 cells)
○ Formed by fusing BALB/c spleen cells (mouse immunized with sheep red blood cells) with the
P3X63Ag8
● The antibody is manufactured by continuous perfusion cell culture.
● Collected harvest are clarified by filtration before further purification.
Indications
Inflammatory diseases such as:
● rheumatoid arthritis
● psoriatic arthritis
● ulcerative colitis
● Crohn's disease
● severe or disabling plaque psoriasis.
Dosage form
● 100 mg of lyophilized infliximab in a 20 mL vial for intravenous infusion.
Mechanism of action
● chimeric monoclonal antibody which binds w/ high affinity to the soluble and
transmembrane forms of tumour necrosis factor-α (TNF-α) thereby inhibiting
binding of TNF-α to its receptors.

*TNFa, a cytokine produced by white blood cells, has an important role in the
body’s protective function, but the overproduction of TNF a leads to inflammation.
Mechanism of Action

Excess amounts of TNF-alpha cause your immune REMICADE® belongs to a class of biologic
system to mistakenly attack healthy cells leading to medications known as TNF-blockers. REMICADE®
inflammation—the underlying cause of Crohn’s binds to TNF-alpha, blocking its actio
symptoms
Adverse Drug Reaction
Patients treated with Remicade are at increased risk for developing serious
infections that may lead to hospitalization or death

● Concomitant immunosuppressants (methotrexate or corticosteroid)

Reported infections:

● Active tuberculosis and reactivation of latent tuberculosis

○ Should be tested and treated prior to initiating Remicade therapy
Adverse Drug Reaction
Other reported infections:

● Invasive fungal infections (histoplasmosis, coccidioidomycosis, candidiasis,

aspergillosis, blastomycosis and pneumocystis)
○ Can develop into serious systemic illness
● Malignancy
○ Lymphoma - Hodgkin and Non-hodgkin lymphoma
● Opportunistic infections
Related Update and Studies
Dosing related studies for the treatment of:

● Rheumatoid arthritis
● Ankylosing spondylitis
● Crohn’s disease
● Ulcerative colitis
● Psoriatic arthritis
● Plaque psoriasis
Related Updates and Studies