Biologics Drugs: Treatment of rheumatoid arthritis

Biologics are treatment derived from a biological process rather than being manufactured chemically.
Biologics can be broadly classified into two major groups;
Anti-Tumour necrosis factor alpha and others.
Among various cytokines, Tumour necrosis factor alpha is the main target of for many biologics
Therefore, will start with the anti-tumour necrosis factor.
In the TNFα producing cells such as phagocytes the transmembrane TNFα is detached from the cell membrane by the action of the TNF converting enzyme
The free-floating molecule is now called soluble TNFα
The soluble TNFα molecules traverse to the TNFα responsive cells
Where they bind to specific receptors called TNF receptors
abbreviated as TNFR.
There are two subtypes of TNF receptors
TNFR1
And
TNFR2
Soluble and transmembrane TNF could bind to either TNFR1 or TNFR2
But transmembrane TNFα prefer binding to TNFR2
TNFR1 are expressed in almost all body cells except erythrocytes
Whereas TNFR2 are strictly expressed in the immune cells.
Generally, activation of TNFR1 lead to sequences of biological reactions end up with cell apoptosis.
On the other hand, activation of TNFR2 promotes cell proliferation.
Both soluble and transmembrane TNFα are the main targets for many biologics
The anti-TNFα biologics can be functionally divided into two groups
Anti TNFα antibodies
And
Soluble TNFα receptors.
The anti TNFα antibodies can be further divided into
Chimeric antibodies
Fully humanized antibodies
Fully humanized with Poly Ethylene Glycol antibodies
Infliximab drug is an example of chimeric antibodies produced from mouse myeloma.
Adalimumab and golimumab are biologics generated completely from human antibodies
The certolizumab is a unique biologic where polyethylene glycol Fab segment is connected to the human monoclonal antibody
Etanercept drug contains soluble TNFR2 receptors that bind and inactivate TNFα.
Over the last twenty years the biologics have significantly improve the remission rates in many rheumatoid arthritis patients
However, 40% of patients do not respond to biologics treatment
To enhance the effectiveness of biologics in resistant patients
The next generation of biologics should work more selectively
They should block TNFR1
and activate the TNRF2
Now we will go through the other biologics
These biologics attack either cytokines or cellular targets
The targeted cytokines include
IL-6
IL-1
And IL-17
Whereas T cell and B cells are the main cellular targets
IL-6 is attacked by tocilizumab antibodies
While IL-1 receptors are blocked by anakinra biologic.
Secukinumab is IL-17 antibody.
T cell are deactivated by abatacept
Whereas B cells are depleted rituximab biologics.
Unfortunately, the cost of biological treatment is very expensive
The one-year treatment course for one patient can cost up to £10 000
Therefore, after the end of patency of famous biologics many biosimilars have been introduced to the clinical practice
Biosimilars Have similar structures, mechanism of actions, clinical efficacy and side effects of original biologics
Fortunately, they cost much less than the original biologics
Dozens of biosimilars have been licenced for clinical practice worldwide and hundreds are tested in clinical trials
This video was designed by Dr Jehad Hammad and Professor Susan brain