Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) were 69% less likely to develop interstitial lung disease (ILD), compared with those treated with adalimumab (Humira), according to a new retrospective study.

About 10% of RA patients develop ILD, but data on how different biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) may affect the risk of developing ILD is lacking, the authors wrote. Identifying treatments that may have protective effects could be useful when prescribing treatments for patients with RA who are at higher risk for ILD, first author Matthew C. Baker, MD, clinical chief in the division of immunology and rheumatology at Stanford (Calif.) University, said in an interview.

In the analysis, published in JAMA Network Open researchers used the Optum Clinformatics Data Mart to identify claims data for patients with RA who were taking b/tsDMARDs from December 2003 to December 2019. Patients were excluded if they had a preexisting diagnosis of ILD or if they had less than 1 year of continuous enrollment in the data set.

The researchers identified 28,559 patients with RA who were treated with adalimumab (13,326), abatacept (Orencia; 5,676), rituximab (Rituxan; 5,444), tocilizumab (Actemra; 2,548), and tofacitinib (1,565). More than three-fourths of patients were female (78%), and their average age was 55.6 years old. During the study period, 276 developed ILD. An adjusted model showed a 69% lower incidence of ILD in patients treated with tofacitinib, compared with those treated with adalimumab (adjusted hazard ratio, 0.31; 95% confidence interval, 0.12-0.78; P = .009). An additional sensitivity analysis also showed a similar reduction in ILD risk in those taking tofacitinib, compared with adalimumab (aHR, 0.32; 95% CI, 0.13-0.82; P < .001). There was no significant difference in risk of developing ILD in the abatacept, rituximab, or tocilizumab groups, compared with the adalimumab group.

“Patients who generally looked similar with RA, but were given different treatments, had different risks of developing ILD,” Dr. Baker said. “Based on what we found, most of the biologic therapies had similar rates of developing ILD, but the JAK inhibitor tofacitinib had a reduced risk.” Additional research is necessary to see if tofacitinib shows the same benefit in prospective studies, he said.

“Even though this wasn’t a clinical trial, it suggested that one of the medications that we use to treat RA could potentially prevent the development of ILD,” Elizabeth Volkmann, MD, codirector of the Connective Tissue Disease-Related Interstitial Lung Disease Program at the University of California, Los Angeles, told this news organization. She was not involved with the study.

With retrospective studies, it is difficult to account for all confounding factors, even with adjusted models, she said. For example, the authors did not have data on patients’ history of smoking, a known risk factor for ILD that could have affected which treatment was selected, they acknowledged. The tofacitinib group was also smaller than other treatment groups, which “may have contributed to a small number of events,” the authors wrote. “However, the follow-up time was similar across all groups, and we used Cox proportional hazard models to investigate the association between time-to-event and use of treatment while controlling for the other baseline characteristics.”

Both Dr. Baker and Dr. Volkmann agreed that future research could also investigate whether tofacitinib prevents the progression of ILD in patients with RA who already have the lung condition. “That’s never been looked at before,” Dr. Volkmann said.

Dr. Baker and a coauthor received support for this work from grants from the National Institutes of Health. Dr. Baker and Dr. Volkmann report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

A version of this article originally appeared on Medscape.com.

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

A version of this article originally appeared on Medscape.com.

NEW ORLEANS – The efficacy and safety of Janus kinase (JAK) inhibitors for hair regrowth in adults with alopecia areata were reinforced by new results from clinical trials of two drugs presented at a late-breaker research session at the annual meeting of the American Academy of Dermatology.

Based on phase 3 studies that document robust hair growth in about one third of patients, deuruxolitinib (CTP-543), an inhibitor of the JAK1 and JAK2 enzymes, has the potential to become the second JAK inhibitor available for the treatment of alopecia areata. If approved, it will join baricitinib (Olumiant), which received U.S. approval almost 1 year ago.

In his talk on THRIVE-AA2, a phase 3 trial of the investigational medicine deuruxolitinib, the principal investigator, Brett A. King, MD, PhD, displayed several before-and-after photos and said, “The photos tell the whole story. This is why there is so much excitement about these drugs.”

THRIVE-AA2 was the second of two phase 3 studies of deuruxolitinib. King was a principal investigator for both pivotal trials, called THRIVE-AA1 and THRIVE AA-2. He characterized the results of the two THRIVE trials as “comparable.”

Dr. King also was a principal investigator for the trials with baricitinib, called BRAVE-AA1 and BRAVE AA-2, which were published last year in the New England Journal of Medicine. The trials for both drugs had similar designs and endpoints.
 

Deuruxolitinib and the THRIVE studies

In the THRIVE-AA2 trial, 517 adult patients were enrolled with moderate to severe alopecia areata, defined as a SALT (Severity of Alopecia Tool) score of ≥ 50%, which signifies a hair loss of at least 50%. Like THRIVE-AA1, patients participated at treatment centers in North America and Europe. About two-thirds were female. The mean age was 39 years. The majority of patients had complete or near complete hair loss at baseline.

“Many of these patients are the ones we have historically characterized as having alopecia totalis or universalis,” Dr. King said.

Participating patients were randomly assigned to 8 mg deuruxolitinib twice daily, 12 mg deuruxolitinib twice daily, or placebo. The primary endpoint was a SALT score of ≤ 20% at week 24.

At 24 weeks, almost no patients in the placebo group (1%) vs. 33% and 38% in the 8 mg and 12 mg twice-daily groups, respectively, met the primary endpoint. Each active treatment group was highly significant vs. placebo.

Of the responders, the majority achieved complete or near complete hair growth as defined by a SALT score of ≤ 10%, Dr. King reported.

Based on a graph that showed a relatively steep climb over the entire 24-week study period, deuruxolitinib “had a really fast onset of action,” Dr. King said. By week 8, which was the time of the first assessment, both doses of deuruxolitinib were superior to placebo.

The majority of patients had complete or significant loss of eyebrows and eye lashes at baseline, but more than two-thirds of these patients had regrowth by week 24, Dr. King said. Again, no significant regrowth was observed in the placebo arm.

On the Satisfaction of Hair Patient Reported Outcomes (SPRO), more than half of patients on both doses reported being satisfied or very satisfied with the improvement when evaluated at 24 weeks.

“The patient satisfaction overshot what one would expect by looking at the SALT scores, but a lot of subjects were at the precipice of the primary endpoint, sitting on SALT scores of 21, 25, or 30,” Dr. King said.
 

High participation in extension trial

More than 90% of the patients assigned to deuruxolitinib completed the trial and have entered an open-label extension (OLE). Dr. King credited the substantial rates of hair growth and the low rate of significant adverse events for the high rate of transition to OLE. Those who experienced the response were motivated to maintain it.  

“This is a devastating disease. Patients want to get better,” Dr. King said.

There were no serious treatment-emergent adverse events associated with deuruxolitinib, including no thromboembolic events or other off-target events that have been reported previously with other JAK inhibitors in other disease states, such as rheumatoid arthritis. Although some adverse events, such as nasopharyngitis, were observed more often in those taking deuruxolitinib than placebo, there were “very few” discontinuations because of an adverse event, he said.

The data of THRIVE-AA2 are wholly compatible with the previously reported 706-patient THRIVE-AA1, according to Dr. King. In THRIVE-AA1, the primary endpoint of SALT ≤ 20% was reached by 29.6%, 41.5%, and 0.8% of the 8 mg, 12 mg, and placebo groups, respectively. Patient satisfaction scores, safety, and tolerability were also similar, according to Dr. King.

The experience with deuruxolitinib in the THRIVE-AA phase 3 program is similar to the experience with baricitinib in the BRAVE-AA trials. Although they cannot be compared directly because of potential differences between study populations, the 4-mg dose of baricitinib also achieved SALT score ≤ 20 in about 35% of patients, he said. The proportion was lower in the 2-mg group but was also superior to the placebo group.

“JAK inhibitors are changing the paradigm of alopecia areata,” Dr. King said. Responding to a question about payers reluctant to reimburse therapies for a “cosmetic” condition, Dr. King added that the effective treatments are “changing the landscape of how we think about this disease.” Dr. King believes these kinds of data show that “we are literally transforming lives forever.”
 

Baricitinib and the BRAVE studies

When baricitinib received regulatory approval for alopecia areata last year, it was not just the first JAK inhibitor approved for this disease, but the first systemic therapy of any kind, according to Maryanne Senna, MD, an assistant professor of dermatology at Harvard Medical School, Boston, and the director of the Lahey Hair Loss Center of Excellence, Burlington, Mass. Dr. Senna was a clinical investigator of BRAVE-AA1, as well as of THRIVE-AA2.

Providing an update on the BRAVE-AA program, Dr. Senna reported 104-week data that appear to support the idea of a life-changing benefit from JAK inhibitor therapy. This is because the effects appear durable.

In the data she presented at the AAD, responders and mixed responders at 52 weeks were followed to 104 weeks. Mixed responders were defined as those without a SALT response of ≤ 20 at week 52 but who had achieved this degree of hair regrowth at some earlier point.

Of the responders, 90% maintained their response at 104 weeks. In addition, many of the mixed responders and patients with a partial response but who never achieved a SALT score ≤ 20% gained additional hair growth, including complete or near complete hair growth, when maintained on treatment over the 2 years of follow-up.

“The follow-up suggests that, if you keep patients on treatment, you can get many of them to a meaningful response,” she said.

Meanwhile, “there have been no new safety signals,” Dr. Senna said. She based this statement not only of the 104-week data but on follow-up of up to 3.6 years among patients who have remained on treatment after participating in previous studies.

According to Dr. Senna, the off-target events that have been reported previously in other diseases with other JAK inhibitors, such as major adverse cardiovascular events and thromboembolic events, have not so far been observed in the BRAVE-AA phase 3 program.

Baricitinib, much like all but one of the JAK inhibitors with dermatologic indications, carries a black box warning that lists multiple risks for drugs in this class, based on a rheumatoid arthritis study.

The Food and Drug Administration has granted deuruxolitinib Breakthrough Therapy designation for the treatment of adult patients with moderate to severe alopecia areata and Fast Track designation for the treatment of alopecia areata, according to its manufacturer Concert Pharmaceuticals.

Dr. King reports financial relationships with more than 15 pharmaceutical companies, including Concert Pharmaceuticals, which provided the funding for the THRIVE-AA trial program, and for Eli Lilly, which provided funding for the BRAVE-AA trial program. Dr. Senna reports financial relationships with Arena pharmaceuticals, Follica, and both Concert Pharmaceuticals and Eli Lilly.

A version of this article originally appeared on Medscape.com.

Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.

The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.

“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.

The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.

Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”

“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.

“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.

“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.

Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.

He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.

“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.

But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
 

‘Denosumab is a more potent antiresorptive than bisphosphonates’

Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.

Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.

Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.

After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.

Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.

Similar results were found for hip and vertebral fractures analyzed individually.  

Women had a lower mortality risk than men.

Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.

Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”

The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.

The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.

“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.

The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.

Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”

“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.

“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.

“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.

Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.

He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.

“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.

But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
 

‘Denosumab is a more potent antiresorptive than bisphosphonates’

Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.

Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.

Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.

After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.

Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.

Similar results were found for hip and vertebral fractures analyzed individually.  

Women had a lower mortality risk than men.

Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.

Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”

The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Long-term osteoporosis medications are associated with a reduced mortality risk following a fracture, new data suggest.

The findings, from nearly 50,000 individuals in a nationwide Taiwanese database from 2009 until 2018, suggest that alendronate/risedronate, denosumab, and zoledronic acid all result in a significantly lower mortality risk post fracture of 17%-22%, compared with raloxifene and bazedoxifene.

“Treatment for osteoporosis has the potential to minimize mortality risk in people of all ages and sexes for any type of fracture. The longer-acting treatments could lower mortality risk,” wrote Chih-Hsing Wu, MD, of the Institute of Gerontology at National Cheng Kung University, Tainan, Taiwan, and colleagues.

The findings have been published online in the Journal of Clinical Endocrinology and Metabolism.

Robert A. Adler, MD, who is chief of endocrinology at the Central Virginia Veterans Affairs Health Care System, Richmond, told this news organization that he hopes these new findings from a “really good database ... may be helpful in talking to a patient about the pros and cons of taking these drugs.”

“Patients have been made very fearful of the unusual side effects, particularly of the antiresorptive drugs,” which he notes include the rare adverse effects of jaw necrosis and atypical femoral fracture, which occur in about 1 per 10,000 patient-years.

“And because of that we have a hard time convincing people to want to take the drug in the first place or to stay on the drug once they start,” said Dr. Adler, who stressed that his viewpoints are his own and not representative of the VA.

“These data should help reinforce the advice already given in professional guidelines that their benefit outweighs any risks,” he stresses.

Dr. Adler also pointed out that both bisphosphonates included in the study, alendronate and zoledronic acid, are now available as generics and therefore inexpensive, but the latter can be subject to facility fees depending on where the infusion is delivered.

He added that hip fracture, in particular, triples the overall 1-year mortality risk in women aged 75-84 years and quadruples the risk in men. The study’s findings suggest that bisphosphonates, in particular, have pleiotropic effects beyond the bone; however, the underlying mechanisms are hard to determine.

“We don’t know all the reasons why people die after a fracture. These are older people who often have multiple medical problems, so it’s hard to dissect that out,” he said.

But whatever the mechanism for the salutary effect of the drugs, Dr. Adler said: “This is one other factor that might change people’s minds. You’re less likely to die. Well, that’s pretty good.”
 

‘Denosumab is a more potent antiresorptive than bisphosphonates’

Dr. Wu and colleagues analyzed data for individuals from Taiwan’s National Health Insurance Research Database. Between 2009 and 2017, 219,461 individuals had been newly diagnosed with an osteoporotic fracture. Of those, 46,729 were aged 40 and older and had been prescribed at least one anti-osteoporosis medication.

Participants were a mean age of 74.5 years, were 80% women, and 32% died during a mean follow-up of 4.7 years. The most commonly used anti-osteoporosis medications were the bisphosphonates alendronate or risedronate, followed by denosumab and the selective estrogen-receptor modulators (SERMs) daily oral raloxifene or bazedoxifene.

Patients treated with SERMs were used as the reference group because those drugs have been shown to have a neutral effect on mortality.

After adjustments, all but one of the medications had significantly lower mortality risks during follow-up, compared with raloxifene and bazedoxifene.

Compared with SERMs, at all fracture sites, the hazard ratios for mortality were 0.83 for alendronate/risedronate, 0.86 for denosumab, and 0.78 for zoledronic acid. Only ibandronate did not show the same protective effect.

Similar results were found for hip and vertebral fractures analyzed individually.  

Women had a lower mortality risk than men.

Dr. Adler wrote an accompanying editorial for the article by Dr. Wu and colleagues.

Regarding the finding of benefit for denosumab, Dr. Adler notes: “I don’t know of another study that found denosumab leads to lower mortality. On the other hand, denosumab is a more potent antiresorptive than bisphosphonates.”

The study was funded by research grants from the Ministry of Science and Technology, Taiwan, partially supported by a research grant from the Taiwanese Osteoporosis Association and grants from National Cheng Kung University Hospital, Taiwan. Dr. Wu has reported receiving honoraria for lectures, attending meetings, and/or travel from Eli Lilly, Roche, Amgen, Merck, Servier, GE Lunar, Harvester, TCM Biotech, and Alvogen/Lotus. Dr. Adler has reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Ascend Laboratories is recalling 10 lots of the oral anticoagulant dabigatran etexilate capsules (75 mg and 150 mg) because of unacceptable levels of a potential carcinogen.

The nationwide recall, to the consumer level, is because of the detection of the nitrosamine impurity, N-nitroso-dabigatran, which may increase the risk of cancer with prolonged exposure to levels higher than acceptable.

To date, Ascend Laboratories has not received any reports of adverse events related to this recall.

The recalled product was distributed nationwide to wholesalers, distributors, and retailers in the United States from June 2022 to October 2022.

Complete details of the recalled product, including national drug code, lot numbers, expiration dates, and configuration/counts, are provided in a company announcement that was posted on the Food and Drug Administration website.

The company is advising patients who have any dabigatran that has been recalled to continue taking their medication and to contact their physician for advice regarding an alternative treatment.

Wholesalers/distributors and pharmacies with an existing inventory of the affected lots should stop use and distribution and quarantine the product immediately. Wholesalers and distributors should also recall the distributed product.

Questions regarding this recall can call Ascend Laboratories at 877.272.7901 (24 hours, 7 days a week).

Problems with this product should be reported to the FDA through MedWatch, its adverse event reporting program.

A version of this article originally appeared on Medscape.com.

Ascend Laboratories is recalling 10 lots of the oral anticoagulant dabigatran etexilate capsules (75 mg and 150 mg) because of unacceptable levels of a potential carcinogen.

The nationwide recall, to the consumer level, is because of the detection of the nitrosamine impurity, N-nitroso-dabigatran, which may increase the risk of cancer with prolonged exposure to levels higher than acceptable.

To date, Ascend Laboratories has not received any reports of adverse events related to this recall.

The recalled product was distributed nationwide to wholesalers, distributors, and retailers in the United States from June 2022 to October 2022.

Complete details of the recalled product, including national drug code, lot numbers, expiration dates, and configuration/counts, are provided in a company announcement that was posted on the Food and Drug Administration website.

The company is advising patients who have any dabigatran that has been recalled to continue taking their medication and to contact their physician for advice regarding an alternative treatment.

Wholesalers/distributors and pharmacies with an existing inventory of the affected lots should stop use and distribution and quarantine the product immediately. Wholesalers and distributors should also recall the distributed product.

Questions regarding this recall can call Ascend Laboratories at 877.272.7901 (24 hours, 7 days a week).

Problems with this product should be reported to the FDA through MedWatch, its adverse event reporting program.

A version of this article originally appeared on Medscape.com.

Ascend Laboratories is recalling 10 lots of the oral anticoagulant dabigatran etexilate capsules (75 mg and 150 mg) because of unacceptable levels of a potential carcinogen.

The nationwide recall, to the consumer level, is because of the detection of the nitrosamine impurity, N-nitroso-dabigatran, which may increase the risk of cancer with prolonged exposure to levels higher than acceptable.

To date, Ascend Laboratories has not received any reports of adverse events related to this recall.

The recalled product was distributed nationwide to wholesalers, distributors, and retailers in the United States from June 2022 to October 2022.

Complete details of the recalled product, including national drug code, lot numbers, expiration dates, and configuration/counts, are provided in a company announcement that was posted on the Food and Drug Administration website.

The company is advising patients who have any dabigatran that has been recalled to continue taking their medication and to contact their physician for advice regarding an alternative treatment.

Wholesalers/distributors and pharmacies with an existing inventory of the affected lots should stop use and distribution and quarantine the product immediately. Wholesalers and distributors should also recall the distributed product.

Questions regarding this recall can call Ascend Laboratories at 877.272.7901 (24 hours, 7 days a week).

Problems with this product should be reported to the FDA through MedWatch, its adverse event reporting program.

A version of this article originally appeared on Medscape.com.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

DENVER – The relationship between nighttime knee pain from osteoarthritis and sleep disturbances is more complex than a simple association, according to new research presented at the Osteoarthritis Research Society International 2023 World Congress.

The findings suggested that the association between knee OA pain and sleep problems was also linked to activities of daily living, which can contribute to pain but are also affected by OA, Takahiro Sasahara, of the department of orthopedics at Juntendo University, Tokyo, and Koshigaya Municipal Hospital, Saitama, Japan, told attendees. The study also found that knee pain and mobility impairment were associated with sleep disturbances in older adults regardless of the severity of knee OA.

Luisa Cedin, a PhD student at Rush University, Chicago, who attended the presentation, noted the clinical implications of the interaction of daily activities with knee pain.

”I’m a physical therapist, and this could have a significant impact on the performance of the exercises that I’m requiring as a physical therapist,” Ms. Cedin said in an interview. “When you ask somebody who is not getting enough rest during the night – not only enough time but enough quality of rest – we know that we can expect a lower performance with any type of exercises, whether it’s less strength or force, less power, less agility, or less resistance or endurance, so this has a big impact on their quality of life.”

Mr. Sasahara cited research noting that acute pain occurs at the beginning of movement and during weight bearing and walking while chronic pain frequently occurs at night and in early morning awakenings. The prevalence of sleep disturbances in patients with chronic pain ranges from 50% to 80%, he said, and past evidence has shown the relationship between sleep and pain to be bidirectional.

For example, insomnia frequency and severity, sleep-onset problems, and sleep efficiency are all positively associated with pain sensitivity, and increasing severity of OA is linked to increasing prevalence of night knee pain and sleep problems, affecting quality of life, he said.

In this new study examining the relationship between sleep disturbance and knee pain and mobility, the researchers focused specifically on a population of older adults with knee OA. They analyzed data from the Bunkyo Health Study, which was conducted at Juntendo University’s Sportology Center to examine the association between metabolic, cardiovascular, cognitive dysfunction, and motor organ disorders in older adults from November 2015 to September 2018.

From the initial population of 1,630 adults, aged 65-84, who did not need medical treatment because of knee pain, the researchers analyzed data from 1,145 adults who the met this study’s criteria, which included MRI imaging of medial type knee OA. A little over half (55.7%) were women, with an average age of 73 and an average body mass index (BMI) of 22.8 kg/m².

In addition to blood and urine sampling, the researchers determined the severity of knee OA based on joint space width, femorotibial angle, and Kellgren and Lawrence (K/L) grade from x-rays in standing position. They also assessed the structure of knee OA using a whole-organ MRI score (WORMS), and pain and mobility with a visual analog scale, the Japan Knee Osteoarthritis Measure (JKOM), and the 25-question geriatric locomotive function scale.

The JKOM, based on the Western Ontario and McMaster Universities quality of life index for general knee OA, is adjusted to account for the Japanese lifestyle and covers four categories: knee pain and stiffness, a score for activities of daily living, a social activities score, and the patient’s health conditions.

Overall, 41.3% of the participants had sleep disturbances, based on a score of 6 or higher on the Pittsburgh Sleep Quality Index–Japanese. More women (55.7%) than men experienced sleep problems (P < .001), but there were no significant differences in the average age between those who did and those who did not have sleep issues. There were also no significance differences in BMI, joint space width, or femorotibial angle, which was an average 177.5 degrees in group with no sleep problems and 177.6 degrees in the group with sleep disturbances.

The proportion of participants experiencing sleep disturbances increased with increasing K/L grade of OA: 56.8% of those with K/L grade 4 had sleep problems, compared with 40.9% of those with K/L grade 3, 42.1% of those with K/L grade 2, and 33.7% of those with K/L grade 1, resulting in 30% greater odds of sleep disturbance with a higher K/L grade (odds ratio, 1.3; P = .011).

Knee pain at night was also significantly associated with severity of OA based on the K/L grade. While only 6.9% of participants reported pain at night overall, nearly 1 in 3 (29.5%) of those with K/L grade 4 reported pain at night, compared with 3.4% of those with K/L grade 1 (P < .001). (Night pain occurred in 5.4% of those with K/L grade 2 and 16.1% with K/L grade 3.)

However, after adjusting for age, gender, and BMI, the severity of knee OA was not significantly associated with sleep disturbance based on K/L grade, joint space width, femoro-tibial angle, and/or WORMS. But knee pain remained significantly associated with sleep disturbance after adjustment based on the visual analog scale and the JKOM (P < .001 for both).

Sleep problems were also significantly associated with each subcategory of the JKOM after adjustment (P < .001 for all but social activities, which was P = .014).

“Activities of daily living may affect the occurrence of knee pain at night,” Mr. Sasahara said, and “sleep disturbance may also disturb quality of life.” If sleep disturbances related to nighttime knee pain are linked to activities of daily living, then “not only knee pain but also activities of daily living need to be improved in order to improve sleep.”

He noted several of the study’s limitations, including the fact that lifestyle habits and work were not taken into account, nor did the researchers evaluate sleep disturbances potentially resulting from a medical illness. The researchers also only examined knee pain, not pain in other parts of the body.

The research was funded by Juntendo University; the Strategic Research Foundation at Private Universities; KAKENHI from the Ministry of Education, Culture, Sports, Science and Technology of Japan; the Mizuno Sports Promotion Foundation; and the Mitsui Life Social Welfare Foundation. Mr. Sasahara and Ms. Cedin had no disclosures.

An electronic nose effectively detected Staphylococcus aureus in children with cystic fibrosis, based on data from 100 individuals.

Staphylococcus aureus is the most common pathogen found in children with cystic fibrosis (CF), but current detection strategies are based on microbiology cultures, wrote Johann-Christoph Licht, a medical student at the University of Toronto, and colleagues.

Noninvasive tools are needed to screen children with CF early for respiratory infections, the researchers said.

The electronic Nose (eNose) is a technology that detects volatile organic compounds (VOCs). Although exhaled breath can be used to create distinct profiles, the ability of eNose to identify S. aureus (SA) in the breath of children with CF remains unclear, they wrote.

In a study published in the Journal of Cystic Fibrosis, the researchers analyzed breath profiles data from 100 children with CF. The study population included children aged 5-18 years with clinically stable CF who were recruited from CF clinics during routine visits. Patients with a CF pulmonary exacerbation were excluded.

The children’s median predicted FEV₁ was 91%. The researchers collected sputum from 67 patients and throat cultures for 33 patients. A group of 25 age-matched healthy controls served for comparison.

Eighty patients were positive for CF pathogens. Of these, 67 were positive for SA (44 with SA only and 23 with SA and at least one other pathogen).

Overall, patients with any CF pathogen on airway cultures were identified compared to airway cultures with no CF pathogens with an area under the curve accuracy of 79.0%.

Previous studies have shown a high rate of accuracy using eNose to detect Pseudomonas aeruginosa (PA). In the current study, the area under the curve accuracy for PA infection compared to no CF pathogens was 78%. Both SA-specific and PA-specific signatures were driven by different sensors in the eNose, which suggests pathogen-specific breath signatures, the researchers wrote.

The study findings were limited by several factors including the small number of patients with positive airway cultures for PA and the lack of data on variability of measures over time or treatment-induced changes, the researchers noted.

However, the results confirm the value of the eNose in real-time point-of-care detection of airway infection in children with CF, and this is the first study known to suggest the potential of an eNose to detect SA infection in particular in a routine clinical setting, the researchers wrote in their discussion.

Other points in favor of eNose compared to current practice include “low cost, ease of use and portability to the point-of-care,” they said. The eNose provides an opportunity for early detection of pathogens that challenges conventional microbiology testing, they concluded.

The study received no outside funding. Two coauthors disclosed fees and/or an interest in the company Breathomix BV.

An electronic nose effectively detected Staphylococcus aureus in children with cystic fibrosis, based on data from 100 individuals.

Staphylococcus aureus is the most common pathogen found in children with cystic fibrosis (CF), but current detection strategies are based on microbiology cultures, wrote Johann-Christoph Licht, a medical student at the University of Toronto, and colleagues.

Noninvasive tools are needed to screen children with CF early for respiratory infections, the researchers said.

The electronic Nose (eNose) is a technology that detects volatile organic compounds (VOCs). Although exhaled breath can be used to create distinct profiles, the ability of eNose to identify S. aureus (SA) in the breath of children with CF remains unclear, they wrote.

In a study published in the Journal of Cystic Fibrosis, the researchers analyzed breath profiles data from 100 children with CF. The study population included children aged 5-18 years with clinically stable CF who were recruited from CF clinics during routine visits. Patients with a CF pulmonary exacerbation were excluded.

The children’s median predicted FEV₁ was 91%. The researchers collected sputum from 67 patients and throat cultures for 33 patients. A group of 25 age-matched healthy controls served for comparison.

Eighty patients were positive for CF pathogens. Of these, 67 were positive for SA (44 with SA only and 23 with SA and at least one other pathogen).

Overall, patients with any CF pathogen on airway cultures were identified compared to airway cultures with no CF pathogens with an area under the curve accuracy of 79.0%.

Previous studies have shown a high rate of accuracy using eNose to detect Pseudomonas aeruginosa (PA). In the current study, the area under the curve accuracy for PA infection compared to no CF pathogens was 78%. Both SA-specific and PA-specific signatures were driven by different sensors in the eNose, which suggests pathogen-specific breath signatures, the researchers wrote.

The study findings were limited by several factors including the small number of patients with positive airway cultures for PA and the lack of data on variability of measures over time or treatment-induced changes, the researchers noted.

However, the results confirm the value of the eNose in real-time point-of-care detection of airway infection in children with CF, and this is the first study known to suggest the potential of an eNose to detect SA infection in particular in a routine clinical setting, the researchers wrote in their discussion.

Other points in favor of eNose compared to current practice include “low cost, ease of use and portability to the point-of-care,” they said. The eNose provides an opportunity for early detection of pathogens that challenges conventional microbiology testing, they concluded.

The study received no outside funding. Two coauthors disclosed fees and/or an interest in the company Breathomix BV.

An electronic nose effectively detected Staphylococcus aureus in children with cystic fibrosis, based on data from 100 individuals.

Staphylococcus aureus is the most common pathogen found in children with cystic fibrosis (CF), but current detection strategies are based on microbiology cultures, wrote Johann-Christoph Licht, a medical student at the University of Toronto, and colleagues.

Noninvasive tools are needed to screen children with CF early for respiratory infections, the researchers said.

The electronic Nose (eNose) is a technology that detects volatile organic compounds (VOCs). Although exhaled breath can be used to create distinct profiles, the ability of eNose to identify S. aureus (SA) in the breath of children with CF remains unclear, they wrote.

In a study published in the Journal of Cystic Fibrosis, the researchers analyzed breath profiles data from 100 children with CF. The study population included children aged 5-18 years with clinically stable CF who were recruited from CF clinics during routine visits. Patients with a CF pulmonary exacerbation were excluded.

The children’s median predicted FEV₁ was 91%. The researchers collected sputum from 67 patients and throat cultures for 33 patients. A group of 25 age-matched healthy controls served for comparison.

Eighty patients were positive for CF pathogens. Of these, 67 were positive for SA (44 with SA only and 23 with SA and at least one other pathogen).

Overall, patients with any CF pathogen on airway cultures were identified compared to airway cultures with no CF pathogens with an area under the curve accuracy of 79.0%.

Previous studies have shown a high rate of accuracy using eNose to detect Pseudomonas aeruginosa (PA). In the current study, the area under the curve accuracy for PA infection compared to no CF pathogens was 78%. Both SA-specific and PA-specific signatures were driven by different sensors in the eNose, which suggests pathogen-specific breath signatures, the researchers wrote.

The study findings were limited by several factors including the small number of patients with positive airway cultures for PA and the lack of data on variability of measures over time or treatment-induced changes, the researchers noted.

However, the results confirm the value of the eNose in real-time point-of-care detection of airway infection in children with CF, and this is the first study known to suggest the potential of an eNose to detect SA infection in particular in a routine clinical setting, the researchers wrote in their discussion.

Other points in favor of eNose compared to current practice include “low cost, ease of use and portability to the point-of-care,” they said. The eNose provides an opportunity for early detection of pathogens that challenges conventional microbiology testing, they concluded.

The study received no outside funding. Two coauthors disclosed fees and/or an interest in the company Breathomix BV.

SAN FRANCISCO – No one yet has figured out how to shrink doctors so they can make house calls inside the human blood stream as they did in the science fiction movie “Fantastic Voyage.” But the founders of a gastroenterology startup think they have the next best thing – a remote-controlled robot so small it can be swallowed like a pill.

The concept captured the imagination of a panel of judges earlier this month at the 2023 American Gastroenterological Association Tech Summit where it was named the winner of the annual Shark Tank innovation competition. The AGA Tech Summit and Shark Tank are the flagship events of the AGA Center for GI Innovation and Technology.

“This could be a game-changing investment down the line,” one of the judges, Amrita Sethi, MD, from Columbia University Medical Center in New York, said in an interview.

Vidyard Video

COURTESY AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Hawyard, Calif.–based Endiatx is early in its voyage. The disposable motorized pill, called PillBot, swims through the stomach beaming video back to its operators, but CEO Torrey Smith, an aerospace engineer, sees future generations of the device operating on any diseased tissues that can be treated with surgery. “We believe teeny robots can go anywhere in the body,” he said.

The company executives envision that one day, robots small enough to enter the human brain will be able to eat away at tumors. “Imagine having your brain surgery while you’re on a ride at Disneyland,” said Endiatx cofounder and chair Alex Luebke. If that sounds fanciful, Mr. Smith cites a case report of a botfly larva that wormed its way into a human skull and ate a golf-ball sized chunk of brain.

Endiatx has raised $3 million and sent 24 of its robots swimming into the stomachs of its founding team. Mr. Smith himself has swallowed 15. Operators can use an external device with a joystick. Engineers have experimented with an Xbox video game controller to navigate around the stomach. The procedure requires no anesthesia.

The company expects to apply for Food and Drug Administration approval in 2025 or 2026. Mr. Smith is hoping the agency will approve it quickly because the robot pills are similar enough to passive camera pills that have been on the market for years.

But he also sees it as a crucial step forward because controlling the robot with three electric motors squirting water in six directions will allow physicians to point it at what they really need to see, not just hope to get a lucky shot of a problem area as the device floats by.

The most immediate technical challenge is improving the quality of the pill’s video. “We’re evaluating different cameras but we know we can’t be inferior on the imaging side,” Mr. Smith said.

Attention from the AGA is crucial because the team of engineers wants physicians to help it improve the robot pill, Mr. Luebeke said. “We can build anything, but we need guidance about what the market needs. Doctors have to say, ‘We need you to tweak it this way or that way.’ ”

The business opportunity is large, Mr. Smith said, with 7.5 million upper endoscopies out of 223 million endoscopic procedures done per year in the United States.

Endiatx figures the gross margin on procedures with the robot pills is 90%-95% because the manufacturing cost is about $50 per pill, but physicians can bill $500 for them using existing CPT codes for passive pill cameras.

Dr. Sethi said the robot pill stood out among other contenders because of the dire need for improved endoscopy technology.

Endiatx will represent AGA at the 2023 Digestive Disease Week® (DDW) Shark Tank pitch competition.

 

 

Four other finalists

The choice that received the most votes from the audience was Ezalife’s Button Huggie, a device for securing gastrostomy and cecostomy buttons. It includes a reusable, child-proof lid with a disposable, biodegradable, gauze sponge and a base layer held in place with a long-wearing adhesive. This prevents button movement in the tract, which can delay wound healing and lead to complications. In addition, the Button Huggie is much easier to put in place. “Our device is novel, with no direct competitors,” said CTO/COO Tyler Mironuck.

Currently patients are advised to fasten gastrostomy and cecostomy buttons with tape, but the buttons are dislodged 7% of the time, he said. The company estimates that patients spend an average of $100 a month on tape and gauze. The Button Huggie can be manufactured for $56, and the company envisions selling them for $300.

The device is exempt from needing a 510K FDA approval, so it can get to the market quickly. Nevertheless, the company is conducting a clinical trial with 200 patients at five children’s hospitals, Mr. Mironuck said.

NovaScan was a finalist for nsCanary, a device that uses electrical impedance to detect cancer. The device hinges on the company’s discovery that the Cole relaxation frequency is orders of magnitude different for cancerous and benign tissue, yet not affected by mass. By measuring this frequency, the nsCanary can find cancer in tissue acquired through biopsy forceps, snare polypectomy, mucosal resection, and endoscopic ultrasound-guided fine needle biopsy. It works in seconds without the need to interpret images.

Atlas Endoscopy was recognized for REN, a robotic colonoscopy system. The operator uses an external actuating magnet above the patient to guide a disposable ultracompliant endoscope through the colon. The company says this form of navigation prevents looping, reduces pain, and minimizes tissue stress.

Limaca Medical was recognized for Precision, a motorized, automated, rotational cutting and coring needle for endoscopic ultrasound biopsy. Manual biopsy needles now on the market require repeat passes in and out of the endoscope to obtain fragments of tissue, but Precision obtains larger intact samples of tumor tissue in a single pass.

Dr. Sethi has served as a consultant for Boston Scientific, Medtronic and Olympus; as a board member for EndoSound and has received grant support from FUJIFILM.
 

SAN FRANCISCO – No one yet has figured out how to shrink doctors so they can make house calls inside the human blood stream as they did in the science fiction movie “Fantastic Voyage.” But the founders of a gastroenterology startup think they have the next best thing – a remote-controlled robot so small it can be swallowed like a pill.

The concept captured the imagination of a panel of judges earlier this month at the 2023 American Gastroenterological Association Tech Summit where it was named the winner of the annual Shark Tank innovation competition. The AGA Tech Summit and Shark Tank are the flagship events of the AGA Center for GI Innovation and Technology.

“This could be a game-changing investment down the line,” one of the judges, Amrita Sethi, MD, from Columbia University Medical Center in New York, said in an interview.

Vidyard Video

COURTESY AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Hawyard, Calif.–based Endiatx is early in its voyage. The disposable motorized pill, called PillBot, swims through the stomach beaming video back to its operators, but CEO Torrey Smith, an aerospace engineer, sees future generations of the device operating on any diseased tissues that can be treated with surgery. “We believe teeny robots can go anywhere in the body,” he said.

The company executives envision that one day, robots small enough to enter the human brain will be able to eat away at tumors. “Imagine having your brain surgery while you’re on a ride at Disneyland,” said Endiatx cofounder and chair Alex Luebke. If that sounds fanciful, Mr. Smith cites a case report of a botfly larva that wormed its way into a human skull and ate a golf-ball sized chunk of brain.

Endiatx has raised $3 million and sent 24 of its robots swimming into the stomachs of its founding team. Mr. Smith himself has swallowed 15. Operators can use an external device with a joystick. Engineers have experimented with an Xbox video game controller to navigate around the stomach. The procedure requires no anesthesia.

The company expects to apply for Food and Drug Administration approval in 2025 or 2026. Mr. Smith is hoping the agency will approve it quickly because the robot pills are similar enough to passive camera pills that have been on the market for years.

But he also sees it as a crucial step forward because controlling the robot with three electric motors squirting water in six directions will allow physicians to point it at what they really need to see, not just hope to get a lucky shot of a problem area as the device floats by.

The most immediate technical challenge is improving the quality of the pill’s video. “We’re evaluating different cameras but we know we can’t be inferior on the imaging side,” Mr. Smith said.

Attention from the AGA is crucial because the team of engineers wants physicians to help it improve the robot pill, Mr. Luebeke said. “We can build anything, but we need guidance about what the market needs. Doctors have to say, ‘We need you to tweak it this way or that way.’ ”

The business opportunity is large, Mr. Smith said, with 7.5 million upper endoscopies out of 223 million endoscopic procedures done per year in the United States.

Endiatx figures the gross margin on procedures with the robot pills is 90%-95% because the manufacturing cost is about $50 per pill, but physicians can bill $500 for them using existing CPT codes for passive pill cameras.

Dr. Sethi said the robot pill stood out among other contenders because of the dire need for improved endoscopy technology.

Endiatx will represent AGA at the 2023 Digestive Disease Week® (DDW) Shark Tank pitch competition.

 

 

Four other finalists

The choice that received the most votes from the audience was Ezalife’s Button Huggie, a device for securing gastrostomy and cecostomy buttons. It includes a reusable, child-proof lid with a disposable, biodegradable, gauze sponge and a base layer held in place with a long-wearing adhesive. This prevents button movement in the tract, which can delay wound healing and lead to complications. In addition, the Button Huggie is much easier to put in place. “Our device is novel, with no direct competitors,” said CTO/COO Tyler Mironuck.

Currently patients are advised to fasten gastrostomy and cecostomy buttons with tape, but the buttons are dislodged 7% of the time, he said. The company estimates that patients spend an average of $100 a month on tape and gauze. The Button Huggie can be manufactured for $56, and the company envisions selling them for $300.

The device is exempt from needing a 510K FDA approval, so it can get to the market quickly. Nevertheless, the company is conducting a clinical trial with 200 patients at five children’s hospitals, Mr. Mironuck said.

NovaScan was a finalist for nsCanary, a device that uses electrical impedance to detect cancer. The device hinges on the company’s discovery that the Cole relaxation frequency is orders of magnitude different for cancerous and benign tissue, yet not affected by mass. By measuring this frequency, the nsCanary can find cancer in tissue acquired through biopsy forceps, snare polypectomy, mucosal resection, and endoscopic ultrasound-guided fine needle biopsy. It works in seconds without the need to interpret images.

Atlas Endoscopy was recognized for REN, a robotic colonoscopy system. The operator uses an external actuating magnet above the patient to guide a disposable ultracompliant endoscope through the colon. The company says this form of navigation prevents looping, reduces pain, and minimizes tissue stress.

Limaca Medical was recognized for Precision, a motorized, automated, rotational cutting and coring needle for endoscopic ultrasound biopsy. Manual biopsy needles now on the market require repeat passes in and out of the endoscope to obtain fragments of tissue, but Precision obtains larger intact samples of tumor tissue in a single pass.

Dr. Sethi has served as a consultant for Boston Scientific, Medtronic and Olympus; as a board member for EndoSound and has received grant support from FUJIFILM.
 

SAN FRANCISCO – No one yet has figured out how to shrink doctors so they can make house calls inside the human blood stream as they did in the science fiction movie “Fantastic Voyage.” But the founders of a gastroenterology startup think they have the next best thing – a remote-controlled robot so small it can be swallowed like a pill.

The concept captured the imagination of a panel of judges earlier this month at the 2023 American Gastroenterological Association Tech Summit where it was named the winner of the annual Shark Tank innovation competition. The AGA Tech Summit and Shark Tank are the flagship events of the AGA Center for GI Innovation and Technology.

“This could be a game-changing investment down the line,” one of the judges, Amrita Sethi, MD, from Columbia University Medical Center in New York, said in an interview.

Vidyard Video

COURTESY AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Hawyard, Calif.–based Endiatx is early in its voyage. The disposable motorized pill, called PillBot, swims through the stomach beaming video back to its operators, but CEO Torrey Smith, an aerospace engineer, sees future generations of the device operating on any diseased tissues that can be treated with surgery. “We believe teeny robots can go anywhere in the body,” he said.

The company executives envision that one day, robots small enough to enter the human brain will be able to eat away at tumors. “Imagine having your brain surgery while you’re on a ride at Disneyland,” said Endiatx cofounder and chair Alex Luebke. If that sounds fanciful, Mr. Smith cites a case report of a botfly larva that wormed its way into a human skull and ate a golf-ball sized chunk of brain.

Endiatx has raised $3 million and sent 24 of its robots swimming into the stomachs of its founding team. Mr. Smith himself has swallowed 15. Operators can use an external device with a joystick. Engineers have experimented with an Xbox video game controller to navigate around the stomach. The procedure requires no anesthesia.

The company expects to apply for Food and Drug Administration approval in 2025 or 2026. Mr. Smith is hoping the agency will approve it quickly because the robot pills are similar enough to passive camera pills that have been on the market for years.

But he also sees it as a crucial step forward because controlling the robot with three electric motors squirting water in six directions will allow physicians to point it at what they really need to see, not just hope to get a lucky shot of a problem area as the device floats by.

The most immediate technical challenge is improving the quality of the pill’s video. “We’re evaluating different cameras but we know we can’t be inferior on the imaging side,” Mr. Smith said.

Attention from the AGA is crucial because the team of engineers wants physicians to help it improve the robot pill, Mr. Luebeke said. “We can build anything, but we need guidance about what the market needs. Doctors have to say, ‘We need you to tweak it this way or that way.’ ”

The business opportunity is large, Mr. Smith said, with 7.5 million upper endoscopies out of 223 million endoscopic procedures done per year in the United States.

Endiatx figures the gross margin on procedures with the robot pills is 90%-95% because the manufacturing cost is about $50 per pill, but physicians can bill $500 for them using existing CPT codes for passive pill cameras.

Dr. Sethi said the robot pill stood out among other contenders because of the dire need for improved endoscopy technology.

Endiatx will represent AGA at the 2023 Digestive Disease Week® (DDW) Shark Tank pitch competition.

 

 

Four other finalists

The choice that received the most votes from the audience was Ezalife’s Button Huggie, a device for securing gastrostomy and cecostomy buttons. It includes a reusable, child-proof lid with a disposable, biodegradable, gauze sponge and a base layer held in place with a long-wearing adhesive. This prevents button movement in the tract, which can delay wound healing and lead to complications. In addition, the Button Huggie is much easier to put in place. “Our device is novel, with no direct competitors,” said CTO/COO Tyler Mironuck.

Currently patients are advised to fasten gastrostomy and cecostomy buttons with tape, but the buttons are dislodged 7% of the time, he said. The company estimates that patients spend an average of $100 a month on tape and gauze. The Button Huggie can be manufactured for $56, and the company envisions selling them for $300.

The device is exempt from needing a 510K FDA approval, so it can get to the market quickly. Nevertheless, the company is conducting a clinical trial with 200 patients at five children’s hospitals, Mr. Mironuck said.

NovaScan was a finalist for nsCanary, a device that uses electrical impedance to detect cancer. The device hinges on the company’s discovery that the Cole relaxation frequency is orders of magnitude different for cancerous and benign tissue, yet not affected by mass. By measuring this frequency, the nsCanary can find cancer in tissue acquired through biopsy forceps, snare polypectomy, mucosal resection, and endoscopic ultrasound-guided fine needle biopsy. It works in seconds without the need to interpret images.

Atlas Endoscopy was recognized for REN, a robotic colonoscopy system. The operator uses an external actuating magnet above the patient to guide a disposable ultracompliant endoscope through the colon. The company says this form of navigation prevents looping, reduces pain, and minimizes tissue stress.

Limaca Medical was recognized for Precision, a motorized, automated, rotational cutting and coring needle for endoscopic ultrasound biopsy. Manual biopsy needles now on the market require repeat passes in and out of the endoscope to obtain fragments of tissue, but Precision obtains larger intact samples of tumor tissue in a single pass.

Dr. Sethi has served as a consultant for Boston Scientific, Medtronic and Olympus; as a board member for EndoSound and has received grant support from FUJIFILM.
 

In a small cohort of patients with hematologic cancer and their caregivers, the use of a financial navigator helped secure cost savings of approximately $2,500 per person. This saving was achieved by helping participants to optimize health insurance, identify different types of assistance for out-of-pocket expenses, or apply for disability or family medical leave.

Cancer patients in the United States face complex financial issues in navigating with medical insurance companies to cover their care. This “financial toxicity” has come to be regarded as a side effect of cancer treatment.

Patients with hematologic malignancies may be particularly vulnerable to financial toxicity, owing to the nature of their treatment, which often includes bone marrow transplantation, lengthy hospital stays, and prolonged intensive follow-up, as well as potential treatment-related complications, such as graft vs. host disease.

The results from this small study suggest that using an oncology financial navigator could be helpful. But not all cancer patients have access to such a person, explained lead author Jean S. Edward, PhD, RN, associate professor in the college of nursing at the University of Kentucky, Lexington.

“Unfortunately, it’s not as common as we would like, especially in underserved areas with patient and caregiver populations that need it the most,” she said. Dr. Edward is hopeful that the results from this study, even though it is small, might help to boost use of this intervention. “OFN [oncology financial navigation] is not necessarily a cutting-edge program or ‘novel’ intervention, but the lack of programs and limitations in implementing in cancer centers does make it a gap in practice,” Dr. Edward told this news organization.

“There are gaps in evidence on how to incorporate an oncology financial navigator in current workflows and sustainability of positions, but as our study has shown, the return on investment to the health care system and/or financial benefits to patients/caregivers could help cover the cost of implementing such programs,” she said.

The study was published in JCO Oncology Practice.

The intervention used in this study, Coverage and Cost-of-Care Links (CC Links), was designed specifically to address financial toxicity among patients with hematologic cancers.

The study’s primary outcomes were defined as improvements in financial distress as well as in physical and mental quality of life.

A total of 54 patients and 32 caregivers completed the intervention and pre-/postintervention surveys. More than half of participants were women. The average age was 63 years. Less than a quarter of the patients were employed (23%), about one-third had income that was below the federal poverty level, and almost all had insurance. About 59% of the caregivers were employed.

The navigators’ functions included screening for financial toxicity using FACIT-Comprehensive Score for Financial Toxicity (COST) and the National Comprehensive Cancer Network’s Distress Thermometer and Problem List. They also helped patients to estimate cost of care, assessed health insurance coverage, and connected patients/caregivers with disease-specific resources and other external assistance programs, among other things.

Participants had an average of three in-person meetings and five telephone interactions with the financial navigator. The most common concern was in regard to high out-of-pocket costs. The most frequently provided services from the navigator were helping with financial assistance programs and grant applications. Overall, the navigator was able to obtain $124,600 in financial benefits for 48 participants, as well as money for travel ($24,000), urgent needs ($16,000), patient financial assistance ($9,100), and copay assistance grants ($75,500).

With regard to scores on the screening tools, the only significant change from pre- to postintervention was in the psychological response score, or COST. It decreased by an average of 2.30 points (P = .019; Hedges’ g = 0.33). For caregivers, there was a significant improvement in COST (average decrease, 2.97 points; P = .021; g = 0.43), material condition scores (average decrease, 0.63 points; P = .031; g = 0.39), and total financial toxicity scores (average decrease, 0.13 points; P = .041; g = 0.37).

Most of the participants gave the intervention high ratings for acceptability (89%) and appropriateness (88%).

“Standardized screening for financial toxicity in cancer care settings is essential to support early identification of financial needs that serve as barriers to care,” the authors conclude. “Close collaboration and coordination with existing services and workflows are essential for the seamless integration of OFN interventions within health systems and to help facilitate contact and communication with participants.”

The study was supported by the National Cancer Institute; the University of Kentucky’s Markey Cancer Center; the Research Communications Office of the Patient Oriented and Population Science Shared Resource Facilities; Joan Scales, LCSW, and the Psych-Oncology Program at the University of Kentucky Markey Cancer Center; and UK HealthCare’s Patient Financial Services. Dr. Edward has disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

In a small cohort of patients with hematologic cancer and their caregivers, the use of a financial navigator helped secure cost savings of approximately $2,500 per person. This saving was achieved by helping participants to optimize health insurance, identify different types of assistance for out-of-pocket expenses, or apply for disability or family medical leave.

Cancer patients in the United States face complex financial issues in navigating with medical insurance companies to cover their care. This “financial toxicity” has come to be regarded as a side effect of cancer treatment.

Patients with hematologic malignancies may be particularly vulnerable to financial toxicity, owing to the nature of their treatment, which often includes bone marrow transplantation, lengthy hospital stays, and prolonged intensive follow-up, as well as potential treatment-related complications, such as graft vs. host disease.

The results from this small study suggest that using an oncology financial navigator could be helpful. But not all cancer patients have access to such a person, explained lead author Jean S. Edward, PhD, RN, associate professor in the college of nursing at the University of Kentucky, Lexington.

“Unfortunately, it’s not as common as we would like, especially in underserved areas with patient and caregiver populations that need it the most,” she said. Dr. Edward is hopeful that the results from this study, even though it is small, might help to boost use of this intervention. “OFN [oncology financial navigation] is not necessarily a cutting-edge program or ‘novel’ intervention, but the lack of programs and limitations in implementing in cancer centers does make it a gap in practice,” Dr. Edward told this news organization.

“There are gaps in evidence on how to incorporate an oncology financial navigator in current workflows and sustainability of positions, but as our study has shown, the return on investment to the health care system and/or financial benefits to patients/caregivers could help cover the cost of implementing such programs,” she said.

The study was published in JCO Oncology Practice.

The intervention used in this study, Coverage and Cost-of-Care Links (CC Links), was designed specifically to address financial toxicity among patients with hematologic cancers.

The study’s primary outcomes were defined as improvements in financial distress as well as in physical and mental quality of life.

A total of 54 patients and 32 caregivers completed the intervention and pre-/postintervention surveys. More than half of participants were women. The average age was 63 years. Less than a quarter of the patients were employed (23%), about one-third had income that was below the federal poverty level, and almost all had insurance. About 59% of the caregivers were employed.

The navigators’ functions included screening for financial toxicity using FACIT-Comprehensive Score for Financial Toxicity (COST) and the National Comprehensive Cancer Network’s Distress Thermometer and Problem List. They also helped patients to estimate cost of care, assessed health insurance coverage, and connected patients/caregivers with disease-specific resources and other external assistance programs, among other things.

Participants had an average of three in-person meetings and five telephone interactions with the financial navigator. The most common concern was in regard to high out-of-pocket costs. The most frequently provided services from the navigator were helping with financial assistance programs and grant applications. Overall, the navigator was able to obtain $124,600 in financial benefits for 48 participants, as well as money for travel ($24,000), urgent needs ($16,000), patient financial assistance ($9,100), and copay assistance grants ($75,500).

With regard to scores on the screening tools, the only significant change from pre- to postintervention was in the psychological response score, or COST. It decreased by an average of 2.30 points (P = .019; Hedges’ g = 0.33). For caregivers, there was a significant improvement in COST (average decrease, 2.97 points; P = .021; g = 0.43), material condition scores (average decrease, 0.63 points; P = .031; g = 0.39), and total financial toxicity scores (average decrease, 0.13 points; P = .041; g = 0.37).

Most of the participants gave the intervention high ratings for acceptability (89%) and appropriateness (88%).

“Standardized screening for financial toxicity in cancer care settings is essential to support early identification of financial needs that serve as barriers to care,” the authors conclude. “Close collaboration and coordination with existing services and workflows are essential for the seamless integration of OFN interventions within health systems and to help facilitate contact and communication with participants.”

The study was supported by the National Cancer Institute; the University of Kentucky’s Markey Cancer Center; the Research Communications Office of the Patient Oriented and Population Science Shared Resource Facilities; Joan Scales, LCSW, and the Psych-Oncology Program at the University of Kentucky Markey Cancer Center; and UK HealthCare’s Patient Financial Services. Dr. Edward has disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

In a small cohort of patients with hematologic cancer and their caregivers, the use of a financial navigator helped secure cost savings of approximately $2,500 per person. This saving was achieved by helping participants to optimize health insurance, identify different types of assistance for out-of-pocket expenses, or apply for disability or family medical leave.

Cancer patients in the United States face complex financial issues in navigating with medical insurance companies to cover their care. This “financial toxicity” has come to be regarded as a side effect of cancer treatment.

Patients with hematologic malignancies may be particularly vulnerable to financial toxicity, owing to the nature of their treatment, which often includes bone marrow transplantation, lengthy hospital stays, and prolonged intensive follow-up, as well as potential treatment-related complications, such as graft vs. host disease.

The results from this small study suggest that using an oncology financial navigator could be helpful. But not all cancer patients have access to such a person, explained lead author Jean S. Edward, PhD, RN, associate professor in the college of nursing at the University of Kentucky, Lexington.

“Unfortunately, it’s not as common as we would like, especially in underserved areas with patient and caregiver populations that need it the most,” she said. Dr. Edward is hopeful that the results from this study, even though it is small, might help to boost use of this intervention. “OFN [oncology financial navigation] is not necessarily a cutting-edge program or ‘novel’ intervention, but the lack of programs and limitations in implementing in cancer centers does make it a gap in practice,” Dr. Edward told this news organization.

“There are gaps in evidence on how to incorporate an oncology financial navigator in current workflows and sustainability of positions, but as our study has shown, the return on investment to the health care system and/or financial benefits to patients/caregivers could help cover the cost of implementing such programs,” she said.

The study was published in JCO Oncology Practice.

The intervention used in this study, Coverage and Cost-of-Care Links (CC Links), was designed specifically to address financial toxicity among patients with hematologic cancers.

The study’s primary outcomes were defined as improvements in financial distress as well as in physical and mental quality of life.

A total of 54 patients and 32 caregivers completed the intervention and pre-/postintervention surveys. More than half of participants were women. The average age was 63 years. Less than a quarter of the patients were employed (23%), about one-third had income that was below the federal poverty level, and almost all had insurance. About 59% of the caregivers were employed.

The navigators’ functions included screening for financial toxicity using FACIT-Comprehensive Score for Financial Toxicity (COST) and the National Comprehensive Cancer Network’s Distress Thermometer and Problem List. They also helped patients to estimate cost of care, assessed health insurance coverage, and connected patients/caregivers with disease-specific resources and other external assistance programs, among other things.

Participants had an average of three in-person meetings and five telephone interactions with the financial navigator. The most common concern was in regard to high out-of-pocket costs. The most frequently provided services from the navigator were helping with financial assistance programs and grant applications. Overall, the navigator was able to obtain $124,600 in financial benefits for 48 participants, as well as money for travel ($24,000), urgent needs ($16,000), patient financial assistance ($9,100), and copay assistance grants ($75,500).

With regard to scores on the screening tools, the only significant change from pre- to postintervention was in the psychological response score, or COST. It decreased by an average of 2.30 points (P = .019; Hedges’ g = 0.33). For caregivers, there was a significant improvement in COST (average decrease, 2.97 points; P = .021; g = 0.43), material condition scores (average decrease, 0.63 points; P = .031; g = 0.39), and total financial toxicity scores (average decrease, 0.13 points; P = .041; g = 0.37).

Most of the participants gave the intervention high ratings for acceptability (89%) and appropriateness (88%).

“Standardized screening for financial toxicity in cancer care settings is essential to support early identification of financial needs that serve as barriers to care,” the authors conclude. “Close collaboration and coordination with existing services and workflows are essential for the seamless integration of OFN interventions within health systems and to help facilitate contact and communication with participants.”

The study was supported by the National Cancer Institute; the University of Kentucky’s Markey Cancer Center; the Research Communications Office of the Patient Oriented and Population Science Shared Resource Facilities; Joan Scales, LCSW, and the Psych-Oncology Program at the University of Kentucky Markey Cancer Center; and UK HealthCare’s Patient Financial Services. Dr. Edward has disclosed no relevant financial relationships.
 

A version of this article first appeared on Medscape.com.

For women who are overdue for cervical cancer screening, mailing self-sampling kits for high-risk human papillomavirus (HPV) is a cost-effective means of increasing screening uptake, reveals an analysis of a large U.S. trial.

The finding comes from a randomized trial in almost 20,000 women, which compared women who received a mailed HPV testing kit with those who did not. The results show that mailing was most cost-effective in women aged 50-64 years and in those who were only recently overdue for cervical screening.

The study was published by JAMA Network Open.

“These results support mailing HPV kits as an efficient outreach strategy for increasing screening rates in U.S. health care systems,” say the authors, led by Rachel L. Winer, PhD, MPH, department of epidemiology, University of Washington, Seattle.

They note that their results are consistent with those from previous studies in other health care contexts, but their analysis “benefited from the randomized clinical trial design and a large sample size,” they write.

However, they point out that the trial was conducted “before the beginning of the COVID-19 pandemic,” and it is “well established” that cancer screening rates “decreased substantially during the pandemic.”

They suggest that mailed HPV self-sampling kits could nevertheless be a “means of overcoming screening barriers among underscreened women,” which may have been exacerbated by the “societal consequences of the pandemic.”


 

Reducing barriers to screening

Cervical screening is associated with “substantial global reductions” in the incidence and mortality of cervical cancer, the authors point out. Because most cases of the disease are consequently preventable, it now occurs “predominantly in individuals who have never or rarely received screening.”

Home-based HPV-only testing reduces the need for office visits and reduces barriers to screening, such as discomfort, embarrassment, and difficulties with scheduling or attending appointments.

Previous studies have shown that the direct mailing of home-based HPV self-collection kits is associated with increased uptake of screening among underscreened women and is cost-effective, although the researchers point out that these previous studies were conducted in countries with “organized national screening programs.”

For their own study, they focused on home-based HPV screening among underscreened individuals in the United States. The team examined data from the Home-based Options to Make cervical cancer screening Easy trial, which has previously showed that mailing kits to women increased screening uptake, compared with usual care alone.

For the current analysis, they conducted an economic evaluation of data on 19,851 trial participants, who were randomized to receive home-based screening or usual care between February 2014 and August 2016 and were followed up to February 2018.

All of the women were aged 30-64 years and had been enrolled in a health plan from Kaiser Permanente Washington (KPW) for at least 3 years and 5 months. They were also required not have undergone a hysterectomy.

Participant-level economic data were collected between June 2019 and March 2021, with intervention delivery costs calculated from the perspective of both the KPW and Medicare health systems and based on the cost of either a wellness visit or Papanicolaou (Pap) test–only visit.

The mean age of the participants was 50.1 years, and the majority (76.7%) were White; 9.7% were Asian and 4.7% were Black or African American.

There were no significant differences in baseline characteristics between the group assigned to usual care, which comprised patient reminders and ad hoc screening outreach, and those in the intervention group, who received usual care and a mailed HPV self-sampling kit.

The researchers report that 1,206 women in the intervention group sent back a mailed HPV kit, with 1,178 (97.7%) meeting the criteria for completed screening uptake.

Overall, screening uptake was higher in the intervention group than in control participants, at 26.3% vs. 17.4%, respectively (relative risk, 1.51).

Intervention participants were also more likely than controls to have a positive test result (relative risk, 1.49) and to receive treatment (relative risk, 1.70).

The incremental cost-effectiveness ratio for increased screening uptake, defined as the incremental difference in cost between the study groups divided by the difference in the number of participants completing screening within 6 months, ranged from $85.84 per additional completed screening to $146.29, depending on the health system and test considered.

In terms of willingness-to-pay (WTP) thresholds for each additional completed screening, the team found that home-based screening achieved a 90% probability of cost-effectiveness, at a WTP of just $148 if the participant’s last Pap test was between 3.4 and 5.0 years before randomization.

A 90% probability of cost-effectiveness was also achieved at a WTP of $198 among participants aged 50-64 years, a threshold that was lower than that among other age groups.

At a WTP threshold of over $350, the intervention was considered to have 100% probability of being cost-effective in all age groups.

The study was supported by a grant from the National Cancer Institute of the National Institutes of Health. Dr. Winer reports a relationship with the National Cancer Institute outside of the submitted work, as do several other authors.

A version of this article first appeared on Medscape.com.

For women who are overdue for cervical cancer screening, mailing self-sampling kits for high-risk human papillomavirus (HPV) is a cost-effective means of increasing screening uptake, reveals an analysis of a large U.S. trial.

The finding comes from a randomized trial in almost 20,000 women, which compared women who received a mailed HPV testing kit with those who did not. The results show that mailing was most cost-effective in women aged 50-64 years and in those who were only recently overdue for cervical screening.

The study was published by JAMA Network Open.

“These results support mailing HPV kits as an efficient outreach strategy for increasing screening rates in U.S. health care systems,” say the authors, led by Rachel L. Winer, PhD, MPH, department of epidemiology, University of Washington, Seattle.

They note that their results are consistent with those from previous studies in other health care contexts, but their analysis “benefited from the randomized clinical trial design and a large sample size,” they write.

However, they point out that the trial was conducted “before the beginning of the COVID-19 pandemic,” and it is “well established” that cancer screening rates “decreased substantially during the pandemic.”

They suggest that mailed HPV self-sampling kits could nevertheless be a “means of overcoming screening barriers among underscreened women,” which may have been exacerbated by the “societal consequences of the pandemic.”


 

Reducing barriers to screening

Cervical screening is associated with “substantial global reductions” in the incidence and mortality of cervical cancer, the authors point out. Because most cases of the disease are consequently preventable, it now occurs “predominantly in individuals who have never or rarely received screening.”

Home-based HPV-only testing reduces the need for office visits and reduces barriers to screening, such as discomfort, embarrassment, and difficulties with scheduling or attending appointments.

Previous studies have shown that the direct mailing of home-based HPV self-collection kits is associated with increased uptake of screening among underscreened women and is cost-effective, although the researchers point out that these previous studies were conducted in countries with “organized national screening programs.”

For their own study, they focused on home-based HPV screening among underscreened individuals in the United States. The team examined data from the Home-based Options to Make cervical cancer screening Easy trial, which has previously showed that mailing kits to women increased screening uptake, compared with usual care alone.

For the current analysis, they conducted an economic evaluation of data on 19,851 trial participants, who were randomized to receive home-based screening or usual care between February 2014 and August 2016 and were followed up to February 2018.

All of the women were aged 30-64 years and had been enrolled in a health plan from Kaiser Permanente Washington (KPW) for at least 3 years and 5 months. They were also required not have undergone a hysterectomy.

Participant-level economic data were collected between June 2019 and March 2021, with intervention delivery costs calculated from the perspective of both the KPW and Medicare health systems and based on the cost of either a wellness visit or Papanicolaou (Pap) test–only visit.

The mean age of the participants was 50.1 years, and the majority (76.7%) were White; 9.7% were Asian and 4.7% were Black or African American.

There were no significant differences in baseline characteristics between the group assigned to usual care, which comprised patient reminders and ad hoc screening outreach, and those in the intervention group, who received usual care and a mailed HPV self-sampling kit.

The researchers report that 1,206 women in the intervention group sent back a mailed HPV kit, with 1,178 (97.7%) meeting the criteria for completed screening uptake.

Overall, screening uptake was higher in the intervention group than in control participants, at 26.3% vs. 17.4%, respectively (relative risk, 1.51).

Intervention participants were also more likely than controls to have a positive test result (relative risk, 1.49) and to receive treatment (relative risk, 1.70).

The incremental cost-effectiveness ratio for increased screening uptake, defined as the incremental difference in cost between the study groups divided by the difference in the number of participants completing screening within 6 months, ranged from $85.84 per additional completed screening to $146.29, depending on the health system and test considered.

In terms of willingness-to-pay (WTP) thresholds for each additional completed screening, the team found that home-based screening achieved a 90% probability of cost-effectiveness, at a WTP of just $148 if the participant’s last Pap test was between 3.4 and 5.0 years before randomization.

A 90% probability of cost-effectiveness was also achieved at a WTP of $198 among participants aged 50-64 years, a threshold that was lower than that among other age groups.

At a WTP threshold of over $350, the intervention was considered to have 100% probability of being cost-effective in all age groups.

The study was supported by a grant from the National Cancer Institute of the National Institutes of Health. Dr. Winer reports a relationship with the National Cancer Institute outside of the submitted work, as do several other authors.

A version of this article first appeared on Medscape.com.

For women who are overdue for cervical cancer screening, mailing self-sampling kits for high-risk human papillomavirus (HPV) is a cost-effective means of increasing screening uptake, reveals an analysis of a large U.S. trial.

The finding comes from a randomized trial in almost 20,000 women, which compared women who received a mailed HPV testing kit with those who did not. The results show that mailing was most cost-effective in women aged 50-64 years and in those who were only recently overdue for cervical screening.

The study was published by JAMA Network Open.

“These results support mailing HPV kits as an efficient outreach strategy for increasing screening rates in U.S. health care systems,” say the authors, led by Rachel L. Winer, PhD, MPH, department of epidemiology, University of Washington, Seattle.

They note that their results are consistent with those from previous studies in other health care contexts, but their analysis “benefited from the randomized clinical trial design and a large sample size,” they write.

However, they point out that the trial was conducted “before the beginning of the COVID-19 pandemic,” and it is “well established” that cancer screening rates “decreased substantially during the pandemic.”

They suggest that mailed HPV self-sampling kits could nevertheless be a “means of overcoming screening barriers among underscreened women,” which may have been exacerbated by the “societal consequences of the pandemic.”


 

Reducing barriers to screening

Cervical screening is associated with “substantial global reductions” in the incidence and mortality of cervical cancer, the authors point out. Because most cases of the disease are consequently preventable, it now occurs “predominantly in individuals who have never or rarely received screening.”

Home-based HPV-only testing reduces the need for office visits and reduces barriers to screening, such as discomfort, embarrassment, and difficulties with scheduling or attending appointments.

Previous studies have shown that the direct mailing of home-based HPV self-collection kits is associated with increased uptake of screening among underscreened women and is cost-effective, although the researchers point out that these previous studies were conducted in countries with “organized national screening programs.”

For their own study, they focused on home-based HPV screening among underscreened individuals in the United States. The team examined data from the Home-based Options to Make cervical cancer screening Easy trial, which has previously showed that mailing kits to women increased screening uptake, compared with usual care alone.

For the current analysis, they conducted an economic evaluation of data on 19,851 trial participants, who were randomized to receive home-based screening or usual care between February 2014 and August 2016 and were followed up to February 2018.

All of the women were aged 30-64 years and had been enrolled in a health plan from Kaiser Permanente Washington (KPW) for at least 3 years and 5 months. They were also required not have undergone a hysterectomy.

Participant-level economic data were collected between June 2019 and March 2021, with intervention delivery costs calculated from the perspective of both the KPW and Medicare health systems and based on the cost of either a wellness visit or Papanicolaou (Pap) test–only visit.

The mean age of the participants was 50.1 years, and the majority (76.7%) were White; 9.7% were Asian and 4.7% were Black or African American.

There were no significant differences in baseline characteristics between the group assigned to usual care, which comprised patient reminders and ad hoc screening outreach, and those in the intervention group, who received usual care and a mailed HPV self-sampling kit.

The researchers report that 1,206 women in the intervention group sent back a mailed HPV kit, with 1,178 (97.7%) meeting the criteria for completed screening uptake.

Overall, screening uptake was higher in the intervention group than in control participants, at 26.3% vs. 17.4%, respectively (relative risk, 1.51).

Intervention participants were also more likely than controls to have a positive test result (relative risk, 1.49) and to receive treatment (relative risk, 1.70).

The incremental cost-effectiveness ratio for increased screening uptake, defined as the incremental difference in cost between the study groups divided by the difference in the number of participants completing screening within 6 months, ranged from $85.84 per additional completed screening to $146.29, depending on the health system and test considered.

In terms of willingness-to-pay (WTP) thresholds for each additional completed screening, the team found that home-based screening achieved a 90% probability of cost-effectiveness, at a WTP of just $148 if the participant’s last Pap test was between 3.4 and 5.0 years before randomization.

A 90% probability of cost-effectiveness was also achieved at a WTP of $198 among participants aged 50-64 years, a threshold that was lower than that among other age groups.

At a WTP threshold of over $350, the intervention was considered to have 100% probability of being cost-effective in all age groups.

The study was supported by a grant from the National Cancer Institute of the National Institutes of Health. Dr. Winer reports a relationship with the National Cancer Institute outside of the submitted work, as do several other authors.

A version of this article first appeared on Medscape.com.

Headache treatment before the early 1990s was marked by decades of improvisation with mostly unapproved agents, followed by an explosion of scientific interest and new treatments developed specifically for migraine.

For practicing neurologists today, headache is one subspecialty in which options and opportunities abound. But this is largely thanks to the sea change that occurred 30 years ago.

In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, past president of the International Headache Society and clinical professor of neurology at UCLA’s David Geffen School of Medicine in Los Angeles, recalled what it was like to treat patients before and after triptan medications came onto the market.

After the first of these anti-migraine agents, sumatriptan, was approved by the Food and Drug Administration in late December 1992, headache specialists found themselves with a powerful, approved treatment that validated their commitment to solving the disorder, and helped put to rest a persistent but mistaken notion that migraine was a psychiatric condition affecting young women.

But in the 1970s and 1980s, “there wasn’t great science explaining the pathophysiology of common primary headaches like tension-type headache, cluster headache, and migraine,” Dr. Rapoport recalled. “There is often comorbid depression and anxiety with migraine, and sometimes more serious psychiatric disease, but it doesn’t mean migraine is caused by psychological issues. Now we see it clearly as a disease of the brain, but it took years of investigation to prove that.”
 

The early years

Dr. Rapoport’s journey with headache began in 1972, when he joined a private neurology practice in Stamford and Greenwich, Conn. Neurologists were frowned upon then for having too much interest in headache, he said. There was poor remuneration for doctors treating headache patients, who were hard to properly diagnose and effectively care for. Few medications could effectively stop a migraine attack or reliably reduce the frequency of headaches or the disability they caused.

On weekends Dr. Rapoport covered emergency departments and ICUs at three hospitals, where standard treatment for a migraine attack was injectable opiates. Not only did this treatment aggravate nausea, a common migraine symptom, “but it did not stop the migraine process.” Once the pain relief wore off, patients woke up with the same headache, Dr. Rapoport recalled. “The other drug that was available was ergotamine tartrate” – a fungal alkaloid used since medieval times to treat headache – “given sublingually. It helped the headache slightly but increased the nausea. DHE, or dihydroergotamine, was available only by injection and not used very much.”

DHE, a semi-synthetic molecule based on ergotamine, had FDA approval for migraine, but was complicated to administer. Like the opioids, it provoked vomiting when given intravenously, in patients already suffering migraine-induced nausea. But Dr. Rapoport, along with some of his colleagues, felt that there was a role for DHE for the most severe subtypes of patients, those with long histories of frequent migraines.

“We put people in the hospital and we gave them intravenous DHE. Eventually I got the idea to give it intramuscularly or subcutaneously in the emergency room or my office. When you give it that way, it doesn’t work as quickly but has fewer side effects.” Dr. Rapoport designed a cocktail by coadministering promethazine for nausea, and eventually added a steroid, dexamethasone. The triple shots worked on most patients experiencing severe daily or near-daily migraine attacks, Dr. Rapoport saw, and he began administering the drug combination at The New England Center for Headache in Stamford and Greenwich, Conn., which he opened with Dr. Fred D. Sheftell in 1979.

“The triple shots really worked,” Dr. Rapoport recalled. “There was no need to keep patients in the office or emergency room for intravenous therapy. The patients never called to complain or came back the next day,” he said, as often occurred with opioid treatment.

Dr. Rapoport had learned early in his residency, in the late 1960s, from Dr. David R. Coddon, a neurologist at Mount Sinai hospital in New York, that a tricyclic antidepressant, imipramine, could be helpful in some patients with frequent migraine attacks. As evidence trickled in that other antidepressants, beta-blockers, and antiepileptic drugs might have preventive properties, Dr. Rapoport and others prescribed them for certain patients. But of all the drugs in the headache specialists’ repertoire, few were approved for either treatment or prevention. “And this continued until the triptans,” Dr. Rapoport said.
 

The triptan era

Sumatriptan was developed by Glaxo for the acute treatment of migraine. The medication, first available only as self-administered subcutaneous injections, was originally designed to bind to vascular serotonin receptors to allow selective constriction of cranial vessels that dilate, causing pain, during a migraine attack. (Years later it was discovered that triptans also worked as anti-inflammatory agents that decreased the release of the neurotransmitter calcitonin gene-related peptide, or CGRP.)

Triptans “changed the world for migraine patients and for me,” Dr. Rapoport said. “I could now prescribe a medication that people could take at home to decrease or stop the migraine process in an hour or two.” The success of the triptans prompted pharmaceutical companies to search for new, more effective ways to treat migraine attacks, with better tolerability.

Seven different triptans were developed, some as injections or tablets and others as nasal sprays. “If one triptan didn’t work, we’d give a second and rarely a third,” Dr. Rapoport said. “We learned that if oral triptans did not work, the most likely issue was that it was not rapidly absorbed from the small intestine, as migraine patients have nausea, poor GI absorption, and slow transit times. This prompted the greater use of injections and nasal sprays.” Headache specialists began combining triptan treatment with nonsteroidal anti-inflammatory drugs, offering further relief for the acute care of migraine.
 

Medication overuse headache

The years between 1993 and 2000, which saw all the current triptan drugs come onto the market, was an exhilarating one for headache specialists. But even those who were thrilled by the possibilities of the triptans, like Dr. Rapoport, soon came to recognize their limitations, in terms of side effects and poor tolerability for some patients.

Specialists also noticed something unsettling about the triptans: that patients’ headaches seemed to recur within a day, or occur more frequently over time, with higher medication use.

Medication overuse headache (MOH) was known to occur when patients treated migraine too often with acute care medications, especially over-the-counter analgesics and prescription opioids and barbiturates. Dr. Rapoport began warning at conferences and in seminars that MOH seemed to occur with the triptans as well. “In the beginning other doctors didn’t think the triptans could cause MOH, but I observed that patients who were taking triptans daily or almost daily were having increased headache frequency and the triptans stopped being effective. If they didn’t take the drug they were overusing, they were going to get much worse, almost like a withdrawal.”

Today, all seven triptans are now generic, and they remain a mainstay of migraine treatment: “Almost all of my patients are using, or have used a triptan,” Dr. Rapoport said. Yet researchers came to recognize the need for treatments targeting different pathways, both for prevention and acute care.
 

The next revolution: CGRP and gepants

Studies in the early 2000s began to show a link between the release of one ubiquitous nervous system neurotransmitter, calcitonin gene-related peptide, or CGRP, and migraine. They also noticed that blocking meningeal inflammation could lead to improvement in headache. Two new drug classes emerged from this science: monoclonal antibodies against CGRP or its receptor that had to be given by injection, and oral CGRP receptor blockers that could be used both as a preventive or as an acute care medication.

In 2018 the first monoclonal antibody against the CGRP receptor, erenumab (Aimovig, marketed by Amgen), delivered by injection, was approved for migraine prevention. Three others followed, most given by autoinjector, and one by IV infusion in office or hospital settings. “Those drugs are great,” Dr. Rapoport said. “You take one shot a month or every 3 months, and your headaches drop by 50% or more with very few side effects. Some patients actually see their migraines disappear.”

The following year ubrogepant (Ubrelvy, marketed by AbbVie), the first of a novel class of oral CGRP receptor blockers known as “gepants,” was approved to treat acute migraine. The FDA soon approved another gepant, rimegepant (Nurtec, marketed by Pfizer), which received indications both for prevention and for stopping a migraine attack acutely.

Both classes of therapies – the antibodies and the gepants – are far costlier than the triptans, which are all generic, and may not be needed for every migraine patient. With the gepants, for example, insurers may restrict use to people who have not responded to triptans or for whom triptans are contraindicated or cause too many adverse events. But the CGRP-targeted therapies as a whole “have been every bit as revolutionary” as the triptans, Dr. Rapoport said. The treatments work quickly to resolve headache and disability and get the patient functioning within an hour or two, and there are fewer side effects.

In a review article published in CNS Drugs in 2021, Dr. Rapoport and his colleagues reported that the anti-CGRP treatment with gepants did not appear linked to medication overuse headache, as virtually all previous acute care medication classes did, and could be used in patients who had previously reported MOH. “I am confident that over the next few years, more people will be using them as insurance coverage will improve for patients living with migraine,” he said.
 

Headache treatment today

Migraine specialists and patients now have a staggering range of therapeutic options. Approved treatments now include prevention of migraine with onabotulinumtoxinA (Botox, marketed by the Allergan division of AbbVie) injections, which work alone and with other medicines; acute care treatment with ditans like lasmiditan (Reyvow, marketed by Lilly*), a category of acute care medicines that work like triptans but target different serotonin receptors. Five devices have been cleared for migraine and other types of headache by the FDA. These work alone or along with medication and can be used acutely or preventively. The devices “should be used more,” Dr. Rapoport said, but are not yet well covered by insurance.

Thirty years after the triptans, scientists and researchers continue to explore the pathophysiology of headache disorders, finding new pathways and identifying new potential targets.

“There are many parts of the brain and brain stem that are involved, as well as the thalamus and hypothalamus,” Dr. Rapoport said. “It’s interesting that the newer medications, and some of the older ones, work in the peripheral nervous system, outside the brain stem in the trigeminovascular system, to modulate the central nervous system. We also know that the CGRP system is involved with cellular second-order messengers. Stimulating and blocking this chain of reactions with newer drugs may become treatments in the future.”

Recent research has focused on a blood vessel dilating neurotransmitter, pituitary adenylate-cyclase-activating polypeptide, or PACAP-38, as a potential therapeutic target. Psychedelic medications such as psilocybin, strong pain medications such as ketamine, and even cannabinoids such as marijuana have all been investigated in migraine. Biofeedback therapies, mindfulness, and other behavioral interventions also have proved effective.

“I expect the next 2-5 years to bring us many important clinical trials on new types of pharmacological treatments,” Dr. Rapoport said. “This is a wonderful time to be a doctor or nurse treating patients living with migraine. When I started out treating headache, 51 years ago, we had only ergotamine tartrate. Today we have so many therapies and combinations of therapies that I hardly know where to start.”

Dr. Rapoport has served as a consultant to or speaker for AbbVie, Amgen, Biohaven, Cala Health, Lundbeck, Satsuma, and Teva, among others.

*Correction, 3/30/23: An earlier version of this article misstated the name of the company that markets Reyvow.

Headache treatment before the early 1990s was marked by decades of improvisation with mostly unapproved agents, followed by an explosion of scientific interest and new treatments developed specifically for migraine.

For practicing neurologists today, headache is one subspecialty in which options and opportunities abound. But this is largely thanks to the sea change that occurred 30 years ago.

In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, past president of the International Headache Society and clinical professor of neurology at UCLA’s David Geffen School of Medicine in Los Angeles, recalled what it was like to treat patients before and after triptan medications came onto the market.

After the first of these anti-migraine agents, sumatriptan, was approved by the Food and Drug Administration in late December 1992, headache specialists found themselves with a powerful, approved treatment that validated their commitment to solving the disorder, and helped put to rest a persistent but mistaken notion that migraine was a psychiatric condition affecting young women.

But in the 1970s and 1980s, “there wasn’t great science explaining the pathophysiology of common primary headaches like tension-type headache, cluster headache, and migraine,” Dr. Rapoport recalled. “There is often comorbid depression and anxiety with migraine, and sometimes more serious psychiatric disease, but it doesn’t mean migraine is caused by psychological issues. Now we see it clearly as a disease of the brain, but it took years of investigation to prove that.”
 

The early years

Dr. Rapoport’s journey with headache began in 1972, when he joined a private neurology practice in Stamford and Greenwich, Conn. Neurologists were frowned upon then for having too much interest in headache, he said. There was poor remuneration for doctors treating headache patients, who were hard to properly diagnose and effectively care for. Few medications could effectively stop a migraine attack or reliably reduce the frequency of headaches or the disability they caused.

On weekends Dr. Rapoport covered emergency departments and ICUs at three hospitals, where standard treatment for a migraine attack was injectable opiates. Not only did this treatment aggravate nausea, a common migraine symptom, “but it did not stop the migraine process.” Once the pain relief wore off, patients woke up with the same headache, Dr. Rapoport recalled. “The other drug that was available was ergotamine tartrate” – a fungal alkaloid used since medieval times to treat headache – “given sublingually. It helped the headache slightly but increased the nausea. DHE, or dihydroergotamine, was available only by injection and not used very much.”

DHE, a semi-synthetic molecule based on ergotamine, had FDA approval for migraine, but was complicated to administer. Like the opioids, it provoked vomiting when given intravenously, in patients already suffering migraine-induced nausea. But Dr. Rapoport, along with some of his colleagues, felt that there was a role for DHE for the most severe subtypes of patients, those with long histories of frequent migraines.

“We put people in the hospital and we gave them intravenous DHE. Eventually I got the idea to give it intramuscularly or subcutaneously in the emergency room or my office. When you give it that way, it doesn’t work as quickly but has fewer side effects.” Dr. Rapoport designed a cocktail by coadministering promethazine for nausea, and eventually added a steroid, dexamethasone. The triple shots worked on most patients experiencing severe daily or near-daily migraine attacks, Dr. Rapoport saw, and he began administering the drug combination at The New England Center for Headache in Stamford and Greenwich, Conn., which he opened with Dr. Fred D. Sheftell in 1979.

“The triple shots really worked,” Dr. Rapoport recalled. “There was no need to keep patients in the office or emergency room for intravenous therapy. The patients never called to complain or came back the next day,” he said, as often occurred with opioid treatment.

Dr. Rapoport had learned early in his residency, in the late 1960s, from Dr. David R. Coddon, a neurologist at Mount Sinai hospital in New York, that a tricyclic antidepressant, imipramine, could be helpful in some patients with frequent migraine attacks. As evidence trickled in that other antidepressants, beta-blockers, and antiepileptic drugs might have preventive properties, Dr. Rapoport and others prescribed them for certain patients. But of all the drugs in the headache specialists’ repertoire, few were approved for either treatment or prevention. “And this continued until the triptans,” Dr. Rapoport said.
 

The triptan era

Sumatriptan was developed by Glaxo for the acute treatment of migraine. The medication, first available only as self-administered subcutaneous injections, was originally designed to bind to vascular serotonin receptors to allow selective constriction of cranial vessels that dilate, causing pain, during a migraine attack. (Years later it was discovered that triptans also worked as anti-inflammatory agents that decreased the release of the neurotransmitter calcitonin gene-related peptide, or CGRP.)

Triptans “changed the world for migraine patients and for me,” Dr. Rapoport said. “I could now prescribe a medication that people could take at home to decrease or stop the migraine process in an hour or two.” The success of the triptans prompted pharmaceutical companies to search for new, more effective ways to treat migraine attacks, with better tolerability.

Seven different triptans were developed, some as injections or tablets and others as nasal sprays. “If one triptan didn’t work, we’d give a second and rarely a third,” Dr. Rapoport said. “We learned that if oral triptans did not work, the most likely issue was that it was not rapidly absorbed from the small intestine, as migraine patients have nausea, poor GI absorption, and slow transit times. This prompted the greater use of injections and nasal sprays.” Headache specialists began combining triptan treatment with nonsteroidal anti-inflammatory drugs, offering further relief for the acute care of migraine.
 

Medication overuse headache

The years between 1993 and 2000, which saw all the current triptan drugs come onto the market, was an exhilarating one for headache specialists. But even those who were thrilled by the possibilities of the triptans, like Dr. Rapoport, soon came to recognize their limitations, in terms of side effects and poor tolerability for some patients.

Specialists also noticed something unsettling about the triptans: that patients’ headaches seemed to recur within a day, or occur more frequently over time, with higher medication use.

Medication overuse headache (MOH) was known to occur when patients treated migraine too often with acute care medications, especially over-the-counter analgesics and prescription opioids and barbiturates. Dr. Rapoport began warning at conferences and in seminars that MOH seemed to occur with the triptans as well. “In the beginning other doctors didn’t think the triptans could cause MOH, but I observed that patients who were taking triptans daily or almost daily were having increased headache frequency and the triptans stopped being effective. If they didn’t take the drug they were overusing, they were going to get much worse, almost like a withdrawal.”

Today, all seven triptans are now generic, and they remain a mainstay of migraine treatment: “Almost all of my patients are using, or have used a triptan,” Dr. Rapoport said. Yet researchers came to recognize the need for treatments targeting different pathways, both for prevention and acute care.
 

The next revolution: CGRP and gepants

Studies in the early 2000s began to show a link between the release of one ubiquitous nervous system neurotransmitter, calcitonin gene-related peptide, or CGRP, and migraine. They also noticed that blocking meningeal inflammation could lead to improvement in headache. Two new drug classes emerged from this science: monoclonal antibodies against CGRP or its receptor that had to be given by injection, and oral CGRP receptor blockers that could be used both as a preventive or as an acute care medication.

In 2018 the first monoclonal antibody against the CGRP receptor, erenumab (Aimovig, marketed by Amgen), delivered by injection, was approved for migraine prevention. Three others followed, most given by autoinjector, and one by IV infusion in office or hospital settings. “Those drugs are great,” Dr. Rapoport said. “You take one shot a month or every 3 months, and your headaches drop by 50% or more with very few side effects. Some patients actually see their migraines disappear.”

The following year ubrogepant (Ubrelvy, marketed by AbbVie), the first of a novel class of oral CGRP receptor blockers known as “gepants,” was approved to treat acute migraine. The FDA soon approved another gepant, rimegepant (Nurtec, marketed by Pfizer), which received indications both for prevention and for stopping a migraine attack acutely.

Both classes of therapies – the antibodies and the gepants – are far costlier than the triptans, which are all generic, and may not be needed for every migraine patient. With the gepants, for example, insurers may restrict use to people who have not responded to triptans or for whom triptans are contraindicated or cause too many adverse events. But the CGRP-targeted therapies as a whole “have been every bit as revolutionary” as the triptans, Dr. Rapoport said. The treatments work quickly to resolve headache and disability and get the patient functioning within an hour or two, and there are fewer side effects.

In a review article published in CNS Drugs in 2021, Dr. Rapoport and his colleagues reported that the anti-CGRP treatment with gepants did not appear linked to medication overuse headache, as virtually all previous acute care medication classes did, and could be used in patients who had previously reported MOH. “I am confident that over the next few years, more people will be using them as insurance coverage will improve for patients living with migraine,” he said.
 

Headache treatment today

Migraine specialists and patients now have a staggering range of therapeutic options. Approved treatments now include prevention of migraine with onabotulinumtoxinA (Botox, marketed by the Allergan division of AbbVie) injections, which work alone and with other medicines; acute care treatment with ditans like lasmiditan (Reyvow, marketed by Lilly*), a category of acute care medicines that work like triptans but target different serotonin receptors. Five devices have been cleared for migraine and other types of headache by the FDA. These work alone or along with medication and can be used acutely or preventively. The devices “should be used more,” Dr. Rapoport said, but are not yet well covered by insurance.

Thirty years after the triptans, scientists and researchers continue to explore the pathophysiology of headache disorders, finding new pathways and identifying new potential targets.

“There are many parts of the brain and brain stem that are involved, as well as the thalamus and hypothalamus,” Dr. Rapoport said. “It’s interesting that the newer medications, and some of the older ones, work in the peripheral nervous system, outside the brain stem in the trigeminovascular system, to modulate the central nervous system. We also know that the CGRP system is involved with cellular second-order messengers. Stimulating and blocking this chain of reactions with newer drugs may become treatments in the future.”

Recent research has focused on a blood vessel dilating neurotransmitter, pituitary adenylate-cyclase-activating polypeptide, or PACAP-38, as a potential therapeutic target. Psychedelic medications such as psilocybin, strong pain medications such as ketamine, and even cannabinoids such as marijuana have all been investigated in migraine. Biofeedback therapies, mindfulness, and other behavioral interventions also have proved effective.

“I expect the next 2-5 years to bring us many important clinical trials on new types of pharmacological treatments,” Dr. Rapoport said. “This is a wonderful time to be a doctor or nurse treating patients living with migraine. When I started out treating headache, 51 years ago, we had only ergotamine tartrate. Today we have so many therapies and combinations of therapies that I hardly know where to start.”

Dr. Rapoport has served as a consultant to or speaker for AbbVie, Amgen, Biohaven, Cala Health, Lundbeck, Satsuma, and Teva, among others.

*Correction, 3/30/23: An earlier version of this article misstated the name of the company that markets Reyvow.

Headache treatment before the early 1990s was marked by decades of improvisation with mostly unapproved agents, followed by an explosion of scientific interest and new treatments developed specifically for migraine.

For practicing neurologists today, headache is one subspecialty in which options and opportunities abound. But this is largely thanks to the sea change that occurred 30 years ago.

In an interview, Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews, past president of the International Headache Society and clinical professor of neurology at UCLA’s David Geffen School of Medicine in Los Angeles, recalled what it was like to treat patients before and after triptan medications came onto the market.

After the first of these anti-migraine agents, sumatriptan, was approved by the Food and Drug Administration in late December 1992, headache specialists found themselves with a powerful, approved treatment that validated their commitment to solving the disorder, and helped put to rest a persistent but mistaken notion that migraine was a psychiatric condition affecting young women.

But in the 1970s and 1980s, “there wasn’t great science explaining the pathophysiology of common primary headaches like tension-type headache, cluster headache, and migraine,” Dr. Rapoport recalled. “There is often comorbid depression and anxiety with migraine, and sometimes more serious psychiatric disease, but it doesn’t mean migraine is caused by psychological issues. Now we see it clearly as a disease of the brain, but it took years of investigation to prove that.”
 

The early years

Dr. Rapoport’s journey with headache began in 1972, when he joined a private neurology practice in Stamford and Greenwich, Conn. Neurologists were frowned upon then for having too much interest in headache, he said. There was poor remuneration for doctors treating headache patients, who were hard to properly diagnose and effectively care for. Few medications could effectively stop a migraine attack or reliably reduce the frequency of headaches or the disability they caused.

On weekends Dr. Rapoport covered emergency departments and ICUs at three hospitals, where standard treatment for a migraine attack was injectable opiates. Not only did this treatment aggravate nausea, a common migraine symptom, “but it did not stop the migraine process.” Once the pain relief wore off, patients woke up with the same headache, Dr. Rapoport recalled. “The other drug that was available was ergotamine tartrate” – a fungal alkaloid used since medieval times to treat headache – “given sublingually. It helped the headache slightly but increased the nausea. DHE, or dihydroergotamine, was available only by injection and not used very much.”

DHE, a semi-synthetic molecule based on ergotamine, had FDA approval for migraine, but was complicated to administer. Like the opioids, it provoked vomiting when given intravenously, in patients already suffering migraine-induced nausea. But Dr. Rapoport, along with some of his colleagues, felt that there was a role for DHE for the most severe subtypes of patients, those with long histories of frequent migraines.

“We put people in the hospital and we gave them intravenous DHE. Eventually I got the idea to give it intramuscularly or subcutaneously in the emergency room or my office. When you give it that way, it doesn’t work as quickly but has fewer side effects.” Dr. Rapoport designed a cocktail by coadministering promethazine for nausea, and eventually added a steroid, dexamethasone. The triple shots worked on most patients experiencing severe daily or near-daily migraine attacks, Dr. Rapoport saw, and he began administering the drug combination at The New England Center for Headache in Stamford and Greenwich, Conn., which he opened with Dr. Fred D. Sheftell in 1979.

“The triple shots really worked,” Dr. Rapoport recalled. “There was no need to keep patients in the office or emergency room for intravenous therapy. The patients never called to complain or came back the next day,” he said, as often occurred with opioid treatment.

Dr. Rapoport had learned early in his residency, in the late 1960s, from Dr. David R. Coddon, a neurologist at Mount Sinai hospital in New York, that a tricyclic antidepressant, imipramine, could be helpful in some patients with frequent migraine attacks. As evidence trickled in that other antidepressants, beta-blockers, and antiepileptic drugs might have preventive properties, Dr. Rapoport and others prescribed them for certain patients. But of all the drugs in the headache specialists’ repertoire, few were approved for either treatment or prevention. “And this continued until the triptans,” Dr. Rapoport said.
 

The triptan era

Sumatriptan was developed by Glaxo for the acute treatment of migraine. The medication, first available only as self-administered subcutaneous injections, was originally designed to bind to vascular serotonin receptors to allow selective constriction of cranial vessels that dilate, causing pain, during a migraine attack. (Years later it was discovered that triptans also worked as anti-inflammatory agents that decreased the release of the neurotransmitter calcitonin gene-related peptide, or CGRP.)

Triptans “changed the world for migraine patients and for me,” Dr. Rapoport said. “I could now prescribe a medication that people could take at home to decrease or stop the migraine process in an hour or two.” The success of the triptans prompted pharmaceutical companies to search for new, more effective ways to treat migraine attacks, with better tolerability.

Seven different triptans were developed, some as injections or tablets and others as nasal sprays. “If one triptan didn’t work, we’d give a second and rarely a third,” Dr. Rapoport said. “We learned that if oral triptans did not work, the most likely issue was that it was not rapidly absorbed from the small intestine, as migraine patients have nausea, poor GI absorption, and slow transit times. This prompted the greater use of injections and nasal sprays.” Headache specialists began combining triptan treatment with nonsteroidal anti-inflammatory drugs, offering further relief for the acute care of migraine.
 

Medication overuse headache

The years between 1993 and 2000, which saw all the current triptan drugs come onto the market, was an exhilarating one for headache specialists. But even those who were thrilled by the possibilities of the triptans, like Dr. Rapoport, soon came to recognize their limitations, in terms of side effects and poor tolerability for some patients.

Specialists also noticed something unsettling about the triptans: that patients’ headaches seemed to recur within a day, or occur more frequently over time, with higher medication use.

Medication overuse headache (MOH) was known to occur when patients treated migraine too often with acute care medications, especially over-the-counter analgesics and prescription opioids and barbiturates. Dr. Rapoport began warning at conferences and in seminars that MOH seemed to occur with the triptans as well. “In the beginning other doctors didn’t think the triptans could cause MOH, but I observed that patients who were taking triptans daily or almost daily were having increased headache frequency and the triptans stopped being effective. If they didn’t take the drug they were overusing, they were going to get much worse, almost like a withdrawal.”

Today, all seven triptans are now generic, and they remain a mainstay of migraine treatment: “Almost all of my patients are using, or have used a triptan,” Dr. Rapoport said. Yet researchers came to recognize the need for treatments targeting different pathways, both for prevention and acute care.
 

The next revolution: CGRP and gepants

Studies in the early 2000s began to show a link between the release of one ubiquitous nervous system neurotransmitter, calcitonin gene-related peptide, or CGRP, and migraine. They also noticed that blocking meningeal inflammation could lead to improvement in headache. Two new drug classes emerged from this science: monoclonal antibodies against CGRP or its receptor that had to be given by injection, and oral CGRP receptor blockers that could be used both as a preventive or as an acute care medication.

In 2018 the first monoclonal antibody against the CGRP receptor, erenumab (Aimovig, marketed by Amgen), delivered by injection, was approved for migraine prevention. Three others followed, most given by autoinjector, and one by IV infusion in office or hospital settings. “Those drugs are great,” Dr. Rapoport said. “You take one shot a month or every 3 months, and your headaches drop by 50% or more with very few side effects. Some patients actually see their migraines disappear.”

The following year ubrogepant (Ubrelvy, marketed by AbbVie), the first of a novel class of oral CGRP receptor blockers known as “gepants,” was approved to treat acute migraine. The FDA soon approved another gepant, rimegepant (Nurtec, marketed by Pfizer), which received indications both for prevention and for stopping a migraine attack acutely.

Both classes of therapies – the antibodies and the gepants – are far costlier than the triptans, which are all generic, and may not be needed for every migraine patient. With the gepants, for example, insurers may restrict use to people who have not responded to triptans or for whom triptans are contraindicated or cause too many adverse events. But the CGRP-targeted therapies as a whole “have been every bit as revolutionary” as the triptans, Dr. Rapoport said. The treatments work quickly to resolve headache and disability and get the patient functioning within an hour or two, and there are fewer side effects.

In a review article published in CNS Drugs in 2021, Dr. Rapoport and his colleagues reported that the anti-CGRP treatment with gepants did not appear linked to medication overuse headache, as virtually all previous acute care medication classes did, and could be used in patients who had previously reported MOH. “I am confident that over the next few years, more people will be using them as insurance coverage will improve for patients living with migraine,” he said.
 

Headache treatment today

Migraine specialists and patients now have a staggering range of therapeutic options. Approved treatments now include prevention of migraine with onabotulinumtoxinA (Botox, marketed by the Allergan division of AbbVie) injections, which work alone and with other medicines; acute care treatment with ditans like lasmiditan (Reyvow, marketed by Lilly*), a category of acute care medicines that work like triptans but target different serotonin receptors. Five devices have been cleared for migraine and other types of headache by the FDA. These work alone or along with medication and can be used acutely or preventively. The devices “should be used more,” Dr. Rapoport said, but are not yet well covered by insurance.

Thirty years after the triptans, scientists and researchers continue to explore the pathophysiology of headache disorders, finding new pathways and identifying new potential targets.

“There are many parts of the brain and brain stem that are involved, as well as the thalamus and hypothalamus,” Dr. Rapoport said. “It’s interesting that the newer medications, and some of the older ones, work in the peripheral nervous system, outside the brain stem in the trigeminovascular system, to modulate the central nervous system. We also know that the CGRP system is involved with cellular second-order messengers. Stimulating and blocking this chain of reactions with newer drugs may become treatments in the future.”

Recent research has focused on a blood vessel dilating neurotransmitter, pituitary adenylate-cyclase-activating polypeptide, or PACAP-38, as a potential therapeutic target. Psychedelic medications such as psilocybin, strong pain medications such as ketamine, and even cannabinoids such as marijuana have all been investigated in migraine. Biofeedback therapies, mindfulness, and other behavioral interventions also have proved effective.

“I expect the next 2-5 years to bring us many important clinical trials on new types of pharmacological treatments,” Dr. Rapoport said. “This is a wonderful time to be a doctor or nurse treating patients living with migraine. When I started out treating headache, 51 years ago, we had only ergotamine tartrate. Today we have so many therapies and combinations of therapies that I hardly know where to start.”

Dr. Rapoport has served as a consultant to or speaker for AbbVie, Amgen, Biohaven, Cala Health, Lundbeck, Satsuma, and Teva, among others.

*Correction, 3/30/23: An earlier version of this article misstated the name of the company that markets Reyvow.