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On Raptiva
by Ed Dewke
posted July 2005

(To read the March, 2009 warnings about PML and other infections associated with Raptiva, Click here and here. U.S. availability of Raptiva will cease on June 8, 2009. For more information visit http://www.raptiva.com)

Four week’s worth of the drug and its associated paraphernalia are shipped as one might expect a donated organ to be shipped.  A cardboard outer-box bearing address, et cetera.  An inner foam lining that opens like a cooler.  In there, wedged between slabs of ice wrapped in plastic, is the actual box, colorfully designed, that contains the Raptiva.  This you refrigerate. 

Every week you remove one “tray.”  These look like a small microwave meal.  A semi-opaque partitioned plastic tray with a peel-away cover (see illustrations).  But all or most of what’s inside is inedible.  A syringe filled with sterile water.  A vial containing a small amount of white powder.  Two alcohol prep pads in tear open pouches, two needles for the syringe, each encased in plastic and sealed in a paper wrapper.  And a 36” by 18” piece of paper on which is printed, both sides, a dissertation. This absolute marvel of modern printing economy has been folded to the size and heft of a cigarette lighter. The dissertation contains instructions (again) on self-administering the medicine AND the FDA-prescribed information that must accompany the drug.   

At a tad over $1,000 per month for Raptiva, each weekly tray is over $250.  And you have to mix the medicine yourself.  As the lady selling $150-per-bottle diet pills on TV would say, “If it works ... it’s worth it.”

I’ve been taking insulin daily — 2 to 4 shots depending on my gluttony — for eight years, so for me the trauma of self-injection was a non-issue.  I can understand, though, the temerity of others who have never self-injected and face this ritual with Raptiva (or any biologic) for the first time.  I’ll say this now (only once) to put we diabetics in our place.  Injecting Raptiva is NOT like injecting insulin — so please, be careful about making comparisons.  The similarity stops at the fact that both are subcutaneous (shot into fat just beneath the skin, not muscle) and the midriff region is the most likely locale.  The significant difference is this:  a much smaller caliber needle is used for insulin, which makes the puncture through the skin easier and less painful.  The fact that I must take several insulin shots daily and only 1 shot of Raptiva per week is, for this reason, evidence that Good still outweighs Evil in the universe I occupy.  If the reverse were the case, there would be cause for despair.

Genentech (the manufacturer of Raptiva) has done everything possible to mitigate the experience of being a “Raptiva user.”  A snappy “kit” sent to the new patient some time before she receives her first monthly supply spells out the administration process in the most minute detail (in a video AND in print).  The kit includes a fold-open “mat” (like a Parker Bros game board) with places marked to set your syringe, the needles, the vial, your alcohol prep pads.... Also included is a miniature red plastic “sharps disposal” container for proper handling of biohazardous waste (a.k.a. a special trash receptacle for used needles).  And with uncanny timing, a new one of these containers arrives in your mail just when needed!  (Note:  Electing to use your sharps container for your used needles is a good idea, but do some research about disposing of these containers — which seal permanently once they’re full.  Laws vary from State to State.  If your State is particularly strict, you might want to ask your doctor if you can bring your “full” sharps containers to his office for disposal.  You can bet his office uses a commercial disposal service.)

To take Raptiva, you must start by injecting the sterile water that comes in the syringe into the vial with the white powder.  The “white powder” is, in fact, the Raptiva (efalizumab) in a dehydrated state.  The reconstituted Raptiva is then drawn back into the syringe.  The amount you actually inject is based on your weight and pre-calculated for you.  Typically the amount is between .6 and 1.2 ml.

You may ask, “Why can’t they put Raptiva in a pill, or at least a serum — like cough syrup — that you simply swallow?”  The answer is that the Raptiva molecule — a protein of biologic origin — would be destroyed in the digestive system.  Whatever part of the stuff that made it into your blood — if any — would no longer work.  The same is true for insulin, which is why we diabetics as well as flakers who use Raptiva or other biologics, must get used to giving ourselves shots.

*****

What has given birth to Raptiva and all the other biologics currently approved or being tested for the treatment of psoriasis is a better understanding of the mechanics of psoriasis on the molecular level.  It’s rather like setting up a long and convoluted chain of dominos in order to knock them down.  Each domino is different.  Each step in the chain of causes and effects that result in psoriasis is different, too.  What the biologic manufacturers try to do is find a domino in the chain that, if removed, will halt the tumble.  Or, put more directly, locate a step in the biochemical psoriasis process which, if removed or inhibited, will prevent psoriasis from being “made.”

This hunting sport is played in a landscape that describes all the various ways our immune systems can affect our skin.  When you are cut, for example, certain immune system responses have been observed and hence are anticipated.  For a few years now scientists have been observing what the immune system does in and around psoriasis lesions.  They have identified a number of cell-types that play a role.  The language of cells is a repertoire of proteins.  There are conditions under which certain cells emit certain proteins and conditions under which certain other cells react in certain ways to those certain proteins.  A dialogue of chemical communication has now been associated — at least rudimentarily — with the “making of psoriasis” and each of our growing raft of new biologic medicines purports to take out a particular domino that will prevent the communication from occurring successfully. 

A pause is in order to describe why this process excites so many doctors and scientists.  There have been immune system therapies for combating psoriasis for a few decades.  The most popular drugs of this kind have been methotrexate and cyclosporine.  Methotrexate is also a chemotherapy drug for cancer.  Cyclosporine is also a powerful immunosuppressive agent used to ensure newly transplanted organs aren’t rejected by needy bodies.  It had been noted peripherally that both these drugs improved or eliminated signs of psoriasis.  Eventually, studies were conducted to determine safe dosages for psoriatics (much smaller dosages than needed to treat cancer or inhibit organ rejection).  As it stands today, psoriatics can take methotrexate so long as they regularly monitor their liver functions.  Methotrexate, a.k.a. MTX, has a cumulative toxicity and it is expected that regular users will eventually have to stop taking MTX — at least for awhile — to reverse adverse effects on the liver.  (Some people have defied this hypothesis by using MTX regularly for 14 or more years without liver disease.)  Cyclosporine is considered by many derms to be a short-term fix for psoriasis hard-cases.  Rarely is it prescribed for longer then 12 consecutive months, though many flakers have been on and off the regimen several times.  Kidneys seem to be particularly vulnerable to cyclosporine’s particular toxicity.  And kidney’s aren’t nearly as reparable as livers.  In the era of repurposing these major immunosuppressive drugs for psoriatics, little-to-nothing was known about the chemical dialogue occurring within and around the immune system in our poor flaking skin.  The dominos weren’t understood.  No single domino could be appreciated.  These drugs worked by blasting away at the immune system in toto.  To make our analogy complete, it would be safe to say the new biologics are plucking key dominos from the domino-chain set up on the table while the older more cataclysmic immunosuppressives knock over the whole table.  The excitement lies in the purported safety of the newer approach.  While it’s dangerous to maneuver through life with a severely drug-compromised immune system, that might not be the case if only one itsy bitsy piece of the chemical dialogue is interrupted.  Wouldn’t it be sweet if turning OFF one’s ability to flake had no effect at all on one’s ability to, say, fight off an infection?  (Don't get too cheery.  All of the biologics compromise our ability to combat infection to some degree. What they DON'T do, however, is ruin the liver or the kidneys or anything else, so far as we know.)

*****

I’ve written about proteins comprising the biochemical language our cells use to communicate.  This is, of course, a figure of speech, a way for me to wrap my aging mind around these newly-discovered, miniature-but-complicated phenomena that comprise our selves.  It is easier for me to understand what was learned next about this protein-based communication if I continue to think of it as a language.  An acquaintance of mine who happens to work for one of the biologic manufacturers, and who is a scientist in this area, suggested to me a while back that “the immune system may have back-up plans.”  We were discussing those enigmatic and statistically less significant number of cases in which flakers do NOT respond well to one or more of the biologics.  If we know from experimentation that by inhibiting the expression of domino X psoriasis lesions will not form, why doesn’t it work for everybody?  The answer to that question isn’t well understood, yet, but one hypothesis is that immune systems have back-ups.  This is easy to fathom as a matter of language.  Most English speakers would understand and act upon this statement if made to them by someone sitting behind them in a theater:

“Sir, the auditorium is filling with smoke and it might be a good idea for us all to leave.”

On the other hand, some people won’t get it.  Which is why, as a back-up, we can shout FIRE! at the top of our lungs and it is likely those remaining in the theater will leave.

It could be that the domino any biologic plucks from our psoriasis-forming-chain is only one expression among several (many?) that can have the undesired effect of making lesions.  Pull that domino — take that drug ... inhibit that protein-response cycle ... silence that little bit of cellular jabber — and the communication may still take place using other options within the language.  (Somewhere in the control center of our immune system, an interpreter chuckles as we mix our medicine and wincingly inject it: Hah hah hah!  While the little cell who had been ordering our skin to Flake! Flake! Flake! is caught unawares by our new medicine and summarily silenced, somewhere else a cousin awakens to take his place:  Flake anyway!  Flake anyway!  Flake anyway!)  Of course, the logic of hypothetical immune system back-up plans has some problems, too.  For example, if this is, in fact, the way immune systems work, how could ANY biologic work?  Wouldn’t MOST patients’ immune systems find a way to keep on flaking?

So far the different biologics available to combat psoriasis all target different dominos in the chain that has been associated with psoriasis.  A few have been available long enough, now, for many of us to have tried several.  It has become clear that if one doesn’t work it doesn’t mean they will all fail.  I tried Enbrel and, while it did help my psoriatic arthritis, after six months my skin lesions were worse because the Enbrel wasn’t working on my skin and I wasn’t using much of anything else to combat them.  My next intended attempt was to be Amevive, but preliminary blood work uncovered an extremely low CD4 lymphocyte count.  As Amevive was supposed to work by suppressing CD4, I was not a likely candidate.  Oddly enough, my psoriasis was raging at this time, suggesting a strong army of CD4 lymphocytes was NOT a requirement for my psoriasis to bloom.  Perhaps CD4 was a back-up plan.  Or maybe I was flaming on a plan that backed-up my diminished CD4 protagonists?  Whatever.  Eventually it came time for me to try Raptiva.

*****

Ironically, by being the “most tested” biologic so far, at FlakeHQ Raptiva had the weightiest bad rep when it was approved by the FDA in October, 2003.  This was because several FlakeHQ correspondents had bad experiences during early trials (search on ‘CD11a’ from the homepage to browse this correspondence).  All of the bad reactions from the trials reported here are listed in the Raptiva “Adverse Events” table, which includes statistics that suggest all of them were rare (less than 2% of the test subjects — click here to peruse this on line).

I wasn't paying attention to statistics about adverse reactions when I made the decision last October to try Raptiva.  My Amevive intentions had been thwarted in January of 2004 so I’d been enjoying near-complete clearance on cyclosporine for most of the year.  By September the signs that I was close to maxing out the “good times” on cyclo were evident (blood pressure elevation, edema...).  Several emails about adverse reactions during Raptiva trials (some from before the name “Raptiva” was fixed) were in the front of my mind when my derm and I decided to wean me off the cyclo and get me “purged” to commence Raptiva in January. 

On October 26, 2004, I attended a Genentech road show about Raptiva in Nashville (click here for report).  What I learned there eased my mind considerably.  It would be safe to say from that point until I actually started using Raptiva I was enthused about the prospects.

*****

Your first dose of Raptiva is called a “conditioning dose.”  It is smaller than the amount you will administer thereafter.  I don’t recall the reasons for the “conditioning dose” being explained in any detail, but I think it’s one way to reduce initial adverse reactions.  (Many if not most of the adverse reactions reported at FlakeHQ occurred at the beginning of trials.)  To count the number of weeks you are “on the regimen,” you start with your second dose, which is calculated according to your body weight. 

Genentech has set up a patient support program called “Clearly You.”  It is a combination web site and email “list.”  You can register for password-protected access to the web site and sign-up to receive regular email newsletters.   Over my first 12 weeks of using Raptiva I came to appreciate “Clearly You.”  It kept me optimistic while my body appeared to be doing nothing.  Be patient, Clearly You opines.  Remember that Raptiva is working from the inside out.

As the 12 week mark approached, my spirit started to sag.  So many people had professed “evident improvement” inside 6 weeks.  Here I was twice that far into the regimen, still flaking.  My larger lesions had flattened and become less inflamed, but they were still flaking.  Some areas showed more improvement than others.  All-in-all I wasn’t experiencing any of the euphoria I dreamed about.  Then the ominous pronouncement from Clearly You:  If you are not seeing improvement at 12 weeks, consult your dermatologist about next steps.  Well dang.  Is Clearly You giving up on me, too?  I was, in fact, seeing some improvement.  But was it enough?  If this were as good as I would get — if somehow a ceiling was hit at 12 weeks — then I wouldn’t be a happy camper.

I think a part of my diminishing positive attitude had to do with my worsening psoriatic arthritis.  This was not a surprise.  Me, my derm and the world at large knew Raptiva was unlikely to palliate PA (click here for relevant Genentech news release). Nonetheless, I’d already tried one of the biologics approved so far that IS KNOWN to palliate PA (Enbrel) and it had done nothing for my skin.  I was more or less resolved to the notion that so long as I was trying biologics, I’d probably get help with skin or joints, but not both.  Being resolved is pretty easy until things start hurting a lot.

I have visible psoriatic arthritis in my fingers, toes and knees.  I suspect it’s present in my hips and lumbar region; however, these may be age-related osteoarthritis (for which I’ve been consuming outrageous quantities of glucosamine and chondroitin for several years).  Of my several joints with PA, the knees are by far the worst.  Without pain medicine, the PA in my knees can be debilitating, preventing me from walking and driving.  (My doctors continue to remind me that this condition isn’t helped by the fact that I work in the attic of my home, requiring me to negotiate a very steep set of stairs several times a day.  I really should videotape myself climbing and descending those stairs when the PA in my knees is bad.  My grandchildren will vouch for the fact that it’s very funny to watch.  All I’ll say right now is, during these bad times going up and down the attic stairs can require four limbs and a rump.  Use your imagination from there.)

At the 12 week mark my PA was bad enough for me to want to do something drastic.  My skin psoriasis was not, in my estimation, improved enough for me to be permanently glued to my Raptiva routine.  A decision was in order.  I didn’t want to toss the whole business into my derm’s lap and wait for an edict from him.  I wanted to work out next steps myself.  I spent time browsing through correspondence at FlakeHQ.  Reviewed my Enbrel experience.  I finally decided I would give Raptiva six months — the same amount of time I’d given Enbrel.

Just making the decision seemed to make a difference in my therapy.  Some people believe ones state-of-mind can affect healing.  I guess I’m on their side.  When I “resolved myself” to another 3 months on Raptiva the 12 week plateau gave way to a new burst of improvement.  In four-or-so more weeks most signs of my old lesions were now gone completely.  I’ve been most impressed with my hands and nails.  There are no lesions on my hands, and all hints of the grotesque nails I began the year with have now been pushed out to the trimming edges of my nails — which means they’ll be lopped off in the coming few weeks.  The new nails that are doing the pushing are nearly perfect. 

 

Nails in April, 2005...

 

Ed's Hand today (June 22, 2005)

*****

Things have been going so well for the past month that now (June 22, 2005), as my six month run on Raptiva is coming to an end, I’ve opted for three more months, through September.  The only fly in the ointment is my psoriatic arthritis.  In May, blood tests showed me anemic and I dropped quite a few pounds unintentionally.  My docs made me undergo a colonoscopy (oh, thrill!) which, fortunately, revealed no problems.  Now we suspect my iron deficiency may be related to stomach or upper intestinal bleeding from excessive use of OTC painkillers (ibuprofen, naproxen) and now even these are being curtailed.  I’m trying to make Tylenol alone work to get me up and down those attic stairs and ... well ... some days are better than others. 

I’m trying to separate, in my mind, the skin psoriasis and the psoriatic arthritis.  Let’s pretend they are two unrelated ailments.  Are you with me?  Then let me introduce you to my new nearly-lesion-free skin, my old and wrinkled but nearly-unblemished hands, my rough-but-not-grotesque fingernails.  All these belong to someone who has his skin psoriasis under control — at least for now.  We won’t talk, now, about my poor joints.  That’s another story for another time.  Would you care for some tea?

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