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Allergic Drug Reactions to Biologics and More
from Peter W.

Dear Ed :  My twenty three year old son has severe psoriatic arthritis and scalp and genital psoriasis.  He can no longer talk, hold a metal fork or walk unaided.  Three years ago he had no symptoms of either PsA or P.  It has been a rapid and devastating attack.

Until the arthritis and psoriasis started three years ago he had hay fever,  asthma and allergies to some foods and meds.  He has rapidly acquired allergies/adverse reactions to many more medications since, including methotrexate, sulfasalazine, Arava (loss of lung function and bloody hives) as well as to analgesics aspirin, Celebrex, and naproxen (loss of lung function).  His doctor has diagnosed him with aspirin induced asthma.

Last spring at two shots a week of Enbrel, he had a brief several week renaissance.  He got his voice back and was able to use a computer mouse again. The psoriasis patches on his head and genitals cleared.  Sadly in less than a month of two a week Enbrel shots, his symptoms got worse again. The psoriasis patches returned. He lost his voice. He was unable to use his computer mouse.

I had read that switching TNF-alfa inhibitors sometimes helped.  I suggested Humira to his doctor. She agreed. Paul had to wait several weeks to start the Humira after stopping Enbrel and during that wait he got much worse.  He used Humira for eight weeks in the summer.  He never recovered any abilities and actually got worse: more joint and tendon pain, more psoriasis patches.

The doctor switched him back to Enbrel shots every other day — 87.5 mg a week.  He has improved a bit but never to where he was last spring let alone three years ago.  We suggested Amevive to the doctor as it was a fusion protein similar to Enbrel but it hit a different target — T-cells. 

Enbrel is one of the very few medications he has not reacted to. Because he reacts to nearly everything and the reactions tend to be life threatening, we wanted a similarly made medication. 
 
The suggestion seemed so logical to me, yet his rheumatologist reacted in anger.  She said she had never heard of Amevive.  She would not prescribe it. 

Instead she wanted to give him Remicade.  I refused as Remicade is a chimeric monoclonal antibody which contains between 30 and 70% mouse proteins.  Because of his adverse reaction history, I felt that he has a greater chance than most to convert and become allergic to mouse proteins.  Once he had converted he likely will have lost a host of other chimeric monoclonals as well, most importantly Rituxan. 

Rituxan is also 30 to 70% mouse.  I do not want to risk losing Rituxan just to try one more TNF alpha inhibitor.  He has failed at two so far.  Why should another TNF alpha inhibitor be any better? Rituxan has a completely different target — namely the B cells including the maladapted ones that are producing the rogue antibodies that are attacking and labeling (for macrophage attack) his skin, tendons and joints.

Rituxan is taken only once every six months.  Remicade is taken much more frequently.  The more exposure Paul has to mouse proteins in his blood the more likely he is to convert. Given his history I feel it quite likely that he will convert at some point to murine proteins but I would like it to be as far in the future as possible.  Less exposure means less chance of converting and a longer time until he does convert.  The more times he is exposed to mouse proteins the more likely his immune system will notice the foreign proteins and go wild giving him an adverse reaction. Then it will never forget the mouse protein and his immune system pooch is screwed for all further uses of monoclonals that are part mouse.

Rituxan wipes out the B cells.  It is currently unique.  There is no other medication that specifically targets B cells. I do not want to risk a unique medication for just another TNF alpha inhibitor.  Two of which have failed him already.

For many RA patients, Rituxan has been miraculous.  Maladapted antibodies seem to play a huge part in the autoimmune cascade.  Recently they were implicated in MS as well.

Sadly the FDA has not approved the use of Rituxan as of yet for PsA or P, but my wife and I would pay for it out of pocket if it would give Paul relief.  However, if he has converted to adverse reactions to murine (mouse) proteins, no amount of money will make his immune system go back to a non-reactive stage.

I see clinical trials for CLL and RA of a three drug "cocktail" consisting of Enbrel, Rituxan and methotrexate.  Enbrel soaks up the inflammatory cytokine TNF alpha, Rituxan knocks out the maladapted B cells and their antibodies, methotrexate stops cell proliferation (of T and B cells).

Paul cannot take methotrexate.  After eight weeks his body converted.  He now has adverse reactions to it in his lungs.  But he can still take Enbrel and likely could take Rituxan as he has yet to be exposed to any murine proteins. But he could not take Rituxan if he has not lost his ability to handle mouse proteins. 

If the RA phase III clinical trials go well, I see Enbrel and Rituxan as a bridge to the future for Paul.  He will only need a few infusions before the new fully human anti-B-cell monoclonal comes on line, HuMax CD-20 which is now in clinical trials.  His condition has worsened so quickly and so inexorably that he needs to have Rituxan as a back up.  I do not want to risk murine conversion of his immune system by giving him Remicade.

How do I get his rheumatologist to understand my concerns about Remicade?  -Peter W.

*****

Ed’s Response:  Your son seems caught in that troublesome place where rheumatology and dermatology overlap but don't comfortably co-exist.  I've been witness, myself, to the tiptoeing and grimacing amicability that defines this state.  When you talk about Enbrel, Humira, Remicade, you are talking about drugs both groups prescribe.  Amevive is foreign to a lot of rheumies.

Your son's condition is too precipitous for you to get stymied by a single doctor.  Can you find another?  (I imagine the dermatologists get very nervous about your son's allergic reactions.)  Dr. Philip Mease is featured at the Rituxan-for-RA web site (http://www.rituxan.com/ra/index.jsp?s_cid=0001&s_src=googleppc).  While it's unlikely he can help your son directly, he may be able to help you either (a) defend your case, or (b) find a more agreeable rheumatologist.  

Best of luck to you and yours.  I'd like to hear back from you if you have the time and inclination.  -Ed

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