RheumNow Week In Review No Good Gout %288.10.18%29 Save

Hi, it's the 08/10/2018. This is a RheumNow we can review. I'm Doctor. Jack Cush, executive editor of roomnow.com. This week in the news, the challenge of gout and Lord knows gout is challenging.

What about back pain? Is it worse in men or women? I've got the data. And lastly, how long does it take from symptom onset to rheumatology referral in your early RA patients? You're going to wish you were from Slovenia, I promise you.

At the top of the news, have a report about myositis and scleroderma specific autoantibodies, specifically anti TIF1, anti NXP2, and anti RNA polymerase used scleroderma. These actually have been occasionally associated with malignancy in both these diseases. And this interesting study looked at sixty or seventy patients with lung cancer and looked for those autoantibodies and found none of them. Actually only one patient had the autoantibody, and it, was thought to be not associated with either of those diseases. So bottom line is that these are myositis specific and scleroderma specific antibodies.

TIF-one and NXP-two are being, incorporated into current myositis panels and may be useful in the diagnosis of these unique subsets which are associated with malignancy or very aggressive disease. So look for them, I think you'll find them clinically useful. How about the Main Ritz Sands study? This is actually published and is an interesting study that compared fixed dosing of rituximab to a tailored dosing of rituximab based on CD19 or ANCA levels in patients who have ANCA associated vasculitis. Specifically one hundred and sixty two patients were studied with either GPA or microscopic polyangiitis.

They assessed them by the Birmingham Vasculitis Activity Scale and relapse rates and they showed that the outcomes were the same. Relapse rates were the same between the fixed dosing given every six months versus tailored dosing every, well according to those levels. The rates were seventeen versus ten percent and that was not statistically significant. However, there were overall less infusions when, tailored dosing was used. It was a total of two forty eight versus three eighty one infusions suggesting that that may be the more cost effective way to go, meaning that you follow CD19 levels and or ANCA titers as an indication for when you should do your next dose of rituximab and someone receiving rituximab for ANCA associated vasculitis.

An interesting study was actually just hit the journals and was reported at this year's EULAR meeting where a number of us found it somewhat unbelievable, but it's out there, it's interesting to look at, it's an open label study, it's from India, it's 60 patients who have diffuse systemic sclerosis and they were treated with either monthly IV cyclophosphamide five hundred milligrams per meter squared or IV rituximab two doses, and they looked at the outcomes. At six months, the FVC and the Rodnan, skin scores were improved in the rituximab group but not in the cyclophosphamide group plus in the cyclophosphamide group that had a lot more toxicity. This is a very uncontrolled study, but it is nonetheless promising and I think that I'd like to see more studies done in this arena with similar, kinds of patients. Lord knows we need an effective therapy in systemic sclerosis. You may have heard over the years reports from the orthopedic literature or your orthopedic colleagues that giving a non steroidal drug to patients with end stage OA of the hip or knee can lead to accelerated, very accelerated and very damaging, disease that leads to hip replacement.

I'm not sure I ever believe that data was mainly implicated with indomethacin. This is a nice match cohort study that examined exposure to nonsteroidals, COX-two agents and acetaminophen and narcotics and glucosamine in the three years prior to, actually having hip or knee surgery and they showed that there was no increased rate of knee replacement surgery, not hip, this is knee replacement surgery in those patients who had knee OA and then were treated for that knee OA prior to surgery suggesting that you can safely use these drugs in patients who are leading up to and may be pre candidates for surgery. Another interesting study about the use of hydroxychloroquine, as you know there is a big issue in lupus and in many of our patients with the issue of non adherence to therapies. This particular study looked at chloroquine levels measured by HPLC and patient surveys looking at, patient adherence, in an international cohort of three zero five SLE patients and very sort of sobering data, surprising data if you will, that eighteen point four percent of lupus patients are categorized as having, being severely non adherent and then another twenty three percent were just classified as adherent.

That's a total of thirty, forty one percent of patients who are non adherent with lupus to hydroxychloroquine, an easy and safe drug to take. There's a gigantic challenge going on here. It may well be, I'm not sure that I really need hydroxychloroquine levels to manage lupus, but if it's going to tell me if my patients are non adherent, maybe that's a good clinical tool. Think about it. Ask Michele Petrie about it, she's actually published on this, wrote a piece for this in the room now, said the same thing, that may be its main use.

An interesting study looked at men and women with ankylosing spondylitis from Sweden 02/2005 specifically and they compared their disease progression using, radiographic scoring using the MSAS scoring methods. They basically showed that men had more aggressive disease than did women according to MSAS scoring, but that you could actually predict, progression in men by CRP levels, but then women that didn't work. In women, it was actually the BASMA, the metrology index and bisphosphonate used that seemed to predict x-ray progression. So x-ray progression was also, indicated by having x-ray findings and by also being obese. So again, men tend to have more aggressive disease than do women.

What about just back pain without ankylosing spondylitis? A very large eleven year Finnish population based studies looked at the risk factors for developing both low back pain and radicular back pain and found both of these to be higher in women, especially those who are obese smokers and were involved in strenuous physical work. Vibrating tool use actually increased the amount of lumbar radicular pain and that low back pain was less in those individuals who were engaged in either walking or cycling to work. This is a very common phenomenon in Europe, less so in The United States, but nonetheless instructive about maybe how to best avoid back pain in both men and women. The sort of bad news about, what's going on in gout, as you know, the recent drugs that were developed by AstraZeneca and then transferred over to Ironwood that includes lisinirad and the combination of lisinirad and allopurinol, drugs called Zorampec and Duzalo, were picked up and sold by Ironwood Pharmaceuticals.

However Ironwood Pharmaceuticals has bailed out on the deal and is no longer going to promote, detail and distribute those products suggesting that the product's responsibility goes back to the original manufacturer AstraZeneca. Again, these products are probably not taking much use in general population right now. It's, not clear where it's going to go in the future. An interesting study about gout also comes from the VA that looked at gout patients, this is overall thirteen thousand gout patients in a ten year study at the VA, and looked at those who either escalated their allopurinol use or those who didn't. What they did find was that dose escalation was seldom associated with achieving your target serum uric acid level of less than six point zero, but it was associated with an increase in mortality suggesting that dose escalations probably indicated, was a surrogate marker for severity and or futility in managing gout and not necessarily an attempt at treat to target management.

And that means that we, and the VA are not doing very good in managing gout. An interesting report about gout comes from JAMA this week. JAMA Internal Medicine looked at specifically the Allopurin hypersensitivity syndrome which is very rare, certainly less than one percent but is higher in individuals who are of Asian descent. Han Chinese, certain Koreans, Thai background individuals have a higher risk of hypersensitivity reactions to allopurinol especially if they bear the HLA haplotype B5801. It turns out in the white population the percentage of finding this, haplotype is very low, less than one percent.

It's a little higher in, African Americans where it's around three percent but much higher in the Asian populations where somewhere between eight and twelve percent it may be seen. Turns out that if you have this haplotype and you're on allopurinol, you may be and Asian that you have a hundredfold increased risk of having the severe allopurinol hypersensitivity syndrome which has a significant risk of mortality. Many of these patients will manifest the most severe manifestations of skin hypersensitivity including Stevens Johnson syndrome, toxic epidermal necrolysis and the DRESS syndrome with hyperious eosinophilia associated with the drug exposure. Good news for those involved in the biosimilar business, the data coming from the National Health Service in The United Kingdom shows that patients who switch to primarily, biosimilars and somewhat to generics save the National Health Service in England, £324,000,000, in a year's time, most recently 2017, 2018. Again, those savings will not be realized in The United States until there's a push for biosimilars and that push is being undermined by, the rebate system and what's going on with drug pricing with our expensive biologics.

There's two interesting studies about fractures that you should probably look at. One has to do that if you have any sort of, incident fragility fracture, and this actually comes from Denmark, a study of over 30,000 individuals over the age of 50. Any sort of incident fracture, not just hip, but any sort of incident fracture actually was associated with an increased ten year mortality rate. It turns out that that risk was highest in the first year following fracture, was highest in hip fractures, but was seen in other fractures as well. With hip fractures, the excess mortality was as much as thirty three percent higher in men and twenty percent higher in women.

When we looked at knee, or other bone fractures, it was like twenty percent higher in men and a little bit lower in women. The point being that that's an important period for which proper management is really called for. There's another study out there about, from the Canadian Medical Journal, this is actually an interesting study that looked at one hundred and thirty fractures and when these fractures were taken care of especially, for hip fracture and it turns out that the mortality rate was about five percent if it was done within the first three days and increased it was done after three days to almost seven percent. It's estimated that if actually these patients actually had earlier hip surgery following hip fracture that they would have avoided up to eleven deaths per 1,000 surgeries if they had done it prior to day three, suggesting that there should be a strong call for early intervention with surgery in those who require surgery, with hip fracture. And lastly, want to, note the passing of a giant in the field of rheumatology, Doctor.

Rollin Moskowitz, who died recently on 08/02/2018 at the age of 88. Rollin Moskowitz was a giant in the field and maybe the role model of a rheumatologist, a man with tremendous clinical skills loved by his patients, a man who was a fabulous teacher, loved by his fellows and all who he taught in his coursework. He inspired many people to go into the difficult and needed area of osteoarthritis research where he was at the pinnacle as a leader. Those who are at the top of their game in osteoarthritis point to him as being the most influential in their career. But on top of that, he was a great man, a great clinician, a man of humor, a man who knew how to relate to people.

Those who were blessed to have worked with him know what it's like to be around a real rheumatologist. Look at the obituary, you can learn a lot about what maybe you should be striving for in your career as a rheumatologist. Lastly, want to end with a plug for two great, lectures that are coming up this weekend. It's Friday and tomorrow Saturday there's a great meeting in Washington DC, what's called the Capital City Rheumatology Review. It's going to be, run by Doctor.

Sergio Schwartzman, and then next weekend in Nashville I'll be running the Music City Rheumatology Review. Both have fabulous faculties. If you're in the DC area or in the Southeast in and around Nashville and Tennessee, go to arthrosand. You can register and go to those meetings, they're free. You'll find the learning to be really, very worthwhile.

Make sure you go to the website to find these citations and more. We'll see you next week on roomnow.com. Take care.