2019 Rheumatology Year In Review Save
2019 Rheumatology Year In Review by Dr. Cush
Transcription
Hey. It's 2020. 01/03/2020, making this the RheumNow podcast year in review, or maybe it's the year looking forward. I'm Jack Cush, executive editor of roomnow.com. In this podcast, we will talk about a lot of different news items from 2019 that I thought were highlights.
It's a hodgepodge. It's quite a mix. It's my first attempt at writing my annual year end review. And some of these are going to make the list and others won't. I'm going to start with a great loss this year, actually several great losses.
We lost a few superheroes in the field of rheumatology, beginning with Gerald Weissman from NYU and Charles Christian from Hospital for Special Surgery, two icons in the world of rheumatology who trained rheumatologists really from the 50s, 60s, 70s, 80s, 90s, and into the 2000s and have quite a legacy. A more recent death was Cal Brown, a fabulous rheumatology from Northwestern who influenced the lives of many. These are major losses in our field, major mentors who had an impact on many of you, including me. I think one of the biggest stories this year was about venous thromboembolic events. And is there a lot to be worried about here or is there not?
As you know, the story goes that Seljans, tofacitinib, and Jakafi, ruxolitinib, another JAK inhibitor made it to the market. No mention of VTEs, venous thromboembolic events. And then baricitinib came along and they found some events and an imbalance of these DVTs and pulmonary emboli. And that became part of its label. It did so in other countries, but became sort of a spectacle here in The US.
And the other ones didn't seem like they were bothered by this. Well, a new JAK inhibitor gets approved and that's upadacitinib, also known as RINVOQ. And it just gets a label warning, a box warning, just like baricitinib did for a potential increased risk. And then out of nowhere, tofacitinib gets slapped with another box warning, this time related to a long term safety study they did where they showed patients who are on the highest dose of tofacitinib, ten milligrams BID, a dose we don't use, was associated with a higher risk of VTEs and cardiac death. So what's the deal?
Is there much to be worried about here? The background risk in the population is what, point three per one hundred patient years. RA patients could be, are increased because of inflammation. That could be up to zero point three, zero point six, zero point five, zero point six per 100 patient years. Once elevated above that, which is the numbers that we've seen in these drugs that we're talking about, we're talking about, you know, zero point six, 0.7, 0.8, meaning we're talking about, you know, one or two more cases per one thousand that are getting these events.
These are still rare events. But the bottom line is you have many choices in RA therapy, PSA therapy, or whatever you're using a JAK inhibitor in. And patients who are at risk, you may not want to use that. Patients who've had VTEs, you may not want to use those drugs. I think one of the big news items was NYU and its free medical tuition deal.
Where were they in 1977 when I wanted to go to medical school and was slapped with a tremendous debt? Not really. I mean, current graduates that are graduating in the field of rheumatology, think the number was something like, most of them have at least a $200,000 debt and like 50% have almost a $300,000 debt. But free medical tuition, it could be a game changer in the development of few doctors for the future. We have to see where that's going to go.
A rising issue, if you certainly have noticed it and if you're not, you're not paying attention. Women in rheumatology, they're taking over guys. If you haven't noticed, the incoming class at every medical school is more than 50% women now. If you haven't noticed the percentages of women in rheumatology, it's one of the highest in all medical subspecialties, over 60% of the fellowship positions are being filled with women. And the question is, how's that going to change rheumatology?
I think it'll change it for the better. You know, women taking over, certainly they run the households better than men. They probably run government better than men and running rheumatology will do a lot for patient care, I believe. The real problem here is, they being recognized? Are they be given the opportunities?
Are they getting this right income? Men get all the credit, men get all the good gigs. There's not enough women who are speakers at major programs, including this past ACR meeting. Remember Fred Astaire got all the glory and all the money, but Ginger Rogers danced the same dance. She just did it backwards and in heels.
And that's what's going on in rheumatology. Pay attention to it. We had 52 new drug approvals in 2019. I believe that's a record. New drugs for rheumatology include Nintedinib, Ovef, which is approved for idiopathic pulmonary fibrosis and now is approved for interstitial lung disease with scleroderma.
RINVOQ, which is upadacitinib, the second, actually third JAK inhibitor to hit the market as a once a day drug. Evenity, roamosuzumab, the anti sclerostatin drug for select cases of post menopausal osteoporosis. Skyrizi, a fun drug to talk about, Skyrizi, an IL-twenty three inhibitor also known as rizikizumab is out there and has been approved. We have approvals of older drugs for newer indications. Otezla got approved for Benlysta.
We have kitty I'm sorry, Otezla got approved for Behcet's. Benlysta, kitty Benlysta got approved for use in children with lupus and now Benlysta is also available as a subcutaneous injection. As you know, Xeljanz, tofacitinib and Stelara, ustekinumab were approved for use in ulcerative colitis. Taltz was approved for use in ankylosing spondylitis and axial spondyloarthritis. I think maybe the biggest approval of the year might be Cimzia for non radiographic axial spondyloarthritis.
If only I knew where to find those patients and then how to code for them. But I still think it's a major achievement and you'll see other drugs coming behind it. Recognize we have 23 biologics and that includes 11 biosimilars. I think we had four or five approved this year. Avsola is an infliximab biosimilar, the same as the other ones that are out there, RENFLEXIS and Inflectra.
Abrolata and HADLEMA are adalimumab biosimilars. ENTYKOVO, ENTYKOVO, ENTYKOVO is an say it 12 times, maybe you'll get it right, is etanercept biosimilar and Ruxience is a rituximab biosimilar only approved for GPA and MPA. It's approved for non Hodgkin's lymphoma, not approved for RA, but nonetheless, go for it if you like. A lot of opportunities creating maybe cheaper drugs, but wait, the other news item is drug prices are going up and up and up. You know that the Democrats are all over this, making this one of their major issues, but so are the Republicans.
Trump has been trying for more than three years now, trying to get some restrictions on the price of drugs and the affordability of drugs. Immediately announced with the new year, three thirty drugs will have a price increase anywhere from one to 11%. And that includes many of our drugs in rheumatology. What else is big? You know, what's always big is what's old and that's methotrexate.
I don't know why, but methotrexate continues to make the headlines. You guys love methotrexate. I love methotrexate. If only we get our patients to go along with us with the same degree of enthusiasm. Nonetheless, good data, reliable data showing that methotrexate is not associated with an increased risk of interstitial lung disease.
However, RA is, no wonder the two get confused, but there's a few reviews of this and this was actually borne out by one of the big presentations from this past ACR by Dan Solomon, talking about the safety of methotrexate from the CERT study, a cardiovascular intervention trial with methotrexate being given to cardiac patients showing, guess what, it didn't work, was stopped prematurely, but they showed the overall side effect rates and showing that the risk I think of interstitial lung disease was really very, very low. I think seven per one thousand or something like that. Nonetheless, methotrexate is still in the news. Guess what else is in the news? You know, there's a lot of problems with burnout and disgruntled physicians and by far and away, the number one report, the number one cause of this is electronic medical records.
You know, I've been dealing with a new one, EPoch, spelled E P O C H, God help me for using this monstrosity, clearly built to make bean counters better at their job, not so much for patient care. And the evidence is pretty clear that while these are hard to deal with getting in the way of how we deal with patients, there's not a lot of evidence that they are improving healthcare, but there is a lot of evidence that you can improve your bottom line financially and a lot of regulatory commitments that one may have or institutions may have. Nonetheless, EMRs, they're killing doctors and nurses daily and killing medicines slowly. I don't know what we're going to do about this. We need solutions.
We need also need solutions for scleroderma. I think we had two major failures this year. The failure of tocilizumab seemed to work well for the lung indications, but not for the skin. And what is scleroderma if not a major skin disorder at its surface, but then obviously beneath the surface there's more, but does it look like tocilizumab is going to be pursued by Genentech for an indication because of some of the negative findings? And the same was shown with nintedinib.
Nintedinib got approval for scleroderma ILD did nothing for the skin or other manifestations of scleroderma. But there is hope. We do have novel new therapies in old diseases, common diseases. Mark Genovese's sort of fascinating presentation at ULAR and ACR on vagal nerve stimulation in rheumatoid arthritis, showing this is yet another way that you can reduce cytokine production, mainly TNF inhibitors and produce clinical benefits without using a drug. Now, they need to work out the installation of the stimulator and the safety of that and there's early studies, but it looks promising.
Also, novel presented at this year's ACR was a recombinant urate degrading enzyme given orally with the hope of sopping up that one third of uric acid produced within the body that's in the GI tract, administered orally, no systemic toxicity, lowers the serum uric acid levels significantly. Yeah, it's only been tested in pigs, but you know, what are men if not grown up pigs? Did I really say that? Big mistake. It'll come back to haunt me someday.
Other novel therapies. What about JAK1? Actually multiple JAK inhibitors, TYK2 inhibitors and ustekinumab and low dose IL-two in lupus all showing promise. That's great news. The modifying issue here is it's still early studies, early phase twos and I really haven't gotten to large scale treatments, but it'll be interesting to see how these pan out.
I think one of the big issues that came up in multiple sources beginning last year and also this year is there are the limitations of MRI in viewing the SI joints of people who you think may have ankylosing spondylitis. Marrow edema, great, but not so great. Not so specific. Turns out it's seen in washer women, hockey players, athletes, people who use trampolines. It's not that specific.
If you really wanna use the MRI to diagnose sacroiliitis and a spondyloarthropathy, you need erosions. That's the most predictive finding. A few more, rituximab is taking over the long term management of ANCA associated vasculitis. A lot of studies, Main Ritzan and a few others in the last year showing that it's the drug to be on as far as chronic maintenance. It's very safe, has good, better or equal effects compared to anything else.
What about the Shingrix vaccine? It's taken off. I mean, I don't know the sales numbers, but I think it's making a bazillion dollars for, I guess it's GSK that's making it. Shame on them for not doing any research on giving this very effective therapy to people with autoimmune diseases. It's got an adjuvant in it, is it safe?
Well, there are two abstracts from ACR suggesting that you can take it if you have an autoimmune disease like rheumatoid arthritis or even lupus without fear of getting worse, but that's all uncontrolled observational data, we're not going to do much better than that. But nonetheless, the drug is much better than the old live virus vaccine. This is an inactive virus. You can give it to your patients on DMARDs, on biologics. The problem was wait list, that's over now.
You'll do just as well with one shot, but you really should get the two. Roughly the same price, way better efficacy and has more side effects, but that's a reasonable price to pay. Low dose prednisone made the news with being very effective at maintaining remission and avoiding flares if you keep people on low dose prednisone as opposed to weeding them off. And also its use in hand OA showed it was very effective but when given for a short course, it only worked when you were using it. As soon as you stopped it, it came back.
And do you really want to use low dose prednisone, ten milligrams in those studies to treat hand I don't think you really want to do that. There are new tests that I'm using a lot of this year and no, that's not Vectra. Vectra is still not a biomarker. It's as much a biomarker that predicts the past, not necessarily the future. Ask me about it sometime.
I like these new myositis antibodies, NXP-two, MDA-five and TIF-one gamma we've talked about before being associated with cancer or amyopathic dermatomyositis or dermatomyositis, semi myositis with skin ulcer to lesions and or interstitial lung disease. This and also calcinosis associated with NXP-two. These are interesting new antibodies that I think we should be aware of. And then lastly, the biggest meeting of the year, that's right, RheumNow Live was in March 2019 in Fort Worth. It was novel because everyone was connected.
It was novel because we streamed it over the internet. It was novel because you were connected and you voted on things. You upvoted questions, you downvoted questions, you got to answer questions. We had more than 25% of the whole meeting devoted to discussion and Q and A. And we had these really cool TED like talks where we heard about empathy and coaching and stealing other people's data and the analogy between playing a piano and being good at medicine and science.
This year, have some great TED Talks lined up. Joseph Smolin is going to talk about what's the deal with treat to target. Was it a big failure or was it the biggest major advance in rheumatology? A whole bunch of other ones you're going to see and love, including the history of rheumatology from some leaders in rheumatology. Go to roomnow.live, check it out.
Great rooms like us, go to great meetings like this. We'll talk to you next week on the podcast.
It's a hodgepodge. It's quite a mix. It's my first attempt at writing my annual year end review. And some of these are going to make the list and others won't. I'm going to start with a great loss this year, actually several great losses.
We lost a few superheroes in the field of rheumatology, beginning with Gerald Weissman from NYU and Charles Christian from Hospital for Special Surgery, two icons in the world of rheumatology who trained rheumatologists really from the 50s, 60s, 70s, 80s, 90s, and into the 2000s and have quite a legacy. A more recent death was Cal Brown, a fabulous rheumatology from Northwestern who influenced the lives of many. These are major losses in our field, major mentors who had an impact on many of you, including me. I think one of the biggest stories this year was about venous thromboembolic events. And is there a lot to be worried about here or is there not?
As you know, the story goes that Seljans, tofacitinib, and Jakafi, ruxolitinib, another JAK inhibitor made it to the market. No mention of VTEs, venous thromboembolic events. And then baricitinib came along and they found some events and an imbalance of these DVTs and pulmonary emboli. And that became part of its label. It did so in other countries, but became sort of a spectacle here in The US.
And the other ones didn't seem like they were bothered by this. Well, a new JAK inhibitor gets approved and that's upadacitinib, also known as RINVOQ. And it just gets a label warning, a box warning, just like baricitinib did for a potential increased risk. And then out of nowhere, tofacitinib gets slapped with another box warning, this time related to a long term safety study they did where they showed patients who are on the highest dose of tofacitinib, ten milligrams BID, a dose we don't use, was associated with a higher risk of VTEs and cardiac death. So what's the deal?
Is there much to be worried about here? The background risk in the population is what, point three per one hundred patient years. RA patients could be, are increased because of inflammation. That could be up to zero point three, zero point six, zero point five, zero point six per 100 patient years. Once elevated above that, which is the numbers that we've seen in these drugs that we're talking about, we're talking about, you know, zero point six, 0.7, 0.8, meaning we're talking about, you know, one or two more cases per one thousand that are getting these events.
These are still rare events. But the bottom line is you have many choices in RA therapy, PSA therapy, or whatever you're using a JAK inhibitor in. And patients who are at risk, you may not want to use that. Patients who've had VTEs, you may not want to use those drugs. I think one of the big news items was NYU and its free medical tuition deal.
Where were they in 1977 when I wanted to go to medical school and was slapped with a tremendous debt? Not really. I mean, current graduates that are graduating in the field of rheumatology, think the number was something like, most of them have at least a $200,000 debt and like 50% have almost a $300,000 debt. But free medical tuition, it could be a game changer in the development of few doctors for the future. We have to see where that's going to go.
A rising issue, if you certainly have noticed it and if you're not, you're not paying attention. Women in rheumatology, they're taking over guys. If you haven't noticed, the incoming class at every medical school is more than 50% women now. If you haven't noticed the percentages of women in rheumatology, it's one of the highest in all medical subspecialties, over 60% of the fellowship positions are being filled with women. And the question is, how's that going to change rheumatology?
I think it'll change it for the better. You know, women taking over, certainly they run the households better than men. They probably run government better than men and running rheumatology will do a lot for patient care, I believe. The real problem here is, they being recognized? Are they be given the opportunities?
Are they getting this right income? Men get all the credit, men get all the good gigs. There's not enough women who are speakers at major programs, including this past ACR meeting. Remember Fred Astaire got all the glory and all the money, but Ginger Rogers danced the same dance. She just did it backwards and in heels.
And that's what's going on in rheumatology. Pay attention to it. We had 52 new drug approvals in 2019. I believe that's a record. New drugs for rheumatology include Nintedinib, Ovef, which is approved for idiopathic pulmonary fibrosis and now is approved for interstitial lung disease with scleroderma.
RINVOQ, which is upadacitinib, the second, actually third JAK inhibitor to hit the market as a once a day drug. Evenity, roamosuzumab, the anti sclerostatin drug for select cases of post menopausal osteoporosis. Skyrizi, a fun drug to talk about, Skyrizi, an IL-twenty three inhibitor also known as rizikizumab is out there and has been approved. We have approvals of older drugs for newer indications. Otezla got approved for Benlysta.
We have kitty I'm sorry, Otezla got approved for Behcet's. Benlysta, kitty Benlysta got approved for use in children with lupus and now Benlysta is also available as a subcutaneous injection. As you know, Xeljanz, tofacitinib and Stelara, ustekinumab were approved for use in ulcerative colitis. Taltz was approved for use in ankylosing spondylitis and axial spondyloarthritis. I think maybe the biggest approval of the year might be Cimzia for non radiographic axial spondyloarthritis.
If only I knew where to find those patients and then how to code for them. But I still think it's a major achievement and you'll see other drugs coming behind it. Recognize we have 23 biologics and that includes 11 biosimilars. I think we had four or five approved this year. Avsola is an infliximab biosimilar, the same as the other ones that are out there, RENFLEXIS and Inflectra.
Abrolata and HADLEMA are adalimumab biosimilars. ENTYKOVO, ENTYKOVO, ENTYKOVO is an say it 12 times, maybe you'll get it right, is etanercept biosimilar and Ruxience is a rituximab biosimilar only approved for GPA and MPA. It's approved for non Hodgkin's lymphoma, not approved for RA, but nonetheless, go for it if you like. A lot of opportunities creating maybe cheaper drugs, but wait, the other news item is drug prices are going up and up and up. You know that the Democrats are all over this, making this one of their major issues, but so are the Republicans.
Trump has been trying for more than three years now, trying to get some restrictions on the price of drugs and the affordability of drugs. Immediately announced with the new year, three thirty drugs will have a price increase anywhere from one to 11%. And that includes many of our drugs in rheumatology. What else is big? You know, what's always big is what's old and that's methotrexate.
I don't know why, but methotrexate continues to make the headlines. You guys love methotrexate. I love methotrexate. If only we get our patients to go along with us with the same degree of enthusiasm. Nonetheless, good data, reliable data showing that methotrexate is not associated with an increased risk of interstitial lung disease.
However, RA is, no wonder the two get confused, but there's a few reviews of this and this was actually borne out by one of the big presentations from this past ACR by Dan Solomon, talking about the safety of methotrexate from the CERT study, a cardiovascular intervention trial with methotrexate being given to cardiac patients showing, guess what, it didn't work, was stopped prematurely, but they showed the overall side effect rates and showing that the risk I think of interstitial lung disease was really very, very low. I think seven per one thousand or something like that. Nonetheless, methotrexate is still in the news. Guess what else is in the news? You know, there's a lot of problems with burnout and disgruntled physicians and by far and away, the number one report, the number one cause of this is electronic medical records.
You know, I've been dealing with a new one, EPoch, spelled E P O C H, God help me for using this monstrosity, clearly built to make bean counters better at their job, not so much for patient care. And the evidence is pretty clear that while these are hard to deal with getting in the way of how we deal with patients, there's not a lot of evidence that they are improving healthcare, but there is a lot of evidence that you can improve your bottom line financially and a lot of regulatory commitments that one may have or institutions may have. Nonetheless, EMRs, they're killing doctors and nurses daily and killing medicines slowly. I don't know what we're going to do about this. We need solutions.
We need also need solutions for scleroderma. I think we had two major failures this year. The failure of tocilizumab seemed to work well for the lung indications, but not for the skin. And what is scleroderma if not a major skin disorder at its surface, but then obviously beneath the surface there's more, but does it look like tocilizumab is going to be pursued by Genentech for an indication because of some of the negative findings? And the same was shown with nintedinib.
Nintedinib got approval for scleroderma ILD did nothing for the skin or other manifestations of scleroderma. But there is hope. We do have novel new therapies in old diseases, common diseases. Mark Genovese's sort of fascinating presentation at ULAR and ACR on vagal nerve stimulation in rheumatoid arthritis, showing this is yet another way that you can reduce cytokine production, mainly TNF inhibitors and produce clinical benefits without using a drug. Now, they need to work out the installation of the stimulator and the safety of that and there's early studies, but it looks promising.
Also, novel presented at this year's ACR was a recombinant urate degrading enzyme given orally with the hope of sopping up that one third of uric acid produced within the body that's in the GI tract, administered orally, no systemic toxicity, lowers the serum uric acid levels significantly. Yeah, it's only been tested in pigs, but you know, what are men if not grown up pigs? Did I really say that? Big mistake. It'll come back to haunt me someday.
Other novel therapies. What about JAK1? Actually multiple JAK inhibitors, TYK2 inhibitors and ustekinumab and low dose IL-two in lupus all showing promise. That's great news. The modifying issue here is it's still early studies, early phase twos and I really haven't gotten to large scale treatments, but it'll be interesting to see how these pan out.
I think one of the big issues that came up in multiple sources beginning last year and also this year is there are the limitations of MRI in viewing the SI joints of people who you think may have ankylosing spondylitis. Marrow edema, great, but not so great. Not so specific. Turns out it's seen in washer women, hockey players, athletes, people who use trampolines. It's not that specific.
If you really wanna use the MRI to diagnose sacroiliitis and a spondyloarthropathy, you need erosions. That's the most predictive finding. A few more, rituximab is taking over the long term management of ANCA associated vasculitis. A lot of studies, Main Ritzan and a few others in the last year showing that it's the drug to be on as far as chronic maintenance. It's very safe, has good, better or equal effects compared to anything else.
What about the Shingrix vaccine? It's taken off. I mean, I don't know the sales numbers, but I think it's making a bazillion dollars for, I guess it's GSK that's making it. Shame on them for not doing any research on giving this very effective therapy to people with autoimmune diseases. It's got an adjuvant in it, is it safe?
Well, there are two abstracts from ACR suggesting that you can take it if you have an autoimmune disease like rheumatoid arthritis or even lupus without fear of getting worse, but that's all uncontrolled observational data, we're not going to do much better than that. But nonetheless, the drug is much better than the old live virus vaccine. This is an inactive virus. You can give it to your patients on DMARDs, on biologics. The problem was wait list, that's over now.
You'll do just as well with one shot, but you really should get the two. Roughly the same price, way better efficacy and has more side effects, but that's a reasonable price to pay. Low dose prednisone made the news with being very effective at maintaining remission and avoiding flares if you keep people on low dose prednisone as opposed to weeding them off. And also its use in hand OA showed it was very effective but when given for a short course, it only worked when you were using it. As soon as you stopped it, it came back.
And do you really want to use low dose prednisone, ten milligrams in those studies to treat hand I don't think you really want to do that. There are new tests that I'm using a lot of this year and no, that's not Vectra. Vectra is still not a biomarker. It's as much a biomarker that predicts the past, not necessarily the future. Ask me about it sometime.
I like these new myositis antibodies, NXP-two, MDA-five and TIF-one gamma we've talked about before being associated with cancer or amyopathic dermatomyositis or dermatomyositis, semi myositis with skin ulcer to lesions and or interstitial lung disease. This and also calcinosis associated with NXP-two. These are interesting new antibodies that I think we should be aware of. And then lastly, the biggest meeting of the year, that's right, RheumNow Live was in March 2019 in Fort Worth. It was novel because everyone was connected.
It was novel because we streamed it over the internet. It was novel because you were connected and you voted on things. You upvoted questions, you downvoted questions, you got to answer questions. We had more than 25% of the whole meeting devoted to discussion and Q and A. And we had these really cool TED like talks where we heard about empathy and coaching and stealing other people's data and the analogy between playing a piano and being good at medicine and science.
This year, have some great TED Talks lined up. Joseph Smolin is going to talk about what's the deal with treat to target. Was it a big failure or was it the biggest major advance in rheumatology? A whole bunch of other ones you're going to see and love, including the history of rheumatology from some leaders in rheumatology. Go to roomnow.live, check it out.
Great rooms like us, go to great meetings like this. We'll talk to you next week on the podcast.
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