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Three years of imatinib may halve death rate in GIST
, phase 3 trial data suggest.
The most recent analysis of the SSGXVIII/AIO trial shows that, in about 400 patients who underwent surgery and had a high estimated risk of recurrence, there was a 50% increase in overall survival with longer treatment at 10 years on an efficacy analysis.
Moreover, there was a 30% improvement in recurrence-free survival (RFS) with 3 years vs 1 year of imatinib, with an even greater benefit seen in patients with a common tumor mutation.
The research was presented at the 2020 annual meeting of the American Society of Clinical Oncology (abstract 11503), held virtually because of the coronavirus pandemic.
Lead author Peter Reichardt, MD, Helios Klinikum Berlin-Buch, Berlin, Germany, said the results show that “3 years of adjuvant imatinib is highly superior” in terms of RFS and overall survival to 1 year of treatment.
“Overall, approximately 50% of deaths can be avoided during the first 10 years of follow-up after surgery with the longer adjuvant imatinib treatment.”
Study discussant Giovanni Grignani, MD, Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy, said that the “burning question” in the sarcoma space is: “Can we improve overall survival by reducing the risk of relapse with a perioperative treatment?
“We would like to able to identify patients for whom the cost of toxicity is paid off by an improvement in their outcome,” he added, noting that this is not achievable “and this is why perioperative treatment is so controversial in oncology.”
Grignani said the picture is a little different for GIST, as the relapse risk is unevenly distributed, the activity of imatinib is “extraordinary,” and the drug toxicity is “certainly bearable but not negligible.”
RFS is, however, affected by the inability of imatinib to eradicate resistant clones left behind by surgery, and replication resumes once the drug is stopped.
The current study nevertheless shows that overall survival “clearly favors 3-year imatinib therapy…with an impressive median follow-up of 119 months [10 years],” commented Patrick Leavey, MD, University of Texas Southwestern Medical Center, Dallas, in a highlights session.
He added that, in GIST, what might be considered “new progress” with the findings “is clarity over the length of imatinib therapy, which ... seems to be safe.”
Reichardt began by noting that several large randomized trials over the past decade have shown that adjuvant imatinib improves both RFS and overall survival.
However, “it is unknown whether imatinib improves overall survival after extended follow-up,” in addition to which “little is known about the long-term safety” of the drug in this setting.
To offer further insights, the protocol of SSGXVIII/AIO was amended in April 2017 to allow for a third analysis to be carried out once the last patient who entered the trial has been followed up for 10 years.
More Details
Reichardt recalled that the study, which was an open-label, multicenter phase 3 trial, involved GIST patients who were randomly assigned following surgery in a 1:1 fashion to imatinib for either 12 months or 36 months.
The patients were required to have a high-risk of recurrence, defined as at least one of the following:
- Tumor size >10 cm
- Tumor mitosis count >10/50 on high-powered microscopy (HPF)
- Tumor size >5 cm and mitosis count >5/50 HPF
- Tumor rupture, either spontaneously or at surgery.
Four hundred patients were recruited between February 2004 and September 2008, and 181 patients who were randomly assigned to 12 months of imatinib and 177 to 36 months were included in the efficacy analysis.
The median age of the patients was approximately 61 years, and half were female. The treatment groups were well-balanced in terms of their baseline characteristics.
Of note, 69% of patients in the 1-year treatment group and 71% of those given imatinib for 3 years had a detectable mutation in the KIT exon 11 site. The mean mitosis count was 10/50 and 8/50, respectively.
Over a median follow-up of 119 months (9 years, 11 months), 53% of 1-year treatment patients experienced a recurrence event, and 30% died, of whom 82% died with metastatic GIST.
In the 3-year treatment group, 44% experienced a recurrence event, and 18% died, with 83% of deaths from metastatic GIST.
On intention-to-treat analysis, RFS at 10 years was significantly higher with 3 years of imatinib than with 1 year, at 53% vs 42% (hazard ratio [HR], 0.66; P = .003).
Overall survival at 10 years was also higher with longer imatinib treatment, at 79% with 3 years of therapy vs 65% with 1 year (HR, 0.55; P = .004).
The team found on subgroup analysis that RFS was significantly better with 3-year than 1-year imatinib in patients with:
- A local mitotic count >10 (HR = 0.42)
- A central mitotic count >10 (HR = 0.50)
- A KIT exon 11 tumor mutation (HR = 0.57).
On the efficacy analysis, which included patients who signed informed consent, had GIST at pathology review, and no overt metastases at study entry, the HR for RFS with 3-year vs 1-year therapy was 0.70, whereas the HR for overall survival was 0.50.
Patients treated with imatinib for 3 years had a higher rate of any new cancer during follow-up, at 17%, vs 12% for those treated with imatinib for 1 year. Prostate cancer was the most common form of the disease in both groups.
Cardiac events were, in contrast, evenly distributed between the two groups, with 5% of 3-year patients and 6% of 1-year patients experiencing an event.
The study was funded by Novartis.
Reichardt reports honoraria from Amgen, Bayer, Lilly, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, Clinigen Group, Decipher, Lilly, Novartis, Pfizer, PharmaMar, and Roche; and receiving research funding from Novartis (Inst). Other authors report potential conflicts of interest.
Grignani reports honoraria from Bayer, EISAI, Lilly, Merck Serono, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, EISAI, and PharmaMar; receiving research funding from PharmaMar (Inst); and travel, accommodations, expenses from PharmaMar and Tesaro.
Leavey reports receiving research funding from Elison Pharmaceuticals (Inst).
This article first appeared on Medscape.com.
, phase 3 trial data suggest.
The most recent analysis of the SSGXVIII/AIO trial shows that, in about 400 patients who underwent surgery and had a high estimated risk of recurrence, there was a 50% increase in overall survival with longer treatment at 10 years on an efficacy analysis.
Moreover, there was a 30% improvement in recurrence-free survival (RFS) with 3 years vs 1 year of imatinib, with an even greater benefit seen in patients with a common tumor mutation.
The research was presented at the 2020 annual meeting of the American Society of Clinical Oncology (abstract 11503), held virtually because of the coronavirus pandemic.
Lead author Peter Reichardt, MD, Helios Klinikum Berlin-Buch, Berlin, Germany, said the results show that “3 years of adjuvant imatinib is highly superior” in terms of RFS and overall survival to 1 year of treatment.
“Overall, approximately 50% of deaths can be avoided during the first 10 years of follow-up after surgery with the longer adjuvant imatinib treatment.”
Study discussant Giovanni Grignani, MD, Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy, said that the “burning question” in the sarcoma space is: “Can we improve overall survival by reducing the risk of relapse with a perioperative treatment?
“We would like to able to identify patients for whom the cost of toxicity is paid off by an improvement in their outcome,” he added, noting that this is not achievable “and this is why perioperative treatment is so controversial in oncology.”
Grignani said the picture is a little different for GIST, as the relapse risk is unevenly distributed, the activity of imatinib is “extraordinary,” and the drug toxicity is “certainly bearable but not negligible.”
RFS is, however, affected by the inability of imatinib to eradicate resistant clones left behind by surgery, and replication resumes once the drug is stopped.
The current study nevertheless shows that overall survival “clearly favors 3-year imatinib therapy…with an impressive median follow-up of 119 months [10 years],” commented Patrick Leavey, MD, University of Texas Southwestern Medical Center, Dallas, in a highlights session.
He added that, in GIST, what might be considered “new progress” with the findings “is clarity over the length of imatinib therapy, which ... seems to be safe.”
Reichardt began by noting that several large randomized trials over the past decade have shown that adjuvant imatinib improves both RFS and overall survival.
However, “it is unknown whether imatinib improves overall survival after extended follow-up,” in addition to which “little is known about the long-term safety” of the drug in this setting.
To offer further insights, the protocol of SSGXVIII/AIO was amended in April 2017 to allow for a third analysis to be carried out once the last patient who entered the trial has been followed up for 10 years.
More Details
Reichardt recalled that the study, which was an open-label, multicenter phase 3 trial, involved GIST patients who were randomly assigned following surgery in a 1:1 fashion to imatinib for either 12 months or 36 months.
The patients were required to have a high-risk of recurrence, defined as at least one of the following:
- Tumor size >10 cm
- Tumor mitosis count >10/50 on high-powered microscopy (HPF)
- Tumor size >5 cm and mitosis count >5/50 HPF
- Tumor rupture, either spontaneously or at surgery.
Four hundred patients were recruited between February 2004 and September 2008, and 181 patients who were randomly assigned to 12 months of imatinib and 177 to 36 months were included in the efficacy analysis.
The median age of the patients was approximately 61 years, and half were female. The treatment groups were well-balanced in terms of their baseline characteristics.
Of note, 69% of patients in the 1-year treatment group and 71% of those given imatinib for 3 years had a detectable mutation in the KIT exon 11 site. The mean mitosis count was 10/50 and 8/50, respectively.
Over a median follow-up of 119 months (9 years, 11 months), 53% of 1-year treatment patients experienced a recurrence event, and 30% died, of whom 82% died with metastatic GIST.
In the 3-year treatment group, 44% experienced a recurrence event, and 18% died, with 83% of deaths from metastatic GIST.
On intention-to-treat analysis, RFS at 10 years was significantly higher with 3 years of imatinib than with 1 year, at 53% vs 42% (hazard ratio [HR], 0.66; P = .003).
Overall survival at 10 years was also higher with longer imatinib treatment, at 79% with 3 years of therapy vs 65% with 1 year (HR, 0.55; P = .004).
The team found on subgroup analysis that RFS was significantly better with 3-year than 1-year imatinib in patients with:
- A local mitotic count >10 (HR = 0.42)
- A central mitotic count >10 (HR = 0.50)
- A KIT exon 11 tumor mutation (HR = 0.57).
On the efficacy analysis, which included patients who signed informed consent, had GIST at pathology review, and no overt metastases at study entry, the HR for RFS with 3-year vs 1-year therapy was 0.70, whereas the HR for overall survival was 0.50.
Patients treated with imatinib for 3 years had a higher rate of any new cancer during follow-up, at 17%, vs 12% for those treated with imatinib for 1 year. Prostate cancer was the most common form of the disease in both groups.
Cardiac events were, in contrast, evenly distributed between the two groups, with 5% of 3-year patients and 6% of 1-year patients experiencing an event.
The study was funded by Novartis.
Reichardt reports honoraria from Amgen, Bayer, Lilly, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, Clinigen Group, Decipher, Lilly, Novartis, Pfizer, PharmaMar, and Roche; and receiving research funding from Novartis (Inst). Other authors report potential conflicts of interest.
Grignani reports honoraria from Bayer, EISAI, Lilly, Merck Serono, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, EISAI, and PharmaMar; receiving research funding from PharmaMar (Inst); and travel, accommodations, expenses from PharmaMar and Tesaro.
Leavey reports receiving research funding from Elison Pharmaceuticals (Inst).
This article first appeared on Medscape.com.
, phase 3 trial data suggest.
The most recent analysis of the SSGXVIII/AIO trial shows that, in about 400 patients who underwent surgery and had a high estimated risk of recurrence, there was a 50% increase in overall survival with longer treatment at 10 years on an efficacy analysis.
Moreover, there was a 30% improvement in recurrence-free survival (RFS) with 3 years vs 1 year of imatinib, with an even greater benefit seen in patients with a common tumor mutation.
The research was presented at the 2020 annual meeting of the American Society of Clinical Oncology (abstract 11503), held virtually because of the coronavirus pandemic.
Lead author Peter Reichardt, MD, Helios Klinikum Berlin-Buch, Berlin, Germany, said the results show that “3 years of adjuvant imatinib is highly superior” in terms of RFS and overall survival to 1 year of treatment.
“Overall, approximately 50% of deaths can be avoided during the first 10 years of follow-up after surgery with the longer adjuvant imatinib treatment.”
Study discussant Giovanni Grignani, MD, Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Turin, Italy, said that the “burning question” in the sarcoma space is: “Can we improve overall survival by reducing the risk of relapse with a perioperative treatment?
“We would like to able to identify patients for whom the cost of toxicity is paid off by an improvement in their outcome,” he added, noting that this is not achievable “and this is why perioperative treatment is so controversial in oncology.”
Grignani said the picture is a little different for GIST, as the relapse risk is unevenly distributed, the activity of imatinib is “extraordinary,” and the drug toxicity is “certainly bearable but not negligible.”
RFS is, however, affected by the inability of imatinib to eradicate resistant clones left behind by surgery, and replication resumes once the drug is stopped.
The current study nevertheless shows that overall survival “clearly favors 3-year imatinib therapy…with an impressive median follow-up of 119 months [10 years],” commented Patrick Leavey, MD, University of Texas Southwestern Medical Center, Dallas, in a highlights session.
He added that, in GIST, what might be considered “new progress” with the findings “is clarity over the length of imatinib therapy, which ... seems to be safe.”
Reichardt began by noting that several large randomized trials over the past decade have shown that adjuvant imatinib improves both RFS and overall survival.
However, “it is unknown whether imatinib improves overall survival after extended follow-up,” in addition to which “little is known about the long-term safety” of the drug in this setting.
To offer further insights, the protocol of SSGXVIII/AIO was amended in April 2017 to allow for a third analysis to be carried out once the last patient who entered the trial has been followed up for 10 years.
More Details
Reichardt recalled that the study, which was an open-label, multicenter phase 3 trial, involved GIST patients who were randomly assigned following surgery in a 1:1 fashion to imatinib for either 12 months or 36 months.
The patients were required to have a high-risk of recurrence, defined as at least one of the following:
- Tumor size >10 cm
- Tumor mitosis count >10/50 on high-powered microscopy (HPF)
- Tumor size >5 cm and mitosis count >5/50 HPF
- Tumor rupture, either spontaneously or at surgery.
Four hundred patients were recruited between February 2004 and September 2008, and 181 patients who were randomly assigned to 12 months of imatinib and 177 to 36 months were included in the efficacy analysis.
The median age of the patients was approximately 61 years, and half were female. The treatment groups were well-balanced in terms of their baseline characteristics.
Of note, 69% of patients in the 1-year treatment group and 71% of those given imatinib for 3 years had a detectable mutation in the KIT exon 11 site. The mean mitosis count was 10/50 and 8/50, respectively.
Over a median follow-up of 119 months (9 years, 11 months), 53% of 1-year treatment patients experienced a recurrence event, and 30% died, of whom 82% died with metastatic GIST.
In the 3-year treatment group, 44% experienced a recurrence event, and 18% died, with 83% of deaths from metastatic GIST.
On intention-to-treat analysis, RFS at 10 years was significantly higher with 3 years of imatinib than with 1 year, at 53% vs 42% (hazard ratio [HR], 0.66; P = .003).
Overall survival at 10 years was also higher with longer imatinib treatment, at 79% with 3 years of therapy vs 65% with 1 year (HR, 0.55; P = .004).
The team found on subgroup analysis that RFS was significantly better with 3-year than 1-year imatinib in patients with:
- A local mitotic count >10 (HR = 0.42)
- A central mitotic count >10 (HR = 0.50)
- A KIT exon 11 tumor mutation (HR = 0.57).
On the efficacy analysis, which included patients who signed informed consent, had GIST at pathology review, and no overt metastases at study entry, the HR for RFS with 3-year vs 1-year therapy was 0.70, whereas the HR for overall survival was 0.50.
Patients treated with imatinib for 3 years had a higher rate of any new cancer during follow-up, at 17%, vs 12% for those treated with imatinib for 1 year. Prostate cancer was the most common form of the disease in both groups.
Cardiac events were, in contrast, evenly distributed between the two groups, with 5% of 3-year patients and 6% of 1-year patients experiencing an event.
The study was funded by Novartis.
Reichardt reports honoraria from Amgen, Bayer, Lilly, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, Clinigen Group, Decipher, Lilly, Novartis, Pfizer, PharmaMar, and Roche; and receiving research funding from Novartis (Inst). Other authors report potential conflicts of interest.
Grignani reports honoraria from Bayer, EISAI, Lilly, Merck Serono, Novartis, Pfizer, and PharmaMar; serving in a consulting or advisory role with Bayer, EISAI, and PharmaMar; receiving research funding from PharmaMar (Inst); and travel, accommodations, expenses from PharmaMar and Tesaro.
Leavey reports receiving research funding from Elison Pharmaceuticals (Inst).
This article first appeared on Medscape.com.
FROM ASCO 2020
Virtual ADA Scientific Sessions to offer full program
The American Diabetes Association’s 80th Scientific Sessions will forge ahead virtually this year in the face of the COVID-19 pandemic, with nearly all of its originally scheduled content to be presented online.
The meeting will take place online June 12-16, the same days it was slated to occur in Chicago and at the same times. All presentations were recorded in advance, but participants will be able to ask real-time questions during some sessions. Registered attendees – who paid a reduced fee – will have access to the online content for 90 days afterward.
ADA announced the shift in plans on April 3, after Chicago’s McCormick Place convention center became unavailable due to the COVID-19 pandemic. While some major medical meetings had to be canceled entirely or trimmed down online, “This is one of the international meetings that has had more time to really get ready to plan such a virtual session,” association co-president Robert H. Eckel, MD, told Medscape Medical News.
This year’s program features fewer blockbuster randomized clinical trials than in years past.
But it does offer a huge amount of clinical research focused on both type 1 and type 2 diabetes, children with diabetes, gestational diabetes, and much more. Also included are deep dives into optimal clinical translation of findings from previous cardiovascular outcomes trials (CVOTs).
Noteworthy sessions include four new automated insulin delivery system trials on Friday, new diabetes-specific data from the DAPA-HF trial on Saturday, and a debate on Sunday about the future of metformin as first-line therapy for people with established heart disease or at high risk.
And on Tuesday morning, full results from the CVOT VERTIS-CV, with the sodium-glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin (Steglatro, Merck), will be reported.
Also presented on Tuesday will be the first cardiovascular and cancer outcomes from the Diabetes Prevention Program Outcomes Study (DPPOS).
The online content will cover roughly 90% of what was originally scheduled, meeting planning committee chair Jose C. Florez, MD, PhD, told Medscape Medical News.
There is no session officially addressing COVID-19, he said, because the topics were already finalized by February, but “I’m sure it will be discussed in informal exchanges ... the data are just coming out,” he said.
Florez also called attention to two symposia addressing the other major topic dominating today’s news: racial disparities. One on Friday will address that topic with regard to maternal/fetal health, and another on Monday will cover disparities in diabetes care generally.
“Both because of COVID-19 and how it has affected people with diabetes, and within that, disadvantaged people, more aggressively, and in the current context of how racism is coming to the surface, these two sessions will become very, very pertinent,” he said.
Putting the Treatment Pieces Together in Type 2 Diabetes
The Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial (VERTIS-CV) session will include the major cardiovascular, metabolic, renal, and safety outcomes for that drug, along with a meta-analysis of outcomes from trials of several different SGLT2 inhibitors.
All eyes will be on the VERTIS-CV presentation because ertugliflozin broke ranks with the other drugs in this class and failed to produce statistically significant drops in the relevant endpoints, as detailed in top-line data issued by the company in April.
And the provocatively titled session, “DAPA-HF Update: Have We Lost SGLT2 inhibitors to Cardiologists?!” will include a review of the trial’s main findings presented at the European Society of Cardiology meeting in September 2019, and published a few weeks later in the New England Journal of Medicine, along with new data on patient-centered and metabolic outcomes, and diabetes prevention. An independent commentator will presumably address the session title’s question.
Eckel, who has been working to establish a new cardiometabolic medicine subspecialty, commented: “I think we have not lost it, but I think SGLT2 inhibitors are a perfect example of why we need physicians trained in this overlap of diabetes medicine and cardiology.”
And, he said, we may be coming to the end of the CVOTs trial phenomenon.
“I think unless there’s a whole new class of drugs developed, we may be done with CVOTs for dipeptidyl peptidase-4 (DPP-4) inhibitors, SGLT2 inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists. We’ve learned a lot, and I’m not sure we need more other than mechanistic studies ... I don’t think we really know yet how SGLT2 inhibitors or GLP-1 agonists work,” Eckel said.
Metformin, on the other hand, has not been subject to a CVOT because it has been available as a generic since long before the US Food and Drug Administration mandated the CVOTs for new drugs for type 2 diabetes in 2008.
Such a trial is unlikely to be conducted at this point, but the new DPPOS data might actually come close, Florez noted.
The DPPOS is the observational follow-up of the landmark randomized DPP trial, which found that intensive lifestyle intervention and metformin reduced progression from prediabetes to type 2 diabetes.
Numerous additional outcomes have been reported over the years, but this will be the first-ever reporting of DPPOS data on both hard cardiovascular events and cancer incidence in people who have been continuously taking metformin for more than 20 years.
“There’s a lot of interest in whether metformin has an effect on cardiovascular events and cancer ... I think that’s going to be a very interesting session,” Florez said, noting that “short of a randomized clinical trial, which it’s hard to imagine would come to be, this is really, really good.”
Also examining metformin will be a debate on Sunday, “Should Metformin Be Considered First-Line Therapy for Individuals with Type 2 Diabetes With Established Arteriosclerotic Cardiovascular Disease (ASCVD) or at High Risk for ASCVD?”
And on Saturday, a debate will address another old-guard diabetes drug class, asking: “Is There a Current Place for Sulfonylureas in the Treatment of Type 2 Diabetes?”
Overall, Florez said, meeting attendees will come away with “a more clear understanding of the placement of SGLT2 inhibitors and GLP-1 agonists in the type 2 diabetes treatment algorithm.”
“What are the settings in which these [newer] drugs ought to be used, compared to the old-timers like metformin and sulfonylureas? One thing is having the trials, but the other is figuring out how you interpret these in deciding what happens at the point of care.”
Two more future-looking type 2 diabetes symposia of potential interest to clinicians are “Unraveling the Heterogeneity in Type 2 Diabetes” on Sunday and “Perspectives on the Future of Precision Diabetes Medicine — A Joint ADA/EASD Symposium” on Monday.
Type 1 Diabetes, Technology, and Kids
A symposium on Friday will feature four new clinical trials of automated insulin delivery systems for people with type 1 diabetes, the “US Advanced Hybrid Closed-Loop (AHCL) Pivotal Safety Study, FLAIR — An NIDDK-Sponsored International, Multi-site Randomized Crossover Trial of AHCL vs 670G,” the New Zealand AHCL randomized crossover trial, and the Horizon Automated Glucose Control System pre-pivotal trial data.
“Closed-loop devices are getting a lot of traction ... These trials will continue to advance the notion that these devices will narrow the glycemic range, prevent hypoglycemia, and improve quality of life because people don’t have to pay as much attention mentally to the management of the diabetes,” Florez said.
He added that although these trials “have been in the works for a while and they’re not big surprises, they continue to build a body of evidence suggesting that these devices will be part of our armamentarium in the very near future.”
And on Saturday, a debate will address the somewhat controversial question of whether continuous glucose monitoring in type 2 diabetes is worth the cost.
There will also be plenty of pediatric diabetes material presented this year, too.
On Sunday, there will be new insights from the Restoring Insulin Secretion (RISE) study, which examines prediabetes and type 2 diabetes in youth, and on Monday, 20-year data from the SEARCH for Diabetes in Youth Study will be reported.
And on Monday, the most recent findings from The Environmental Determinants of Diabetes in the Young (TEDDY) study of environmental triggers of type 1 diabetes will be presented.
All-Virtual Meeting: Pros and Cons
The all-virtual meeting format will have pluses and minuses, Eckel predicts.
Advantages include the fact that attendees don’t have to physically run from room to room or make difficult decisions about conflicting sessions.
“The fact that this meeting will be taking place in reality in terms of the timing of sessions, one can transition from one room to another in a matter of seconds if you want to,” he noted.
However, he observed, “a lot of interesting things happen in the hallways at meetings. Colleagues from around the world get together and knock heads about their ongoing research and potential collaborations can be formulated.
“Opportunities to engage with one another beyond the formality of the meeting is going to be lost to some extent.”
What’s more, the sessions will all be in Central US (Chicago) time, “So if you live in Thailand, the session may be occurring at a time when you’re in bed. If you want to see it live, then you’ve got to get up. Then you can ask a question.”
On the other hand, since all the content will be available online for 90 days, “if you want to stay in bed and you live in Thailand, you can get up a week from now during the day and log into a session you may have missed.”
Indeed, Florez said, “One silver lining of this virtual conference is that we’ve lowered the barriers for people to attend. It’s much more global. We’ve had an amazing influx of new registrants who were not planning on coming and were not registered for the original meeting and have registered since [more than 10,000 at the time of writing], and they continue to pile in.”
“We plan to reach people we haven’t reached before. The big question for ADA moving forward will be how much this can become a permanent feature, where even if we do it in person in the future, maybe we offer at least some virtual options so that our reach can go farther.”
Eckel has reported sitting on the scientific advisory board for a Kowa Company trial of pemafibrate and on an advisory board for Novo Nordisk. Florez has reported being a speaker for Novo Nordisk and receiving an honorarium from ADA for chairing the conference planning committee.
This article originally appeared on Medscape.com.
The American Diabetes Association’s 80th Scientific Sessions will forge ahead virtually this year in the face of the COVID-19 pandemic, with nearly all of its originally scheduled content to be presented online.
The meeting will take place online June 12-16, the same days it was slated to occur in Chicago and at the same times. All presentations were recorded in advance, but participants will be able to ask real-time questions during some sessions. Registered attendees – who paid a reduced fee – will have access to the online content for 90 days afterward.
ADA announced the shift in plans on April 3, after Chicago’s McCormick Place convention center became unavailable due to the COVID-19 pandemic. While some major medical meetings had to be canceled entirely or trimmed down online, “This is one of the international meetings that has had more time to really get ready to plan such a virtual session,” association co-president Robert H. Eckel, MD, told Medscape Medical News.
This year’s program features fewer blockbuster randomized clinical trials than in years past.
But it does offer a huge amount of clinical research focused on both type 1 and type 2 diabetes, children with diabetes, gestational diabetes, and much more. Also included are deep dives into optimal clinical translation of findings from previous cardiovascular outcomes trials (CVOTs).
Noteworthy sessions include four new automated insulin delivery system trials on Friday, new diabetes-specific data from the DAPA-HF trial on Saturday, and a debate on Sunday about the future of metformin as first-line therapy for people with established heart disease or at high risk.
And on Tuesday morning, full results from the CVOT VERTIS-CV, with the sodium-glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin (Steglatro, Merck), will be reported.
Also presented on Tuesday will be the first cardiovascular and cancer outcomes from the Diabetes Prevention Program Outcomes Study (DPPOS).
The online content will cover roughly 90% of what was originally scheduled, meeting planning committee chair Jose C. Florez, MD, PhD, told Medscape Medical News.
There is no session officially addressing COVID-19, he said, because the topics were already finalized by February, but “I’m sure it will be discussed in informal exchanges ... the data are just coming out,” he said.
Florez also called attention to two symposia addressing the other major topic dominating today’s news: racial disparities. One on Friday will address that topic with regard to maternal/fetal health, and another on Monday will cover disparities in diabetes care generally.
“Both because of COVID-19 and how it has affected people with diabetes, and within that, disadvantaged people, more aggressively, and in the current context of how racism is coming to the surface, these two sessions will become very, very pertinent,” he said.
Putting the Treatment Pieces Together in Type 2 Diabetes
The Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial (VERTIS-CV) session will include the major cardiovascular, metabolic, renal, and safety outcomes for that drug, along with a meta-analysis of outcomes from trials of several different SGLT2 inhibitors.
All eyes will be on the VERTIS-CV presentation because ertugliflozin broke ranks with the other drugs in this class and failed to produce statistically significant drops in the relevant endpoints, as detailed in top-line data issued by the company in April.
And the provocatively titled session, “DAPA-HF Update: Have We Lost SGLT2 inhibitors to Cardiologists?!” will include a review of the trial’s main findings presented at the European Society of Cardiology meeting in September 2019, and published a few weeks later in the New England Journal of Medicine, along with new data on patient-centered and metabolic outcomes, and diabetes prevention. An independent commentator will presumably address the session title’s question.
Eckel, who has been working to establish a new cardiometabolic medicine subspecialty, commented: “I think we have not lost it, but I think SGLT2 inhibitors are a perfect example of why we need physicians trained in this overlap of diabetes medicine and cardiology.”
And, he said, we may be coming to the end of the CVOTs trial phenomenon.
“I think unless there’s a whole new class of drugs developed, we may be done with CVOTs for dipeptidyl peptidase-4 (DPP-4) inhibitors, SGLT2 inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists. We’ve learned a lot, and I’m not sure we need more other than mechanistic studies ... I don’t think we really know yet how SGLT2 inhibitors or GLP-1 agonists work,” Eckel said.
Metformin, on the other hand, has not been subject to a CVOT because it has been available as a generic since long before the US Food and Drug Administration mandated the CVOTs for new drugs for type 2 diabetes in 2008.
Such a trial is unlikely to be conducted at this point, but the new DPPOS data might actually come close, Florez noted.
The DPPOS is the observational follow-up of the landmark randomized DPP trial, which found that intensive lifestyle intervention and metformin reduced progression from prediabetes to type 2 diabetes.
Numerous additional outcomes have been reported over the years, but this will be the first-ever reporting of DPPOS data on both hard cardiovascular events and cancer incidence in people who have been continuously taking metformin for more than 20 years.
“There’s a lot of interest in whether metformin has an effect on cardiovascular events and cancer ... I think that’s going to be a very interesting session,” Florez said, noting that “short of a randomized clinical trial, which it’s hard to imagine would come to be, this is really, really good.”
Also examining metformin will be a debate on Sunday, “Should Metformin Be Considered First-Line Therapy for Individuals with Type 2 Diabetes With Established Arteriosclerotic Cardiovascular Disease (ASCVD) or at High Risk for ASCVD?”
And on Saturday, a debate will address another old-guard diabetes drug class, asking: “Is There a Current Place for Sulfonylureas in the Treatment of Type 2 Diabetes?”
Overall, Florez said, meeting attendees will come away with “a more clear understanding of the placement of SGLT2 inhibitors and GLP-1 agonists in the type 2 diabetes treatment algorithm.”
“What are the settings in which these [newer] drugs ought to be used, compared to the old-timers like metformin and sulfonylureas? One thing is having the trials, but the other is figuring out how you interpret these in deciding what happens at the point of care.”
Two more future-looking type 2 diabetes symposia of potential interest to clinicians are “Unraveling the Heterogeneity in Type 2 Diabetes” on Sunday and “Perspectives on the Future of Precision Diabetes Medicine — A Joint ADA/EASD Symposium” on Monday.
Type 1 Diabetes, Technology, and Kids
A symposium on Friday will feature four new clinical trials of automated insulin delivery systems for people with type 1 diabetes, the “US Advanced Hybrid Closed-Loop (AHCL) Pivotal Safety Study, FLAIR — An NIDDK-Sponsored International, Multi-site Randomized Crossover Trial of AHCL vs 670G,” the New Zealand AHCL randomized crossover trial, and the Horizon Automated Glucose Control System pre-pivotal trial data.
“Closed-loop devices are getting a lot of traction ... These trials will continue to advance the notion that these devices will narrow the glycemic range, prevent hypoglycemia, and improve quality of life because people don’t have to pay as much attention mentally to the management of the diabetes,” Florez said.
He added that although these trials “have been in the works for a while and they’re not big surprises, they continue to build a body of evidence suggesting that these devices will be part of our armamentarium in the very near future.”
And on Saturday, a debate will address the somewhat controversial question of whether continuous glucose monitoring in type 2 diabetes is worth the cost.
There will also be plenty of pediatric diabetes material presented this year, too.
On Sunday, there will be new insights from the Restoring Insulin Secretion (RISE) study, which examines prediabetes and type 2 diabetes in youth, and on Monday, 20-year data from the SEARCH for Diabetes in Youth Study will be reported.
And on Monday, the most recent findings from The Environmental Determinants of Diabetes in the Young (TEDDY) study of environmental triggers of type 1 diabetes will be presented.
All-Virtual Meeting: Pros and Cons
The all-virtual meeting format will have pluses and minuses, Eckel predicts.
Advantages include the fact that attendees don’t have to physically run from room to room or make difficult decisions about conflicting sessions.
“The fact that this meeting will be taking place in reality in terms of the timing of sessions, one can transition from one room to another in a matter of seconds if you want to,” he noted.
However, he observed, “a lot of interesting things happen in the hallways at meetings. Colleagues from around the world get together and knock heads about their ongoing research and potential collaborations can be formulated.
“Opportunities to engage with one another beyond the formality of the meeting is going to be lost to some extent.”
What’s more, the sessions will all be in Central US (Chicago) time, “So if you live in Thailand, the session may be occurring at a time when you’re in bed. If you want to see it live, then you’ve got to get up. Then you can ask a question.”
On the other hand, since all the content will be available online for 90 days, “if you want to stay in bed and you live in Thailand, you can get up a week from now during the day and log into a session you may have missed.”
Indeed, Florez said, “One silver lining of this virtual conference is that we’ve lowered the barriers for people to attend. It’s much more global. We’ve had an amazing influx of new registrants who were not planning on coming and were not registered for the original meeting and have registered since [more than 10,000 at the time of writing], and they continue to pile in.”
“We plan to reach people we haven’t reached before. The big question for ADA moving forward will be how much this can become a permanent feature, where even if we do it in person in the future, maybe we offer at least some virtual options so that our reach can go farther.”
Eckel has reported sitting on the scientific advisory board for a Kowa Company trial of pemafibrate and on an advisory board for Novo Nordisk. Florez has reported being a speaker for Novo Nordisk and receiving an honorarium from ADA for chairing the conference planning committee.
This article originally appeared on Medscape.com.
The American Diabetes Association’s 80th Scientific Sessions will forge ahead virtually this year in the face of the COVID-19 pandemic, with nearly all of its originally scheduled content to be presented online.
The meeting will take place online June 12-16, the same days it was slated to occur in Chicago and at the same times. All presentations were recorded in advance, but participants will be able to ask real-time questions during some sessions. Registered attendees – who paid a reduced fee – will have access to the online content for 90 days afterward.
ADA announced the shift in plans on April 3, after Chicago’s McCormick Place convention center became unavailable due to the COVID-19 pandemic. While some major medical meetings had to be canceled entirely or trimmed down online, “This is one of the international meetings that has had more time to really get ready to plan such a virtual session,” association co-president Robert H. Eckel, MD, told Medscape Medical News.
This year’s program features fewer blockbuster randomized clinical trials than in years past.
But it does offer a huge amount of clinical research focused on both type 1 and type 2 diabetes, children with diabetes, gestational diabetes, and much more. Also included are deep dives into optimal clinical translation of findings from previous cardiovascular outcomes trials (CVOTs).
Noteworthy sessions include four new automated insulin delivery system trials on Friday, new diabetes-specific data from the DAPA-HF trial on Saturday, and a debate on Sunday about the future of metformin as first-line therapy for people with established heart disease or at high risk.
And on Tuesday morning, full results from the CVOT VERTIS-CV, with the sodium-glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin (Steglatro, Merck), will be reported.
Also presented on Tuesday will be the first cardiovascular and cancer outcomes from the Diabetes Prevention Program Outcomes Study (DPPOS).
The online content will cover roughly 90% of what was originally scheduled, meeting planning committee chair Jose C. Florez, MD, PhD, told Medscape Medical News.
There is no session officially addressing COVID-19, he said, because the topics were already finalized by February, but “I’m sure it will be discussed in informal exchanges ... the data are just coming out,” he said.
Florez also called attention to two symposia addressing the other major topic dominating today’s news: racial disparities. One on Friday will address that topic with regard to maternal/fetal health, and another on Monday will cover disparities in diabetes care generally.
“Both because of COVID-19 and how it has affected people with diabetes, and within that, disadvantaged people, more aggressively, and in the current context of how racism is coming to the surface, these two sessions will become very, very pertinent,” he said.
Putting the Treatment Pieces Together in Type 2 Diabetes
The Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial (VERTIS-CV) session will include the major cardiovascular, metabolic, renal, and safety outcomes for that drug, along with a meta-analysis of outcomes from trials of several different SGLT2 inhibitors.
All eyes will be on the VERTIS-CV presentation because ertugliflozin broke ranks with the other drugs in this class and failed to produce statistically significant drops in the relevant endpoints, as detailed in top-line data issued by the company in April.
And the provocatively titled session, “DAPA-HF Update: Have We Lost SGLT2 inhibitors to Cardiologists?!” will include a review of the trial’s main findings presented at the European Society of Cardiology meeting in September 2019, and published a few weeks later in the New England Journal of Medicine, along with new data on patient-centered and metabolic outcomes, and diabetes prevention. An independent commentator will presumably address the session title’s question.
Eckel, who has been working to establish a new cardiometabolic medicine subspecialty, commented: “I think we have not lost it, but I think SGLT2 inhibitors are a perfect example of why we need physicians trained in this overlap of diabetes medicine and cardiology.”
And, he said, we may be coming to the end of the CVOTs trial phenomenon.
“I think unless there’s a whole new class of drugs developed, we may be done with CVOTs for dipeptidyl peptidase-4 (DPP-4) inhibitors, SGLT2 inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists. We’ve learned a lot, and I’m not sure we need more other than mechanistic studies ... I don’t think we really know yet how SGLT2 inhibitors or GLP-1 agonists work,” Eckel said.
Metformin, on the other hand, has not been subject to a CVOT because it has been available as a generic since long before the US Food and Drug Administration mandated the CVOTs for new drugs for type 2 diabetes in 2008.
Such a trial is unlikely to be conducted at this point, but the new DPPOS data might actually come close, Florez noted.
The DPPOS is the observational follow-up of the landmark randomized DPP trial, which found that intensive lifestyle intervention and metformin reduced progression from prediabetes to type 2 diabetes.
Numerous additional outcomes have been reported over the years, but this will be the first-ever reporting of DPPOS data on both hard cardiovascular events and cancer incidence in people who have been continuously taking metformin for more than 20 years.
“There’s a lot of interest in whether metformin has an effect on cardiovascular events and cancer ... I think that’s going to be a very interesting session,” Florez said, noting that “short of a randomized clinical trial, which it’s hard to imagine would come to be, this is really, really good.”
Also examining metformin will be a debate on Sunday, “Should Metformin Be Considered First-Line Therapy for Individuals with Type 2 Diabetes With Established Arteriosclerotic Cardiovascular Disease (ASCVD) or at High Risk for ASCVD?”
And on Saturday, a debate will address another old-guard diabetes drug class, asking: “Is There a Current Place for Sulfonylureas in the Treatment of Type 2 Diabetes?”
Overall, Florez said, meeting attendees will come away with “a more clear understanding of the placement of SGLT2 inhibitors and GLP-1 agonists in the type 2 diabetes treatment algorithm.”
“What are the settings in which these [newer] drugs ought to be used, compared to the old-timers like metformin and sulfonylureas? One thing is having the trials, but the other is figuring out how you interpret these in deciding what happens at the point of care.”
Two more future-looking type 2 diabetes symposia of potential interest to clinicians are “Unraveling the Heterogeneity in Type 2 Diabetes” on Sunday and “Perspectives on the Future of Precision Diabetes Medicine — A Joint ADA/EASD Symposium” on Monday.
Type 1 Diabetes, Technology, and Kids
A symposium on Friday will feature four new clinical trials of automated insulin delivery systems for people with type 1 diabetes, the “US Advanced Hybrid Closed-Loop (AHCL) Pivotal Safety Study, FLAIR — An NIDDK-Sponsored International, Multi-site Randomized Crossover Trial of AHCL vs 670G,” the New Zealand AHCL randomized crossover trial, and the Horizon Automated Glucose Control System pre-pivotal trial data.
“Closed-loop devices are getting a lot of traction ... These trials will continue to advance the notion that these devices will narrow the glycemic range, prevent hypoglycemia, and improve quality of life because people don’t have to pay as much attention mentally to the management of the diabetes,” Florez said.
He added that although these trials “have been in the works for a while and they’re not big surprises, they continue to build a body of evidence suggesting that these devices will be part of our armamentarium in the very near future.”
And on Saturday, a debate will address the somewhat controversial question of whether continuous glucose monitoring in type 2 diabetes is worth the cost.
There will also be plenty of pediatric diabetes material presented this year, too.
On Sunday, there will be new insights from the Restoring Insulin Secretion (RISE) study, which examines prediabetes and type 2 diabetes in youth, and on Monday, 20-year data from the SEARCH for Diabetes in Youth Study will be reported.
And on Monday, the most recent findings from The Environmental Determinants of Diabetes in the Young (TEDDY) study of environmental triggers of type 1 diabetes will be presented.
All-Virtual Meeting: Pros and Cons
The all-virtual meeting format will have pluses and minuses, Eckel predicts.
Advantages include the fact that attendees don’t have to physically run from room to room or make difficult decisions about conflicting sessions.
“The fact that this meeting will be taking place in reality in terms of the timing of sessions, one can transition from one room to another in a matter of seconds if you want to,” he noted.
However, he observed, “a lot of interesting things happen in the hallways at meetings. Colleagues from around the world get together and knock heads about their ongoing research and potential collaborations can be formulated.
“Opportunities to engage with one another beyond the formality of the meeting is going to be lost to some extent.”
What’s more, the sessions will all be in Central US (Chicago) time, “So if you live in Thailand, the session may be occurring at a time when you’re in bed. If you want to see it live, then you’ve got to get up. Then you can ask a question.”
On the other hand, since all the content will be available online for 90 days, “if you want to stay in bed and you live in Thailand, you can get up a week from now during the day and log into a session you may have missed.”
Indeed, Florez said, “One silver lining of this virtual conference is that we’ve lowered the barriers for people to attend. It’s much more global. We’ve had an amazing influx of new registrants who were not planning on coming and were not registered for the original meeting and have registered since [more than 10,000 at the time of writing], and they continue to pile in.”
“We plan to reach people we haven’t reached before. The big question for ADA moving forward will be how much this can become a permanent feature, where even if we do it in person in the future, maybe we offer at least some virtual options so that our reach can go farther.”
Eckel has reported sitting on the scientific advisory board for a Kowa Company trial of pemafibrate and on an advisory board for Novo Nordisk. Florez has reported being a speaker for Novo Nordisk and receiving an honorarium from ADA for chairing the conference planning committee.
This article originally appeared on Medscape.com.
TKI plus SBRT tops TKI alone for oligometastatic EGFRm NSCLC
Adding aggressive local radiotherapy to treatment with tyrosine kinase inhibitor (TKI) significantly improved progression-free and overall survival in patients with previously untreated, EGFR-mutated, oligometastatic non–small cell lung cancer (NSCLC) in a phase 3 trial presented as part of the American Society of Clinical Oncology virtual scientific program.
Sixty-eight patients were randomized at diagnosis to receive a first-generation TKI plus stereotactic body radiation therapy (SBRT) to all disease sites. The other 68 patients were randomized to receive a TKI alone, but 3 patients were lost follow-up and not included in the analysis. The TKIs used were gefitinib, erlotinib, and icotinib.
At baseline, patients had a maximum of two lesions in any one organ and no more than five metastases overall. Patients with brain metastases were excluded.
The median progression-free survival was 20.2 months in the SBRT arm and 12.5 months in the TKI-only arm (hazard ratio, 0.618; P < .001). The median overall survival was 25.5 months and 17.4 months, respectively (HR, 0.682; P < .001).
There were no grade 4/5 adverse events nor any statistically significant between-group differences in grade 3 events.
‘Compelling’ data with caveats
The study results suggest that “aggressive local therapy to sites at diagnosis should be explored further in large cohort phase 3 trials as a standard treatment option in this clinical scenario,” said investigator Xiao-shan Wang, MD, PhD, of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital in Chengdu.
“The data are compelling,” Dr. Wang added. “As we attempt to maximize the benefits of EGFR-directed targeted therapies, we are likely going to be moving away from a sequentially administered approach to treatment and considering combinations.”
The new findings, combined with prior phase 2 results, support “incorporation of upfront SBRT with TKI into practice for selected patients with oligometastatic disease, with the open question remaining of how many metastases are too many,” said study discussant Rachel Sanborn, MD, of Providence Cancer Institute Franz Clinic in Portland, Ore.
However, “it’s important to make note of the baseline characteristics of the patients enrolled,” she said.
Twelve percent of patients in the control arm and 4% of those in the SBRT group had EGFR exon 20 insertions. This “imbalance could have negatively impacted the outcomes in the TKI-alone arm,” Dr. Sanborn said.
Also, a higher proportion of patients in the TKI-alone arm received gefitinib, and “there was no information offered on second-line therapies in the study, which might have also affected outcomes,” Dr. Sanborn added.
Additional details
The study (NCT02893332) enrolled NSCLC patients with a life expectancy of at least 6 months and an Eastern Cooperative Oncology Group performance status score of 0-2. NSCLC was confirmed by pathology and EGFR mutations by gene sequencing.
The radiation dose was 25-40 Gy in five fractions. Gefitinib was used in 47% of patients in the SBRT arm and 58% of the control group. Erlotinib was used in 44% of the SBRT arm and 35% of controls. Icotinib was used by less than 10% of patients in each group.
Grade 3 skin rash occurred in 50% of patients in the SBRT arm and 62% of those in the TKI-alone arm. Grade 3 pneumonitis occurred in 30% and 15%, respectively. Grade 3 esophagitis occurred in 15% of patients in both arms.
One patient in the TKI arm had severe liver injury. One patient in the SBRT arm fractured a rib, which was considered probably related to the radiation.
Multivariate analysis revealed that, in addition to SBRT, lower baseline performance status score (0 vs. 1-2) and fewer metastases (<2 vs. ≥3) were protective for progression-free survival. Lower performance scores, fewer metastases, lower T stage (T1-2 vs. T3-4), and exon 19 versus exon 20 and 21 mutations were protective for overall survival.
The study arms were well balanced at baseline. The mean patient age was 66.9 years in the SBRT arm and 63.32 years in the TKI-only arm. In both arms, most patients were women (63% and 60%, respectively).
The study was sponsored by Sichuan Provincial People’s Hospital. The investigators and Dr. Sanborn have no relevant disclosures.
aotto@mdedge.com
SOURCE: Wang X et al. ASCO 2020, Abstract 9508.
Adding aggressive local radiotherapy to treatment with tyrosine kinase inhibitor (TKI) significantly improved progression-free and overall survival in patients with previously untreated, EGFR-mutated, oligometastatic non–small cell lung cancer (NSCLC) in a phase 3 trial presented as part of the American Society of Clinical Oncology virtual scientific program.
Sixty-eight patients were randomized at diagnosis to receive a first-generation TKI plus stereotactic body radiation therapy (SBRT) to all disease sites. The other 68 patients were randomized to receive a TKI alone, but 3 patients were lost follow-up and not included in the analysis. The TKIs used were gefitinib, erlotinib, and icotinib.
At baseline, patients had a maximum of two lesions in any one organ and no more than five metastases overall. Patients with brain metastases were excluded.
The median progression-free survival was 20.2 months in the SBRT arm and 12.5 months in the TKI-only arm (hazard ratio, 0.618; P < .001). The median overall survival was 25.5 months and 17.4 months, respectively (HR, 0.682; P < .001).
There were no grade 4/5 adverse events nor any statistically significant between-group differences in grade 3 events.
‘Compelling’ data with caveats
The study results suggest that “aggressive local therapy to sites at diagnosis should be explored further in large cohort phase 3 trials as a standard treatment option in this clinical scenario,” said investigator Xiao-shan Wang, MD, PhD, of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital in Chengdu.
“The data are compelling,” Dr. Wang added. “As we attempt to maximize the benefits of EGFR-directed targeted therapies, we are likely going to be moving away from a sequentially administered approach to treatment and considering combinations.”
The new findings, combined with prior phase 2 results, support “incorporation of upfront SBRT with TKI into practice for selected patients with oligometastatic disease, with the open question remaining of how many metastases are too many,” said study discussant Rachel Sanborn, MD, of Providence Cancer Institute Franz Clinic in Portland, Ore.
However, “it’s important to make note of the baseline characteristics of the patients enrolled,” she said.
Twelve percent of patients in the control arm and 4% of those in the SBRT group had EGFR exon 20 insertions. This “imbalance could have negatively impacted the outcomes in the TKI-alone arm,” Dr. Sanborn said.
Also, a higher proportion of patients in the TKI-alone arm received gefitinib, and “there was no information offered on second-line therapies in the study, which might have also affected outcomes,” Dr. Sanborn added.
Additional details
The study (NCT02893332) enrolled NSCLC patients with a life expectancy of at least 6 months and an Eastern Cooperative Oncology Group performance status score of 0-2. NSCLC was confirmed by pathology and EGFR mutations by gene sequencing.
The radiation dose was 25-40 Gy in five fractions. Gefitinib was used in 47% of patients in the SBRT arm and 58% of the control group. Erlotinib was used in 44% of the SBRT arm and 35% of controls. Icotinib was used by less than 10% of patients in each group.
Grade 3 skin rash occurred in 50% of patients in the SBRT arm and 62% of those in the TKI-alone arm. Grade 3 pneumonitis occurred in 30% and 15%, respectively. Grade 3 esophagitis occurred in 15% of patients in both arms.
One patient in the TKI arm had severe liver injury. One patient in the SBRT arm fractured a rib, which was considered probably related to the radiation.
Multivariate analysis revealed that, in addition to SBRT, lower baseline performance status score (0 vs. 1-2) and fewer metastases (<2 vs. ≥3) were protective for progression-free survival. Lower performance scores, fewer metastases, lower T stage (T1-2 vs. T3-4), and exon 19 versus exon 20 and 21 mutations were protective for overall survival.
The study arms were well balanced at baseline. The mean patient age was 66.9 years in the SBRT arm and 63.32 years in the TKI-only arm. In both arms, most patients were women (63% and 60%, respectively).
The study was sponsored by Sichuan Provincial People’s Hospital. The investigators and Dr. Sanborn have no relevant disclosures.
aotto@mdedge.com
SOURCE: Wang X et al. ASCO 2020, Abstract 9508.
Adding aggressive local radiotherapy to treatment with tyrosine kinase inhibitor (TKI) significantly improved progression-free and overall survival in patients with previously untreated, EGFR-mutated, oligometastatic non–small cell lung cancer (NSCLC) in a phase 3 trial presented as part of the American Society of Clinical Oncology virtual scientific program.
Sixty-eight patients were randomized at diagnosis to receive a first-generation TKI plus stereotactic body radiation therapy (SBRT) to all disease sites. The other 68 patients were randomized to receive a TKI alone, but 3 patients were lost follow-up and not included in the analysis. The TKIs used were gefitinib, erlotinib, and icotinib.
At baseline, patients had a maximum of two lesions in any one organ and no more than five metastases overall. Patients with brain metastases were excluded.
The median progression-free survival was 20.2 months in the SBRT arm and 12.5 months in the TKI-only arm (hazard ratio, 0.618; P < .001). The median overall survival was 25.5 months and 17.4 months, respectively (HR, 0.682; P < .001).
There were no grade 4/5 adverse events nor any statistically significant between-group differences in grade 3 events.
‘Compelling’ data with caveats
The study results suggest that “aggressive local therapy to sites at diagnosis should be explored further in large cohort phase 3 trials as a standard treatment option in this clinical scenario,” said investigator Xiao-shan Wang, MD, PhD, of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital in Chengdu.
“The data are compelling,” Dr. Wang added. “As we attempt to maximize the benefits of EGFR-directed targeted therapies, we are likely going to be moving away from a sequentially administered approach to treatment and considering combinations.”
The new findings, combined with prior phase 2 results, support “incorporation of upfront SBRT with TKI into practice for selected patients with oligometastatic disease, with the open question remaining of how many metastases are too many,” said study discussant Rachel Sanborn, MD, of Providence Cancer Institute Franz Clinic in Portland, Ore.
However, “it’s important to make note of the baseline characteristics of the patients enrolled,” she said.
Twelve percent of patients in the control arm and 4% of those in the SBRT group had EGFR exon 20 insertions. This “imbalance could have negatively impacted the outcomes in the TKI-alone arm,” Dr. Sanborn said.
Also, a higher proportion of patients in the TKI-alone arm received gefitinib, and “there was no information offered on second-line therapies in the study, which might have also affected outcomes,” Dr. Sanborn added.
Additional details
The study (NCT02893332) enrolled NSCLC patients with a life expectancy of at least 6 months and an Eastern Cooperative Oncology Group performance status score of 0-2. NSCLC was confirmed by pathology and EGFR mutations by gene sequencing.
The radiation dose was 25-40 Gy in five fractions. Gefitinib was used in 47% of patients in the SBRT arm and 58% of the control group. Erlotinib was used in 44% of the SBRT arm and 35% of controls. Icotinib was used by less than 10% of patients in each group.
Grade 3 skin rash occurred in 50% of patients in the SBRT arm and 62% of those in the TKI-alone arm. Grade 3 pneumonitis occurred in 30% and 15%, respectively. Grade 3 esophagitis occurred in 15% of patients in both arms.
One patient in the TKI arm had severe liver injury. One patient in the SBRT arm fractured a rib, which was considered probably related to the radiation.
Multivariate analysis revealed that, in addition to SBRT, lower baseline performance status score (0 vs. 1-2) and fewer metastases (<2 vs. ≥3) were protective for progression-free survival. Lower performance scores, fewer metastases, lower T stage (T1-2 vs. T3-4), and exon 19 versus exon 20 and 21 mutations were protective for overall survival.
The study arms were well balanced at baseline. The mean patient age was 66.9 years in the SBRT arm and 63.32 years in the TKI-only arm. In both arms, most patients were women (63% and 60%, respectively).
The study was sponsored by Sichuan Provincial People’s Hospital. The investigators and Dr. Sanborn have no relevant disclosures.
aotto@mdedge.com
SOURCE: Wang X et al. ASCO 2020, Abstract 9508.
FROM ASCO 2020
Cannabis misconceptions still common among MS clinicians
experts say.
“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.
As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
Misconceptions common among clinicians
Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.
Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.
In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.
Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.
There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.
Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.
Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.
And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.
Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.
However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.
Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.
However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.
He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.
While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.
“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
Addiction, distinguishing cannabis from MS symptoms
Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”
Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”
The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.
“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”
“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”
Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.
Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.
A version of this article originally appeared on Medscape.com.
experts say.
“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.
As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
Misconceptions common among clinicians
Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.
Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.
In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.
Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.
There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.
Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.
Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.
And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.
Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.
However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.
Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.
However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.
He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.
While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.
“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
Addiction, distinguishing cannabis from MS symptoms
Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”
Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”
The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.
“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”
“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”
Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.
Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.
A version of this article originally appeared on Medscape.com.
experts say.
“There is evidence of a ‘clinical void,’ with clinicians on one side and people with MS and other conditions on the other that doesn’t usually exist regarding therapies that people with MS are using,” said Allen C. Bowling, MD, PhD, director of the NeuroHealth Institute and clinical professor of neurology at the University of Colorado, in Aurora. His presentation was part of the virtual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
While approximately 8% of the general population uses cannabis, evidence shows that the proportion of people with MS who do so ranges from 9% to 38%, for an average of about 20%, Dr. Bowling noted. Yet, according to research, only about 20% of those actually discuss their cannabis use with their clinicians, which could have potentially adverse implications in the management of the disease.
As an example, Dr. Bowling described a case of his own involving a stroke syndrome associated with cannabis use – reversible cerebral vasoconstriction syndrome (RCVS), which he mistook for an MS flare-up. “I had a patient who developed RCVS, but because it appeared to be an MS attack, I was treating her with corticosteroids, and she kept getting worse,” he said. “It’s very important for MS clinicians to be aware of this stroke syndrome that can mimic an MS attack. The way to rule it out is with CT angiography.”
Misconceptions common among clinicians
Studies underscore that such misconceptions could be common. One recent study showed that as many as 90% of residents and fellows did not feel prepared to recommend or answer questions on cannabis use, and in fact, most states do not even require physicians to have training in medical uses of cannabis, Dr. Bowling noted.
Other research shows that the rates of clinicians with high knowledge in medical cannabis use are in the single digits, while many have no cannabis training at all.
In a survey of 556 physicians taken as recently as January 2020, 47% gave incorrect responses regarding tetrahydrocannabinol (THC), while 33% reported being familiar with “nano-cannabinoids” – which don’t even exist, and the term was created for the sake of the survey.
Clinicians’ misconceptions about the regulation of cannabis was especially eyebrow raising, Dr. Bowling indicated. “The part that concerns me the most is regarding dispensary cannabis products – 17% of respondents thought the products were Food and Drug Administration–controlled and 25% said they thought that dispensary products were FDA approved,” he said.
There are, meanwhile, no formal clinical studies evaluating the medical efficacy of any products sold in U.S. cannabis dispensaries, much less FDA regulation, Dr. Bowling said.
Among the most recent research of cannabis use among MS patients is a real-world study of more than 2,000 patients with MS in Denmark. Said to be the most comprehensive survey of cannabis use among MS patients to date, the researchers found that 21% of patients reported cannabis use in the past year, with only 21% of those having a prescription to use the drug legally because of strict regulations in Denmark.
Respondents reported that the primary reasons for use in MS were to alleviate pain (61%), spasticity (52%), and sleep disturbances (46%). The most common adverse effects were drowsiness (30%), feeling quiet/subdued (23%), and dizziness (13%), with effects that were mild to moderate.
And a 2019 study of electronic medical record data for 561 patients with multiple sclerosis in British Columbia, Canada, showed that 19% reported using cannabis, with 71% reporting use for alleviation of pain, 71% for sleep, 44% for mood, and 40% for spasticity.
Dr. Bowling said the findings are consistent with his clinical experience in treating patients in Colorado, where medical cannabis has been legal for about 2 decades. “It seems that people who benefit most are those who use small amounts and typically use it for alleviation of pain and/or spasticity that interferes with sleep,” he said.
However, with a lack of regulation about the true components in dispensary products, there are many uncertainties about what works or doesn’t. “Very anecdotally, preparations that are high in cannabidiol (CBD) and low in tetrahydrocannabinol (THC, the main psychoactive compound in cannabis) seem the most helpful. Pure CBD preparations (i.e., with no THC) seem less effective,” Dr. Bowling noted.
Other recent evidence on cannabis use in MS, however, suggests important benefits once patients abstain from its use.
However, the exceptionally wide array of components in unregulated cannabis accounts for substantial variety in potency, benefits, and side effects, Dr. Bowling said.
He pointed out one recent study looking mainly at patients with MS who regularly smoked cannabis and showed cognitive improvements upon abstaining. The study included 40 MS patients who reported smoking cannabis regularly – at least 4 days per week for multiple years – who were randomized to continue their cannabis use or withdraw.
While there were no cognitive differences among the patients at baseline, after 28 days, the abstinence group showed significant improvements on functional MRI in every cognitive index (P < .0001 for all). On the Symbol Digit Modalities Test at day 28, the withdrawal group completed more trials correctly (P < .012) and had a faster reaction time (P < .002) that was associated with significantly increased activation in brain regions known to be associated with performance of the test, including the bilateral inferior frontal gyri, caudate, and declive/cerebellum (P < .001 for all regions), the authors said.
“These results reveal that patients with multiple sclerosis who are frequent, long-term cannabis users can show significant improvements in memory, processing speed, and executive function after 28 days of drug abstinence,” the authors reported.
Addiction, distinguishing cannabis from MS symptoms
Dr. Bowling said that, while the findings are consistent with his own clinical observations, abstinence isn’t always easy. “I’ve seen patients with cognitive impairment whose cognition and overall day-to-day function have improved with discontinuation of cannabis,” he said. “For some of these patients, however, it was a long-term challenge to discontinue cannabis because they were addicted.”
Addiction to cannabis in MS in fact may be more common than many realize, and comes with a host of other adverse effects, Dr. Bowling said. “In my practice, I have definitely seen many cases of addiction. I think that it’s very underdiagnosed. In addition to cognitive dysfunction, it can worsen anxiety and depression and decrease balance, leading to falls.”
The RCVS risk is another concern, and changes in liver enzymes should also raise a red flag when MS patients are cannabis users, Bowling added.
“I’ve seen in multiple patients where the liver enzymes went up and I thought it was because of the disease-modifying therapy, but it turned out to have been because the patient had started CBD, so you need to be aware of potential hepatotoxicity.”
“The bottom line is that we don’t have strong data in this area and herbs are extremely complex with many unknown constituents.”
Dr. Bowling noted that pure CBD or CBD-enriched products would be expected to produce less cognitive dysfunction than does regular cannabis smoking, “however, it’s important to keep in mind that a ‘CBD-enriched’ product could have low but still significant THC content,” he said.
Dr. Bowling reported relationships with Bristol-Myers Squibb, EMD Serono, Genentech, Genzyme, Greenwich Biosciences, and Novartis, and he received royalties from Springer Publishing.
A version of this article originally appeared on Medscape.com.
From CMSC 2020
Today’s Top News Highlights: Your coding questions answered, biologics and melanoma, and more
Here are the stories our MDedge editors across specialties think you need to know about today:
Answers to your top telehealth coding questions
How long can we continue using telehealth? How do I select a level of office visit? How do I bill for behavioral health services if I am not able to conduct in-person visits?
Our coding expert has fielded these and other questions from physicians ever since the Centers for Medicare & Medicaid Services expanded use of telehealth during the COVID-19 emergency. Find the answers to these questions and get more expert tips on how to code properly to miximize reimbursement.
Read more.
Asymptomatic COVID-19 spread
A WHO official has stated that it appears to be “rare” that an asymptomatic individual can pass SARS-CoV-2 to someone else.
“From the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, said June 8 at a news briefing from the agency’s Geneva headquarters.
This announcement came on the heels of the publication of an analysis in the Annals of Internal Medicine, which suggested that as many as 40-45% of COVID-19 cases may be asymptomatic. In this paper, the authors, Daniel P. Oran, AM, and Eric J. Topol, MD, of the Scripps Research Translational Institute in La Jolla, Calif stated: “The likelihood that approximately 40%-45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.” Read more.
Biologics and melanoma risk
New data suggest patients taking biologics for inflammatory bowel disease, rheumatoid arthritis, or psoriasis may have an increased risk of melanoma, but the association was not statistically significant in a systematic review and meta-analysis.
The study, published in JAMA Dermatology, assessed melanoma risk in 34,029 patients receiving biologics and 135,370 patients receiving conventional systemic therapy for IBD, RA, or psoriasis, using data from seven cohort studies.
The researchers analyzed the pooled relative risk across all studies. Compared with patients who received conventional systemic therapy, there was a nonsignificant association with risk of melanoma in patients with psoriasis (hazard ratio, 1.57), RA (pooled relative risk, 1.20), and IBD (pRR, 1.20).
Previous studies that have found an increased risk of melanoma in patients on biologics for these three conditions have “typically used the general population as the comparator,” the investigators noted. There is a large amount of evidence that has established short-term efficacy and safety of biologics, compared with conventional systemic treatments, but concerns about longer-term cancer risk associated with biologics remains a concern. “We advocate for more large, well-designed studies of this issue to be performed to help improve certainty,” the researchers said.
Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
Answers to your top telehealth coding questions
How long can we continue using telehealth? How do I select a level of office visit? How do I bill for behavioral health services if I am not able to conduct in-person visits?
Our coding expert has fielded these and other questions from physicians ever since the Centers for Medicare & Medicaid Services expanded use of telehealth during the COVID-19 emergency. Find the answers to these questions and get more expert tips on how to code properly to miximize reimbursement.
Read more.
Asymptomatic COVID-19 spread
A WHO official has stated that it appears to be “rare” that an asymptomatic individual can pass SARS-CoV-2 to someone else.
“From the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, said June 8 at a news briefing from the agency’s Geneva headquarters.
This announcement came on the heels of the publication of an analysis in the Annals of Internal Medicine, which suggested that as many as 40-45% of COVID-19 cases may be asymptomatic. In this paper, the authors, Daniel P. Oran, AM, and Eric J. Topol, MD, of the Scripps Research Translational Institute in La Jolla, Calif stated: “The likelihood that approximately 40%-45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.” Read more.
Biologics and melanoma risk
New data suggest patients taking biologics for inflammatory bowel disease, rheumatoid arthritis, or psoriasis may have an increased risk of melanoma, but the association was not statistically significant in a systematic review and meta-analysis.
The study, published in JAMA Dermatology, assessed melanoma risk in 34,029 patients receiving biologics and 135,370 patients receiving conventional systemic therapy for IBD, RA, or psoriasis, using data from seven cohort studies.
The researchers analyzed the pooled relative risk across all studies. Compared with patients who received conventional systemic therapy, there was a nonsignificant association with risk of melanoma in patients with psoriasis (hazard ratio, 1.57), RA (pooled relative risk, 1.20), and IBD (pRR, 1.20).
Previous studies that have found an increased risk of melanoma in patients on biologics for these three conditions have “typically used the general population as the comparator,” the investigators noted. There is a large amount of evidence that has established short-term efficacy and safety of biologics, compared with conventional systemic treatments, but concerns about longer-term cancer risk associated with biologics remains a concern. “We advocate for more large, well-designed studies of this issue to be performed to help improve certainty,” the researchers said.
Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Here are the stories our MDedge editors across specialties think you need to know about today:
Answers to your top telehealth coding questions
How long can we continue using telehealth? How do I select a level of office visit? How do I bill for behavioral health services if I am not able to conduct in-person visits?
Our coding expert has fielded these and other questions from physicians ever since the Centers for Medicare & Medicaid Services expanded use of telehealth during the COVID-19 emergency. Find the answers to these questions and get more expert tips on how to code properly to miximize reimbursement.
Read more.
Asymptomatic COVID-19 spread
A WHO official has stated that it appears to be “rare” that an asymptomatic individual can pass SARS-CoV-2 to someone else.
“From the data we have, it still seems to be rare that an asymptomatic person actually transmits onward to a secondary individual,” Maria Van Kerkhove, PhD, WHO’s COVID-19 technical lead and an infectious disease epidemiologist, said June 8 at a news briefing from the agency’s Geneva headquarters.
This announcement came on the heels of the publication of an analysis in the Annals of Internal Medicine, which suggested that as many as 40-45% of COVID-19 cases may be asymptomatic. In this paper, the authors, Daniel P. Oran, AM, and Eric J. Topol, MD, of the Scripps Research Translational Institute in La Jolla, Calif stated: “The likelihood that approximately 40%-45% of those infected with SARS-CoV-2 will remain asymptomatic suggests that the virus might have greater potential than previously estimated to spread silently and deeply through human populations.” Read more.
Biologics and melanoma risk
New data suggest patients taking biologics for inflammatory bowel disease, rheumatoid arthritis, or psoriasis may have an increased risk of melanoma, but the association was not statistically significant in a systematic review and meta-analysis.
The study, published in JAMA Dermatology, assessed melanoma risk in 34,029 patients receiving biologics and 135,370 patients receiving conventional systemic therapy for IBD, RA, or psoriasis, using data from seven cohort studies.
The researchers analyzed the pooled relative risk across all studies. Compared with patients who received conventional systemic therapy, there was a nonsignificant association with risk of melanoma in patients with psoriasis (hazard ratio, 1.57), RA (pooled relative risk, 1.20), and IBD (pRR, 1.20).
Previous studies that have found an increased risk of melanoma in patients on biologics for these three conditions have “typically used the general population as the comparator,” the investigators noted. There is a large amount of evidence that has established short-term efficacy and safety of biologics, compared with conventional systemic treatments, but concerns about longer-term cancer risk associated with biologics remains a concern. “We advocate for more large, well-designed studies of this issue to be performed to help improve certainty,” the researchers said.
Read more.
For more on COVID-19, visit our Resource Center. All of our latest news is available on MDedge.com.
Doctors’ top telehealth coding questions answered
The coding expert answers your questions
Betsy Nicoletti, MS, a nationally recognized coding expert, will take your coding questions via email and provide guidance on how to code properly to maximize reimbursement. Have a question about coding? Send it here.
Telehealth: Frequently asked questions
Since the Centers for Medicare & Medicaid Services (CMS) expanded use of telehealth during the COVID-19 emergency, I’ve seen various follow-up questions coming from physicians. Here are the most common ones received and some guidance.
Q: How long can we continue using telehealth?
A: Private payers will set their own rules for the end date. For Medicare, telehealth is allowed until the end of the public health emergency. Department of Health & Human Services Secretary Alex M. Azar II renewed the status of the public health emergency, effective April 26, 2020, for an additional 90 days.
Q: Can I bill Medicare annual wellness visits via telehealth?
A: Yes, you can bill the initial and subsequent Medicare wellness visits (G0438, G0439) via telehealth, but the Welcome to Medicare visit (G0402) is not on the list of telehealth services.
In fact, the wellness visits mentioned above may be billed with audio-only communications because of the expansion of telehealth services, although these visits require height, weight, BMI calculation, and blood pressure, and CMS has not issued guidance about whether the patient’s self-reported measurements are sufficient or whether they can be deferred.
Q: Can I bill an office visit via telehealth?
A: Yes, you may bill new and established patient visits 99201-99215 via telehealth, but for Medicare, these still require the use of real-time, audio-visual communications equipment.
Q: Can I bill an office visit conducted via telephone only?
A: For Medicare patients, you may not bill office visit codes for audio only communication. If there is audio only, use phone call codes 99441-99443. In order to bill an office visit, with codes 99201-99215 to a Medicare patient, audio and visual, real time communication is required. Some state Medicaid programs and private insurers allow office visits to be billed with audio equipment only, so check your state requirements.
Q: How do I select a level of office visit?
A: CMS’s announcement on March 31 relaxed the rules for practitioners to select a level of service for office and other patient services (99201-99215). CMS stated that clinicians could use either total time or medical decision-making to select a code.
If using time, count the practitioner’s total time for the visit, both face to face and non–face to face. It does not need to be greater than 50% in counseling. If using medical decision-making, history and exam are not needed to select the level of service. Medical decision-making alone can be used to select the code.
Q: Can I count the time it takes my medical assistant to set up the audio-visual communication with a patient?
A: No, you cannot count staff time in coding and billing a patient visit in this manner.
Q: Is there a code for a registered nurse to use for making phone calls with patients?
A: No, unfortunately.
Q: How do I know if a service can be billed with phone only?
A: These are indicated as “yes” on CMS’s list of covered telehealth services as allowed via audio only.
Providing mental health services during COVID-19
Q: I am a mental health provider who finds himself trying to provide the best care for my patients during this pandemic. How do I bill for behavioral health services if I am not able to conduct in-person visits?
A: Psychiatrists and behavioral health professionals can perform psychiatric diagnostic evaluations and psychotherapy over the phone during the public health emergency.
The use of real-time, audio-visual communication equipment is not required. This is one of the many changes CMS made in its interim final rule regarding COVID-19, released April 30.
Not only did CMS update the list of Current Procedural Terminology (CPT) and Healthcare Common Procedure Coding System (HCPCS) codes that could be reported via real-time, audio-visual communication, but it also added a column to guidance on covered telehealth services: “Can Audio-only Interaction Meet the Requirements?” The codes for psychiatric diagnostic evaluations and psychotherapy are indicated as “yes.”
In addition to psychiatric diagnostic evaluations and time-based psychotherapy codes, psychotherapy for crisis, family, and group psychotherapy can be done with audio-only technology.
CMS has issued multiple waivers and two major rules that greatly expand the ability of medical practices to treat patients without requiring an in-person visit. This latest change, allowing some services to be performed with audio equipment only, is remarkable.
For Medicare patients, report the place of service that would have been used if the patient was seen in person. This could be office (POS 11), outpatient department (POS 19, 21), or community mental health center (POS 53).
Some private payers require the place of service for telehealth (02). The lack of consistency between payers is difficult for practices. Append modifier 95 to the CPT code for all payers. The definition of modifier 95 is “synchronous telemedicine service using audio and visual communication.” However, as CMS added these services to the telehealth list, use modifier 95.
Have a coding question? Send it in and it may be answered in a future column. (Please be sure to note your specialty in the text of the question.)
Betsy Nicoletti, MS, is a consultant, author, and speaker, as well as the founder of CodingIntel.com, a library of medical practice coding resources.
A version of this article originally appeared on Medscape.com.
The coding expert answers your questions
Betsy Nicoletti, MS, a nationally recognized coding expert, will take your coding questions via email and provide guidance on how to code properly to maximize reimbursement. Have a question about coding? Send it here.
Telehealth: Frequently asked questions
Since the Centers for Medicare & Medicaid Services (CMS) expanded use of telehealth during the COVID-19 emergency, I’ve seen various follow-up questions coming from physicians. Here are the most common ones received and some guidance.
Q: How long can we continue using telehealth?
A: Private payers will set their own rules for the end date. For Medicare, telehealth is allowed until the end of the public health emergency. Department of Health & Human Services Secretary Alex M. Azar II renewed the status of the public health emergency, effective April 26, 2020, for an additional 90 days.
Q: Can I bill Medicare annual wellness visits via telehealth?
A: Yes, you can bill the initial and subsequent Medicare wellness visits (G0438, G0439) via telehealth, but the Welcome to Medicare visit (G0402) is not on the list of telehealth services.
In fact, the wellness visits mentioned above may be billed with audio-only communications because of the expansion of telehealth services, although these visits require height, weight, BMI calculation, and blood pressure, and CMS has not issued guidance about whether the patient’s self-reported measurements are sufficient or whether they can be deferred.
Q: Can I bill an office visit via telehealth?
A: Yes, you may bill new and established patient visits 99201-99215 via telehealth, but for Medicare, these still require the use of real-time, audio-visual communications equipment.
Q: Can I bill an office visit conducted via telephone only?
A: For Medicare patients, you may not bill office visit codes for audio only communication. If there is audio only, use phone call codes 99441-99443. In order to bill an office visit, with codes 99201-99215 to a Medicare patient, audio and visual, real time communication is required. Some state Medicaid programs and private insurers allow office visits to be billed with audio equipment only, so check your state requirements.
Q: How do I select a level of office visit?
A: CMS’s announcement on March 31 relaxed the rules for practitioners to select a level of service for office and other patient services (99201-99215). CMS stated that clinicians could use either total time or medical decision-making to select a code.
If using time, count the practitioner’s total time for the visit, both face to face and non–face to face. It does not need to be greater than 50% in counseling. If using medical decision-making, history and exam are not needed to select the level of service. Medical decision-making alone can be used to select the code.
Q: Can I count the time it takes my medical assistant to set up the audio-visual communication with a patient?
A: No, you cannot count staff time in coding and billing a patient visit in this manner.
Q: Is there a code for a registered nurse to use for making phone calls with patients?
A: No, unfortunately.
Q: How do I know if a service can be billed with phone only?
A: These are indicated as “yes” on CMS’s list of covered telehealth services as allowed via audio only.
Providing mental health services during COVID-19
Q: I am a mental health provider who finds himself trying to provide the best care for my patients during this pandemic. How do I bill for behavioral health services if I am not able to conduct in-person visits?
A: Psychiatrists and behavioral health professionals can perform psychiatric diagnostic evaluations and psychotherapy over the phone during the public health emergency.
The use of real-time, audio-visual communication equipment is not required. This is one of the many changes CMS made in its interim final rule regarding COVID-19, released April 30.
Not only did CMS update the list of Current Procedural Terminology (CPT) and Healthcare Common Procedure Coding System (HCPCS) codes that could be reported via real-time, audio-visual communication, but it also added a column to guidance on covered telehealth services: “Can Audio-only Interaction Meet the Requirements?” The codes for psychiatric diagnostic evaluations and psychotherapy are indicated as “yes.”
In addition to psychiatric diagnostic evaluations and time-based psychotherapy codes, psychotherapy for crisis, family, and group psychotherapy can be done with audio-only technology.
CMS has issued multiple waivers and two major rules that greatly expand the ability of medical practices to treat patients without requiring an in-person visit. This latest change, allowing some services to be performed with audio equipment only, is remarkable.
For Medicare patients, report the place of service that would have been used if the patient was seen in person. This could be office (POS 11), outpatient department (POS 19, 21), or community mental health center (POS 53).
Some private payers require the place of service for telehealth (02). The lack of consistency between payers is difficult for practices. Append modifier 95 to the CPT code for all payers. The definition of modifier 95 is “synchronous telemedicine service using audio and visual communication.” However, as CMS added these services to the telehealth list, use modifier 95.
Have a coding question? Send it in and it may be answered in a future column. (Please be sure to note your specialty in the text of the question.)
Betsy Nicoletti, MS, is a consultant, author, and speaker, as well as the founder of CodingIntel.com, a library of medical practice coding resources.
A version of this article originally appeared on Medscape.com.
The coding expert answers your questions
Betsy Nicoletti, MS, a nationally recognized coding expert, will take your coding questions via email and provide guidance on how to code properly to maximize reimbursement. Have a question about coding? Send it here.
Telehealth: Frequently asked questions
Since the Centers for Medicare & Medicaid Services (CMS) expanded use of telehealth during the COVID-19 emergency, I’ve seen various follow-up questions coming from physicians. Here are the most common ones received and some guidance.
Q: How long can we continue using telehealth?
A: Private payers will set their own rules for the end date. For Medicare, telehealth is allowed until the end of the public health emergency. Department of Health & Human Services Secretary Alex M. Azar II renewed the status of the public health emergency, effective April 26, 2020, for an additional 90 days.
Q: Can I bill Medicare annual wellness visits via telehealth?
A: Yes, you can bill the initial and subsequent Medicare wellness visits (G0438, G0439) via telehealth, but the Welcome to Medicare visit (G0402) is not on the list of telehealth services.
In fact, the wellness visits mentioned above may be billed with audio-only communications because of the expansion of telehealth services, although these visits require height, weight, BMI calculation, and blood pressure, and CMS has not issued guidance about whether the patient’s self-reported measurements are sufficient or whether they can be deferred.
Q: Can I bill an office visit via telehealth?
A: Yes, you may bill new and established patient visits 99201-99215 via telehealth, but for Medicare, these still require the use of real-time, audio-visual communications equipment.
Q: Can I bill an office visit conducted via telephone only?
A: For Medicare patients, you may not bill office visit codes for audio only communication. If there is audio only, use phone call codes 99441-99443. In order to bill an office visit, with codes 99201-99215 to a Medicare patient, audio and visual, real time communication is required. Some state Medicaid programs and private insurers allow office visits to be billed with audio equipment only, so check your state requirements.
Q: How do I select a level of office visit?
A: CMS’s announcement on March 31 relaxed the rules for practitioners to select a level of service for office and other patient services (99201-99215). CMS stated that clinicians could use either total time or medical decision-making to select a code.
If using time, count the practitioner’s total time for the visit, both face to face and non–face to face. It does not need to be greater than 50% in counseling. If using medical decision-making, history and exam are not needed to select the level of service. Medical decision-making alone can be used to select the code.
Q: Can I count the time it takes my medical assistant to set up the audio-visual communication with a patient?
A: No, you cannot count staff time in coding and billing a patient visit in this manner.
Q: Is there a code for a registered nurse to use for making phone calls with patients?
A: No, unfortunately.
Q: How do I know if a service can be billed with phone only?
A: These are indicated as “yes” on CMS’s list of covered telehealth services as allowed via audio only.
Providing mental health services during COVID-19
Q: I am a mental health provider who finds himself trying to provide the best care for my patients during this pandemic. How do I bill for behavioral health services if I am not able to conduct in-person visits?
A: Psychiatrists and behavioral health professionals can perform psychiatric diagnostic evaluations and psychotherapy over the phone during the public health emergency.
The use of real-time, audio-visual communication equipment is not required. This is one of the many changes CMS made in its interim final rule regarding COVID-19, released April 30.
Not only did CMS update the list of Current Procedural Terminology (CPT) and Healthcare Common Procedure Coding System (HCPCS) codes that could be reported via real-time, audio-visual communication, but it also added a column to guidance on covered telehealth services: “Can Audio-only Interaction Meet the Requirements?” The codes for psychiatric diagnostic evaluations and psychotherapy are indicated as “yes.”
In addition to psychiatric diagnostic evaluations and time-based psychotherapy codes, psychotherapy for crisis, family, and group psychotherapy can be done with audio-only technology.
CMS has issued multiple waivers and two major rules that greatly expand the ability of medical practices to treat patients without requiring an in-person visit. This latest change, allowing some services to be performed with audio equipment only, is remarkable.
For Medicare patients, report the place of service that would have been used if the patient was seen in person. This could be office (POS 11), outpatient department (POS 19, 21), or community mental health center (POS 53).
Some private payers require the place of service for telehealth (02). The lack of consistency between payers is difficult for practices. Append modifier 95 to the CPT code for all payers. The definition of modifier 95 is “synchronous telemedicine service using audio and visual communication.” However, as CMS added these services to the telehealth list, use modifier 95.
Have a coding question? Send it in and it may be answered in a future column. (Please be sure to note your specialty in the text of the question.)
Betsy Nicoletti, MS, is a consultant, author, and speaker, as well as the founder of CodingIntel.com, a library of medical practice coding resources.
A version of this article originally appeared on Medscape.com.
Prolonged azithromycin Tx for asthma?
In “Asthma: Newer Tx options mean more targeted therapy” (J Fam Pract. 2020;65:135-144), Rali et al recommend azithromycin as an add-on therapy to ICS-LABA for a select group of patients with uncontrolled persistent asthma (neutrophilic phenotype)—a Grade C recommendation. However, the best available evidence demonstrates that azithromycin is equally efficacious for uncontrolled persistent eosinophilic asthma.1,2 Thus, family physicians need not refer patients for bronchoscopy to identify the inflammatory “phenotype.”
An important unanswered question is whether azithromycin needs to be administered continuously. Emerging evidence indicates that some patients may experience prolonged benefit after time-limited azithromycin treatment. This suggests that the mechanism of action, which has been described as anti-inflammatory, is (at least in part) antimicrobial.3
For azithromycin-treated asthma patients who experience a significant clinical response after 3 to 6 months of treatment, I recommend that the prescribing clinician try taking the patient off azithromycin to assess whether clinical improvement persists or wanes. Nothing is lost, and much is gained, by this approach; patients who relapse can resume azithromycin, and patients who remain improved are spared exposure to an unnecessary and prolonged treatment.
David L. Hahn, MD, MS
Madison, WI
1. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390: 659-668.
2. Gibson PG, Yang IA, Upham JW, et al. Efficacy of azithromycin in severe asthma from the AMAZES randomised trial. ERJ Open Res. 2019;5.
3. Hahn D. When guideline treatment of asthma fails, consider a macrolide antibiotic. J Fam Pract. 2019;68:536-545.
In “Asthma: Newer Tx options mean more targeted therapy” (J Fam Pract. 2020;65:135-144), Rali et al recommend azithromycin as an add-on therapy to ICS-LABA for a select group of patients with uncontrolled persistent asthma (neutrophilic phenotype)—a Grade C recommendation. However, the best available evidence demonstrates that azithromycin is equally efficacious for uncontrolled persistent eosinophilic asthma.1,2 Thus, family physicians need not refer patients for bronchoscopy to identify the inflammatory “phenotype.”
An important unanswered question is whether azithromycin needs to be administered continuously. Emerging evidence indicates that some patients may experience prolonged benefit after time-limited azithromycin treatment. This suggests that the mechanism of action, which has been described as anti-inflammatory, is (at least in part) antimicrobial.3
For azithromycin-treated asthma patients who experience a significant clinical response after 3 to 6 months of treatment, I recommend that the prescribing clinician try taking the patient off azithromycin to assess whether clinical improvement persists or wanes. Nothing is lost, and much is gained, by this approach; patients who relapse can resume azithromycin, and patients who remain improved are spared exposure to an unnecessary and prolonged treatment.
David L. Hahn, MD, MS
Madison, WI
In “Asthma: Newer Tx options mean more targeted therapy” (J Fam Pract. 2020;65:135-144), Rali et al recommend azithromycin as an add-on therapy to ICS-LABA for a select group of patients with uncontrolled persistent asthma (neutrophilic phenotype)—a Grade C recommendation. However, the best available evidence demonstrates that azithromycin is equally efficacious for uncontrolled persistent eosinophilic asthma.1,2 Thus, family physicians need not refer patients for bronchoscopy to identify the inflammatory “phenotype.”
An important unanswered question is whether azithromycin needs to be administered continuously. Emerging evidence indicates that some patients may experience prolonged benefit after time-limited azithromycin treatment. This suggests that the mechanism of action, which has been described as anti-inflammatory, is (at least in part) antimicrobial.3
For azithromycin-treated asthma patients who experience a significant clinical response after 3 to 6 months of treatment, I recommend that the prescribing clinician try taking the patient off azithromycin to assess whether clinical improvement persists or wanes. Nothing is lost, and much is gained, by this approach; patients who relapse can resume azithromycin, and patients who remain improved are spared exposure to an unnecessary and prolonged treatment.
David L. Hahn, MD, MS
Madison, WI
1. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390: 659-668.
2. Gibson PG, Yang IA, Upham JW, et al. Efficacy of azithromycin in severe asthma from the AMAZES randomised trial. ERJ Open Res. 2019;5.
3. Hahn D. When guideline treatment of asthma fails, consider a macrolide antibiotic. J Fam Pract. 2019;68:536-545.
1. Gibson PG, Yang IA, Upham JW, et al. Effect of azithromycin on asthma exacerbations and quality of life in adults with persistent uncontrolled asthma (AMAZES): a randomised, double-blind, placebo-controlled trial. Lancet. 2017;390: 659-668.
2. Gibson PG, Yang IA, Upham JW, et al. Efficacy of azithromycin in severe asthma from the AMAZES randomised trial. ERJ Open Res. 2019;5.
3. Hahn D. When guideline treatment of asthma fails, consider a macrolide antibiotic. J Fam Pract. 2019;68:536-545.
Include a behavioral health specialist in ADHD evaluations
The basic primary care evaluation recommended by Dr. Brieler et al in “Working adeptly to diagnose and treat adult ADHD” (J Fam Pract. 2020;69:145-149) is a step up from what occurs in some practices. Nonetheless, I was concerned about the idea that an attention-deficit/hyperactivity disorder (ADHD) evaluation in a primary care office might not include a behavioral health specialist. The gold standard remains a comprehensive, multidisciplinary evaluation.
As a family physician who has performed comprehensive ADHD evaluations for more than 25 years, I have frequently seen adults with ADHD who were diagnosed elsewhere, without a comprehensive evaluation, and had various undiagnosed comorbidities. Unless these other problems are addressed, treatment focused only on ADHD often yields suboptimal results.
We, as primary care physicians, can provide better care for our patients if we include a behavioral health specialist in the evaluation process.
H. C. Bean, MD, FAAFP, CPE
MGC Carolina Family Physicians
Spartanburg, SC
The basic primary care evaluation recommended by Dr. Brieler et al in “Working adeptly to diagnose and treat adult ADHD” (J Fam Pract. 2020;69:145-149) is a step up from what occurs in some practices. Nonetheless, I was concerned about the idea that an attention-deficit/hyperactivity disorder (ADHD) evaluation in a primary care office might not include a behavioral health specialist. The gold standard remains a comprehensive, multidisciplinary evaluation.
As a family physician who has performed comprehensive ADHD evaluations for more than 25 years, I have frequently seen adults with ADHD who were diagnosed elsewhere, without a comprehensive evaluation, and had various undiagnosed comorbidities. Unless these other problems are addressed, treatment focused only on ADHD often yields suboptimal results.
We, as primary care physicians, can provide better care for our patients if we include a behavioral health specialist in the evaluation process.
H. C. Bean, MD, FAAFP, CPE
MGC Carolina Family Physicians
Spartanburg, SC
The basic primary care evaluation recommended by Dr. Brieler et al in “Working adeptly to diagnose and treat adult ADHD” (J Fam Pract. 2020;69:145-149) is a step up from what occurs in some practices. Nonetheless, I was concerned about the idea that an attention-deficit/hyperactivity disorder (ADHD) evaluation in a primary care office might not include a behavioral health specialist. The gold standard remains a comprehensive, multidisciplinary evaluation.
As a family physician who has performed comprehensive ADHD evaluations for more than 25 years, I have frequently seen adults with ADHD who were diagnosed elsewhere, without a comprehensive evaluation, and had various undiagnosed comorbidities. Unless these other problems are addressed, treatment focused only on ADHD often yields suboptimal results.
We, as primary care physicians, can provide better care for our patients if we include a behavioral health specialist in the evaluation process.
H. C. Bean, MD, FAAFP, CPE
MGC Carolina Family Physicians
Spartanburg, SC
24-year-old man • prednisone therapy for nephrotic syndrome • diffuse maculopapular rash • pruritis
THE CASE
A 24-year-old man with no past medical history was referred to a nephrologist for a 5-month history of leg swelling and weight gain. His only medication was furosemide 40 mg/d, prescribed by his primary care physician. His physical examination was unremarkable except for lower extremity and scrotal edema.
Laboratory values included a creatinine of 0.8 mg/dL (reference range, 0.6 to 1.2 mg/dL); hemoglobin concentration, 14.4 g/dL (reference range, 14 to 18 g/dL); albumin, 1.9 g/dL (reference range, 3.5 to 5.5 g/dL); and glucose, 80 mg/dL (reference range, 74 to 106 mg/dL). Electrolyte levels were normal. Urinalysis revealed 3+ blood and 4+ protein on dipstick, as well as the presence of granular and lipid casts on microscopic exam. A 24-hour urine collection contained 10.5 g of protein. Antinuclear antibody titers, complement levels, hepatitis serologies, and antineutrophil cytoplasmic antibody titers were all normal.
A renal biopsy revealed idiopathic focal segmental glomerulosclerosis. The patient was started on oral prednisone 40 mg twice daily.
Two days later, he developed a diffuse pruritic maculopapular rash. He stopped taking the prednisone, and the rash resolved over the next 3 to 5 days. He was then instructed to restart the prednisone for his nephrotic syndrome. When he developed a new but similar rash, the prednisone was discontinued. The rash again resolved.
THE DIAGNOSIS
Since the patient had already been taking furosemide for 6 weeks without an adverse reaction, it was presumed that the prednisone tablet was causing his rash. It would be unusual for prednisone itself to cause a drug eruption, so an additive or coloring agent in the tablet was thought to be responsible for the reaction.
We noted that the patient had been taking a 20-mg orange tablet of prednisone. So we opted to “tweak” the prescription and prescribe the same daily dose but in the form of 10-mg white tablets. The patient tolerated this new regimen without any adverse effects and completed a full 9 months of prednisone therapy without any recurrence of skin lesions. His glomerular disease went into remission.
DISCUSSION
Excipients are inert substances that are added to a food or drug to provide the desired consistency, appearance, or form. They are also used as a preservative for substance stabilization.
Continue to: There are many reports in the literature...
There are many reports in the literature of adverse reactions to excipients.1-3 These include skin rashes induced by the coloring agent in the capsule shell of rifampicin2 and a rash that developed from a coloring agent in oral iron.3 Other reports have noted dyes in foods and even toothpaste as triggers.4,5
Hypersensitivity. Although a specific reaction to prednisone was considered unlikely in this case, type IV delayed hypersensitivity reactions to corticosteroids have been reported. The most common type of corticosteroid-related allergy is contact dermatitis associated with topical corticosteroid use.6 Many cases of delayed maculopapular reactions are thought to be T-cell–mediated type IV reactions.6
Type I immediate hypersensitivity reactions to corticosteroids are also well documented. In a literature review of 120 immediate hypersensitivity reactions to corticosteroids, anaphylactic symptoms were more commonly reported than urticaria or angioedema.7 Intravenous exposure was most frequently associated with reactions, followed by the intra-articular and oral routes of administration.7
Causative agents. The same literature review identified methylprednisolone as the most common steroid to cause a reaction; dexamethasone and prednisone were the least frequently associated with reactions.7 Pharmacologically inactive ingredients were implicated in 28% of the corticosteroid hypersensitivity reactions.7
Additives suspected to be triggers include succinate and phosphate esters, carboxymethylcellulose, polyethylene glycol, and lactose. Interestingly, there have been reports of acute allergic reactions to methylprednisolone sodium succinate 40 mg/mL intravenous preparation in children with milk allergy, due to lactose contaminated with milk protein.8,9
Continue to: Yellow dye was to blame
Yellow dye was to blame. In our case, the 20-mg tablet that the patient had been taking contained the coloring agent FD&C yellow #6, an azo dye also known as sunset yellow or E-110 in Europe. Several reports have described adverse reactions to this coloring agent.1,3 There were other additives in the 20-mg tablet, but a comparison revealed that the 10-mg tablet contained identical substances—but no dye. Thus, it was most likely that the coloring agent was the cause of the patient’s probable type IV exanthematous drug reaction.
Our patient
The patient was instructed to avoid all medications and food containing FD&C yellow #6. No formal allergy testing or re-challenge was performed, since the patient did well under the care of his nephrologist.
THE TAKEAWAY
It’s important to recognize that adverse drug reactions can occur from any medication—not only from the drug itself, but also from excipients contained within. This case reminds us that when a patient complains of an adverse effect to a medication, dyes and inactive ingredients need to be considered as possible inciting agents.
CORRESPONDENCE
Neil E. Soifer, MD, Lakeside Nephrology, 2277 West Howard, Chicago, IL 60645; nsoifer@aol.com
1. Swerlick RA, Campbell CF. Medication dyes as a source of drug allergy. J Drugs Dermatol. 2013;12:99-102.
2. Calişkaner Z, Oztürk S, Karaayvaz M. Not all adverse drug reactions originate from active component: coloring agent-induced skin eruption in a patient treated with rifampicin. Allergy. 2003;58:1077-1079.
3. Rogkakou A, Guerra L, Scordamaglia A, et al. Severe skin reaction to excipients of an oral iron treatment. Allergy. 2007;62:334-335.
4. Zaknun D, Schroecksnadel S, Kurz K, et al. Potential role of antioxidant food supplements, preservatives and colorants in the pathogenesis of allergy and asthma. Int Arch Allergy Immunol. 2012;157:113-124.
5. Barbaud A. Place of excipients in systemic drug allergy. Immunol Allergy Clin N Am. 2014;34:671-679.
6. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105:259-273.
7. Patel A, Bahna S. Immediate hypersensitivity reactions to corticosteroids. Ann Allergy Asthma Immunol. 2015;115:178-182.
8. Eda A, Sugai K, Shioya H, et al. Acute allergic reaction due to milk proteins contaminating lactose added to corticosteroid for injection. Allergol Int. 2009;58:137-139.
9. Levy Y, Segal N, Nahum A, et al. Hypersensitivity to methylprednisolone sodium succinate in children with milk allergy. J Allergy Clin Immunol Pract. 2014;2:471-474.
THE CASE
A 24-year-old man with no past medical history was referred to a nephrologist for a 5-month history of leg swelling and weight gain. His only medication was furosemide 40 mg/d, prescribed by his primary care physician. His physical examination was unremarkable except for lower extremity and scrotal edema.
Laboratory values included a creatinine of 0.8 mg/dL (reference range, 0.6 to 1.2 mg/dL); hemoglobin concentration, 14.4 g/dL (reference range, 14 to 18 g/dL); albumin, 1.9 g/dL (reference range, 3.5 to 5.5 g/dL); and glucose, 80 mg/dL (reference range, 74 to 106 mg/dL). Electrolyte levels were normal. Urinalysis revealed 3+ blood and 4+ protein on dipstick, as well as the presence of granular and lipid casts on microscopic exam. A 24-hour urine collection contained 10.5 g of protein. Antinuclear antibody titers, complement levels, hepatitis serologies, and antineutrophil cytoplasmic antibody titers were all normal.
A renal biopsy revealed idiopathic focal segmental glomerulosclerosis. The patient was started on oral prednisone 40 mg twice daily.
Two days later, he developed a diffuse pruritic maculopapular rash. He stopped taking the prednisone, and the rash resolved over the next 3 to 5 days. He was then instructed to restart the prednisone for his nephrotic syndrome. When he developed a new but similar rash, the prednisone was discontinued. The rash again resolved.
THE DIAGNOSIS
Since the patient had already been taking furosemide for 6 weeks without an adverse reaction, it was presumed that the prednisone tablet was causing his rash. It would be unusual for prednisone itself to cause a drug eruption, so an additive or coloring agent in the tablet was thought to be responsible for the reaction.
We noted that the patient had been taking a 20-mg orange tablet of prednisone. So we opted to “tweak” the prescription and prescribe the same daily dose but in the form of 10-mg white tablets. The patient tolerated this new regimen without any adverse effects and completed a full 9 months of prednisone therapy without any recurrence of skin lesions. His glomerular disease went into remission.
DISCUSSION
Excipients are inert substances that are added to a food or drug to provide the desired consistency, appearance, or form. They are also used as a preservative for substance stabilization.
Continue to: There are many reports in the literature...
There are many reports in the literature of adverse reactions to excipients.1-3 These include skin rashes induced by the coloring agent in the capsule shell of rifampicin2 and a rash that developed from a coloring agent in oral iron.3 Other reports have noted dyes in foods and even toothpaste as triggers.4,5
Hypersensitivity. Although a specific reaction to prednisone was considered unlikely in this case, type IV delayed hypersensitivity reactions to corticosteroids have been reported. The most common type of corticosteroid-related allergy is contact dermatitis associated with topical corticosteroid use.6 Many cases of delayed maculopapular reactions are thought to be T-cell–mediated type IV reactions.6
Type I immediate hypersensitivity reactions to corticosteroids are also well documented. In a literature review of 120 immediate hypersensitivity reactions to corticosteroids, anaphylactic symptoms were more commonly reported than urticaria or angioedema.7 Intravenous exposure was most frequently associated with reactions, followed by the intra-articular and oral routes of administration.7
Causative agents. The same literature review identified methylprednisolone as the most common steroid to cause a reaction; dexamethasone and prednisone were the least frequently associated with reactions.7 Pharmacologically inactive ingredients were implicated in 28% of the corticosteroid hypersensitivity reactions.7
Additives suspected to be triggers include succinate and phosphate esters, carboxymethylcellulose, polyethylene glycol, and lactose. Interestingly, there have been reports of acute allergic reactions to methylprednisolone sodium succinate 40 mg/mL intravenous preparation in children with milk allergy, due to lactose contaminated with milk protein.8,9
Continue to: Yellow dye was to blame
Yellow dye was to blame. In our case, the 20-mg tablet that the patient had been taking contained the coloring agent FD&C yellow #6, an azo dye also known as sunset yellow or E-110 in Europe. Several reports have described adverse reactions to this coloring agent.1,3 There were other additives in the 20-mg tablet, but a comparison revealed that the 10-mg tablet contained identical substances—but no dye. Thus, it was most likely that the coloring agent was the cause of the patient’s probable type IV exanthematous drug reaction.
Our patient
The patient was instructed to avoid all medications and food containing FD&C yellow #6. No formal allergy testing or re-challenge was performed, since the patient did well under the care of his nephrologist.
THE TAKEAWAY
It’s important to recognize that adverse drug reactions can occur from any medication—not only from the drug itself, but also from excipients contained within. This case reminds us that when a patient complains of an adverse effect to a medication, dyes and inactive ingredients need to be considered as possible inciting agents.
CORRESPONDENCE
Neil E. Soifer, MD, Lakeside Nephrology, 2277 West Howard, Chicago, IL 60645; nsoifer@aol.com
THE CASE
A 24-year-old man with no past medical history was referred to a nephrologist for a 5-month history of leg swelling and weight gain. His only medication was furosemide 40 mg/d, prescribed by his primary care physician. His physical examination was unremarkable except for lower extremity and scrotal edema.
Laboratory values included a creatinine of 0.8 mg/dL (reference range, 0.6 to 1.2 mg/dL); hemoglobin concentration, 14.4 g/dL (reference range, 14 to 18 g/dL); albumin, 1.9 g/dL (reference range, 3.5 to 5.5 g/dL); and glucose, 80 mg/dL (reference range, 74 to 106 mg/dL). Electrolyte levels were normal. Urinalysis revealed 3+ blood and 4+ protein on dipstick, as well as the presence of granular and lipid casts on microscopic exam. A 24-hour urine collection contained 10.5 g of protein. Antinuclear antibody titers, complement levels, hepatitis serologies, and antineutrophil cytoplasmic antibody titers were all normal.
A renal biopsy revealed idiopathic focal segmental glomerulosclerosis. The patient was started on oral prednisone 40 mg twice daily.
Two days later, he developed a diffuse pruritic maculopapular rash. He stopped taking the prednisone, and the rash resolved over the next 3 to 5 days. He was then instructed to restart the prednisone for his nephrotic syndrome. When he developed a new but similar rash, the prednisone was discontinued. The rash again resolved.
THE DIAGNOSIS
Since the patient had already been taking furosemide for 6 weeks without an adverse reaction, it was presumed that the prednisone tablet was causing his rash. It would be unusual for prednisone itself to cause a drug eruption, so an additive or coloring agent in the tablet was thought to be responsible for the reaction.
We noted that the patient had been taking a 20-mg orange tablet of prednisone. So we opted to “tweak” the prescription and prescribe the same daily dose but in the form of 10-mg white tablets. The patient tolerated this new regimen without any adverse effects and completed a full 9 months of prednisone therapy without any recurrence of skin lesions. His glomerular disease went into remission.
DISCUSSION
Excipients are inert substances that are added to a food or drug to provide the desired consistency, appearance, or form. They are also used as a preservative for substance stabilization.
Continue to: There are many reports in the literature...
There are many reports in the literature of adverse reactions to excipients.1-3 These include skin rashes induced by the coloring agent in the capsule shell of rifampicin2 and a rash that developed from a coloring agent in oral iron.3 Other reports have noted dyes in foods and even toothpaste as triggers.4,5
Hypersensitivity. Although a specific reaction to prednisone was considered unlikely in this case, type IV delayed hypersensitivity reactions to corticosteroids have been reported. The most common type of corticosteroid-related allergy is contact dermatitis associated with topical corticosteroid use.6 Many cases of delayed maculopapular reactions are thought to be T-cell–mediated type IV reactions.6
Type I immediate hypersensitivity reactions to corticosteroids are also well documented. In a literature review of 120 immediate hypersensitivity reactions to corticosteroids, anaphylactic symptoms were more commonly reported than urticaria or angioedema.7 Intravenous exposure was most frequently associated with reactions, followed by the intra-articular and oral routes of administration.7
Causative agents. The same literature review identified methylprednisolone as the most common steroid to cause a reaction; dexamethasone and prednisone were the least frequently associated with reactions.7 Pharmacologically inactive ingredients were implicated in 28% of the corticosteroid hypersensitivity reactions.7
Additives suspected to be triggers include succinate and phosphate esters, carboxymethylcellulose, polyethylene glycol, and lactose. Interestingly, there have been reports of acute allergic reactions to methylprednisolone sodium succinate 40 mg/mL intravenous preparation in children with milk allergy, due to lactose contaminated with milk protein.8,9
Continue to: Yellow dye was to blame
Yellow dye was to blame. In our case, the 20-mg tablet that the patient had been taking contained the coloring agent FD&C yellow #6, an azo dye also known as sunset yellow or E-110 in Europe. Several reports have described adverse reactions to this coloring agent.1,3 There were other additives in the 20-mg tablet, but a comparison revealed that the 10-mg tablet contained identical substances—but no dye. Thus, it was most likely that the coloring agent was the cause of the patient’s probable type IV exanthematous drug reaction.
Our patient
The patient was instructed to avoid all medications and food containing FD&C yellow #6. No formal allergy testing or re-challenge was performed, since the patient did well under the care of his nephrologist.
THE TAKEAWAY
It’s important to recognize that adverse drug reactions can occur from any medication—not only from the drug itself, but also from excipients contained within. This case reminds us that when a patient complains of an adverse effect to a medication, dyes and inactive ingredients need to be considered as possible inciting agents.
CORRESPONDENCE
Neil E. Soifer, MD, Lakeside Nephrology, 2277 West Howard, Chicago, IL 60645; nsoifer@aol.com
1. Swerlick RA, Campbell CF. Medication dyes as a source of drug allergy. J Drugs Dermatol. 2013;12:99-102.
2. Calişkaner Z, Oztürk S, Karaayvaz M. Not all adverse drug reactions originate from active component: coloring agent-induced skin eruption in a patient treated with rifampicin. Allergy. 2003;58:1077-1079.
3. Rogkakou A, Guerra L, Scordamaglia A, et al. Severe skin reaction to excipients of an oral iron treatment. Allergy. 2007;62:334-335.
4. Zaknun D, Schroecksnadel S, Kurz K, et al. Potential role of antioxidant food supplements, preservatives and colorants in the pathogenesis of allergy and asthma. Int Arch Allergy Immunol. 2012;157:113-124.
5. Barbaud A. Place of excipients in systemic drug allergy. Immunol Allergy Clin N Am. 2014;34:671-679.
6. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105:259-273.
7. Patel A, Bahna S. Immediate hypersensitivity reactions to corticosteroids. Ann Allergy Asthma Immunol. 2015;115:178-182.
8. Eda A, Sugai K, Shioya H, et al. Acute allergic reaction due to milk proteins contaminating lactose added to corticosteroid for injection. Allergol Int. 2009;58:137-139.
9. Levy Y, Segal N, Nahum A, et al. Hypersensitivity to methylprednisolone sodium succinate in children with milk allergy. J Allergy Clin Immunol Pract. 2014;2:471-474.
1. Swerlick RA, Campbell CF. Medication dyes as a source of drug allergy. J Drugs Dermatol. 2013;12:99-102.
2. Calişkaner Z, Oztürk S, Karaayvaz M. Not all adverse drug reactions originate from active component: coloring agent-induced skin eruption in a patient treated with rifampicin. Allergy. 2003;58:1077-1079.
3. Rogkakou A, Guerra L, Scordamaglia A, et al. Severe skin reaction to excipients of an oral iron treatment. Allergy. 2007;62:334-335.
4. Zaknun D, Schroecksnadel S, Kurz K, et al. Potential role of antioxidant food supplements, preservatives and colorants in the pathogenesis of allergy and asthma. Int Arch Allergy Immunol. 2012;157:113-124.
5. Barbaud A. Place of excipients in systemic drug allergy. Immunol Allergy Clin N Am. 2014;34:671-679.
6. Joint Task Force on Practice Parameters; American Academy of Allergy, Asthma and Immunology; American College of Allergy, Asthma and Immunology; Joint Council of Allergy, Asthma and Immunology. Drug allergy: an updated practice parameter. Ann Allergy Asthma Immunol. 2010;105:259-273.
7. Patel A, Bahna S. Immediate hypersensitivity reactions to corticosteroids. Ann Allergy Asthma Immunol. 2015;115:178-182.
8. Eda A, Sugai K, Shioya H, et al. Acute allergic reaction due to milk proteins contaminating lactose added to corticosteroid for injection. Allergol Int. 2009;58:137-139.
9. Levy Y, Segal N, Nahum A, et al. Hypersensitivity to methylprednisolone sodium succinate in children with milk allergy. J Allergy Clin Immunol Pract. 2014;2:471-474.
Do cinnamon supplements improve glycemic control in adults with T2DM?
EVIDENCE SUMMARY
A 2013 systematic review of 10 randomized controlled trials (RCTs) with a total of 543 patients with type 2 diabetes evaluated the effect of cinnamon (120 mg/d to 6 g/d) on measures of glycemic control.1 Study duration ranged from 4 to 18 weeks. Fasting glucose levels demonstrated small but statistically significant reductions (−24.6 mg/dL; 95% confidence interval [CI], −40.5 to −8.7 mg/dL), whereas hemoglobin A1C levels didn’t differ between treatment and control groups (−0.16%; 95% CI, −0.39% to 0.02%). Study limitations included heterogeneity of cinnamon dosing and formulation and concurrent use of oral hypoglycemic agents.
Studies of glycemic control produce mixed results
A 2012 systematic review of 10 RCTs comprising 577 patients with type 1 (72 patients) or type 2 (505 patients) diabetes evaluated the effects of cinnamon supplements (mean dose, 1.9 g/d) on glycemic control compared with placebo, active control, or no treatment.2 Study duration ranged from 4.3 to 16 weeks (mean, 10.8 weeks). Studies evaluating hemoglobin A1C lasted at least 12 weeks.
Fasting glucose as measured in 8 studies (338 patients) and hemoglobin A1C as measured in 6 studies (405 patients) didn’t differ between treatment groups (mean fasting glucose difference = −0.91 mmol/L; 95% CI, −1.93 to 0.11; mean hemoglobin A1C difference = −0.06; 95% CI, −0.29 to 0.18). The risk for bias was assessed as high or unclear in 8 studies and moderate in 2 studies.
A 2012 systematic review and meta-analysis of 6 RCTs including 435 patients with type 2 diabetes evaluated the impact of cinnamon supplements (1 to 6 g/d) on glycemic control.3 Participants consumed cinnamon for 40 to 160 days. Hemoglobin A1C decreased by 0.09% (95% CI, 0.04% to 0.14%) in 5 trials (375 patients), and fasting glucose decreased by 0.84 mmol/L (CI, 0.66 to 1.02) in 5 trials (326 patients). Study limitations included heterogeneity of cinnamon dosing and study population.
RECOMMENDATIONS
The American Diabetes Association finds insufficient evidence to support the use of herbs or spices, including cinnamon, in treating diabetes.4
Editor’s Takeaway
Meta-analyses of multiple small, lower-quality studies yield uncertain conclusions. If cinnamon does improve glycemic control, the benefit is minimal—but so is therisk.
1. Allen RW, Schwartzman E, Baker WL, et al. Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. Ann Fam Med. 2013;11:452-459.
2. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Database Syst Rev. 2012;(9):CD007170.
3. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: systematic review and meta-analysis. Clin Nutr. 2012;31:609-615.
4. American Diabetes Association. Standards of medical care in diabetes—2017. 4. Lifestyle management. Diabetes Care. 2017;40(suppl 1):S33-S43.
EVIDENCE SUMMARY
A 2013 systematic review of 10 randomized controlled trials (RCTs) with a total of 543 patients with type 2 diabetes evaluated the effect of cinnamon (120 mg/d to 6 g/d) on measures of glycemic control.1 Study duration ranged from 4 to 18 weeks. Fasting glucose levels demonstrated small but statistically significant reductions (−24.6 mg/dL; 95% confidence interval [CI], −40.5 to −8.7 mg/dL), whereas hemoglobin A1C levels didn’t differ between treatment and control groups (−0.16%; 95% CI, −0.39% to 0.02%). Study limitations included heterogeneity of cinnamon dosing and formulation and concurrent use of oral hypoglycemic agents.
Studies of glycemic control produce mixed results
A 2012 systematic review of 10 RCTs comprising 577 patients with type 1 (72 patients) or type 2 (505 patients) diabetes evaluated the effects of cinnamon supplements (mean dose, 1.9 g/d) on glycemic control compared with placebo, active control, or no treatment.2 Study duration ranged from 4.3 to 16 weeks (mean, 10.8 weeks). Studies evaluating hemoglobin A1C lasted at least 12 weeks.
Fasting glucose as measured in 8 studies (338 patients) and hemoglobin A1C as measured in 6 studies (405 patients) didn’t differ between treatment groups (mean fasting glucose difference = −0.91 mmol/L; 95% CI, −1.93 to 0.11; mean hemoglobin A1C difference = −0.06; 95% CI, −0.29 to 0.18). The risk for bias was assessed as high or unclear in 8 studies and moderate in 2 studies.
A 2012 systematic review and meta-analysis of 6 RCTs including 435 patients with type 2 diabetes evaluated the impact of cinnamon supplements (1 to 6 g/d) on glycemic control.3 Participants consumed cinnamon for 40 to 160 days. Hemoglobin A1C decreased by 0.09% (95% CI, 0.04% to 0.14%) in 5 trials (375 patients), and fasting glucose decreased by 0.84 mmol/L (CI, 0.66 to 1.02) in 5 trials (326 patients). Study limitations included heterogeneity of cinnamon dosing and study population.
RECOMMENDATIONS
The American Diabetes Association finds insufficient evidence to support the use of herbs or spices, including cinnamon, in treating diabetes.4
Editor’s Takeaway
Meta-analyses of multiple small, lower-quality studies yield uncertain conclusions. If cinnamon does improve glycemic control, the benefit is minimal—but so is therisk.
EVIDENCE SUMMARY
A 2013 systematic review of 10 randomized controlled trials (RCTs) with a total of 543 patients with type 2 diabetes evaluated the effect of cinnamon (120 mg/d to 6 g/d) on measures of glycemic control.1 Study duration ranged from 4 to 18 weeks. Fasting glucose levels demonstrated small but statistically significant reductions (−24.6 mg/dL; 95% confidence interval [CI], −40.5 to −8.7 mg/dL), whereas hemoglobin A1C levels didn’t differ between treatment and control groups (−0.16%; 95% CI, −0.39% to 0.02%). Study limitations included heterogeneity of cinnamon dosing and formulation and concurrent use of oral hypoglycemic agents.
Studies of glycemic control produce mixed results
A 2012 systematic review of 10 RCTs comprising 577 patients with type 1 (72 patients) or type 2 (505 patients) diabetes evaluated the effects of cinnamon supplements (mean dose, 1.9 g/d) on glycemic control compared with placebo, active control, or no treatment.2 Study duration ranged from 4.3 to 16 weeks (mean, 10.8 weeks). Studies evaluating hemoglobin A1C lasted at least 12 weeks.
Fasting glucose as measured in 8 studies (338 patients) and hemoglobin A1C as measured in 6 studies (405 patients) didn’t differ between treatment groups (mean fasting glucose difference = −0.91 mmol/L; 95% CI, −1.93 to 0.11; mean hemoglobin A1C difference = −0.06; 95% CI, −0.29 to 0.18). The risk for bias was assessed as high or unclear in 8 studies and moderate in 2 studies.
A 2012 systematic review and meta-analysis of 6 RCTs including 435 patients with type 2 diabetes evaluated the impact of cinnamon supplements (1 to 6 g/d) on glycemic control.3 Participants consumed cinnamon for 40 to 160 days. Hemoglobin A1C decreased by 0.09% (95% CI, 0.04% to 0.14%) in 5 trials (375 patients), and fasting glucose decreased by 0.84 mmol/L (CI, 0.66 to 1.02) in 5 trials (326 patients). Study limitations included heterogeneity of cinnamon dosing and study population.
RECOMMENDATIONS
The American Diabetes Association finds insufficient evidence to support the use of herbs or spices, including cinnamon, in treating diabetes.4
Editor’s Takeaway
Meta-analyses of multiple small, lower-quality studies yield uncertain conclusions. If cinnamon does improve glycemic control, the benefit is minimal—but so is therisk.
1. Allen RW, Schwartzman E, Baker WL, et al. Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. Ann Fam Med. 2013;11:452-459.
2. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Database Syst Rev. 2012;(9):CD007170.
3. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: systematic review and meta-analysis. Clin Nutr. 2012;31:609-615.
4. American Diabetes Association. Standards of medical care in diabetes—2017. 4. Lifestyle management. Diabetes Care. 2017;40(suppl 1):S33-S43.
1. Allen RW, Schwartzman E, Baker WL, et al. Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. Ann Fam Med. 2013;11:452-459.
2. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Database Syst Rev. 2012;(9):CD007170.
3. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: systematic review and meta-analysis. Clin Nutr. 2012;31:609-615.
4. American Diabetes Association. Standards of medical care in diabetes—2017. 4. Lifestyle management. Diabetes Care. 2017;40(suppl 1):S33-S43.
EVIDENCE-BASED ANSWER:
The answer isn’t clear. Cinnamon supplements for adults with type 2 diabetes haven’t been shown to decrease hemoglobin A1C (strength of recommendation [SOR]: C, multiple systematic reviews of disease-oriented outcomes).
Cinnamon supplements have shown inconsistent effects on fasting glucose levels (SOR: C, multiple systematic reviews and a single meta-analysis of disease-oriented outcomes). Supplements decreased fasting glucose levels in some studies, but the evidence isn’t consistent and hasn’t been correlated with clinically significant improvements in glycemic control.
