New arthritis drug tofacitinib may be available soon

Robin Wulffson MD's picture
rheumatoid arthritis, tofacitinib, FDA approval, side-effects, safety
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On May 9, a Food and Drug Administration (FDA) voted 8-2 to recommend the approval of tofacitinib, the first oral drug of its kind to treat rheumatoid arthritis. The 10-member panel reviewed the application made by the drug’s manufacturer Pfizer Inc. for the treatment of adult patients with moderate to severe rheumatoid arthritis who experienced an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). The committee was requested to consider four questions.

The first question was “Do the data provide substantial evidence of the efficacy of tofacitinib for radiographic [X-ray] outcomes?" Two panel members voted yes and eight voted no. Leslie Crofford, MD, from the University of Kentucky School of Medicine in Lexington, voted yes. She noted that the evidence of radiographic efficacy was substantial and that she did not interpret substantial to mean "definitive." A panel member who voted no on the question, Elizabeth Smith, a patient representative from Burke, Virginia, noted that she did not consider the evidence of radiographic efficacy to be substantial. However, she agreed with other panel members that a better answer might not be available.

The second question was "Overall, do the data provide substantial evidence of the efficacy of tofacitinib for the treatment of moderately to severely active rheumatoid arthritis in patients who have had inadequate response to one or more [DMARDs]?" All 10 committee members voted yes. They noted that the data were consistent across studies.

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The third question was "Is the safety profile of tofacitinib adequate to support approval of tofacitinib for the treatment of moderately to severely active rheumatoid arthritis in patients who have had inadequate response to one or more DMARDs?" Seven panel members voted yes, two voted no, and one abstained.

On the basis of preclinical and clinical research, Pfizer proposed that 5 mg and 10 mg doses of tofacitinib to be taken twice a day on the basis of its preclinical and clinical research. The FDA noted that the medication was associated with dose- and/or treatment duration-dependent increases in malignancy rates, lipid and cholesterol levels, and serious infection rates. The abstaining panel member, James Ware, PhD, from the Harvard School of Public Health in Boston, Massachusetts, noted that he understood the value of the drug; however, he was concerned about its safety profile. The majority of the panel members who voted yes expressed a preference for the 5 mg dose because it appeared to be comparable in effectiveness to the 10 mg dose. Furthermore, several committee members expressed concern that the indication for the drug was too broad. Lenore Buckley, MD, MPH, from the Virginia Commonwealth University School of Medicine in Richmond, voted no. She noted that she would have voted yes for this question if the indications were limited to high-risk patients.

The fourth question was "Do the efficacy and safety data provide substantial evidence to support approval of tofacitinib for the treatment of moderately to severely active rheumatoid arthritis in patients who have had inadequate response to one or more DMARDs?" Eight panel members voted yes and two voted no. Many of the panel members echoed their preference for the 5 mg dose over the 10 mg dose as well as the need for longer-term safety data. Sherine Gabriel, MD, from Mayo Medical School in Rochester, Minnesota, who voted no, agreed with Dr. Buckley that the indication was too broad and said that she would have supported approval with a more limited indication.

During the open public hearing session of the meeting, David Mandel, MD, a rheumatologist from Ohio, supported the approval of the drug. He noted, "As an oral medication, tofacitinib offers some very promising advantages to patients of ours who do not have access to infusion, who are 'needle-phobic,' or who [have difficulty in traveling to the clinic for infusions]," Dr. Mandel stated during the meeting. "This medication will improve the care of our patients with rheumatoid arthritis."

Take home message:

I find the side-effects of increases in malignancy rates, lipid and cholesterol levels, and serious infection rates to be disturbing. Although individuals suffering from rheumatoid arthritis are anxious to try a new medication, which might provide them with relief, they might be trading the possible improvement of their arthritis with another, possibly serious problem. Just a few days ago, the Institute of Medicine noted that the type, frequency, and severity of side-effects may be higher in the general population than a study group. It also noted that side-effects often do not appear months or even years after a drug receives FDA approval and released on the marketplace.

Reference:
FDA

See also: Closer scrutiny of prescription drugs recommended to protect public

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Comments

I would like to ask where the writer obtained information as follows: "Arthritis sufferers who have not tried aspirin should discuss its use with a healthcare professional, ideally a rheumatologist." This is the treatment that was used back in the '60's, when doctors didn't know any better. I feel very strongly that the promotion of this old fashioned treatment is very wrong. Rheumatoid Arthritis isn't just a little bit of joint pain. It attacks not only joints, but internal organs such as the heart, lungs, eyes, blood vessels etc etc etc as well. It can cause SEVERE disability if left untreated. Aspirin doesn't treat the disease, it probably won't even be strong enough to deal with the pain that is experienced. Thus, any patient who only takes aspirin is in for a NASTY surprise with regards long term prognosis. It would be helpful if the writer in question had taken the time to research the topic better, as sadly all you've done is increase the misconception of a very cruel disease (look at the Wikipedia article as an idea). No one wants to take medication that could potentially cause death or cancer or other side effects, but unfortunately the alternative is much, much worse for most of us. So we will gladly take this kind of medication if it provides some sort of relief. Most of us don't have the luxury to wait 20 years to see what side effects are attached to a drug, we have lives to live now and because this disease causes most of it's damage early on and usually just after symptoms start. This medication might be the difference between being wheelchair bound and being able to walk for some patients for whom all other approved treatments have failed and most will probably take it gladly......Just take the time to think about that.....
I did not recommend that patients suffering from rheumatoid arthritis should start taking aspirin; rather, I recommended that they discuss its use with a healthcare professional, preferably a rheumatologist. Aspirin is an anti-inflammatory agent that has a long and well documented history of benefits and adverse effects. It is still used and being evaluated for use in patients with rheumatoid arthritis. A representative review study was published last year: http://www.ncbi.nlm.nih.gov/pubmed/21975788. The viewpoint I was presenting was that new investigative drugs may have significant untoward side effects that only become apparent after release to the public. Clinical trials found that tofacitinib was reported to have increases in malignancy rates, lipid and cholesterol levels, and serious infection rates; this finding is of significant concern.
Just the fact that you would mention the use Aspirin in arthritis sufferers, shows you do not know RA It is not Osteoarthritis! For me an RD (rheumatoid Disease as it should be called) no OTC pain works at all! None! I have suffered on Methotrexate, had no relief from Enbrel or Humira and have been on prednisone for months and am unable to wean off of it as I get raging flares when we try. I find the end of this article to a very poor choice in wording or a very poor understandi of what we as RA patients have gone through and continue to go through in order to find relief, regain our lives and hopefully prevent early mortality from organ damage. Aspirin! Really!!!!
AMEN!
The hidden surprise in Tofacitinib is that it is also active against ATL and HAM, two serious conditions caused by HTLV. Once this drug is approved, HTLV sufferers will take it to avoid being wheelchair bound by HAM or dead with leukemia from ATL.
There's a serious risk to taking aspirin over drugs that actually treat the disease, too. Namely disease progression, deformity and disability. Please don't give the public the idea that RA can be treated with aspirin or other NSAIDs. Patients need to discuss real RA treatments with their rheumatologists. Minor symptom relief is not the same is disease treatment. There are many patients who don't respond to current treatments, who live with severe pain and disability (despite taking high doses of NSAIDs on a daily basis) and are very eager for a new option. I hear you on the fact that we may not know the full extent of side effects immediately; but there's always a risk-benefit analysis that has to be done. There's also a huge potential upside to this drug. And don't forget that other currently approved RA drugs also come with a long list of potential side effects...and yet patients gladly take them for the chance at getting their lives back.
And the viewpoint that we are presenting is that of the patient. We are all aware of the "benefits" of NSAIDs such as aspirin and the other non-steroidals. They may very well provide a certain amount of relief to those who have mild disease. DMARDs however, are prescribed for moderate to severe disease, in which case non-steroidals are only mildly effective. Your response is a clear picture of the disconnect those in the medical community (and I include myself in that category) have with actual knowledge of the extent of these diseases. Pain, being a completely subjective symptom, is easy to dismiss; "I can't feel your pain, therefore it must not exist". Unless you actually experience the severe and constant pain of autoimmune arthritis and the constant loss of ability you will never understand why we choose these dangerous drugs. My advice is find a few medical professionals who live with RA and ask their opinion. They are just as angry at the minimization of pain and negation of suffering as everyone else on this page.
Aspirin. Wow. So the weekly hangovers from the methotrexate injections have been totally unnecessary? The biweekly ones from the double shots of methotrexate and Humira? The hair loss, the constant nausea, the random vomiting, the plethora of meds and supplements to counteract the side effects...all of it could have been avoided if only my rheumatologist was smart enough to recommend aspirin! I'm 31 years old. I was diagnosed with sero-negative RA 3.5 years ago after the birth of my third child. 2 years ago, I had to stop working. Every day is a struggle just to get out of bed, to get through the day, to take care of my kids. Some days are ok. Other days (like today), I'm sobbing just getting from the couch to the bed at the end of the day. Three and a half years of treatment and my disease is still nowhere close to being under control. The visible damage in my hands and feet make me want to cry. The curious looks from strangers when they see a seemingly healthy young woman ranging from limping to barely able to walk to being pushed in a wheelchair are humiliating. The broken marriage and number of friends lost because they didn't know how to deal with it is heartbreaking. The vast majority of people have NO idea just how serious RA is. They have NO idea what the reality of RA is. There are warriors online who fight every day to correct that. And this article just undid so much of their work. You should be ashamed of yourself!
I followed the link for this study. Did you actually read the study, doctor? All but one of the studies reviewed were conducted PRIOR TO 1990, before biologics were introduced. The following is the author's conclusion: "Based on 23 trials, all at high risk of bias, there is insufficient evidence to establish the value of combination therapy over monotherapy for people with IA. Importantly, there are no studies addressing the value of combination therapy for patients with IA who have persistent pain despite optimal disease suppression. Well designed trials are needed to address this question." I noted in your Bio that you are an OB GYN. How does this make you an expert in the treatment of autoimmune diseases? I respect your knowledge as a physician and as a decorated veteran, but I would suggest you educate yourself from the view of the patient. I'm sure you will admit that as a male GYN you know labor is painful, but you have no idea how the process actually feels. Until you educate yourself on the disease with which we live every day you'll never understand the frustration expressed in this thread.
First of all, it's Rheumatoid Arthritis, not Rheumatoid Uterus. Do you even proof read your ariticles? Secondly, you seem to have the mistaken idea that this is a general arthritis by suggesting it be treated with aspirin. Arthritis is only one symptom of this very serious auto-immune disease. Would you treat MS or Lupus with aspirin? I think not. The idea is ridiculous. It would be like prescribing an ice pack for a broken leg. I am a 46 year old female who was diagnosed over 4 years ago with Rheumatoid Arthritis and articles like these only further confuse the public about this disease. I can no longer work and have tried many, many medications on the market. All biologics carry inherent risks but considering the alternative of permanent, severely damaged joints and all the other complications of RA, most of us would risk these side effects to stop the damage of RA.
First of all, your last paragraph says, "rheumatoid uterus" and second of all, this article is riddled with inaccuracies. "Arthritis sufferers who have not tried aspirin.." Seriously? This website should be ashamed that this article is posted here. Clearly, whoever wrote it knows absolutely nothing about Rheumatoid Arthritis and didn't bother to actually do any real research at reputable sites or with reputable people.
I find it incredibly difficult to believe that this article was written by an MD. The statement that "arthritis sufferers who have not tried aspirin should discuss It's use with a healthcare professional..." seems to have come from an era when RA sufferers often suffered the fate of disfigurement and/or a life confined to a bed or wheelchair. To compare aspirin to this breakthrough disease modifying treatment is misguided at best, and negligent at worst. I would ask the author of this clearly unedited piece about "rheumatoid uterus" to please educate himself or herself as to the seriousness of this disease. Rheumatoid Arthritis is much more than "arthritis" or achy joints. It is an incurable, destructive auto-immune disease which can cause fevers, severe weight loss, muscle wasting, joint destruction, heart disease, periodontal disease, Osteoporosis, kidney disease, lung disease, anemia and serious eye problems. Please don't trivialize a serious disease like this by suggesting that aspirin is some type of cure-all. This author, as well as this website, owe the over 1 million RA sufferers in the US alone an apology. -an RA sufferer
I have submitted this article to IAAM under their Awareness Hotline. Hopefully they can help.
Thank you, Melissa, they can and they will.
Whatever bone-headed thinking ( non-thinking ) person suggested that patients should use ASPRIN for Rheumatoid Athritis is either delussional, uninformed or plain evil. RA is NOT! NOT! Granny Rhematiz folks. It is an Autoimmune Disease that affects far more than the joints in hands and feet including ALL internal organs and all joints in the body including the voice box. As a possible " informed source" that people will read and possibly believe- you have a DUTY to know what the heck you are telling people and that it be truth and not fairy tales. ASPRIN will do nothing but upset the stomach in the case of RA. Get your facts straight and report responsibly!
Aspirin? Those of us with RA should speak to our medical team about aspirin? That is like telling a cancer patient they should speak to their doctor about tylenol. As an autoimmune disease the real breakthroughs will come with treatments that address the source of the inflammation - the immune system. To suggest that what a sufferer of RA needs is aspirin either at beast demonstrates a complete lack of understanding of the disease and at worst it insults RA suffers who deal with a myriad of health issues daily.
This Asprin thing is a joke and Mr. Wulffson isn't a real doctor right? If not, EMAX HEALTH - you should be ashamed of yourselves.
If only someone had told me I could take ASPIRIN to help my RA earlier! It would have saved me from having to take Methotrexate, Arava, Prednisone and all of those Humira injections! Why didn't my Rheumatologist tell me that if I took aspirin it would stop the damage RA is doing to my heart and lungs? All those mornings I couldn't get out of bed despite being on some of the most expensive drugs available could have been avoided with an aspirin! I guess that means that if I go take aspirin I won't have to be legally disabled at 29 and I'll be able to return to work. Hopefully the aspirin will also fill in the erosions in my bones (not the small ones in my hands and feet, but the bigger joints as well). One question...Will aspirin also be able to cure my Sjogrens since it has the ability to cure other autoimmune diseases and when will aspirin FINALLY be approved for the treatment of Lupus and MS? Thanks for your insightful article!
Aspirin. Why of course! Silly me, there's a wonder drug out there for those of us who "suffer from arthritis", and we never considered that. Well actually, in the first 8 years of my disease I took nothing but aspirin because my physician kept telling me I didn't have RA. Since then I've learned I'm sero negative, and yes indeed, I don have RA. Eight years of aspirin therapy gave me zero relief, however, it did result in severe ulnar drift in both hands and salicylate toxicity. Yes, we are all aware of the poor safety profile of the DMARDs and biologics. Stand in front of a speeding freight train, then attempt to live life as you normally do and you may then realize why we take the chance with these dangerous drugs. DMARDs did not give me "relief". They gave me my life back. Shame on you for suggesting that in our anxiousness to find "relief" we would throw caution to the wind and take these drugs. And as for recommending we speak to our rheumatologists about aspirin use, we'll do that, right after you speak to newly diagnosed breast cancer patients and suggest they speak to their oncologists about using less dangerous wheat grass. RA patients are not just concerned about the level of pain we live with every day, we are also concerned about the damage to our cardiopulmonary system, our eyes, our livers. RA doesn't simply damage joints. I am absolutly outraged at this egregious "take home message". Take this home.
RA is not treated the same way as it was treated 20 or even 10 years ago. Through research Drs have found that an aggressive treatment is the course to follow to slow or stop the progression of the disease thus preventing joint deformation. The most common drug used to treat RA is Methotraxate. If the author of this article had done just a bit of research she would know that taking aspirin along with Methotraxate is a no,no. They put the warning label on the bottle when the dispense the medication. You can not take aspirin while on Methotraxate because it increases the toxicity level of the methotraxate in your body. I am not a Dr this is something I learned simply by reading the warning labels on my medicine bottles. I am 35 yrs old and have been living with this horrible, painful, selfish, robbing disease. Please don't tell me aspirin will help because my aunt has lived with this disease for over 30 yrs and all that aspiring did for her is give her a hip and knee replacement, open heart surgery, asthma, diabetes, a brain tumor, and more deformed body parts than I can remember. It doesn't require a genius to learn about this disease all it takes is a bit of effort and the desire to want to learn and educate yourself about something that affects more people than you would think, if I did it anyone can. And if anyone is interested in educating themselves the first thing you should know is that RA and arthritis are two separate conditions. RA is an autoimmune disease that attacks your whole body while arthritis is the wear and tear of the joints that comes with time. By the way to the author of this article my RA started in my eye with severe iritis(I know it's not a joint but because RA is an autoimmune disease it does affect all body systems) to the point I was in danger of loosing that eye. I was placed on hourly drops of steroids and Enbrel shots TWICE A WEEK(the standard is weekly) I'm sure that if I had resorted to aspirin I would definitely be blind in that eye.
Dr. Robin Wulffson, I would encourage you to do your research before writing articles on topics you're so clearly uninformed on. The misinformation your putting out to the public is damaging and unacceptable. The treatment decisions RA patients have to make are very hard. But when facing the daunting RA disability statistics that (even with PROPER TREATMENT) leave 35% of patients unable to work due to disability 10 years after onset and 51% after 20, the choice gets much easier. (statistis from the Arthritis Care & Research Study)) It's incredibly unprofessional of you to suggest asprin as a stand alone RA treatment. Come on. Couldn't you have at least looked this up on WebMD?? NSAIDs only treat symptoms. We need the DMARDs to treat the disease. Dr. Wulffson, please stick to the field of medicine you chose to study and leave rheumatology to the experts. This article is an embarrassment and it should be taken down.
Oh, wait, you mean I've been on infused and oral chemo, but you think I should talk to my doc about aspirin before considering tofacitinib? You mean I sit hooked up to a bag of liquid biologic mouse protein dripping into my vein for 3 hrs every month when I could have popped a Bayer? Why didn't you say so? Dr.... PLEASE go to any reliable internet site for a definition of RA, which should send you to your room in embarrassment for suggesting aspirin to combat a crippling systemic disease that affects multi-organ systems and joints of the body. Aspirin, my a...
Seriously? My rheumatologist should have his license revoked for prescribing dangerous medications to me when I could have just been taking aspirin! Dr. Wullfson, please educate yourself before commenting on a disease about which you clearly know nothing. No wonder rheumatoid autoimmune disease is so misunderstood by the public when they are being fed inaccurate information such as this. What if a patient decided to forego real treatment based on this rubbish?
Obviously written by a totally clueless quack. This is the problem RA sufferers have. Ignorance. A perfect example of ignorance being published. Aspirin for Rheumatoid Arthritis? Does this quack still bleed his patients? Shame on you for publishing this garbage.