RheumNow Podcast Fight Or Switching (DMARDs) (10.18.19) Save

It's the 10/18/2019. This is the RheumNow podcast, and I am Doctor. Jack Cush, again, with the RheumNow podcast. This week, we're going to talk about the perils of joint injection, the real skinny on statins, and shamefully low change rates for DMARDs in the face of disease activity. Yes, by the rheumatologists.

We're going to start with a UK study of the risks associated with RA. This was, I think in the National Inpatient Sample Database from 02/2014 that showed RA patients had a higher risk of MI. Not surprising. COPD should not be surprising, should be very worrisome. CVA, renal disease, and the thing that really struck me here was a two point seven fold increase in alcohol abuse.

Now, are RA patients who end up getting hospitalized. Not many of RA patients do, but I would certainly recognize the risk of MI, CVA, COPD, and even renal disease, given the drugs we use and the condition. But alcohol abuse is a bit surprising to me. The mortality trends were higher for those with CHF. AFib stood out.

So, again, our RA patients do have comorbidities, cardiovascular, but we do need to be aware of others, including renal and alcohol abuse. Similarly, a UK population study compared the population to almost seven thousand incident RA patients and looked at comorbidity and its influence on all cause mortality. Overall, the adjusted hazard ratio showed that if you had comorbidity, you had a twenty five, twenty six percent increase in mortality. Whereas joint destruction, joint damage had no effect on mortality. Things like COPD had significantly higher, two point eight four higher rates of mortality in RA patients.

What do rheumatologists love more than methotrexate? Talk about lab tests. And if any, ANAs. Well, there's a really nice review that you can find referenced on the website on this particular podcast and we can review that looks at the value of ANA testing in autoimmune disease overall. It's really quite nice.

It shows you that in general, ANAs really have very low predictive value for autoimmune disease. We know that. I tell my patients The United States, there's twenty million Americans who have a positive ANA, but only three hundred thousand who actually have lupus. And those are epidemiologic data, not lupus foundation data on lupus, which really isn't actually accurate. They showed that the most predictive ANAs were ones with a central mirror pattern, predictive for systemic sclerosis, and at a titer of one to 160 was twenty nine percent positive predictive value, higher at one to three twenty at forty two percent, and seventy seven percent predictive if the titer was one to six forty or greater, and even 82% for one to twelve eighty.

And they look at all the patterns and what they mean. The speckled pattern, as you might guess, was really poorly predictive with very low predictive value numbers, less than twenty percent, until you got to like titers of one to twelve eighty. There, the predictive value for autoimmune disease was seventy one percent. Speaking about autoantibodies, what about the anti phospholipid antibodies and what it means to patients with lupus? Well, this particular study looked at 149 patients who had biopsy proven lupus nephritis and looked at the association with antiphospholipid antibodies.

Overall, thirty six percent of those patients, or a third, had APL antibodies, nineteen percent IgG, eighteen percent IgM, eleven percent for glycoprotein, one in eight percent who had an LAC, liposcentic coagulant. When they followed these people for about, looks like thirteen, fourteen years, the patients who are APL positive had a lower ten year survival rate, ninety one percent survival, whereas those who weren't APL positive had a ten year survival rate of ninety nine percent. We're doing pretty good in either group, but an eight percent drop in survival associated with the APL antibodies means that it might mean something to you who are managing patients with lupus. Turns out that most of those, that impact in survival was associated with lower GFRs, more thrombotic events and miscarriages. Interesting data comes from the RISE registry.

This is a prospective registry run by the ACR. It now has seven thousand two hundred RA patients and they looked at the value of the disease activity measures, Rapid three, which many of you do, was done by almost eighty percent of you in this particular study, and the C Dye done by thirty four percent in the study. Turns out that when they looked at patients who had physicians declared moderate or high disease activity based on the Rapid three or C Dye, the rate of DMARR changes was abysmally low, thirty six to fifty five percent. You are less likely to change DMARDs in the face of moderate or high disease in people who are elderly, people already on combos and already on combinations with DMARDs. Again, there's a lot of data like this that says, for all of us who are measuring, we pay no attention to measuring because it sometimes takes up to a year.

A year of follow-up writing moderate to severe disease activity in the chart of a patient who has no DMAR change until six or twelve months. If you're doing measurements, look at them and then make a case for why you're not going to change DMARs in people who have moderate or high disease activity by whatever measure you use, either a Rapid three, a C die, I use a GAS score, it doesn't really matter. They all work. So, when you're advising your patients about JAK inhibitors and the risk of hyperlipidemia, what do you say? I generally say fifteen to twenty percent of patients will develop hyperlipidemia.

All lipids will go up and half of them might need to be on therapy. If you're already on a statin, you probably won't develop this particular complication. Now, that's data drawn from the trials in the package insert. You can reference that number if you like. But a nice study done, a prospective study of real world patients treated with tofacitinib for psoriatic arthritis, where maybe LDL, HDL is the same as RA, I think it is, finds that HDL and LDL only increased in fourteen or nine percent respectively when patients were followed for up to six months.

It turns out that patients who did have these increases in LDL or HDL really had no greater risk of hypertension or major coronary events, MACE events, follow-up. Now, short term follow-up, but there are a lot of studies now that have looked at either registry studies or the INTRACT study, which compared patients who developed hyperlipidemia on an IL-six inhibitor. And then, there's claims data showing hyperlipidemia on a JAK inhibitor compared to control showing no higher rate of that hyperlipidemia with significant cardiovascular or cerebrovascular events in the long run. So, who gets infection in lupus? Well, you can imagine sick patients, patients who have a lot of activity by the measures that you usually do.

A nice analysis looked at the comparison of lupus patients who had infection, culture proven infection versus sixty nine patients who did not have a culture proven infection. They were matched appropriately. And they looked at the utility of labs in predicting infection. It turns out that procalcitonin, an S100 protein, often advocated as being helpful in inflammatory states and maybe the infection really did not distinguish patients who had infection from those who did not, but as you would expect, C reactive protein was quite successful in identifying those who had serious infections in lupus and those who did not. I have always been very concerned about the risk of infection in patients with dermatomyositis.

Not often talked about, but when I look at the data, serious infectious event rates are really high in dermatomyositis. And that may be because of the strong dependence on high dose steroids, especially at the outset, trying to find the right steroid sparing drug and staying on steroids probably too long. Well, a Taiwanese claims based study looked at the risk of opportunistic infections, not regular infections, in seventy seven thousand autoimmune patients. And it turns out that maybe the highest that they saw was in dermatomyositis, polymyositis, that the OI event rates, which across the board, with most biologics you'll use, is about a one in one thousand risk of an opportunistic infection. We're talking about, yes, maybe shingles, quite common, but things like nocardia and bizarro, atypical mycobacterial fungal infections.

The OI event rate with PMDM was sixty one per one thousand. That's six per one thousand. Sixty one per one thousand patient years. That's really high. Sixty one per one thousand patient years, followed by lupus at forty three per 1,000 patient years, thirty one for scleroderma, twenty five for RA, twenty four for, other forms of scleroderma, the first one being systemic sclerosis.

The risk of all operative infections is highest in the first year. That goes to the line I've given you in the past, which is you tell your patients, these drugs that you're on for a long time, the longer you're on them, the safer it is because all the events, the bad events happen in the first year or six months. That's what we're seeing with this opportunistic infection study. So, I would worry about infections in general in dermatomyositis, maybe even more than lupus and worry about the steroids you use. So, I put a tweet out this week as a reminder about the risks of muscle disease with statins, that the risk of statin induced myopathy is about one percent and that rhabdo or necrotizing myositis are very rare by comparison.

We do have a marker for the patients who will get statin induced necrotizing myositis. These are patients who have HMG CoA reductase antibodies, HMGCR antibodies, which are not widely available, but can be found, especially labs in California does them. And it turns out that again patients who have these antibodies, these are seen in about two or three out of every one hundred thousand patients treated with statins. That means you're likely to see one or two of these in the next year or two or three. So, consider patients who have necrotizing myositis could be due to their statin.

Are there benefits to being on statin? Clearly, are many benefits. I think before we talked about statins actually have lower rates of joint replacement surgery. This particular study shows that patients who are on statins have an increased odds of osteoporosis if you're on high dose, but a decreased odds if you're on low dose. This particular study looked at a large cohort, looked at patients who were on low doses, less than ten milligrams of lovastatin, pravastatin, simvastatin, etc, rosuvastatin, and the odds ratios of developing osteoporosis was point three nine, point six eight, point seven, point six nine.

So, about a thirty percent lower rate if you're on low dose statins. But if you're on a high dose, greater than forty milligrams of simvastatin or greater than twenty milligrams of atorvastatin or rosuvastatin, your rates were over two to three fold higher. So, overall statins can be associated with a higher risk of developing statin related osteoporosis, but it is dose dependent. You should think about that. Lastly, we're going to end with a discussion of, oh, I got two more.

One is the risk of joint surgery in patients with psoriatic arthritis. The headline was a third of patients will need joint replacement surgery. This is a Danish study of 12,000 patients followed over time and showed that amongst psoriatic arthritis patients, the need for joint replacement was two percent at five years, was ten percent at ten years, good number to remember, ten and ten. But by, what was it, fifteen years, the risk is twenty nine percent. Not quite a third, almost thirty percent.

But I just generally don't think of my psoriatic arthritis patients going to joint replacement surgery. Maybe I'm not following them long enough. Maybe this is old data. Again, it's accrued up until I think 2015 or so. And maybe newer therapies might be better, but again, this is a significant risk for patients with that disease.

Stress and inflammatory arthritis, you say, is there an association? You know, used to have, I have this questionnaire. It's great. You can find it on roomnow.com. It's a downloadable.

It's the new patient questionnaire. It's two sides. Been using it for years. It's fabulous. I used to have a question on there, Do you have stress?

And just left a blank. I've used it for about three or four years and everyone filled in the blank with high. Not no, not little, everyone said high. It didn't matter whether you were unemployed, a school teacher, a CEO, you know, it didn't really matter. Everybody perceives their rate of stress as being very high.

There was an old report, I think in seminars on arthritis and rheumatism that examined by sort of a review of the literature the associations with stress, and it was kind of compelling, suggesting that there might be an association between stressful events and the onset of RA and other forms of inflammatory arthritis. Well, here comes this study which says the same thing, and I don't know what to make of it, but it looked at the risk of incident inflammatory arthritis if you had stress. They surveyed a large number of patients. They used a tool called the Perceived Stress Scale, 14. The numbers on this thing go from zero to fifty six.

And overall, their RA cohort had an increased rate of stress with a scale of 20.4. More importantly, they showed that for every one point increase, I guess over that 20, there was a ten percent increase in the risk of inflammatory arthritis. What? Again, stress is ubiquitous, inflammatory arthritis is not, and then even better, vitamin D where the associations are always there, but what does it mean and does the intervention mean anything? Could you actually lessen stress as a way of avoiding RA?

If you can figure out how to do that, please email me, JackCushRoomNow dot com. Our last report actually comes from MedPageToday. We publish a lot of their stuff. They sometimes publish our stuff. Nancy Walsh wrote a nice review of an article that appeared in Radiology that basically sheds a big spotlight on, Are joint injections worth the risk?

Is there a downside that really should argue strongly against the use of joint injections? And I think it does make a case. Now, this is written by a bunch of radiologists who are reviewing the literature and coming up with stuff to say that they don't generally deal with, but it's kind of negative. Not gigantically negative, a little bit negative. But they did their own review of their single center study and what they showed, I think they had four fifty nine steroid injections done in 2018 and they found four areas of concern.

One, they found evidence of accelerated osteoarthritis progression, like twenty cases and most of them were hip progression, more so than knee progression, seen in six percent of the injections they did. Second, subchondral insufficiency fracture, very uncommon, but zero point nine percent or about one percent risk of a subchondral insufficiency fracture, again most of them in the hip as compared to the knee. Complications of osteonecrosis, again less than one percent, zero point seven percent. And lastly rapid joint destruction with bone loss seen zero point seven percent. Now these numbers may not worry you, but are these numbers that you're quoting to your patients when you do a knee injection or you send them for a radiographically guided hip injection, I think it's important to consider this.

We all know that sometimes these are great. You can get six months, three months of relief, but usually the numbers are one to six weeks of relief, especially if they are repeat injections. So, that's for you to consider when you're using these in your patients. That's it for this week on the RheumNow report. You can go to the website, click on the links that we've provided for these many articles.

Make sure you tune in to what we're going to be doing at ACR. We have expanded coverage. It's going be really exciting. We're going to highlight things in PSA and AS and RA and gout and a bunch of other things. A new format, a new look to the website.

It's going to be all covered on our website. A lot of video, lot of one liner tweets. I think you're going to like it. That's this year at ACR twenty nineteen in Atlanta. We'll see you there.

If not, tune in the room now and see what we do. Bye.