The RheumNow Week In Review Good News For GPA%2C CZP%2C Tofa But Not ERA %286.1.18%29 Save
The RheumNow Week In Review Good News For GPA%2C CZP%2C Tofa But Not ERA %286.1.18%29 by Dr. Cush
Transcription
It's 06/01/2018. We're days away from my birthday and days away from the start of EULAR, but this is the RheumNow we can review. I'm doctor Jack Cush, executive editor of roomnow.com. In the news this week, have FDA approvals for old drugs and new indications. We get some information about what to do when considering transplant in our GPA patients.
And there's some bad news to take note of for patients with early arthritis from a few different studies. But first the scoop on FDA approvals. UCB announced this week that cerdulizumab Cimzia was approved for moderate to severe plaque psoriasis based on over a thousand patients in three very large phase three trials wherein the PASI 75 results were somewhere around seventy five to eighty two percent by week sixteen. This now makes psoriasis amongst a few other indications that are FDA approved for cerdulizumab including rheumatoid arthritis, Crohn's disease, ankylosing spondylitis and psoriatic arthritis. This week Pfizer announced that the FDA also approved Xeljanz for use in patients with moderate to severe active ulcerative colitis.
The interesting thing about the use of tofacitinib here is it's approved at a higher dose than is what usually is used in rheumatoid arthritis. The ten milligrams BID dose is the starting dose is used for eight weeks and thereafter the patients can be lowered to five milligrams BID. This is notable and that it is the first ten milligram BID dosing indication for this drug that was originally sought for, for rheumatoid arthritis but denied for lack of efficacy and maybe some concern about safety. Speaking of safety and tofacitinib, Kevin Winthrop reported in the Crohn's and Colitis Foundation Journal IBD that among, their clinical trials for ulcerative colitis that involved eleven fifty seven patients, there was a five point six percent risk of developing herpes zoster That's a total of sixty five cases, eleven of which were multidermatoma and it was one case of herpes encephalitis. That makes the hazard ratio a fourfold increased risk, which is about on par what's been seen for tofacitinib in rheumatoid arthritis and where it's been studied elsewhere.
Those at risk for zoster in the ulcerative colitis population include the elderly, Asians, those who had prior exposure to a TNF inhibitor, and those who are receiving the higher dose of ten milligrams BID. So again, maybe while there is some added benefit with a higher dose, maybe there's an added risk, especially in just these patients with ulcerative colitis. An interesting report comes out of the Canadian Medical Journal. This is on a population based study looking at almost 300,000 young girls between the ages of 12 and 17 who received the quadrivalent HPV vaccine. And specifically what they were looking at was would there be an increased risk or an increased observance of autoimmune diseases when these people were followed for a number of years?
They looked at a number of them including Graves' disease, Bell's palsy, JIA, lupus and lupus like diseases, autoimmune hemolytic anemia, etc. And there was no increased risk of autoimmune disease in patients who receive the inactive quadrivalent HPV vaccine. A very interesting study comes out this week from Annals Rheumatic Disease where investigators looked at The US Renal Transplant System. And specifically they looked at those patients who had end stage renal disease due to GPA, granulomatous polyangiitis, and saw what happened as far as their outcomes once they did receive transplant. So amongst fifteen twenty five such patients who were waitlisted, nine forty six went on to receive a renal transplant and what was noted was that receiving a renal transplant was associated with a seventy percent reduction in all cause mortality.
And that was largely because of a ninety percent reduction in cardiovascular deaths. So again, it used to be that patients who had diseased kidneys from lupus and scleroderma and in this case GPA were not supposedly good transplant recipients, but that's changed. And this is good evidence in favor of transplantation in those who achieve end stage renal disease as a result of their GPA. So that's good news for your patients. What about the early arthritis patients that we talked about the front end of the study of this report?
The ESPLA study, that's a French early RA cohort study of 500, excuse me, a 400 patient five year study of RA patients. And what they found in this study was that radiographic progression occurred in almost thirty six percent. Now, it's great to actually get early RA patients and because they're very amenable to treatment, but again, they also have more aggressive disease, they're more likely to have radiographic progression, they can be more difficult at the outset. This study says a very high rate. If you look at a lot of the x-ray outcome studies and look at the number of people who don't progress as far as their x rays, it's usually around ninety percent when you take all comers.
But this is an early RA cohort, where they get a myriad of different therapies. Specifically, they found in this study is that those who are going to progress to radiographic damage were those who are on high dose steroids, suggesting that steroids was a surrogate for those with more aggressive disease. Those who weren't going to progress were those who received more than three years of biologic therapy. I think that's very interesting data and it jives with what's been out there before about the protective effects of methotrexate and TNF inhibitors when, they clearly have some benefits, especially with regard to cardiovascular risk, but mainly it's after the patients have been on those therapies for two to three years or more. So again, I think this is important to realize that we need to find these patients early, we need to intervene aggressively right from the outset.
Another study called the UAC study was also reported in the literature, came from Alzheimer's disease, one hundred and eight patients who had DMAR naive early RA and they were treated with methotrexate right from the outset. The bad news is that after a year, only fifty two percent of them, actually forty eight percent of them achieved a response. Fifty two percent were deemed methotrexate incomplete responders meaning they did not achieve a -twenty eight of less than 2.6 or achieve less than four swollen joints at one year. So that's good but not great, but what are the predictors of not achieving a methotrexate response? Their analysis shows that having a high -twenty eight gave you a twofold increased risk.
Current smoking gave you a threefold increased risk and also was not receiving alcohol. So therefore alcohol, which we know is anti inflammatory, may have some protective effects in patients with early disease. Again, these two studies underscore the need to be aggressive and to find these patients and treat them early. A very interesting study came from the British Biologics Registry and they've had many reports about, serious infectious rates in their almost 20,000 patients that they followed longitudinally. In this particular report, they had an SIE rate of five point five per 100 patient years, meaning one hundred patients followed for a year that five of them would end up in the hospital with a serious infection like pneumonia or sepsis or meningitis or septic arthritis, etc.
But what I found interesting about this study was this stat. And that stat was for those that had an SIE within the first thirty days following the SIE, risk of death was ten percent. I don't think anybody's really talked about that before. So developing a real SIE in patients on a biologic does carry a significant morbid if not mortal risk. And again, this is something that we need to be vigilant about and educate our patients about.
Two more reports, one an interesting study from Canada, from Manitoba, Calgary, a very large population based study looked at those with incident RA and specifically looked at the risk of developing depression, anxiety, schizophrenia and bipolar disorders. What they found was that there was a forty six percent risk of depression in these patients, a twenty four percent risk of anxiety, a twenty one percent of bipolar disorder and schizophrenia was not increased in these patients. However, those that were at the greatest risk tended to be women and tend to be those in lower socioeconomic groups. So again, this is important because RA is hard to manage. Or rheumatologists struggle with managing the disease but may not be aware of or be looking for signs of depression, anxiety and bipolar disorder.
That again can be a complication as far as pain management, compliance, achieving best outcomes for the rheumatoid arthritis and this needs to be considered and watched for. The last report was actually reported in MedPageToday and also in room now. It's about the cancer risk in patients with psoriatic arthritis. A bunch of Chinese investigators got together and did a meta analysis of nine studies in over forty three thousand PSA patients and showed that the overall risk of malignancy was increased twenty nine percent in PSA patients compared to the general population. That went for an SIE, an SIR of 1.29.
This was higher in patients who were taking conventional DMARDs where that rate went up to seventy five percent increased risk with an SIR of 1.75 compared to the general population. Interestingly, if patients were on a biologic, there was no increased risk of malignancy in PSA patients. And not surprisingly, as has been seen in many other studies of psoriasis and psoriatic arthritis patients, the primary malignancy that they will experience is non melanoma skin cancers, where the rate is about two point five fold higher risk in patients with PSA. That's it for RheumNow and this week's review. Be sure to go to the website to click on these links to learn more about these reports.
Be sure to follow us in the next, two weeks from now when we head to EULAR and report about what's going on there. Be sure to tell your friends to sign up for the regular daily, emails and or for the podcast. We'll see you next week. Take care.
And there's some bad news to take note of for patients with early arthritis from a few different studies. But first the scoop on FDA approvals. UCB announced this week that cerdulizumab Cimzia was approved for moderate to severe plaque psoriasis based on over a thousand patients in three very large phase three trials wherein the PASI 75 results were somewhere around seventy five to eighty two percent by week sixteen. This now makes psoriasis amongst a few other indications that are FDA approved for cerdulizumab including rheumatoid arthritis, Crohn's disease, ankylosing spondylitis and psoriatic arthritis. This week Pfizer announced that the FDA also approved Xeljanz for use in patients with moderate to severe active ulcerative colitis.
The interesting thing about the use of tofacitinib here is it's approved at a higher dose than is what usually is used in rheumatoid arthritis. The ten milligrams BID dose is the starting dose is used for eight weeks and thereafter the patients can be lowered to five milligrams BID. This is notable and that it is the first ten milligram BID dosing indication for this drug that was originally sought for, for rheumatoid arthritis but denied for lack of efficacy and maybe some concern about safety. Speaking of safety and tofacitinib, Kevin Winthrop reported in the Crohn's and Colitis Foundation Journal IBD that among, their clinical trials for ulcerative colitis that involved eleven fifty seven patients, there was a five point six percent risk of developing herpes zoster That's a total of sixty five cases, eleven of which were multidermatoma and it was one case of herpes encephalitis. That makes the hazard ratio a fourfold increased risk, which is about on par what's been seen for tofacitinib in rheumatoid arthritis and where it's been studied elsewhere.
Those at risk for zoster in the ulcerative colitis population include the elderly, Asians, those who had prior exposure to a TNF inhibitor, and those who are receiving the higher dose of ten milligrams BID. So again, maybe while there is some added benefit with a higher dose, maybe there's an added risk, especially in just these patients with ulcerative colitis. An interesting report comes out of the Canadian Medical Journal. This is on a population based study looking at almost 300,000 young girls between the ages of 12 and 17 who received the quadrivalent HPV vaccine. And specifically what they were looking at was would there be an increased risk or an increased observance of autoimmune diseases when these people were followed for a number of years?
They looked at a number of them including Graves' disease, Bell's palsy, JIA, lupus and lupus like diseases, autoimmune hemolytic anemia, etc. And there was no increased risk of autoimmune disease in patients who receive the inactive quadrivalent HPV vaccine. A very interesting study comes out this week from Annals Rheumatic Disease where investigators looked at The US Renal Transplant System. And specifically they looked at those patients who had end stage renal disease due to GPA, granulomatous polyangiitis, and saw what happened as far as their outcomes once they did receive transplant. So amongst fifteen twenty five such patients who were waitlisted, nine forty six went on to receive a renal transplant and what was noted was that receiving a renal transplant was associated with a seventy percent reduction in all cause mortality.
And that was largely because of a ninety percent reduction in cardiovascular deaths. So again, it used to be that patients who had diseased kidneys from lupus and scleroderma and in this case GPA were not supposedly good transplant recipients, but that's changed. And this is good evidence in favor of transplantation in those who achieve end stage renal disease as a result of their GPA. So that's good news for your patients. What about the early arthritis patients that we talked about the front end of the study of this report?
The ESPLA study, that's a French early RA cohort study of 500, excuse me, a 400 patient five year study of RA patients. And what they found in this study was that radiographic progression occurred in almost thirty six percent. Now, it's great to actually get early RA patients and because they're very amenable to treatment, but again, they also have more aggressive disease, they're more likely to have radiographic progression, they can be more difficult at the outset. This study says a very high rate. If you look at a lot of the x-ray outcome studies and look at the number of people who don't progress as far as their x rays, it's usually around ninety percent when you take all comers.
But this is an early RA cohort, where they get a myriad of different therapies. Specifically, they found in this study is that those who are going to progress to radiographic damage were those who are on high dose steroids, suggesting that steroids was a surrogate for those with more aggressive disease. Those who weren't going to progress were those who received more than three years of biologic therapy. I think that's very interesting data and it jives with what's been out there before about the protective effects of methotrexate and TNF inhibitors when, they clearly have some benefits, especially with regard to cardiovascular risk, but mainly it's after the patients have been on those therapies for two to three years or more. So again, I think this is important to realize that we need to find these patients early, we need to intervene aggressively right from the outset.
Another study called the UAC study was also reported in the literature, came from Alzheimer's disease, one hundred and eight patients who had DMAR naive early RA and they were treated with methotrexate right from the outset. The bad news is that after a year, only fifty two percent of them, actually forty eight percent of them achieved a response. Fifty two percent were deemed methotrexate incomplete responders meaning they did not achieve a -twenty eight of less than 2.6 or achieve less than four swollen joints at one year. So that's good but not great, but what are the predictors of not achieving a methotrexate response? Their analysis shows that having a high -twenty eight gave you a twofold increased risk.
Current smoking gave you a threefold increased risk and also was not receiving alcohol. So therefore alcohol, which we know is anti inflammatory, may have some protective effects in patients with early disease. Again, these two studies underscore the need to be aggressive and to find these patients and treat them early. A very interesting study came from the British Biologics Registry and they've had many reports about, serious infectious rates in their almost 20,000 patients that they followed longitudinally. In this particular report, they had an SIE rate of five point five per 100 patient years, meaning one hundred patients followed for a year that five of them would end up in the hospital with a serious infection like pneumonia or sepsis or meningitis or septic arthritis, etc.
But what I found interesting about this study was this stat. And that stat was for those that had an SIE within the first thirty days following the SIE, risk of death was ten percent. I don't think anybody's really talked about that before. So developing a real SIE in patients on a biologic does carry a significant morbid if not mortal risk. And again, this is something that we need to be vigilant about and educate our patients about.
Two more reports, one an interesting study from Canada, from Manitoba, Calgary, a very large population based study looked at those with incident RA and specifically looked at the risk of developing depression, anxiety, schizophrenia and bipolar disorders. What they found was that there was a forty six percent risk of depression in these patients, a twenty four percent risk of anxiety, a twenty one percent of bipolar disorder and schizophrenia was not increased in these patients. However, those that were at the greatest risk tended to be women and tend to be those in lower socioeconomic groups. So again, this is important because RA is hard to manage. Or rheumatologists struggle with managing the disease but may not be aware of or be looking for signs of depression, anxiety and bipolar disorder.
That again can be a complication as far as pain management, compliance, achieving best outcomes for the rheumatoid arthritis and this needs to be considered and watched for. The last report was actually reported in MedPageToday and also in room now. It's about the cancer risk in patients with psoriatic arthritis. A bunch of Chinese investigators got together and did a meta analysis of nine studies in over forty three thousand PSA patients and showed that the overall risk of malignancy was increased twenty nine percent in PSA patients compared to the general population. That went for an SIE, an SIR of 1.29.
This was higher in patients who were taking conventional DMARDs where that rate went up to seventy five percent increased risk with an SIR of 1.75 compared to the general population. Interestingly, if patients were on a biologic, there was no increased risk of malignancy in PSA patients. And not surprisingly, as has been seen in many other studies of psoriasis and psoriatic arthritis patients, the primary malignancy that they will experience is non melanoma skin cancers, where the rate is about two point five fold higher risk in patients with PSA. That's it for RheumNow and this week's review. Be sure to go to the website to click on these links to learn more about these reports.
Be sure to follow us in the next, two weeks from now when we head to EULAR and report about what's going on there. Be sure to tell your friends to sign up for the regular daily, emails and or for the podcast. We'll see you next week. Take care.
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