Intended for healthcare professionals

Rapid response to:

Analysis And Comment Drugs

Lessons for clinical trials from natalizumab in multiple sclerosis

BMJ 2006; 332 doi: (Published 16 February 2006) Cite this as: BMJ 2006;332:416

Rapid Response:

True costs of Miracle Drugs?

Abhijit Chaudhuri has written a thorough, detailed and damning
article on the perils of rushing drugs to market too fast.

So many comments spring to mind, but I will explore only two:

(1) One of the attractions of biological therapies is that we think
we know how they work, because they specifically target certain molecules.
In my field, we understand that anti-TNF-alpha antibodies target TNF-
alpha; because we think we know what TNF-alpha does, we delude ourselves
that we can predict the toxicity and that it should be limited to our
understanding of TNF-alpha's role (contrast this with Methotrexate, where
our understanding of mechanism of action is limited). To our cost (or the
cost of the patients in the trials) we found that blockading TNF-alpha
actually makes heart failure and multiple sclerosis worse; TNF-alpha is
one of the body's defences in these conditions and interfering with it is
not advised.

(1a) As a brief aside; Dr. Chaudhuri mentions that Case 1 was exposed
to both infliximab (for Crohn's disease) and Natalizumab (for MS). One
wonders whether the patient's physicians considered whether the infliximab
might have caused or aggravated the MS ...

(2) A fractional prevention of relapses may make little sense to the
patient but it does enable calculation of an NNT. In the AFFIRM trial a
difference in relapses of 0.49 per annum between the two groups equates
roughly to an NNT of 200 to prevent one relapse per annum... or about $4.7
million in Natalizumab infusions. In SENTINEL a difference in rate of 0.42
per annum equates to an NNT of 238, or $5.6 million to prevent one
relapse. Once more, presentation of trial results in terms of relative
risk reduction obscures the true cost / benefit of treatment. How the drug
company ever thought it would be worthwhile for a regulatory agency to
approve this therapy is beyond me.

In conclusion, I would argue that not only do we need a debate about
whether fast-tracking medicines increases the likelihood of harm to the
patient, but more importantly at what point we decide the costs of therapy
are not justified -even if the benefits exist.

I will leave the obvious parallels with herceptin to other posters -
I'm sure several people will comment ...

Competing interests:
None declared

Competing interests: No competing interests

17 February 2006
Matthew L Grove
Consultant Rheumatologist