The RheumNow Week In Review - 9 March 2018 Save
The RheumNow Week In Review - 9 March 2018 by Dr. Cush
Transcription
Hi, it's 03/09/2018. This is the RheumNow we can review. I'm Doctor. Jack Cush, Executive Editor of roomnow.com. This week we have a few new regulatory announcements that are of a surprise.
Second, have the rise and fall of opioids. Lastly, what you can prevent either with a FISH diet or with bariatric surgery. At the top of the news, it's a report about GCA and MRA. You may remember last week in, our review, we discussed the use of PET scanning in large vessel vasculitis having an eighty five percent predictive value and eighty five percent or so sensitivity, Nice numbers in a difficult to diagnose and manage condition. This week, we have a report of thirty patients with GCA who are monitored by magnetic resonance angiography or MRA.
The problem with this assay in this study is that even at baseline as they started the assay, as they started the study, less than half of the patients had a normal MRA at baseline and then during the study, over time, the MRI was weakly sensitive to change such that it didn't really discriminate responders from non responders, although clinically patients in this study GCA treated with tocilizumab did have a clinical response. So this preliminary report suggests that MRA is probably not a good tool, or assessment tool in the outcome measures, and assessment of patients with large vessel vasculitis, in this case giant cell arteritis. News from NICE this week, that is The UK organization that approves therapy, made a reversal in that, December 2017 NICE actually came up with a decision that it would not approve tocilizumab for use in GCA talking to cost effectiveness, issues, obviously expensive therapy, for which they were spending pennies treating it with steroids in the past. But new analyses and new data submitted and discussions with multiple, stakeholders has led NICE to reverse this decision and now approve tocilizumab for giant cell arteritis especially in patients with repeated relapses or those who don't respond to steroids.
If you know of patients who have total joint and total hip replacement, you do know that they are, at risk for venous thromboembolic events, especially if they've had bilateral surgeries. The question is at some point, do their venous thromboembolic event risks go away? This study was actually done and compared a large number of patients who traveled by air and those who traveled by land and they had to do I think almost three hours of travel by air to make their follow-up visits. They found that patients who are traveling by air to and from the hospital after their hip replacement or knee replacement, that those patients had a doubling of the rate, excuse me, a tripling of the rate of venous thromboembolic events one point six four percent versus zero point five eight percent. I myself have had bilateral knee replacements and do wear, know, TED hose compression stockings when I'm taking airplane trips and it seems to be a wise idea, in patients who had these procedures.
So again, there is a low risk but it is more in people who are traveling who've had major lower limb surgery. A study of one hundred and seventy six RA patients looked at those, and what they ate as far as their diet and they showed that you could actually significantly lower your DAS scores by increasing the amount of fish in your diet, such that those patients who ate more than two servings of fish two or more times, per week tended to have better disease control and significantly lowered DAS scores. The more you increased it, the more you had a lowering of your DAS scores such that for each additional serving of fish, the DAS CRP was lowered by 0.18. Good reason to suggest fish for your patients. There's also historic data that says that patients who eat a lot of fish are more at a lesser risk of developing rheumatoid arthritis.
Bariatric surgery was looked into this week comparing it to lifestyle modification in obese diabetic patients. There's no arthritis outcomes here, just looking at the benefits of weight loss and how you do it. If you do it through lifestyle modification and diet, you're less likely to achieve your goals and if you use bariatric surgery. The bottom line is that for the different methods of bariatric surgery, was significantly better, and measured in all ways including those who were able to stop their diabetes medicine. So if you actually had a gastric bypass surgery, the more radical procedure, you are seventeen times more likely to go off your diabetes medicine.
If you actually use gastric sleeve, also effective therapy, less radical, you are seven times more likely to go off your diabetes medicines, and if you had the, less effective but nonetheless often done gastric lap band surgery, you are only four times more likely to go off your diabetes medicines. Again, for patients who are problematic diabetics, are obese, who are struggling with their weight, this may be the right solution. An interesting study by the name of the Humira trial looked at the efficacy of patients on Humira who have erosive osteoarthritis. It's a relatively small trial of 51 patients, but it did show that patients who were taking adalimumab for erosive RA, there was no benefit as far as a reduction in pain, reductions in synovitis, or in reductions in bone marrow lesions, adding it to the stockpile, the large stockpile of drugs that do not work in erosive osteoarthritis. This is problematic.
We do need therapies. We do need more research in this area. Rituximab, as you know is a common drug that's used in both rheumatology and in oncology, and unfortunately patients who read the package inserts on these drugs are often dissuaded because of the many side effects that you see, which are often related to what you see when rituximab is given to patients with non Hodgkin's lymphoma or sometimes with leukemia. What is actually known though from this review was that the adverse event rates are much, much higher in patients who are on, rituximab for lymphoma leukemia range from twenty five to thirty six percent of patients and was much lower in those who received it for autoimmune disease where it was only nine to seventeen percent. You're more likely to have adverse events if you had splenomegaly, anemia, a history of, drug allergies, and increasing age.
Tofacitinib is in the news this week and I threw a tweet out there about its dosing in, renal impairment. Should know that you don't have to adjust the dose of tofacitinib if you have mild to moderate renal impairment, But you should know also that the drug was really never studied in patients with a, creatinine clearance of less than 40 in RA and less than 50 in PSA, but for most patients who have mild renal impairment, there is no need to dose adjust. The big news is that today, Friday March 9, we actually have, a news that from yesterday where the FDA panel, the GI panel voted in favor of approving tofacitinib for the treatment of moderate to severely active ulcerative colitis. This is a study of adult patients. They looked at multiple studies, looked at multiple regimens.
They voted unanimously across the board 15 to zero for approval and for approval at a dose of ten milligrams BID. They actually voted against requiring or suggesting a study where there would be an induction study of ten milligrams BID followed by five milligrams BID maintenance. Obviously, they were persuaded strongly by the ten milligram data. Now, again, usually the FDA follows the recommendation of the advisory panel, but in this case, that would be a breakthrough because, ten milligram dose BID was sought for with other indications and denied largely because it was not thought to have additional benefit, and with no risk. In fact, they were concerned about the risks of ten milligram BID and there's some suggestion it might be a little bit more side effects at that dose.
Here, this would be the first time that ten milligram BID would be the recommended dose if it is to be approved for ulcerative colitis as recommended by the panel. Now the FDA could come back and say, no, we're only going to approve the lower dose, but the strength of the data was not quite as great as with ten milligrams BID. Opioids are in the news this week, sad news from the CDC. CDC had a webinar where it reported that in a one year timeframe from July 2016 to July 2017, opioid related overdoses increased by thirty percent nationwide. Regionally it varied and was high as seventy percent in some places, and it's really quite shocking this problem continues.
We do need better education to curtail the use and abuse of opioids. There was another important paper that was found in JAMA which studied the use of either opioids or non opioid analgesic medicines in patients requiring pain meds for either chronic back pain, chronic, hip or knee pain usually due to osteoarthritis. This is a two forty patient study from the Veterans Administration where patients either received an opioid that could be escalated to many different forms of opioid starting out with, hydrocodone and ending up with fentanyl and even more stronger, OxyContin like medicines, or they were randomized to receive acetaminophen and then escalated to receive nonsteroidals and maybe at the very end tramadol. So opioid versus non opioid, no difference in overall functional outcomes nor in reductions in pain. Both groups started out with a pain score of about 5.4.
Those that went on the non opioids dropped to 3.5 and opioids dropped to four point zero. While that is slightly significant in favor of the non opioids, it's not a major difference. Hence opioids are not definitely better in these patients who have chronic pain. Moreover, the opioid patients were more likely to have more adverse events double the rate one point eight versus zero point nine percent and that was significant. Again, is important because in the initial management of chronic pain, patients that opioids should not be the first choice, that there are other agents that work just as well if not better.
Lastly, there's an interesting report about severe cytotoxic T cell mediated skin disorders like Stevens Johnson syndrome and toxic epidermal necrolysis. These are very, very dangerous conditions arising from drug reactions for which they may be hard to treat. This particular study looked at ninety six patients with either TENS or SJS, Stevens Johnson syndrome, or toxic epidermal necrolysis and looked at the efficacy of etanercept and showed that, etanercept was able to decrease mortality, reduce the time to resolution of skin lesions and also reduce the amount of GI hemorrhage. I was unaware of TNF inhibitors prior to this being used for this purpose and I think this is a nice advantage and an interesting study. That's it for this week at rheumnow.
Tune into the website to find more of these reports, to get the links, to read more on these articles. Be sure to sign up for the podcast on iTunes or on Stitcher or whoever you listen to your podcast on. That's it. We'll see you next week on RheumNow. Enjoy.
Second, have the rise and fall of opioids. Lastly, what you can prevent either with a FISH diet or with bariatric surgery. At the top of the news, it's a report about GCA and MRA. You may remember last week in, our review, we discussed the use of PET scanning in large vessel vasculitis having an eighty five percent predictive value and eighty five percent or so sensitivity, Nice numbers in a difficult to diagnose and manage condition. This week, we have a report of thirty patients with GCA who are monitored by magnetic resonance angiography or MRA.
The problem with this assay in this study is that even at baseline as they started the assay, as they started the study, less than half of the patients had a normal MRA at baseline and then during the study, over time, the MRI was weakly sensitive to change such that it didn't really discriminate responders from non responders, although clinically patients in this study GCA treated with tocilizumab did have a clinical response. So this preliminary report suggests that MRA is probably not a good tool, or assessment tool in the outcome measures, and assessment of patients with large vessel vasculitis, in this case giant cell arteritis. News from NICE this week, that is The UK organization that approves therapy, made a reversal in that, December 2017 NICE actually came up with a decision that it would not approve tocilizumab for use in GCA talking to cost effectiveness, issues, obviously expensive therapy, for which they were spending pennies treating it with steroids in the past. But new analyses and new data submitted and discussions with multiple, stakeholders has led NICE to reverse this decision and now approve tocilizumab for giant cell arteritis especially in patients with repeated relapses or those who don't respond to steroids.
If you know of patients who have total joint and total hip replacement, you do know that they are, at risk for venous thromboembolic events, especially if they've had bilateral surgeries. The question is at some point, do their venous thromboembolic event risks go away? This study was actually done and compared a large number of patients who traveled by air and those who traveled by land and they had to do I think almost three hours of travel by air to make their follow-up visits. They found that patients who are traveling by air to and from the hospital after their hip replacement or knee replacement, that those patients had a doubling of the rate, excuse me, a tripling of the rate of venous thromboembolic events one point six four percent versus zero point five eight percent. I myself have had bilateral knee replacements and do wear, know, TED hose compression stockings when I'm taking airplane trips and it seems to be a wise idea, in patients who had these procedures.
So again, there is a low risk but it is more in people who are traveling who've had major lower limb surgery. A study of one hundred and seventy six RA patients looked at those, and what they ate as far as their diet and they showed that you could actually significantly lower your DAS scores by increasing the amount of fish in your diet, such that those patients who ate more than two servings of fish two or more times, per week tended to have better disease control and significantly lowered DAS scores. The more you increased it, the more you had a lowering of your DAS scores such that for each additional serving of fish, the DAS CRP was lowered by 0.18. Good reason to suggest fish for your patients. There's also historic data that says that patients who eat a lot of fish are more at a lesser risk of developing rheumatoid arthritis.
Bariatric surgery was looked into this week comparing it to lifestyle modification in obese diabetic patients. There's no arthritis outcomes here, just looking at the benefits of weight loss and how you do it. If you do it through lifestyle modification and diet, you're less likely to achieve your goals and if you use bariatric surgery. The bottom line is that for the different methods of bariatric surgery, was significantly better, and measured in all ways including those who were able to stop their diabetes medicine. So if you actually had a gastric bypass surgery, the more radical procedure, you are seventeen times more likely to go off your diabetes medicine.
If you actually use gastric sleeve, also effective therapy, less radical, you are seven times more likely to go off your diabetes medicines, and if you had the, less effective but nonetheless often done gastric lap band surgery, you are only four times more likely to go off your diabetes medicines. Again, for patients who are problematic diabetics, are obese, who are struggling with their weight, this may be the right solution. An interesting study by the name of the Humira trial looked at the efficacy of patients on Humira who have erosive osteoarthritis. It's a relatively small trial of 51 patients, but it did show that patients who were taking adalimumab for erosive RA, there was no benefit as far as a reduction in pain, reductions in synovitis, or in reductions in bone marrow lesions, adding it to the stockpile, the large stockpile of drugs that do not work in erosive osteoarthritis. This is problematic.
We do need therapies. We do need more research in this area. Rituximab, as you know is a common drug that's used in both rheumatology and in oncology, and unfortunately patients who read the package inserts on these drugs are often dissuaded because of the many side effects that you see, which are often related to what you see when rituximab is given to patients with non Hodgkin's lymphoma or sometimes with leukemia. What is actually known though from this review was that the adverse event rates are much, much higher in patients who are on, rituximab for lymphoma leukemia range from twenty five to thirty six percent of patients and was much lower in those who received it for autoimmune disease where it was only nine to seventeen percent. You're more likely to have adverse events if you had splenomegaly, anemia, a history of, drug allergies, and increasing age.
Tofacitinib is in the news this week and I threw a tweet out there about its dosing in, renal impairment. Should know that you don't have to adjust the dose of tofacitinib if you have mild to moderate renal impairment, But you should know also that the drug was really never studied in patients with a, creatinine clearance of less than 40 in RA and less than 50 in PSA, but for most patients who have mild renal impairment, there is no need to dose adjust. The big news is that today, Friday March 9, we actually have, a news that from yesterday where the FDA panel, the GI panel voted in favor of approving tofacitinib for the treatment of moderate to severely active ulcerative colitis. This is a study of adult patients. They looked at multiple studies, looked at multiple regimens.
They voted unanimously across the board 15 to zero for approval and for approval at a dose of ten milligrams BID. They actually voted against requiring or suggesting a study where there would be an induction study of ten milligrams BID followed by five milligrams BID maintenance. Obviously, they were persuaded strongly by the ten milligram data. Now, again, usually the FDA follows the recommendation of the advisory panel, but in this case, that would be a breakthrough because, ten milligram dose BID was sought for with other indications and denied largely because it was not thought to have additional benefit, and with no risk. In fact, they were concerned about the risks of ten milligram BID and there's some suggestion it might be a little bit more side effects at that dose.
Here, this would be the first time that ten milligram BID would be the recommended dose if it is to be approved for ulcerative colitis as recommended by the panel. Now the FDA could come back and say, no, we're only going to approve the lower dose, but the strength of the data was not quite as great as with ten milligrams BID. Opioids are in the news this week, sad news from the CDC. CDC had a webinar where it reported that in a one year timeframe from July 2016 to July 2017, opioid related overdoses increased by thirty percent nationwide. Regionally it varied and was high as seventy percent in some places, and it's really quite shocking this problem continues.
We do need better education to curtail the use and abuse of opioids. There was another important paper that was found in JAMA which studied the use of either opioids or non opioid analgesic medicines in patients requiring pain meds for either chronic back pain, chronic, hip or knee pain usually due to osteoarthritis. This is a two forty patient study from the Veterans Administration where patients either received an opioid that could be escalated to many different forms of opioid starting out with, hydrocodone and ending up with fentanyl and even more stronger, OxyContin like medicines, or they were randomized to receive acetaminophen and then escalated to receive nonsteroidals and maybe at the very end tramadol. So opioid versus non opioid, no difference in overall functional outcomes nor in reductions in pain. Both groups started out with a pain score of about 5.4.
Those that went on the non opioids dropped to 3.5 and opioids dropped to four point zero. While that is slightly significant in favor of the non opioids, it's not a major difference. Hence opioids are not definitely better in these patients who have chronic pain. Moreover, the opioid patients were more likely to have more adverse events double the rate one point eight versus zero point nine percent and that was significant. Again, is important because in the initial management of chronic pain, patients that opioids should not be the first choice, that there are other agents that work just as well if not better.
Lastly, there's an interesting report about severe cytotoxic T cell mediated skin disorders like Stevens Johnson syndrome and toxic epidermal necrolysis. These are very, very dangerous conditions arising from drug reactions for which they may be hard to treat. This particular study looked at ninety six patients with either TENS or SJS, Stevens Johnson syndrome, or toxic epidermal necrolysis and looked at the efficacy of etanercept and showed that, etanercept was able to decrease mortality, reduce the time to resolution of skin lesions and also reduce the amount of GI hemorrhage. I was unaware of TNF inhibitors prior to this being used for this purpose and I think this is a nice advantage and an interesting study. That's it for this week at rheumnow.
Tune into the website to find more of these reports, to get the links, to read more on these articles. Be sure to sign up for the podcast on iTunes or on Stitcher or whoever you listen to your podcast on. That's it. We'll see you next week on RheumNow. Enjoy.
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