RheumNow Podcast Antibiotics Increase RA Risk (8.16.19) Save

It's the 08/16/2019. This is a RheumNow podcast. I'm Doctor. Jack Cush, executive editor of roomnow.com. This week in the news, the risk of rheumatoid arthritis with antibiotics, up or down?

What do you think? Barristers doing battles over biosimilars, and trends in care for RA, spondy, PSA, lupus from Germany. Let's start with the nurses' health study. They come up with great data with large numbers, but are they really the answer? This particular nurse's health study looked at the risk of developing psoriasis, psoriatic arthritis, or atopic dermatitis based on diet and specifically based on whether or not you were on a lot of gluten or very little gluten.

I've made the claim that a gluten free diet, a no carb, low carb diet is incredibly effective in psoriasis, psoriatic arthritis, maybe even spondy, but that's just observational. Hasn't been really studied. And this is not really studying it either. It's looking at what happens when you compare high gluten intake to low gluten intake. And they found no, difference in the risk of developing either psoriasis, psoriatic arthritis, or atopic dermatitis.

I'm not sure that's the same as doing an interventional trial in someone who has those disorders and, restricting their dietary intake of gluten. That might yield different results, but so far, there's not a lot of enthusiasm for diet in psoriasis, other than losing weight clearly reduces risk and improves disease. A study about gout patients and their risks. So, this comes from China, and they do have a higher rate of Hashimoto's thyroiditis over there. It's not surprising they saw an association between gout and Hashimoto's thyroiditis.

But what they did was a study of almost 3,000 patients, and then they backed it up with a meta analysis of 14 different studies and showed that gout patients have a higher risk of developing hypothyroid disease. The odds ratio for women only was two point four four, significantly being higher. In meta analyses, the odds ratio was higher for gout patients and hypothyroidism at an odds ratio of zero point one five one or fifty one percent higher and one point three four, thirty four percent higher if you were just looking at hyperuricemic individuals. Interesting data, they did find, again, a significant association with thyroiditis, but I don't know what to make of that. That might need a study in other populations to be conclusive.

This week, Lilly announced the results of a phase four trial that compares head to head their IL-seventeen inhibitor, Taltz, to J and J Tremfya or guselkumab, their IL-twenty three inhibitor in patients with severe plaque psoriasis. This is a skin study, dermatology only study. And you give them credit in dermatology. They do a lot of head to head trials, and it does seem to make a difference in the prescribing patterns of docs. But I'm not sure if head to head trials have really made that big a difference yet in rheumatology.

Nonetheless, this particular study did show significant benefit to Taltz over Tremfya, as far as PASI 100 or total skin clearance at week 12, better Posse 75s at week two, and better Posse 90s at week four and eight, and I think also 12 for, again, the aisle 17 over the Aisle 23. Leave it up to my friends, the other podcasters in the world, Mike Putnam, who also looked at this and Adam J. Brown, who commented on this. Mike Putnam has the evidence based rheumatology podcast. Adam J.

Brown has the ruminations podcast from Healio. Check them out. But Mike pointed out that Lancet study that compared Cosentyx to guselkumab, or secukinumab versus guselkumab seventeen versus twenty three favored the 23 at the six month time point. Early on, there seemed to be an advantage for the IL-seventeen inhibitor. So, maybe Lilly's preliminary results in their phase four trial only reflect early responses, which may favor IL-seventeen.

They haven't presented all the data. They haven't shown the numbers, but they will show that at an upcoming interim meeting. We'll have to wait and see what that shows. I did a Twitter poll this week on the issue of when do you use a steroid sparing agent in patients with GCA? So, when would you start a demarterer of biologic in someone who has a diagnosis of GCA?

Over 200, I don't know, two seventy responses, the answer was not diabetes two percent or after an initial flare eight percent. More people were inclined to use a biologic or a DMARC at the start in twenty nine percent, but primarily after they were unable to taper steroids, that was sixty percent of respondents, suggesting that maybe a third of you might consider using this early on. I doubt that the usage pattern reflects that, You're thinking about it, but not really doing it. A study of osteoarthritis and quality of life looked at three thousand patients with osteoarthritis and did an analysis on what leads to worsening of quality of life. And not surprisingly, was female gender, higher BMI, smoking, knee pain, and lower income, such that the patients who had rapid progression of their osteoarthritis to total knee replacement had these features and the risk of total knee replacement was six fold higher if they had these features.

So if you're a woman, a smoker, and you're overweight, and your knee hurts with osteoarthritis, the only thing you can do to save yourself is make more money. And maybe that'll help, I don't know. But obviously that's a bad combination right there. Another study about osteoarthritis and our use of opioids. Do we really care anymore about opioids?

Is it really beating us down? Are we just avoiding it by not prescribing opioids? Well, this particular study looked at the use of opioids in pre surgical osteoarthritis, where it was primarily being used pre surgically in spine OA or degenerative arthritis patients, less so in hip and knee. I think it was like fifty percent of the use and 25 in spine and twenty five and twenty five in knee. So, the rate was about thirty percent use in presurgical OA, and it was used in mostly spine OA compared to knee, but also in obese smokers, depression, greater pain, higher total joint count, and concurrent use of other pain medicines.

Like the other study, it shows that being a smoker, being overweight, and having these other co factors are bad prognostic features for not just outcomes, but also how you're going to manage them therapeutically. Opioids are needed pre surgically. I think we're sort of wimping out and going along with the flow here. I know it creates a lot of trouble for us, but our job is to treat these patients. And I have no problem using opioids in patients who are pre surgical, Not for a long time and not for a long time post surgically, but again, to expect them to get by on ibuprofen and acetaminophen and a dollop of tramadol is kind of idiotic.

A case control study from The UK clinical practice database examined twenty two thousand patients with RA and compared them to ninety thousand people in the general population. This was between the years of 1995 and 2017, and found that RA patients who had received antibiotics had a sixty percent higher risk of developing RA. So that's surprising. Why would it? Remember Thomas McPherson Brown, who was treating RA with tetracyclines and pictured having great response.

Again, these are people who had received antibiotics prior to developing RA and showed an odds ratio of one point six zero or sixty percent higher. The authors postulated that antibiotic use could be detrimental, especially if used inadvertently or inappropriately, and it may do so by changing the microbiome. A nice report comes from the BRASS registry and their researchers showing that RA disease activity drives interstitial lung disease in RA. They looked at 1,500 patients in BRASS registry and showed that compared to those who are in remission, people who had low disease activity, moderate and high disease activity had an increased risk of developing RA interstitial lung disease. So, the odds ratio here, the hazard ratio here was one point four one for low dose activity, forty one percent higher.

You had a doubling of the risk with a hazard ratio to zero point zero eight if you had moderate dose activity and high dose activity gave you a 3.48 fold increase risk. They calculated that each unit increase in the dash 28 score led to an increased risk of ILD by as much as thirty five percent. So disease activity, very important in averting one of the worst complications of RA, which is RA lung disease. You may have seen this week that Amgen won its court case against Sandoz in the battle over the patent restriction that currently exists for Enbrel, whereas patent protected in The United States until 2029, Sandoz with its new biosimilar Gorelzi, which is also known as etanercept SZZS or SZZS, That's the suffix abbreviation, which is only seen here in The United States. Anyway, a New York excuse me, a US District Court Judge upheld, the current status and rejected Novartis' arguments stating that the Enbrel's claim was based on claims that have been in existence prior to the current patent restrictions.

So, they had extensions on their patent based on new developments in Enbrel as the drug progressed from its original approval in 1998. That's why it's patent protected until 2029. The problem here is of course, we've got a lot of biologics currently in play and the only ones that actually are available to us are the infliximab and those are not at a very good discount compared to what's happening in Europe. So, the whole biosimilar promise of saving money and allowing more patients to be treated will not be realized in United States until they are available. And it looks like Novartis is going to appeal this particular decision, but where it's going to go is unknown.

I'll direct you to the last installment or the fourth installment, may not be the last installment of the Warren RA. This one is called Desperado. It's time to open the gate. As you know, I've been doing a series called the War on RA for the last month with four installments. And in this one, I wrap up why I've had all those Eagle song drops in there.

Why talk so much about the Eagles and Glen Fry who died in January 2016 from rheumatoid arthritis and IBD and complications thereof, including pneumonia. That he died from in New York in January 2016. It's a story about why we can do better, why it should inspire us to be greater than we currently are. And we are currently great at managing RA, But where is the innovation going to come from? I like the line, Innovation is when you drive a pirate ship into the yacht club and see what happens.

Innovation involves taking chances, knowing that you may fail, but knowing that taking chances leads to greater or newer or better outcomes. We need a war on RA. Lastly, an interesting report comes from Germany where they talk about trends in the care of not just rheumatoid arthritis, but a host of autoimmune disorders or inflammatory disorders, specifically rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and lupus. So, what they found was a number of things. There's an increasing use of biologics, a decreasing reliance on steroids.

Methotrexate remains a standard of care and RA not surprising. Worked absenteeism has actually decreased. Looking at the epidemiology, it looks like the age of onset has actually increased over time for many of these disorders, particularly so in seronegative RA, where the age of onset has increased from 95 to twenty fifteen by as much as six years later. The age of onset has not changed in patients with lupus. The use of rheumatologists, kind of interesting in that we'd like to see patients earlier and we think that we should see most of these patients.

While the use of rheumatology as a consultant has increased for all the diseases, it still remains very low in ankylosing spondylitis. So, in RA patients are seen by rheumatologists seventy three percent of the time, lupus seventy one percent of the time, PSA sixty six percent of time, but only forty five percent of the time with ankylosing spondylitis. The time to referral has decreased from ninety five to twenty fifteen from one year to a half year in RA. From, five years to two point one years in AS, still too long, from, what was it, two years to zero point six years in PSA. These are all encouraging data.

I don't think we're doing that well in The United States as far as referral and being seen by the rheumatologists. And lastly, trends in drug therapy were interesting. Biologics have increased to about thirty percent across the board, twenty eight percent in RA by 2016, thirty three percent in PSA, and fifty percent of AS patients are taking a biologic in 2016. These trends have gone up quite a bit since they were first introduced at the turn of the century in 2000. So that's it for this week on RheumNow.

You can go to the website to see these links, and read up more about these interesting studies. Tune in next week to the RheumNow podcast.