Biological Weapons in the Fight Against Rheumatoid Arthritis

Biological warfare generally refers to the use of pathogens (infectious agents) such as viruses or bacteria that are delivered to an enemy. The term, as applied to the treatment of RA, really refers to the use of antibodies produced via biological processes. These antibodies are designed to target biological processes of RA.

Wikipedia Commons

The biological basis for RA was outlined in an earlier blog post. In that post, the biochemical picture of RA in simplistic terms was outlined as follows:

• Something unknown triggers lymphocytes (T-cells, B-cells)
• Lymphocytes trigger Tumor Necrosis Factor (TNF) and inflammation
• TNF induces another chemical called RANKL
• RANKL promotes the production of osteoclasts (special bone cells)
• Osteoclasts erode bone tissue.

Once these processes began to be understood in the 1980s and 90s, scientists starting developing and testing biological treatments for RA. These treatments are disease modifying (DMARDs) in the sense that they modify or slow the effects of the disease. Compared to other traditional weapons in the fight against RA, biologicals demonstrate more effectiveness in disease modification. They are even more effective when combined with the use of methotrexate. There are currently 18 biological treatments approved by the FDA and eight are approved for use in rheumatoid arthritis. [i] Being that these treatments consist of complex and fragile proteins, they must be injected into the body.

http://www.flickr.com/photos/42dreams/

Due to the complex procedures needed to develop and manufacture biological treatments, they are very expensive, typically costing $15,000 – $30,000 per year. Pharmaceutical companies currently have a 14 year lock on the copyright on biologicals (it’s 7 years for small chemical drugs). But there may be traction in the Congress and by President Obama to change this so cheaper, generic versions are available. [ii] [iii] The cost of these treatments raises cost/benefit questions (“pharmacoeconomics”-hopefully a future blog topic). Never the less, it has been shown that the effectiveness of biologics reduces the number of work days missed and disability claims. [iv]

Like many chemical RA drugs, biological treatments suppress the immune system in the fight against RA. This leads to higher incidents of lymphomas and serious infections in patients who use them. But most RA patients would agree that the benefits far outweigh potential risks.

Below is a table displaying the currently approved biological treatments for RA. [v] [vi] [vii] [viii]

Common Name	Antibody Name	Manufacturer	Mechanism	Date FDA Approved in U.S. for RA	Typical Administration
Enbrel	Etanercept	Amgen &  Wyeth	Inhibits TNF	1998	Weekly subcutaneous injection
Remicade	Infliximab	Centocor Ortho Biotech	Inhibits TNF	1999	Infusion every 8 weeks
Kineret	Anakinra	Amgen	Inhibits Interlukin-1	2001	Daily subcutaneous injection
Humira	Adalimumab	Abbott	Inhibits TNF	2002	Twice monthly subcutaneous injection
Rituxan	Rituximab	Genentech	Inhibits B-cells	2006	Two initial infusions then every 24 weeks
Simponi	Golimumab	Centocor Ortho Biotech	Inhibits TNF	2009	Monthly subcutaneous injection
Cimzia	Certolizumab pegol	UCB	Inhibits TNF	2009	Monthly subcutaneous injection
Orencia	Abatacept	Bristol-Myers Squibb	Inhibits T-cells	2009	Monthly infusion

Many of the RA blogosphere community members have experience with these biological treatments. I had an initial five month experience injecting Enbrel every week. Monday morning brought with it the joy of using their autoinjector pens. Within a few weeks I felt like I got my life back. My energy levels soared and my rheumatologist was quite pleased with my progress. But after 3-4 months I could feel myself slipping back into full blown RA symptoms. My rheumatologist suggested that I try a newly approved TNF inhibitor called Cimzia. It is designed to stay in the body longer and only requires monthly injections. I’m heading into my third month and while I can see an improvement, the jury is still out on its long term effectiveness (see previous post). But the past three days have been wonderful and I’m thankful for these treatments (in spite of the fact that I must jab myself). Some even experience remission after being on biological treatments – this is my hope and dream.

I feel fortunate that I have not experienced any infections since being on biological treatments. Colds and swine flu visited several members of my household and I was spared every time. I suspect that having a strong immune system prior to treatment helps. My entire professional career has been working in K-12 schools and universities and I’m guessing that I’ve been exposed to plenty infectious pathogens! Getting regular vaccinations to seasonal and H1N1 flu viruses is important (I got both).

Even though RA may take a back seat to other diseases like cancer and heart disease, plenty of scientists continue to hunt for more successful biological treatments (see earlier post). Of all of the weapons currently used in the war against RA, they represent the most effective to date. But there remain several sticky points to their use…costs and infections. Hopefully these issues will be resolved in the future.

Next post…Natural Treatments for RA

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[i] http://www.consumer-health.com/services/biological_drugs.htm

[ii] http://www.news-medical.net/news/20090722/Costly-biologics-drugs-prompt-exclusivity-debate.aspx

[iii] http://www.tri-cityherald.com/1182/story/810461.html

[iv] http://ezinearticles.com/?Are-The-New-Biologic-Drugs-For-Rheumatoid-Arthritis-Worth-The-Cost?&id=559432

[v] http://en.wikipedia.org/wiki/Monoclonal_antibodies

[vi] http://en.wikipedia.org/wiki/List_of_monoclonal_antibodies

[vii] http://www.arthritistoday.org/DrugGuide/drug-chart.php

[viii] http://www.physorg.com/news174077828.html

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