Today begins year five of RAW

Four years ago today, RA Warrior was born. I’d been studying, writing, and talking to patients for a few months. But that Sunday, the planning came to an end. No one was more surprised than I was. I just couldn’t wait another moment to break loose and communicate my thoughts. I just had to write.

I couldn’t imagine why there was so much confusion about a serious disease that affects millions of people. Why are people told they are atypical for symptoms that so many encounter? Why do so many people have friends offer them Tylenol or a juice cure or tell them they have a little “Rheumatoid Arthritis” in their knee?

Why was there no Rheumatoid Awareness Day? Why does insurance cover self-injection of insulin, but not methotrexate? Why was there no Rheumatoid Patient Foundation?

Eventually I understood the reason was the impractical label “arthritis.”

It became obvious how unworkable it is to refer to a systemic disease by one of its symptoms: joint inflammation. One issue at a time, I wrote about the disease that people experienced, including numerous subjects that were not being addressed, like cricoarytenoid arthritis (CA) – see my 2009 article on Health Care Professionals Live. Over and over, I hear from patients, “I had NO idea the hoarseness (or choking feeling or painful voice box, or difficulty breathing…) had anything to do with RA. I just try to ignore it because there are so many issues.”

Just today, I read a new study on CA, Laryngeal involvement in rheumatoid arthritis, in a Brazilian otolaryngology journal. It’s not the definitive piece on CA, but it is one more proof that the many patients who say they experience symptoms of CA, without it ever being treated, acknowledged, or recorded in their charts, are not imagining it. And when you read my BMJ article, you’ll see many other topics documented with similar evidence. Evidence that demands we call it Rheumatoid Disease. Evidence that is the basis for my first book (almost finished – I have to regularly stop to work on other projects and answer piles of emails or read to Roo!)

Facing fears – keeping on

Even though I wanted to write, I faced fears in being the first website to write certain things. Often, I had to make up my own words to describe realities only people living with Rheumatoid Disease seemed to know – like the Usage Principle (stay tuned for big news on that in the next couple months). Here’s a brand new word you’ll read in my book: drumroll… PRD, people living with Rheumatoid Disease, as many use PWD for “persons living with diabetes.”

Repeatedly I wrote of things that doctors did not readily acknowledge, and PRD responded in large numbers, “You’re writing about MY life.” Sometimes, a rheumatologist tells patients that RA cannot affect the neck, but then the RA in the spine is treated by a neurosurgeon. Or the same scenario plays out with many other symptoms. And the saddest thing of course is when symptoms are not addressed at all.

Together we are changing that. I can’t tell you how many people have said they’ve become empowered to seek the care they need. And did you notice the title of the BMJ article? They called it “Rheumatoid disease.” We’re hearing it more often now.

In a speech I heard recently, someone said, “What are you afraid of? They are NOT going to EAT you!” I don’t know why it’s so hard, but I’ve overcome it repeatedly, putting myself on the line to say what I know to be true. Two years ago, on the blog’s birthday I realized there were still things I was stating too gently that needed to be said more bluntly, so I began the Frying Pan post series. There is a long way to go with most of those issues, but today let’s wish the blog Happy Birthday and think of how far we’ve come.

Postblog: Today I packed my suitcase for the Gathering, in Phoenix this year. Saturday I’ll be speaking on “The Extreme Sport of Fighting RA.” My vocal cords have been very sore the past couple months, but I still can’t wait. There will be so many laughs and hugs. Last time I flew to Phoenix my knees didn’t straighten for 5 months – it’s worth it, but this time I won’t sit hours in ridiculous chairs, and I’ll be more empowered to stand up a couple of times during the flight.

Click here to listen to an audio interview with British Medical Journal last month.

Recommended reading

• How Many People Have Rheumatoid Arthritis?
• Rheumatoid Arthritis Swelling, Take Two
• 2 Reasons Monitoring Rheumatoid Arthritis Matters
• Poll Shows Textbooks Wrong on Rheumatoid Arthritis Morning Stiffness
• The Powerful Health Care Role No One Really Wants: Being a Patient
• What about a Clinical Protocol for Rheumatoid Arthritis Disease?

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Pregnancy planning is a common challenge for people diagnosed with Rheumatoid Arthritis. Concerns include infertility, disease activity, pain control, and possible disability, which can interfere with caring for a child. Valuable resources include clinical studies and other publications, and the practical stories of other patients. While there is no clear roadmap, patients need to be informed about various issues and options.

Infertility and Rheumatoid

It’s not our imagination that women with Rheumatoid Disease have fewer children. Recent research confirms that “more than one-half of young women with RA or SLE (Lupus) had fewer biologic children than desired,” Arthritis Care & Research. Rheumatoid patients were more likely to experience infertility, while Lupus patients had greater miscarriage risk.

The risk of infertility can impact whether or not to delay pregnancy. It is unknown yet the reasons for infertility related to Rheumatoid disease and whether disease treatment impacts the likelihood of successful pregnancy. More study is needed. The Rheumatoid Patient Foundation (RPF) is collaborating with a researcher to study pregnancy and RA, so if you plan to get pregnant and want to be notified when the study starts, please let me know on the comments’ page or in an email.

Which Rheumatoid Arthritis medications are safe to continue?

Recently posted on the blog: “I’m 30 years old and trying to conceive our first child. I have RA and currently on Actemra and I was wondering if anybody has had a child while in this med or currently pregnant? Should I continue or stop and what should I expect? Super scared and need some help please”

It’s clear which medications are considered unsafe to continue, such as methotrexate and leflunomide. It’s less clear which ones are actually safe, so many doctors recommend discontinuation of all DMARDs. However, data presented by Organization of Teratology Information Specialists (OTIS) provides some reassurance that other DMARDs, including Biologics, might eventually be considered safe during pregnancy. Clearly, much more study is needed here too. The OTIS registry studies those who have become pregnant while taking medications, and provides related resources. You can contact OTIS at this link.

How soon do I give up Rheumatoid Arthritis medications for pregnancy?

A question posted recently on Facebook shows concerns that are common for patients considering pregnancy: “How does anyone give up meds for 6 months before trying to get pregnant. I would love another baby but couldn’t give up meds 6 months before trying to conceive and then after having the baby getting meds in before the pain starts. Any advice?”

Rheumatoid patients who intend to become pregnant should discuss all medications with both an obstetrician and a Rheumatoid Arthritis specialist. Usually, they will be counseled to stop using medications that are known to be unsafe three months prior to becoming pregnant. Leflunomide can remain in the body longer than other DMARDs, and there is a washout procedure to remove it, but a rheumatologist I know called it “unpleasant.” If planning a pregnancy, it would probably be best to not begin medicines that are considered unsafe, but that does not mean a woman will necessarily have to endure nine months of unrelieved pain.

Successful pregnancies with RA?

Many women have had successful pregnancies with Rheumatoid Disease, as they have discussed in comments on RAW, and in social media, and on their own blogs. Frequently, women experience an improvement of disease symptoms during pregnancy. But that is not universal, and there is no guarantee. Pregnancy with disabling Rheumatoid symptoms can be difficult, but some symptom relieving medications may be prescribed to provide relief, including low dose prednisone, acetaminophen, and ibuprofen during the first and second trimester. Since many pregnant women prefer not to take any medication during pregnancy, planning should be considered for alternative methods for pain relief in case it is needed. I love how one blog ends after the completion of a successful pregnancy with Rheumatoid Arthritis. You might also enjoy reading the story of a successful pregnancy with Psoriatic Arthritis.

Men, pregnancy planning, and Rheumatoid Disease

Certain issues are equally relevant for men with Rheumatoid disease. Medications that can affect the baby’s health would need to be curtailed, just as for women. Physical disability and financial difficulty caused by the disease are similarly significant as they are for women.

Important note: RPF is working with a researcher to study pregnancy and Rheumatoid Disease, so if you plan to get pregnant and want to be notified when the study starts please let me know in a comment using a first name only or email me.

Recommended reading

Rheumatoid Arthritis and Pregnancy – This page has links to several resources, and dozens of helpful comments from other patients.

RPF Pregnancy and Rheumatoid Arthritis brochure – click here to view. Link to order page.

• The “Can’t” Question with Rheumatoid Arthritis
• Living with Rheumatoid Arthritis: Tips for Parents
• 20 Questions RA Patients Should Ask a Doctor

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We probably agree it’s unfair to say, “patients fail treatments” instead of the reverse, but there is still disappointment. I was optimistic that my Rheumatoid disease would respond to Xeljanz, the new oral DMARD (disease modifying anti-rheumatic drug) from Pfizer. Unfortunately, my joint stiffness and inflammation, hoarseness, and fevers continued. However, the vascular rash on my leg (diagnosed as livedo reticularis) improved while taking Xeljanz, and it worsened after I stopped taking it.

Should any of this help you decide whether to try Xeljanz? Probably not. The data shows:

• a difference exists between placebo and tofacitinib (Xeljanz);
• a wide variety of response exists between patients; and
• a small minority respond really well.

A minority has an excellent response to Xeljanz and Biologics

The efficacy data with Xeljanz differ among their various trials, but they are similar. And response levels are comparable to those of Biologics, using ACR20, ACR50, and ACR70. Three years ago on RAW, we discussed some comparisons of efficacy of Biologics, according to a Cochrane review of 31 studies of ACR50 and Danish study of ACR70. Looking at trial data and comparison studies, on average, about 34% are non-responders, which means they do not meet the primary endpoint of ACR20 (an assessment of 20% improvement according to specific measures of disease activity). The remaining 66%, considered responders, are divided between ACR20, ACR50, and ACR70. On average, 20% or fewer people experience 70 percent improvement, and about 29% reach ACR20 only. The remainder are ACR50 only.

Remember, the ACR response levels are usually reported with all higher responses included, so the traditional ACR20 number includes all responders (including ACR50 and ACR70). It may be easier to understand showing all groups separated in a traditional pie chart (see images to right and at top). That method is discussed here on RAW: New Way to Report Response in RA Clinical Trials?

Are Biologics and Xeljanz more effective than traditional DMARDs like methotrexate?

Sometimes people assume that shots are stronger than pills, and IV infusions are stronger than shots. But that’s not accurate; the medications work by different mechanisms, so they are effective on different patients with different disease mechanisms and progression of disease. It’s true that Biologics and Xeljanz are considered more effective than other DMARDs, but that could be misleading in some ways: To people who respond well to methotrexate alone, or even Plaquenil, DMARDs are sufficiently effective.

The complexity of Rheumatoid disease, its heterogeneity, and tendency to change in the same patient over time all complicate measurement of efficacy, as well as development of new treatments.

That said, traditional DMARDs are considered less effective, and this has been shown in head to head studies. As a matter of fact, one thing companies do during trials is attempt to show their new product is more effective than methotrexate. As RAW reported last year, Xeljanz was found superior to methotrexate. A couple of years ago, RAW reported on testing of a new possible methotrexate alternative and a British Medical Journal review of methotrexate studies showing 46% reached ACR20 and only 23% reached ACR50 (by the inclusive method).

Some trials have also compared combinations of DMARDs together (triple therapy) or combinations of a DMARD and a Biologic. So far, it has often been concluded that methotrexate with a Biologic is best at preventing radiologic damage (joint damage as studied on x-ray).

Bottom line for Rheumatoid patients choosing therapies

The bottom line is that some respond very well to currently available therapies, but the range of responses is wide, and there is no way to predict yet which treatment or combination will work best. As we discussed recently on RAW, people often weigh risks and benefits for choices, including medications. It has been my own personal choice to try every opportunity available to increase function and get relief from pain, and I’ve made that choice with no regrets.

Recommended reading

• Xeljanz Rejected by European Medicines Agency
• Which Biologic Treatment Should RA Patients Try Next?
• Comparison of Biologics for Rheumatoid Arthritis (RA)
• A Methotrexate Alternative for Rheumatoid Arthritis?
• Rheumatoid Arthritis Drug Approved by US FDA: Pfizer’s Xeljanz Pill (Tofacitinib)
• Xeljanz Cost with a Copay Card, Free Samples, Efficacy, & Side Effects: Gathering Rheumatoid Arthritis Patient Stories
• All articles on Biologics on RAW

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I got a kidney infection shortly after starting Enbrel. It was Good Friday 2009. My kidney hurt and fever spiked to 104.5, after 3 days of UTI. Before then, I’d only had a minor UTI  with pregnancy. This is when my GP got the nickname “Good GP” because of responding quickly with an antibiotic. In two days, the infection symptoms were gone, but something was wrong with my Achilles tendons: they were inflamed and too painful to walk on. Living with Rheumatoid, I’m used to walking through lots of pain, but I knew something was wrong. When the sensation didn’t subside, I called a few pharmacists, describing my situation. There was a consensus to stop the ciprofloxacin, and I did. The tendons recovered. Monday, I called the rheumatologist (Dr. Dolittle) who had prescribed the Enbrel. I’d seen him only once, after 3 years of Dr. KBC. I called to find out whether to take the Enbrel and whether he thought I needed another antibiotic. He told me: “That’s not a real side effect.” I could tell he didn’t believe me, and I shouldn’t have, but I went back there one more time.

Others’ stories about fluoroquinolones and Rheumatoid Arthritis

A few patients have sent me emails about the dangers of ciprofloxacin and other medicines in the fluoroquinolone class, asking me to discuss the issue. One patient I know believes Levaquin, a fluoroquinolone, triggered her Rheumatoid Arthritis diagnosis. I tend to believe patient stories, since my kids and I have been disbelieved so many times and turned out to be right (examples in an article I wrote for e-patients.net a few years ago). But I’m also a healthy skeptic and lover of evidence. First, let’s look at some medical literature, then an astonishing conversation between a doctor and dozens of patients.

Facts about ciprofloxacin / fluoroquinolones and Rheumatoid Disease

Cipro, made by Bayer (generic name ciprofloxacin), is the most commonly prescribed fluoroquinolone antibiotic. The National Institutes of Health website has an article that’s written in a friendly question and answer format: “The Risk of Fluoroquinolone-induced Tendinopathy and Tendon Rupture What Does The Clinician Need To Know?” There are 48 footnotes of previous studies, dating back to 1979, declaring, “Risk factors associated with FQ-induced tendon disorders include age greater than 60 years, corticosteroid therapy, renal failure, diabetes mellitus, and a history of musculoskeletal disorders.”

How might fluoroquinolones (FQ) damage tendons?

“(I)t is possible that FQs have a direct cytotoxic effect on enzymes found in mammalian musculoskeletal tissue… In-vitro studies in cultured tendon cells have confirmed the clinical observation that FQs can increase the risk of tendon rupture.”

What happens if FQ damages tendons?

“Because rupture can occur even late in the course of treatment or after discontinuation of FQ use, patients receiving a FQ should be counseled to seek medical attention immediately if symptoms, such as redness, pain, swelling, and stiffness, develop. Tendinosis usually recovers over a time course of weeks, usually within two months, after cessation of FQ therapy. Early diagnosis based on recognition of symptoms suggestive of tendinopathy, followed by FQ discontinuation and supportive treatment, may prevent tendon rupture and tendinitis.”

FDA warning guide for ciprofloxacin

The FDA.gov page places less emphasis on musculoskeletal risk, but does say to tell your doctor if “Have rheumatoid arthritis (RA) or other history of joint problems,” or take anti-inflammatories, or take steroids, or take methotrexate, or take omeprazole or a list of other drugs. There are further warnings, but these commonly pertain to people with Rheumatoid disease.

NIH Medline Plus ciprofloxacin warnings about tendons

The “IMPORTANT WARNING” describes an increased risk of tendonitis and tendon rupture and lists specific populations at greater risk: “Tell your doctor if you have or have ever had a kidney, heart, or lung transplant; kidney disease; a joint or tendon disorder such as rheumatoid arthritis (a condition in which the body attacks its own joints, causing pain, swelling, and loss of function)...” Also, “Tell your doctor and pharmacist if you are taking oral or injectable steroids.”

I was about finished with this post last week when I saw a doctor’s conversion worth showing you:

Side effects have often been a point of doubt, so that patients are not always warned in case they might imagine or exaggerate. Obviously, I think people who become patients can be trusted with as much information as they feel comfortable with. On this blog, I’ve always been cautious in mentioning adverse events so that I don’t frighten others (while Enbrel gave me hives and Orencia severe bronchitis, many have taken them safely). Reporting any side effects to your doctor is important, and doctors should take it seriously. The case of Cipro / FQ’s shows sometimes doctors are unaware of serious possible side effects.

In 2008, a doctor complained on his blog that the FDA had “caved” to consumer groups to add the boxed warning about tendon rupture to Cipro. He said a small number of people had been affected and the warning was unwarranted. About 150 comments followed, including much published data and testimonials, several from medical professionals who had become victims of adverse events. Eventually, the doc posted: “Based on your posts and post by others experiencing severe consequences from fluoroquinolones, it appears there may be more to the story.” After more comments, a year later he said, “Based on the responses to this post, there may be more to the Cipro issue than the FDA is letting us know. However, withot data, it is impossible to make a decision for a patient…. However, we also need to accept that there are some pills that may help millions of people but hurt a few in the process.”

I’m glad he changed his mind, but doctors and patients both need to be informed. Usually, the patient will know best his/her complicated health profile with a chronic disease. Since my Cipro – Achilles tendon incident a few years ago, Dr. GP and I make medication decisions together. In my electronic chart, doc has a list of which meds I shouldn’t take; we look at that and doc asks, “Can you take _____ for _____?” out loud and looks it up online to check for warnings. A Medline search can be done in seconds.

After four years of comments on his blog, the doctor who had complained about the FDA warning wrote, “Truly sorry for your suffering and the effects you may have suffered from Cipro. Sadly, despite the now known dangers caused by Cipro, how these medications lead to these damages is unclear.” He repeatedly stated that all drugs have risks, and as I kept reading, I kept thinking that was not the main issue. A commenter said it perfectly: “I hope you learned something from the discussion on the fluoroquinolones. Doctors need to become much better educated about medications and stop being so dismissive of patient complaints about their experiences on prescription drugs.”

Rheumatoid patients have increased risk with fluoroquinolones / ciprofloxacin

Apparently there are books, support groups, and citizen protests opposing this class of antibiotics. The PBS NewsHour even did a segment about quinolone antibiotics. There may be some hype in some of the campaigns, but it is clear that after a surprising number of adverse events, the FDA increased the warnings, and people with Rheumatoid Disease are identified as having greater risk.

List of medications in the same class as Cipro: quinolone or fluoroquinolone antibiotics such as gatifloxacin (Tequin) (not available in the U.S.), gemifloxacin (Factive), levofloxacin (Levaquin), lomefloxacin (Maxaquin) (not available in the U.S.), moxifloxacin (Avelox), nalidixic acid (NegGram), norfloxacin (Noroxin), ofloxacin (Floxin), and sparfloxacin (Zagam) (not available in the U.S.).

Recommended reading

• Aspirin and Rheumatoid Arthritis
• Does Rheumatoid Arthritis Affect Tendons?
• Side Effects and Genes: More Evidence for Listening to Patients
• Reliable Sources: Orencia Cough Side Effect & Notions of e-Patients

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So, I finally saw the dermatologist about the non-rash on my leg that has been present for 18 months and seemed permanent for nearly a year now. My GP had wanted the dermatologist to have a look at it since she was concerned that the rheum docs (Dr. Tylenol and partner Dr. Shrug) I’d seen over the past year and a half said they had no idea what it is. She and I both suspected what it was, partly because I’ve had other symptoms of skin vasculitis over the years.

The dermatologist’s physician’s assistant (PA) who usually sees us is out on family leave so we saw another PA. My family has gotten good care there for years. The mom of my usual PA has rheumatoid, so I’ve shared with them about the Rheumatoid Patient Foundation (RPF) and the work I’ve done through RAW.

The PA read my referral; listened to my report about the history with my vascular rash; and examined me. It sounds so simple.

She rubbed over the skin and then looked me in the eye and said, “I know what this is. Let me go get something to show you. I’ll be right back.”

We waited 15 minutes. We never have to wait there because it’s such an efficient office, so we were laughing that perhaps she’d forgotten me.

Then, she walked back in with a big medical book in her hand, “You have something called livedo reticularis. This can happen with immune diseases. I’d be suspicious that it was from lupus, but with your history, we know it’s related to the rheumatoid.” She knelt down next to me and read to me from the book and answered a few questions. So simple.

Even though this was not my usual care provider, she went on, “I’ll be sending a letter to Dr. GP because we have to be on the same page with this. It’s not something you need to worry too much about now unless it gets worse, but it shows you have uncontrolled disease. We’re concerned because that can lead to damage and severe pain.” (I didn’t say anything, but I wondered why they always assume I don’t have severe pain already…)

She asked, “Don’t you see a rheumatologist? Didn’t she know what this is?”

I told her, “Yes I showed it to her. But she had no idea.”

She got an astonished look on her face and said, “I bet Dr. GP got the same look on her face. Look, we really need to know that you are getting better care than this. Maybe she can help you find a better rheumatologist. You need to…” and she went on a little more. (I didn’t say anything; we’ll solve that problem another day.)

I tried to hide it, but I think I looked more shocked than she did because even though I wasn’t even her regular patient, she was so concerned. That, plus hearing the confirmation of a diagnosis I’d long suspected.

This story answers those who’ve asked me whether I got a final diagnosis on my leg, but it’s more important for the good example of communication. So simple. It reminds me of a great story Dana told the other day on the RPF blog about how her doctor has the heart of a teacher – click here to read.

Note: Female gender is used for all healthcare professionals in this post, to help protect the identity of each.

Recommended reading

• 3 Reasons to Stop Saying “Complications of Rheumatoid Arthritis”
• Livedo Reticularis & Rheumatoid Arthritis: Nothing Rash about It
• Health Data Is Like Yogurt: Full of Possibilities
• Dr. Tylenol Keeper or Loser: I’m Not Giving Up, But What Do You Think?
• Dr. Shrug Inadequate & stupid? No, just a victim of someone’s training

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A couple of special coincidences occurred in February when I was in Washington. As my friend Leslie and I took off from Orlando, I got a text message from my friend Dave deBronkart that he’d gotten an earlier flight to D.C. and, we’d arrive to the same airport only an hour apart! When Leslie and I got to the baggage area, my cell phone buzzed with a text that Dave’s plane had landed even earlier so we decided to join up and share a cab. We stashed our luggage at the hotel and went for coffee (ok, I got juice).

Dave and Leslie hit it off, and I don’t know why I was surprised. Only because Dave is over six foot, an MIT graduate, and world-traveled public speaker, and Leslie is a petite, quiet wallflower who didn’t go to college. But, they’re both exceptionally bright, creative, and dear friends. Leslie is the one true friend who stayed by my side when the Rheumatoid disease stole so much; since she knew the old me, there was never a doubt or accusation that my illness wasn’t real. Each of them has been an astonishing encouragement in my life over the past few years.

That day in the lobby, the conversation turned to attention deficit disorder (ADD), and what it is or isn’t, and that they both have it, whatever “it” is. In an extraordinary twist we realized that twenty years ago Dave helped to write the very book that had been so valuable to some in Leslie’s family. The book by Thom Hartmann is about the “Hunter/Farmer Hypothesis.”

That night, Leslie and I found one copy of the book online and bought it. The next three days were full with the Institute of Medicine event, and meetings at PCORI. Then, Leslie got a message that the book had arrived – there was just enough time to get to our hotel lobby for Dave to autograph the book while his cab waited, and then rush to catch his plane.

The whole turn of events astounded me. How validated my dearest friend and others in her family had been by the words in a book written long before she knew about it – and all thanks to my other friend.

Postblog: Another book – time warp – validation story

Researching last month, I stumbled across a sixty-year-old book about Rheumatoid disease, by someone who would know – a patient. Through this difficult week, I’ve felt like I’m not alone, as I read so many parallels to my own experiences. The author is a friend I never met.

I’ll review the book soon and tell you more about it.

NOTE: Dave has a new book, Let Patient’s Help – here’s the link.

Recommended reading

• Another story about Leslie
• Where the Rubber Meets the Road or What If Only the Cancer in Dave’s Kidneys Was Treated?
• Health Data Is Like Yogurt: Full of Possibilities
• What Drives Patients to Get Engaged in Healthcare?
• When Eventually Is Now: the Rheumatoid Time Warp

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This site has always been dedicated to “presenting the patient story in a way that may increase understanding of the disease by doctors and researchers” as one of its three goals. The Onset Story project has been an important part of that, both for patients and for healthcare professionals searching to understand this disease better. Many of you also participated in a 2011 Rheumatoid Patient Foundation (RPF) survey about your experiences with Rheumatoid disease.

Last week RPF published a white paper which included results of the survey, Unmasking Rheumatoid Disease: The Patient Experience of Rheumatoid Arthritis. Previously, an overview of results was presented in a poster for the RPF exhibit at the 2012 American College of Rheumatology meeting. The RPF is grateful to everyone who participated in the original survey which made this report possible. From the RPF:

A professional’s perspective on patient experiences

Late in 2011, at the same time many of us were answering the original survey, Dr. Ted Pincus wrote an important editorial: The Science of MDHAQ/RAPID3 Scores: Do patient self-reports provide valid data for evidence-based care in rheumatology practice?

Some of his words will resonate with many of you:

Concerning the importance of patient self-reports:

“Self-report questionnaires could document patient history information concerning physical function and pain as quantitative scores, rather than as gestalt, nonquantitative descriptions (e.g., ‘ “doing well” while the patient has become progressively crippled before their eyes’). Standard, quantitative, patient self-report data could meet criteria for ‘scientific’ measures, similar to laboratory tests.”

Concerning how seldom patient self-report questionnaires are used in rheumatology practice:

“Patient self-report questionnaires—the most significant predictor of work disability and mortality in RA—have been introduced into only about 20% of rheumatology usual care settings”

Concerning how textbook opinions can vary greatly from patients’ reality:

“Treatment at that time, although described as ‘remission-inducing’ in textbooks, was not adequate for favorable long-term results.”

That change is slow.

“Nonetheless, most rheumatology visits are conducted largely as they were 50 years ago when I started in rheumatology as a student”

Connecting the dots

Dr. Pincus has been quoted several times on RAW over the past four years because his work improving and supporting patient questionnaires has been invaluable. RPF patient surveys are also a crucial step toward improving understanding of Rheumatoid disease, which will ultimately be needed to improve care. Significant change cannot come until actual patient experiences with the disease are recognized generally, and considered in individual patients.

Postblog: The Pincus article is also an insightful story of his own journey, like an onset story to becoming a patient reported outcomes researcher. I love also reading much older medical history and I’ve recently read a lot of it in research for a book I’m writing on Rheumatoid disease. One research article led me to a book by a patient, written 60 years ago. I’ll post more on that I hope, but I’m somehow comforted by her story: to know that things patients in this community experience, that are often disputed or discounted as atypical or wrong, were also experienced by her. Maybe another result of the white paper will be to reassure patients.

Recommended reading

• Weight of Patient Reported Outcome Measures on Diagnosis & Treatment of RA
• The Value of Patient Reported Outcome Measures of Rheumatoid Arthritis
• The HAQ’s, the RAPID’s & the Rest: 3 Reasons It’s a Moot Point

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Late yesterday, the European Medicines Agency (EMA) rejected the Pfizer’s application to market Xeljanz (tofacitinib). The EMA application was refused because the Committee for Medicinal Products for Human Use (CHMP) “adopted a negative opinion” on approving Xeljanz, stating they were unconvinced its risks outweighed benefits. Last November, the FDA approved the 5mg dose of Xeljanz in the U.S. for “moderate to severely active rheumatoid arthritis” after “inadequate response or intolerance to methotrexate.” Tofacitinib has also been approved for use with Rheumatoid patients in Japan (5 mg) and Russia (5 and 10 mg).

Today, I spoke with Andrew Koenig, Pfizer’s North American Inflammation/Immunology Group Leader, about the decision. He said, “While they (CHMP) believed in the effect for signs and symptoms, they were unsure about the benefit with structural damage. And they were concerned about infections.” The EMA document concerning authorization of Xeljanz acknowledged “Xeljanz resulted in an improvement in the signs and symptoms of rheumatoid arthritis and the physical function of patients.”

Koenig indicated that Xeljanz is approved in the U.S. to treat “signs and symptoms” of RA, but not for structural damage: “We are working with the FDA to expand its label over time.”

Excerpt from the EMA refusal of Xeljanz

What evidence of risks and benefits did the CHMP consider?

“We do know this submission was the same as to FDA,” Koenig told me. He confirmed the same data were used for approval in Japan, Russia, and the U.S. The best way for the public to view that data is in the briefing document submitted in a public hearing at the FDA last May.

RISKS

If you view the document, it’s important to recognize which data apply to the 5 mg dose.

Several pages of charts cover various types of infection risk. While the disease itself is known to increase infections, the risks of the drug must be identified. Therefore, detailed infection data is presented for the nearly 5,000 patients included in the different clinical trials, which shows an increased infection risk with Xeljanz. As with other disease-modifying antirheumatic drugs or immunosuppressants, as well as prednisone, there were several types of infections encountered. Age groups are specified because infection risk is greatly increased in the over-65 age group, independent of any disease or medication.

While it is easy to determine that an increased infection risk exists, it is a complicated question. For example, while tofacitinib risk seems comparable to adalimumab (Humira) or other biologics in some circumstances, Table 31 shows that people who take steroids with tofacitinib had a much higher infection incidence. And in some cases, the lower dose of tofacitinib showed higher risk. Even looking at it in black and white, the risk is easy to recognize, but not as simple to calculate. (I’ve read the sections on the other risks several times; but it’s too much to cover here in one post, and the dilemmas are similar.)

BENEFITS

The CHMP held that improvement in “signs and symptoms” and “physical function” was seen, but there was not consistent evidence of prevention of structural damage. Figure 18 of the FDA briefing compares the treated patients to placebo patients. While the effect looks obvious, it was only statistically significant in some groups.

A company’s view of benefits of treatment

The executive summary of the Pfizer FDA briefing provided a discussion of Rheumatoid disease in order to portray the “unmet need,” an important argument in why any new treatment should be approved: “Because RA is currently incurable, the goals of treatment are to reduce disease activity, improve physical function and health-related quality of life and inhibit progression of structural damage throughout the course of the patient’s disease.” I agree with this broad focus.

In the section called “Summary of benefit-risk,” we read, “Up to one-third of RA patients receiving currently approved DMARD therapies show inadequate response in this serious, chronic, progressive and disabling disease that lasts 20 to 40 years and for which there is no cure.” It’s true that one-third of patients are “non-responders,” but remember that the FDA bar for “response” with RA is only a 20% improvement. I’m not sure how anyone’s Rheumatoid disease expires in 20-40 years except by death. I doubt that’s what they meant, but I cannot fathom where they got such an idea.

Risks and benefits from the patient point of view

Two things are missing in this discussion.

First, patients. The CHMP did not allow an opportunity for public comment, nor does it publish minutes or agendas. That is different from the FDA, which allows citizens like me to apply to speak at committee hearings, publishes agendas, and provides a live video feed of meeting activities.

Second, a disease perspective.

Last night I wondered who wrote the useless definition of RA in Pfizer’s press release: “About Rheumatoid Arthritis: RA is a chronic inflammatory autoimmune disease that typically affects the hands and feet, although any joint lined by a synovial membrane may be affected.”

This lack of communication of disease impact is partially responsible for thoughtless media coverage about their product and I would be surprised if it doesn’t impact people who make decisions about approving medications. Sometime this year, I hope you’ll be able to read my first book on Rheumatoid disease. When I look at the 200 footnotes, I see that if the evidence is there for a lay researcher like me to gather, it’s certainly available to Pfizer with its resources.

People with rheumatoid disease always have to weigh risks & benefits

My only question is whether authorities, the public, or perhaps even companies who create medicines, recognize what the disease impact is so that they can weigh risk to benefits accurately on our behalf.

People encounter risks every day that are higher than the risks with DMARDs: smoking increases cancer risks; obesity increases diabetes risk; tanning beds still find customers. But people faced with a harmful chronic disease have to choose whether to take certain risks with medications that may enable them to continue be functional, active members of society, or possibly live longer, when the medications work well. The risks should be clear, but many people with Rheumatoid Disease will choose to take them, because they see the alternative is so much worse.

Important related reading

• Health Data Is Like Yogurt: Full of Possibilities
• Xeljanz Cost with a Copay Card, Free Samples, Efficacy, & Side Effects: Gathering Rheumatoid Arthritis Patient Stories
• Aftermath of the FDA Vote on Pfizer’s RA JAK Inhibitor, Tofacitinib
• Mind-boggling! – Aftermath of Tofacitinib FDA Hearing Part 2

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First major study in Rheumatoid Arthritis to explore risk factors of falling

In a recent study “Risk factors for falls in Adults with Rheumatoid arthritis,” 525 people diagnosed with Rheumatoid Arthritis (RA) were followed for one year to examine risk factors for falling. Thirty-six percent of patients in the study fell at least once during the year. Neither age nor gender increased fall risk.

The authors determined that the data show “falls in adults with RA are not just random events but may be predicted and possibly prevented by assessing and treating a number of independent risk factors.”

Factors that increased fall risk in people with Rheumatoid disease

Tender or swollen lower limb joints doubled fall in risk. Other factors that increased the likelihood of falling included higher HAQ score, previous falls, greater fear of falling, taking four or more medicines or psychotropic medicines, and higher pain and fatigue levels. People who felt “dizzy or unsteady” also had an 80% increased risk of falling.

The investigators concluded: “Adults with RA are at high risk of falls. In clinical practice high risk falls patients with RA can be identified by asking whether patients have fallen in the past year. Important risk factors highlighted in this study included: swollen and tender lower limb joints; fatigue and use of psychotropic medicines.”

Interventions to reduce fall risk with Rheumatoid disease

Recommendations for lowering fall risks included, reducing psychotropic medications, assessing joints in feet and legs, increasing strength in feet and legs. Risk of fall should be assessed since Rheumatoid disease activity increases risk, regardless of age. Assessing fall risk should include inquiries about previous falls.

Have you fallen? What were the factors? Did you fit the patterns in this study?

Click here to download the new RPF white paper reporting your survey responses.

Recommended reading

• Rheumatoid Arthritis Joint Protection
• Brain Fog: Testing Cognitive Dysfunction with Rheumatoid Arthritis / Disease
• New Blood Test for Rheumatoid Arthritis: 14-3-3eta

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Enjoy a laugh with this short adaptation of the legendary “Show me the money” scene from Jerry Maguire created by Dr. Eric Topol of Scripps Translational Science Institute. “Show me the money” has become a kind of motto that also reminds me of Wendy’s old “Where’s the beef?” ads. People want to see proof. And people who get sick (patients) are the same way: they want to see what proof exists that a medication is safe and effective to possibly judge the likelihood it would work for them. People use data to decide which is the best dog food to buy, juice to drink, or food to eat.

The health data spectrum

Many collect data about their own health through devices like the Fitbit to measure personal metrics such as number of steps walked and sleep quality. For the past few years, I’ve recommended to patients to get personal copies of lab reports, which seemed like a simple logical step for people with a chronic disease that’s so heterogeneous and unpredictable. While many are talking about the best ways to access and use EHRs (electronic health records), many others still have no idea even what lab tests have been run with their blood. This is what it’s like to live on the cusp of change.

Will clinical trial data be opened?

Last week, I read “I’m a patient: show me the trial data” in British Medical Journal’s personal view column. Alex Lomas, a person who takes adalimumab (Humira in the U.S.), wants to have access to Abbvie’s (formerly Abbott) clinical trial data for that drug. According to the article, Abbott is seeking an injunction in Europe to prevent disclosure of certain trial data.

Would you like blueberries on that?

In the past, few people read clinical trial data – patients or doctors, but that’s changing. Health data could be the new Greek yogurt: everyone wants more of it than we ever expected. And they want to do lots of things with it we would never have imagined before.

It’s a good thing.

Recommended reading

• 21 Tips to Prepare for a Biologic Infusion
• 10 Answers to “When Do I Start a Biologic Treatment for Rheumatoid Arthritis?”
• Antibodies Lessen Effectiveness of Adalimumab / Humira
• Consumer Reports Absurd Best Buy Rheumatoid Arthritis Drug List

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