Chronic pain relief: too much of a good thing?

Since I wrote about knee replacements for arthritis yesterday, now seems to be a good time to note a puzzling development with a new class of pain medicines known as anti-nerve growth factors that are being developed to treat everything from osteoarthritis to cancer pain.

The need for new pain meds - especially non addictive, non-opiate drugs - is high, and this would be the "first important new class of drugs for general pain since the prototype non-steroidal anti-inflammatory drug (NSAID), came into general use at the end of the 19th century," according to Nature Biotechnology.

The anti-NGF drugs have a lot of promise for severe osteoarthritis, and seem to have offered good pain control in ongoing trials - but those trials have also been halted by the FDA over worries that the drugs may be causing rapid joint necrosis and joint failure in some patients. (Clinical trials for other indications, like cancer pain, are ongoing.)

The FDA is holding an advisory committee meeting next week to review the full data on the medicines and to try and parse exactly what is happening.

One theory is that the drugs actually worked so well at dulling pain that patients became much more physically active - and basically exercised to the point that they did extensive damage to their own joints. If this theory bears itself out, the FDA will likely let trials on the drugs continue, perhaps with a warning that patients should limit their physician exertion after beginning treatment so as not to overstress their joints.

Earlier, Phase II studies with one drug in 2006-07 didn't uncover any joint problems, which only emerged after 16 (out of 6800) patients in Phase III trials developed the problems in 2011.

The drug won't be out of the woods until the FDA has some assurance that joint necrosis isn't an on-target (or off-target) effect of the entire class (several drug companies are developing competing anti-NGF monoclonal antibodies). Some researchers (quoted in the same Nature Biotechnology article) suggested that joint necrosis might be directly related to the drugs' mechanism of action.

Even if the question isn't totally resolved at the advisory committee meeting, the FDA also has additional tools at its disposal to monitor potential adverse effects in the post-market environment (if one or more anti-NGF's are eventually approved for marketing), where patients could be tracked to see if their joint failure rates exceeds the background rate in the osteoarthritis population, and why.

We'll have a much better picture of the benefits and risks of the anti-NGF class after the FDA's advisory committee meeting.

For more background on the drug class, and the FDA's clinical hold, see this Bloomberg article.

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