nos-trum. pronunciation: \nos'-trum\. noun. Etymology: Latin, neuter of noster our, ours.
1. a medicine of secret composition recommended by its preparer but usually without scientific proof of its effectiveness.
2. a usually questionable remedy or scheme.
See here for more discussion.

Thursday, October 14, 2010

A New Approach To Degenerative Arthritis. Promising, But Nowhere Near Practical Yet

For those of us who have chronic joint pain, a potential treatment using a monoclonal antibody to inhibit pain generators. 

A study in the New England Journal of Medicine (Oct 14) looks at using an antibody to reduce knee pain for those who have osteoarthritis (the degenerative type of arthritis; i.e., due to wear-and-tear).

The pathology goes like this:  over time, the inner surfaces of our joints become worn down by rubbing together for years, or due to imbalances (or increased weight) that create increased pressure, or by scarring from trauma.  Once the cushioning and protective surfaces are gone, then bone begins to grind against bone, and we get inflammation and pain.  The process continues and we are treated with Motrin-type drugs to reduce inflammation and therefore lower the pain.  But as long as mechanism that started the problem continues, the condition worsens.  In severe cases, the answer is replacement of the joint with an artificial unit (definitely not minor surgery).

[Note:  the other types of arthitis, like rheumatoid arthritis, are caused by different mechanisms...and treatment is likewise different]

It would be great if you could reduce the pain, and increase patients' mobility without the need to take non-steroidal anti-inflammatory drugs (Motrin, Celebrex, etc), that only last for hours and can occasionally cause GI bleeding.

It turns out tha,t in inflamed joints, there's a protein called nerve growth factor (NGF) that acts on the pain nerve fibers to increase the sensitivity of these pain nerves, leading to increased pain.

The hypothesis is, if you inhibit NGF, you will decrease the pain.

The study referenced above gave an inhibitor of NGF called tanezumab or placebo to 460 patients with moderate to severe knee pain.  It was given by two injection--at increasing doses--two months apart, while monitoring pain (using standard survey measurements).

The results were pretty good.

The upper graph is reduction in pain, the lower is how good the response was.  There was also a trend toward a better response with higher doses.

Conversely, adverse reactions increased with dose.  About 6% dropped out of the study due to reactions.  Most common was headache after injection.

1.  Intermittent injections are more prone to safety concerns and practical considerations.  A better route of administration would be good.  Every two months is not bad, but...
2.  Safety in the long run is not addressed here.  More work to be done.
3.  No evidence that this slows the progression of the just reduces the pain (which is good in itself)
4.  No comparison to the relief of pain using other drugs.

For Onion Peelers,
Mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P-value <0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients' global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P-value ≤0.001).

Unlike chemical agents, which can have broad effects throughout the body, antibodies are targeted to specific agents of disease and symptoms.  On the other hand they are more complicated compounds and can cause immune reactions themselves, sometimes.

Still, this line of research is very interesting and worth exploring further.

Doc D

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