Ted Bosworth

MADRID – Low-dose azithromycin prophylaxis significantly reduced exacerbations and hospitalizations in patients with primary antibody deficiency relative to placebo, according to a randomized multicenter phase 2 trial.

The study results support routine use of low-dose azithromycin in patients with primary antibody deficiency, according to Cinzia Milito, MD, PhD, department of molecular medicine, Sapienza University, Rome. Perhaps more importantly, the long-term benefits might be even greater.

“In patients with primary antibody deficiency, the respiratory tract is the major target of acute infections, leading to inflammation, increased airway reactivity, and over time to tissue remodeling and chronic lung disease,” Dr. Milito said at the annual congress of the European Respiratory Society. “Chronic lung disease is a major cause of death in this population.”

In this study 89 patients with primary antibody deficiency were randomized at seven centers in Italy to 250 mg per day of azithromycin or placebo administered on three consecutive days of each week for three years. Patients were maintained on other treatments, such as IgG replacement.

At the end of study, 33 of the 44 patients randomized to azithromycin and 34 of the 45 patients randomized to placebo remained on therapy. When compared for the primary endpoint of exacerbations, the median incidence rates were 3.6 episodes in the azithromycin group and 5.2 episodes in the placebo group, providing a 1.6 episode or 31% relative reduction (P=0.02).

The median number of hospitalizations for any cause, which was a secondary endpoint, was also significantly lower in the azithromycin arm (0.1 vs. 0.3 episodes).

In addition, the number of additional courses of antibiotics was significantly lower (2.3 vs. 3.6), and the time to the first course of antibiotic course was significantly longer (181.5 vs. 122.4 days) in the azithromycin group, reported Dr. Milito, whose study is now published (Milito C et al. J Allergy Clin Immunol 2019;144: 584-593).

“In a six-month washout at the end of the study, the relative advantages seen for azithromycin were lost,” Dr. Milito said.

Quality of life measured with the St. George’s Respiratory Questionnaire showed an association between low-dose azithromycin prophylaxis and significant improvement in the symptom domain when evaluated during and at the end of the study. Improvement on the Short-Form 36, which was observed one year into the study, was no longer significant at the end of the study.

Azithromycin was well tolerated with no significant differences in the rate of serious adverse events observed between the experimental and control arms of the study. Over the course of the study, however, azithromycin was associated with a significant protective effect against diarrhea (13% vs. 53%) and acute rhinosinusitus (4% vs. 27%).

There was no observed increase in macrolide resistance associated with azithromycin prophylaxis.

Macrolides have been evaluated for preventing progression of several chronic lung diseases, including chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. Like other drugs in its class, “azithromycin, in addition to its antimicrobial effect, has anti-inflammatory properties,” Dr. Milito said. This increases its potential to slow the time to airway damage in patients with primary antibiotic deficiency.

“Chronic lung disease is the result of a vicious cycle that begins with the inflammatory response to infection,” Dr. Milito explained. On the basis of these data, she believes azithromycin “should be considered a valuable addition to usual treatment” for primary antibody deficiencies.
 

SOURCE: EUROPEAN RESPIRATORY SOCIETY 2019 INTERNATIONAL CONGRESS

MADRID – Low-dose azithromycin prophylaxis significantly reduced exacerbations and hospitalizations in patients with primary antibody deficiency relative to placebo, according to a randomized multicenter phase 2 trial.

The study results support routine use of low-dose azithromycin in patients with primary antibody deficiency, according to Cinzia Milito, MD, PhD, department of molecular medicine, Sapienza University, Rome. Perhaps more importantly, the long-term benefits might be even greater.

“In patients with primary antibody deficiency, the respiratory tract is the major target of acute infections, leading to inflammation, increased airway reactivity, and over time to tissue remodeling and chronic lung disease,” Dr. Milito said at the annual congress of the European Respiratory Society. “Chronic lung disease is a major cause of death in this population.”

In this study 89 patients with primary antibody deficiency were randomized at seven centers in Italy to 250 mg per day of azithromycin or placebo administered on three consecutive days of each week for three years. Patients were maintained on other treatments, such as IgG replacement.

At the end of study, 33 of the 44 patients randomized to azithromycin and 34 of the 45 patients randomized to placebo remained on therapy. When compared for the primary endpoint of exacerbations, the median incidence rates were 3.6 episodes in the azithromycin group and 5.2 episodes in the placebo group, providing a 1.6 episode or 31% relative reduction (P=0.02).

The median number of hospitalizations for any cause, which was a secondary endpoint, was also significantly lower in the azithromycin arm (0.1 vs. 0.3 episodes).

In addition, the number of additional courses of antibiotics was significantly lower (2.3 vs. 3.6), and the time to the first course of antibiotic course was significantly longer (181.5 vs. 122.4 days) in the azithromycin group, reported Dr. Milito, whose study is now published (Milito C et al. J Allergy Clin Immunol 2019;144: 584-593).

“In a six-month washout at the end of the study, the relative advantages seen for azithromycin were lost,” Dr. Milito said.

Quality of life measured with the St. George’s Respiratory Questionnaire showed an association between low-dose azithromycin prophylaxis and significant improvement in the symptom domain when evaluated during and at the end of the study. Improvement on the Short-Form 36, which was observed one year into the study, was no longer significant at the end of the study.

Azithromycin was well tolerated with no significant differences in the rate of serious adverse events observed between the experimental and control arms of the study. Over the course of the study, however, azithromycin was associated with a significant protective effect against diarrhea (13% vs. 53%) and acute rhinosinusitus (4% vs. 27%).

There was no observed increase in macrolide resistance associated with azithromycin prophylaxis.

Macrolides have been evaluated for preventing progression of several chronic lung diseases, including chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. Like other drugs in its class, “azithromycin, in addition to its antimicrobial effect, has anti-inflammatory properties,” Dr. Milito said. This increases its potential to slow the time to airway damage in patients with primary antibiotic deficiency.

“Chronic lung disease is the result of a vicious cycle that begins with the inflammatory response to infection,” Dr. Milito explained. On the basis of these data, she believes azithromycin “should be considered a valuable addition to usual treatment” for primary antibody deficiencies.
 

SOURCE: EUROPEAN RESPIRATORY SOCIETY 2019 INTERNATIONAL CONGRESS

MADRID – Low-dose azithromycin prophylaxis significantly reduced exacerbations and hospitalizations in patients with primary antibody deficiency relative to placebo, according to a randomized multicenter phase 2 trial.

The study results support routine use of low-dose azithromycin in patients with primary antibody deficiency, according to Cinzia Milito, MD, PhD, department of molecular medicine, Sapienza University, Rome. Perhaps more importantly, the long-term benefits might be even greater.

“In patients with primary antibody deficiency, the respiratory tract is the major target of acute infections, leading to inflammation, increased airway reactivity, and over time to tissue remodeling and chronic lung disease,” Dr. Milito said at the annual congress of the European Respiratory Society. “Chronic lung disease is a major cause of death in this population.”

In this study 89 patients with primary antibody deficiency were randomized at seven centers in Italy to 250 mg per day of azithromycin or placebo administered on three consecutive days of each week for three years. Patients were maintained on other treatments, such as IgG replacement.

At the end of study, 33 of the 44 patients randomized to azithromycin and 34 of the 45 patients randomized to placebo remained on therapy. When compared for the primary endpoint of exacerbations, the median incidence rates were 3.6 episodes in the azithromycin group and 5.2 episodes in the placebo group, providing a 1.6 episode or 31% relative reduction (P=0.02).

The median number of hospitalizations for any cause, which was a secondary endpoint, was also significantly lower in the azithromycin arm (0.1 vs. 0.3 episodes).

In addition, the number of additional courses of antibiotics was significantly lower (2.3 vs. 3.6), and the time to the first course of antibiotic course was significantly longer (181.5 vs. 122.4 days) in the azithromycin group, reported Dr. Milito, whose study is now published (Milito C et al. J Allergy Clin Immunol 2019;144: 584-593).

“In a six-month washout at the end of the study, the relative advantages seen for azithromycin were lost,” Dr. Milito said.

Quality of life measured with the St. George’s Respiratory Questionnaire showed an association between low-dose azithromycin prophylaxis and significant improvement in the symptom domain when evaluated during and at the end of the study. Improvement on the Short-Form 36, which was observed one year into the study, was no longer significant at the end of the study.

Azithromycin was well tolerated with no significant differences in the rate of serious adverse events observed between the experimental and control arms of the study. Over the course of the study, however, azithromycin was associated with a significant protective effect against diarrhea (13% vs. 53%) and acute rhinosinusitus (4% vs. 27%).

There was no observed increase in macrolide resistance associated with azithromycin prophylaxis.

Macrolides have been evaluated for preventing progression of several chronic lung diseases, including chronic obstructive pulmonary disease, bronchiectasis, and cystic fibrosis. Like other drugs in its class, “azithromycin, in addition to its antimicrobial effect, has anti-inflammatory properties,” Dr. Milito said. This increases its potential to slow the time to airway damage in patients with primary antibiotic deficiency.

“Chronic lung disease is the result of a vicious cycle that begins with the inflammatory response to infection,” Dr. Milito explained. On the basis of these data, she believes azithromycin “should be considered a valuable addition to usual treatment” for primary antibody deficiencies.
 

SOURCE: EUROPEAN RESPIRATORY SOCIETY 2019 INTERNATIONAL CONGRESS

MADRID – Consistent with previous evidence of higher relative rates of drug delivery, mesh nebulizers offer several advantages over jet nebulizers for treatment of acute asthma in children presenting to an emergency department, according to results of a randomized trial presented at the annual congress of the European Respiratory Society.

For the primary outcome of hospital admission, the advantage of the mesh over the jet nebulizer only reached significance when used with a mask, rather than a valve, but trial results overall support the conclusion that the mesh device delivers drug more efficiently, according to Gerald Moody, RRT-NPS, clinical research coordinator at Children’s Medical Center, Dallas.

In this multicenter, single-blinded trial, 217 children presenting to an ED with acute asthma of moderate or greater severity were randomized to receive bronchodilator treatment delivered with a mesh device or a jet device. For drug delivery, aerosol masks or mouthpiece valves were permitted and selected at the discretion of the clinician administrating treatment. Masks were used in 80% of cases.

Patients remained in the study until either symptom control was achieved or a decision was reached to advise hospital admission. Patients with complex comorbidities or who had received oral corticosteroids within the previous 24 hours were excluded.

For the primary outcome of hospital discharge, the 31% reduction (P = .22) in hospitalization in favor of the mesh nebulizer failed to reach statistical significance. Although the study is likely to have been underpowered, Mr. Moody also pointed out an uneven distribution in severity of disease at baseline. In addition to a significantly higher median asthma score (9.0 vs. 8.0; P = .042) in the mesh nebulizer group, there was also a significantly higher percentage with severe disease (57% vs. 42%; P = .025).

“There were no significant differences in any of the other variables we evaluated, such as age, gender, race, or body mass index,” Mr. Moody reported.

Despite the higher disease burden in the mesh nebulizer group, there was a 48% reduction (P = .03) in hospital admissions among those randomized to the mesh nebulizer when both groups received treatment through a mask.

In addition, those treated with the mask required on average only two treatments before achieving symptom control whether they met criteria for moderate or severe asthma at baseline. The median numbers of treatments in the jet nebulizer group for moderate and severe asthma were 3 and 3.5, respectively.

In previous experimental studies, which ultimately provided the rationale for this trial, the estimated amount of drug reaching the airways with a mesh nebulizer was approximately twice as great as that estimated in the model when delivery was performed with a jet device, according to Mr. Moody.

This study appeared to corroborate that advantage. Both the median doses of albuterol (10 mg vs. 15 mg) and ipratropium (1,000 mcg vs. 1,500 mcg) were significantly lower (P less than .001 for both) among the patients randomized to the mesh nebulizer.

Although the jet nebulizers are widely employed “for their ease of use and low cost,” Mr. Moody characterized mesh nebulizers as an advance in technology. In this study, which Mr. Moody said is the first to evaluate whether the experimental evidence of greater drug delivery efficiency translates into a clinical advantage, the primary endpoint was missed, but Mr. Moody indicated that the overall findings support the potential for a difference.

The ERS-invited discussant on this study, Celeste Michala Porsbjerg, MD, Bispebjerg Hospital, Copenhagen University, expressed a concern that might deserve attention in a larger trial. Based on the premise that more efficient delivery increases drug exposure, she questioned whether it might not also increase risks.

There were no significant treatment-related adverse events reported in either arm of this study, Mr. Moody responded, but he conceded that this is an appropriate focus of attention for future studies.

Mr. Moody reported a financial relationship with Aerogen, which produces the mesh device tested in this trial.

MADRID – Consistent with previous evidence of higher relative rates of drug delivery, mesh nebulizers offer several advantages over jet nebulizers for treatment of acute asthma in children presenting to an emergency department, according to results of a randomized trial presented at the annual congress of the European Respiratory Society.

For the primary outcome of hospital admission, the advantage of the mesh over the jet nebulizer only reached significance when used with a mask, rather than a valve, but trial results overall support the conclusion that the mesh device delivers drug more efficiently, according to Gerald Moody, RRT-NPS, clinical research coordinator at Children’s Medical Center, Dallas.

In this multicenter, single-blinded trial, 217 children presenting to an ED with acute asthma of moderate or greater severity were randomized to receive bronchodilator treatment delivered with a mesh device or a jet device. For drug delivery, aerosol masks or mouthpiece valves were permitted and selected at the discretion of the clinician administrating treatment. Masks were used in 80% of cases.

Patients remained in the study until either symptom control was achieved or a decision was reached to advise hospital admission. Patients with complex comorbidities or who had received oral corticosteroids within the previous 24 hours were excluded.

For the primary outcome of hospital discharge, the 31% reduction (P = .22) in hospitalization in favor of the mesh nebulizer failed to reach statistical significance. Although the study is likely to have been underpowered, Mr. Moody also pointed out an uneven distribution in severity of disease at baseline. In addition to a significantly higher median asthma score (9.0 vs. 8.0; P = .042) in the mesh nebulizer group, there was also a significantly higher percentage with severe disease (57% vs. 42%; P = .025).

“There were no significant differences in any of the other variables we evaluated, such as age, gender, race, or body mass index,” Mr. Moody reported.

Despite the higher disease burden in the mesh nebulizer group, there was a 48% reduction (P = .03) in hospital admissions among those randomized to the mesh nebulizer when both groups received treatment through a mask.

In addition, those treated with the mask required on average only two treatments before achieving symptom control whether they met criteria for moderate or severe asthma at baseline. The median numbers of treatments in the jet nebulizer group for moderate and severe asthma were 3 and 3.5, respectively.

In previous experimental studies, which ultimately provided the rationale for this trial, the estimated amount of drug reaching the airways with a mesh nebulizer was approximately twice as great as that estimated in the model when delivery was performed with a jet device, according to Mr. Moody.

This study appeared to corroborate that advantage. Both the median doses of albuterol (10 mg vs. 15 mg) and ipratropium (1,000 mcg vs. 1,500 mcg) were significantly lower (P less than .001 for both) among the patients randomized to the mesh nebulizer.

Although the jet nebulizers are widely employed “for their ease of use and low cost,” Mr. Moody characterized mesh nebulizers as an advance in technology. In this study, which Mr. Moody said is the first to evaluate whether the experimental evidence of greater drug delivery efficiency translates into a clinical advantage, the primary endpoint was missed, but Mr. Moody indicated that the overall findings support the potential for a difference.

The ERS-invited discussant on this study, Celeste Michala Porsbjerg, MD, Bispebjerg Hospital, Copenhagen University, expressed a concern that might deserve attention in a larger trial. Based on the premise that more efficient delivery increases drug exposure, she questioned whether it might not also increase risks.

There were no significant treatment-related adverse events reported in either arm of this study, Mr. Moody responded, but he conceded that this is an appropriate focus of attention for future studies.

Mr. Moody reported a financial relationship with Aerogen, which produces the mesh device tested in this trial.

MADRID – Consistent with previous evidence of higher relative rates of drug delivery, mesh nebulizers offer several advantages over jet nebulizers for treatment of acute asthma in children presenting to an emergency department, according to results of a randomized trial presented at the annual congress of the European Respiratory Society.

For the primary outcome of hospital admission, the advantage of the mesh over the jet nebulizer only reached significance when used with a mask, rather than a valve, but trial results overall support the conclusion that the mesh device delivers drug more efficiently, according to Gerald Moody, RRT-NPS, clinical research coordinator at Children’s Medical Center, Dallas.

In this multicenter, single-blinded trial, 217 children presenting to an ED with acute asthma of moderate or greater severity were randomized to receive bronchodilator treatment delivered with a mesh device or a jet device. For drug delivery, aerosol masks or mouthpiece valves were permitted and selected at the discretion of the clinician administrating treatment. Masks were used in 80% of cases.

Patients remained in the study until either symptom control was achieved or a decision was reached to advise hospital admission. Patients with complex comorbidities or who had received oral corticosteroids within the previous 24 hours were excluded.

For the primary outcome of hospital discharge, the 31% reduction (P = .22) in hospitalization in favor of the mesh nebulizer failed to reach statistical significance. Although the study is likely to have been underpowered, Mr. Moody also pointed out an uneven distribution in severity of disease at baseline. In addition to a significantly higher median asthma score (9.0 vs. 8.0; P = .042) in the mesh nebulizer group, there was also a significantly higher percentage with severe disease (57% vs. 42%; P = .025).

“There were no significant differences in any of the other variables we evaluated, such as age, gender, race, or body mass index,” Mr. Moody reported.

Despite the higher disease burden in the mesh nebulizer group, there was a 48% reduction (P = .03) in hospital admissions among those randomized to the mesh nebulizer when both groups received treatment through a mask.

In addition, those treated with the mask required on average only two treatments before achieving symptom control whether they met criteria for moderate or severe asthma at baseline. The median numbers of treatments in the jet nebulizer group for moderate and severe asthma were 3 and 3.5, respectively.

In previous experimental studies, which ultimately provided the rationale for this trial, the estimated amount of drug reaching the airways with a mesh nebulizer was approximately twice as great as that estimated in the model when delivery was performed with a jet device, according to Mr. Moody.

This study appeared to corroborate that advantage. Both the median doses of albuterol (10 mg vs. 15 mg) and ipratropium (1,000 mcg vs. 1,500 mcg) were significantly lower (P less than .001 for both) among the patients randomized to the mesh nebulizer.

Although the jet nebulizers are widely employed “for their ease of use and low cost,” Mr. Moody characterized mesh nebulizers as an advance in technology. In this study, which Mr. Moody said is the first to evaluate whether the experimental evidence of greater drug delivery efficiency translates into a clinical advantage, the primary endpoint was missed, but Mr. Moody indicated that the overall findings support the potential for a difference.

The ERS-invited discussant on this study, Celeste Michala Porsbjerg, MD, Bispebjerg Hospital, Copenhagen University, expressed a concern that might deserve attention in a larger trial. Based on the premise that more efficient delivery increases drug exposure, she questioned whether it might not also increase risks.

There were no significant treatment-related adverse events reported in either arm of this study, Mr. Moody responded, but he conceded that this is an appropriate focus of attention for future studies.

Mr. Moody reported a financial relationship with Aerogen, which produces the mesh device tested in this trial.

NEW YORK – For women with pseudofolliculitis barbae, an empirically-based strategy of microdermabrasion, laser treatment, emollients, and maintenance retinoids has been found highly effective, Wendy Roberts, MD, reported at the Skin of Color Update 2019.

“We didn’t have great treatments for this problem in the past, but the technology has evolved, and you can now get most women clear,” Dr. Roberts, a dermatologist who practices in Rancho Mirage, Calif., said at the meeting.

This approach is appropriate in all women, but Dr. Roberts focused on her experience with black patients, for whom an antioxidant cream is added to address the inflammatory-associated hyperpigmentation that often accompanies pseudofolliculitis barbae, a chronic inflammatory skin condition typically characterized by small, painful papules and pustules.

Start with microdermabrasion to treat the hypertrophic hair follicles and address keratin plugs, Dr. Roberts said. The microdermabrasion smooths the skin and increases penetration of subsequent creams and topics, she said.

“In the same session, I treat with Nd-YAG 1064 nm laser using short pulses,” she noted. For black women, she makes four passes with the laser at a level of moderate intensity. For those with lighter skin, she might perform as many as six passes with the laser set higher.

The microdermabrasion is repeated monthly for three or four treatments, but can be extended for those with persistent symptoms, Dr. Roberts pointed out. She presented a case of a patient who required seven treatments to achieve a satisfactory response.

Patients are instructed to avoid hair plucking and over the course of treatment nightly topical tretinoin is recommended for maintenance. Regular use of emollients is also recommended. For black women who have developed hyperpigmentation as a complication of pseudofolliculitis barbae, Dr. Roberts prescribes a lightening cream.

“I have pretty much moved away from hydroquinone,” said Dr. Roberts, explaining that she has achieved better results with topical cysteamine, a product that she has been using for about 3 years.

In outlining her treatment strategy, she employed case studies of two black women, both of whom achieved resolution of the problem and were satisfied with the results. She said that the same approach is suitable for women of other racial and ethnic groups.

Most commonly seen in black men, pseudofolliculitis barbae – also known as razor bumps – can occur as a complication of shaving in men or women from any racial and ethnic group. However, because of their embarrassment, women often fail to volunteer that they are struggling with this problem. Some women have been afflicted for years and have developed a regular routine of shaving or plucking hairs and then applying makeup for camouflage, Dr. Roberts said.

“This is a patient who rarely presents the problem to the dermatologist. Yet, she is in every one of our practices,” she added. Due to the frequency with which she has identified pseudofolliculitis barbae in patients who are being seen for a different complaint, she now routinely asks patients about this issue when taking a history. Early detection is useful because pseudofolliculitis barbae is more easily resolved in younger women than in older women.

When the problem is resolved, patient satisfaction is very high. For this reason, Dr. Roberts called diagnosis and treatment of pseudofolliculitis barbae “a practice builder.” Based on her approach, “you can really get these ladies clear.”

Dr. Roberts reports financial relationships with an extensive list of companies that market dermatologic and cosmetic products.

NEW YORK – For women with pseudofolliculitis barbae, an empirically-based strategy of microdermabrasion, laser treatment, emollients, and maintenance retinoids has been found highly effective, Wendy Roberts, MD, reported at the Skin of Color Update 2019.

“We didn’t have great treatments for this problem in the past, but the technology has evolved, and you can now get most women clear,” Dr. Roberts, a dermatologist who practices in Rancho Mirage, Calif., said at the meeting.

This approach is appropriate in all women, but Dr. Roberts focused on her experience with black patients, for whom an antioxidant cream is added to address the inflammatory-associated hyperpigmentation that often accompanies pseudofolliculitis barbae, a chronic inflammatory skin condition typically characterized by small, painful papules and pustules.

Start with microdermabrasion to treat the hypertrophic hair follicles and address keratin plugs, Dr. Roberts said. The microdermabrasion smooths the skin and increases penetration of subsequent creams and topics, she said.

“In the same session, I treat with Nd-YAG 1064 nm laser using short pulses,” she noted. For black women, she makes four passes with the laser at a level of moderate intensity. For those with lighter skin, she might perform as many as six passes with the laser set higher.

The microdermabrasion is repeated monthly for three or four treatments, but can be extended for those with persistent symptoms, Dr. Roberts pointed out. She presented a case of a patient who required seven treatments to achieve a satisfactory response.

Patients are instructed to avoid hair plucking and over the course of treatment nightly topical tretinoin is recommended for maintenance. Regular use of emollients is also recommended. For black women who have developed hyperpigmentation as a complication of pseudofolliculitis barbae, Dr. Roberts prescribes a lightening cream.

“I have pretty much moved away from hydroquinone,” said Dr. Roberts, explaining that she has achieved better results with topical cysteamine, a product that she has been using for about 3 years.

In outlining her treatment strategy, she employed case studies of two black women, both of whom achieved resolution of the problem and were satisfied with the results. She said that the same approach is suitable for women of other racial and ethnic groups.

Most commonly seen in black men, pseudofolliculitis barbae – also known as razor bumps – can occur as a complication of shaving in men or women from any racial and ethnic group. However, because of their embarrassment, women often fail to volunteer that they are struggling with this problem. Some women have been afflicted for years and have developed a regular routine of shaving or plucking hairs and then applying makeup for camouflage, Dr. Roberts said.

“This is a patient who rarely presents the problem to the dermatologist. Yet, she is in every one of our practices,” she added. Due to the frequency with which she has identified pseudofolliculitis barbae in patients who are being seen for a different complaint, she now routinely asks patients about this issue when taking a history. Early detection is useful because pseudofolliculitis barbae is more easily resolved in younger women than in older women.

When the problem is resolved, patient satisfaction is very high. For this reason, Dr. Roberts called diagnosis and treatment of pseudofolliculitis barbae “a practice builder.” Based on her approach, “you can really get these ladies clear.”

Dr. Roberts reports financial relationships with an extensive list of companies that market dermatologic and cosmetic products.

NEW YORK – For women with pseudofolliculitis barbae, an empirically-based strategy of microdermabrasion, laser treatment, emollients, and maintenance retinoids has been found highly effective, Wendy Roberts, MD, reported at the Skin of Color Update 2019.

“We didn’t have great treatments for this problem in the past, but the technology has evolved, and you can now get most women clear,” Dr. Roberts, a dermatologist who practices in Rancho Mirage, Calif., said at the meeting.

This approach is appropriate in all women, but Dr. Roberts focused on her experience with black patients, for whom an antioxidant cream is added to address the inflammatory-associated hyperpigmentation that often accompanies pseudofolliculitis barbae, a chronic inflammatory skin condition typically characterized by small, painful papules and pustules.

Start with microdermabrasion to treat the hypertrophic hair follicles and address keratin plugs, Dr. Roberts said. The microdermabrasion smooths the skin and increases penetration of subsequent creams and topics, she said.

“In the same session, I treat with Nd-YAG 1064 nm laser using short pulses,” she noted. For black women, she makes four passes with the laser at a level of moderate intensity. For those with lighter skin, she might perform as many as six passes with the laser set higher.

The microdermabrasion is repeated monthly for three or four treatments, but can be extended for those with persistent symptoms, Dr. Roberts pointed out. She presented a case of a patient who required seven treatments to achieve a satisfactory response.

Patients are instructed to avoid hair plucking and over the course of treatment nightly topical tretinoin is recommended for maintenance. Regular use of emollients is also recommended. For black women who have developed hyperpigmentation as a complication of pseudofolliculitis barbae, Dr. Roberts prescribes a lightening cream.

“I have pretty much moved away from hydroquinone,” said Dr. Roberts, explaining that she has achieved better results with topical cysteamine, a product that she has been using for about 3 years.

In outlining her treatment strategy, she employed case studies of two black women, both of whom achieved resolution of the problem and were satisfied with the results. She said that the same approach is suitable for women of other racial and ethnic groups.

Most commonly seen in black men, pseudofolliculitis barbae – also known as razor bumps – can occur as a complication of shaving in men or women from any racial and ethnic group. However, because of their embarrassment, women often fail to volunteer that they are struggling with this problem. Some women have been afflicted for years and have developed a regular routine of shaving or plucking hairs and then applying makeup for camouflage, Dr. Roberts said.

“This is a patient who rarely presents the problem to the dermatologist. Yet, she is in every one of our practices,” she added. Due to the frequency with which she has identified pseudofolliculitis barbae in patients who are being seen for a different complaint, she now routinely asks patients about this issue when taking a history. Early detection is useful because pseudofolliculitis barbae is more easily resolved in younger women than in older women.

When the problem is resolved, patient satisfaction is very high. For this reason, Dr. Roberts called diagnosis and treatment of pseudofolliculitis barbae “a practice builder.” Based on her approach, “you can really get these ladies clear.”

Dr. Roberts reports financial relationships with an extensive list of companies that market dermatologic and cosmetic products.

NEW YORK – The request for skin lightening agents by nonwhite patients for purely cosmetic purposes is uncomfortable for at least some American dermatologists, judging from an informal survey of those attending the Skin of Color Update 2019, where this topic was introduced.

Ted Bosworth/MDedge News

When the Skin of Color conference chair, Eliot Battle, MD, founder of Cultura Dermatology and Laser Center, Washington, asked who in the audience considered total body whitening to be “wrong,” the show of hands was substantial. He then offered some perspective.

“How many think breast augmentation is wrong?” he asked. “How many think changing your hair color is wrong? Before we cast judgment, let’s think a little about how our patients feel.”

Although he acknowledged the difficulty of separating a racial context from the cultural perception of lighter skin as desirable, Dr. Battle contended that choices regarding appearance are complex. He cautioned against moral judgments blind to this complexity.

“As physicians we need to keep ourselves in check, to keep ourselves from making judgments [regarding lightening agents],” he said.

The two other panelists participating in the same session made compatible observations. Although the other two panelists limited most of their presentations to skin lightening for clinical indications, such as melasma and other disorders of hyperpigmentation, they acknowledged and addressed the sense of discomfort the topic raises.

“To many patients, depigmentation is a passport to society,” said Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute, Los Angeles. Although she considers this a global issue, not an issue unique to the black population, she counseled dermatologists to “respect the vicissitudes and issues of pigmentation” that she said include the patient’s concerns about beauty, class, and privilege.

Sensitive to the desire of some patients for lighter skin, Cheryl Burgess, MD, founder of the Center for Dermatology and Dermatologic Surgery, Washington, opened her talk by displaying the Time Magazine cover of O.J. Simpson at the time he was accused of murder. The photo appeared to have been intentionally darkened in an effort that was thought by many to make him appear more sinister.

This might be an appropriate example of what skin pigment represents to some segments of American society, but Dr. Battle said that the quest for lighter skin is a global phenomenon. He claims that Asia, India, and Africa are now among the fastest growing and largest markets for skin lightening strategies. The options in those areas of the world, like the United States, are proliferating quickly.

Many of the rapidly expanding options have not yet proved to be effective or safe. The antioxidant glutathione, which is being used for a long list of proven and unproven indications, is among these, according to Dr. Battle. In many clinics where this drug is administered intravenously to avoid degradation in the gastrointestinal tract, he suggested there is reason to believe the staff has little training in safety monitoring.

There are no long-term studies evaluating the safety and efficacy of glutathione for skin lightening, according to Dr. Battle, but there are many case reports of serious toxicities, including death. He listed thyroid dysfunction, renal impairment, and liver dysfunction among adverse events potentially related to glutathione.

“When I gave this talk a year ago, there were no clinics in Washington [offering glutathione]. Now there are seven,” he said.

Even for those dermatologists uncomfortable offering skin lightening for cosmetic purposes, ignoring the demand is ill advised, he said. Evaluating and advising patients on the safety of these agents is one reason to become involved, said Dr. Battle, who noted that specialists in dermatology are uniquely trained to monitor drugs for this application.

“You can tell a patient to stop, but they won’t stop,” said Dr. Battle. He maintained that organized medicine, including the American Academy of Dermatology, should take a role in evaluating the safety and efficacy of lightening agents even when used only for cosmetic indications.

Currently, there are no Food and Drug Administration–approved therapies for whitening of the skin.

“This is such an important question, and I think we need to figure it out,” Dr. Battle said. “Not a day goes by in our practice when we are not asked about skin lightening.”

Dr. Battle reported no relevant disclosures; Dr. Grimes and Dr. Burgess reported multiple financial relationships with industry that are not necessarily relevant to this topic.

NEW YORK – The request for skin lightening agents by nonwhite patients for purely cosmetic purposes is uncomfortable for at least some American dermatologists, judging from an informal survey of those attending the Skin of Color Update 2019, where this topic was introduced.

Ted Bosworth/MDedge News

When the Skin of Color conference chair, Eliot Battle, MD, founder of Cultura Dermatology and Laser Center, Washington, asked who in the audience considered total body whitening to be “wrong,” the show of hands was substantial. He then offered some perspective.

“How many think breast augmentation is wrong?” he asked. “How many think changing your hair color is wrong? Before we cast judgment, let’s think a little about how our patients feel.”

Although he acknowledged the difficulty of separating a racial context from the cultural perception of lighter skin as desirable, Dr. Battle contended that choices regarding appearance are complex. He cautioned against moral judgments blind to this complexity.

“As physicians we need to keep ourselves in check, to keep ourselves from making judgments [regarding lightening agents],” he said.

The two other panelists participating in the same session made compatible observations. Although the other two panelists limited most of their presentations to skin lightening for clinical indications, such as melasma and other disorders of hyperpigmentation, they acknowledged and addressed the sense of discomfort the topic raises.

“To many patients, depigmentation is a passport to society,” said Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute, Los Angeles. Although she considers this a global issue, not an issue unique to the black population, she counseled dermatologists to “respect the vicissitudes and issues of pigmentation” that she said include the patient’s concerns about beauty, class, and privilege.

Sensitive to the desire of some patients for lighter skin, Cheryl Burgess, MD, founder of the Center for Dermatology and Dermatologic Surgery, Washington, opened her talk by displaying the Time Magazine cover of O.J. Simpson at the time he was accused of murder. The photo appeared to have been intentionally darkened in an effort that was thought by many to make him appear more sinister.

This might be an appropriate example of what skin pigment represents to some segments of American society, but Dr. Battle said that the quest for lighter skin is a global phenomenon. He claims that Asia, India, and Africa are now among the fastest growing and largest markets for skin lightening strategies. The options in those areas of the world, like the United States, are proliferating quickly.

Many of the rapidly expanding options have not yet proved to be effective or safe. The antioxidant glutathione, which is being used for a long list of proven and unproven indications, is among these, according to Dr. Battle. In many clinics where this drug is administered intravenously to avoid degradation in the gastrointestinal tract, he suggested there is reason to believe the staff has little training in safety monitoring.

There are no long-term studies evaluating the safety and efficacy of glutathione for skin lightening, according to Dr. Battle, but there are many case reports of serious toxicities, including death. He listed thyroid dysfunction, renal impairment, and liver dysfunction among adverse events potentially related to glutathione.

“When I gave this talk a year ago, there were no clinics in Washington [offering glutathione]. Now there are seven,” he said.

Even for those dermatologists uncomfortable offering skin lightening for cosmetic purposes, ignoring the demand is ill advised, he said. Evaluating and advising patients on the safety of these agents is one reason to become involved, said Dr. Battle, who noted that specialists in dermatology are uniquely trained to monitor drugs for this application.

“You can tell a patient to stop, but they won’t stop,” said Dr. Battle. He maintained that organized medicine, including the American Academy of Dermatology, should take a role in evaluating the safety and efficacy of lightening agents even when used only for cosmetic indications.

Currently, there are no Food and Drug Administration–approved therapies for whitening of the skin.

“This is such an important question, and I think we need to figure it out,” Dr. Battle said. “Not a day goes by in our practice when we are not asked about skin lightening.”

Dr. Battle reported no relevant disclosures; Dr. Grimes and Dr. Burgess reported multiple financial relationships with industry that are not necessarily relevant to this topic.

NEW YORK – The request for skin lightening agents by nonwhite patients for purely cosmetic purposes is uncomfortable for at least some American dermatologists, judging from an informal survey of those attending the Skin of Color Update 2019, where this topic was introduced.

Ted Bosworth/MDedge News

When the Skin of Color conference chair, Eliot Battle, MD, founder of Cultura Dermatology and Laser Center, Washington, asked who in the audience considered total body whitening to be “wrong,” the show of hands was substantial. He then offered some perspective.

“How many think breast augmentation is wrong?” he asked. “How many think changing your hair color is wrong? Before we cast judgment, let’s think a little about how our patients feel.”

Although he acknowledged the difficulty of separating a racial context from the cultural perception of lighter skin as desirable, Dr. Battle contended that choices regarding appearance are complex. He cautioned against moral judgments blind to this complexity.

“As physicians we need to keep ourselves in check, to keep ourselves from making judgments [regarding lightening agents],” he said.

The two other panelists participating in the same session made compatible observations. Although the other two panelists limited most of their presentations to skin lightening for clinical indications, such as melasma and other disorders of hyperpigmentation, they acknowledged and addressed the sense of discomfort the topic raises.

“To many patients, depigmentation is a passport to society,” said Pearl Grimes, MD, director of the Vitiligo and Pigmentation Institute, Los Angeles. Although she considers this a global issue, not an issue unique to the black population, she counseled dermatologists to “respect the vicissitudes and issues of pigmentation” that she said include the patient’s concerns about beauty, class, and privilege.

Sensitive to the desire of some patients for lighter skin, Cheryl Burgess, MD, founder of the Center for Dermatology and Dermatologic Surgery, Washington, opened her talk by displaying the Time Magazine cover of O.J. Simpson at the time he was accused of murder. The photo appeared to have been intentionally darkened in an effort that was thought by many to make him appear more sinister.

This might be an appropriate example of what skin pigment represents to some segments of American society, but Dr. Battle said that the quest for lighter skin is a global phenomenon. He claims that Asia, India, and Africa are now among the fastest growing and largest markets for skin lightening strategies. The options in those areas of the world, like the United States, are proliferating quickly.

Many of the rapidly expanding options have not yet proved to be effective or safe. The antioxidant glutathione, which is being used for a long list of proven and unproven indications, is among these, according to Dr. Battle. In many clinics where this drug is administered intravenously to avoid degradation in the gastrointestinal tract, he suggested there is reason to believe the staff has little training in safety monitoring.

There are no long-term studies evaluating the safety and efficacy of glutathione for skin lightening, according to Dr. Battle, but there are many case reports of serious toxicities, including death. He listed thyroid dysfunction, renal impairment, and liver dysfunction among adverse events potentially related to glutathione.

“When I gave this talk a year ago, there were no clinics in Washington [offering glutathione]. Now there are seven,” he said.

Even for those dermatologists uncomfortable offering skin lightening for cosmetic purposes, ignoring the demand is ill advised, he said. Evaluating and advising patients on the safety of these agents is one reason to become involved, said Dr. Battle, who noted that specialists in dermatology are uniquely trained to monitor drugs for this application.

“You can tell a patient to stop, but they won’t stop,” said Dr. Battle. He maintained that organized medicine, including the American Academy of Dermatology, should take a role in evaluating the safety and efficacy of lightening agents even when used only for cosmetic indications.

Currently, there are no Food and Drug Administration–approved therapies for whitening of the skin.

“This is such an important question, and I think we need to figure it out,” Dr. Battle said. “Not a day goes by in our practice when we are not asked about skin lightening.”

Dr. Battle reported no relevant disclosures; Dr. Grimes and Dr. Burgess reported multiple financial relationships with industry that are not necessarily relevant to this topic.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

MADRID –  In the context of three previous trials, a new phase 3 trial demonstrates that the efficacy of as-needed inhaled corticosteroids (ICS) plus a long-acting beta agonist (LABA) is at least comparable to  maintenance ICS for preventing severe exacerbations in the routine care of patients with mild to moderate asthma, according to a presentation at the 2019 ERS International Congress.

Ted Bosworth/MDedge News

This “real-world” study, called PRACTICAL, produced results similar to those of the previous three studies. It showed similar or modestly improved efficacy for the as-needed approach in patients enrolled with mild to moderate asthma, according to Joanna Hardy, MD, a research fellow at the Medical Research Institute of New Zealand, Wellington.

Currently, the Global Initiative for Asthma (GINA) guidelines identify either of the two strategies tested in this trial as acceptable for patients eligible for step 2 asthma control. This study, as in the three trials published previously, provided reassurance that an as-needed approach is adequate for patients insufficiently adherent to daily maintenance therapy.

In PRACTICAL, the results of which were published just prior to the 2019 ERS Congress (Lancet 2019;394:919-28), 890 patients were randomized to use of a single inhaler containing 200 mcg budesonide plus 6 mcg formoterol as needed for symptoms or to a maintenance regimen with the same dose of budesonide taken twice daily. The protocol allowed 250 mcg terbutaline as needed for symptom control in the maintenance arm. The patients were followed for 52 weeks.

For the primary endpoint of the per-patient number of severe exacerbations, defined as need for 3 consecutive days of oral corticosteroids or an emergency department visit to receive oral corticosteroids, the as-needed approach reduced the relative risk by 31% (hazard ratio, 0.69; P = .049). The per-patient rates of exacerbations for the as-needed and maintenance arms were 0.0119 and 0.172, respectively.

The time to first exacerbation, a secondary endpoint, approached significance in favor of as-needed treatment (HR 0.6; P = .05). There was no difference in asthma control as measured with the Asthma Control Questionnaire or in lung function as measured with forced expiratory volume in 1 second (FEV₁₎ at any visit or at the end of the study.

Two SYGMA trials (SYGMA 1 and SYGMA 2), both published in the New England Journal of Medicine in 2018, addressed the same question. Most like PRACTICAL, SYGMA 2 randomized 4,215 patients with mild asthma and found as-needed budesonide/formoterol noninferior to budesonide maintenance for preventing severe exacerbations.

In SYGMA 1, which included an as-needed terbutaline arm, 3,849 patients were randomized. Although as-needed budesonide-formoterol was inferior to budesonide maintenance in that study (but superior to as-needed to terbutaline), the adherence to budesonide maintenance was 78.9%, which Dr. Hardy said does not reflect real-world patient behavior.

“The problem is that we have a lot of data to show that adherence to maintenance asthma therapy in mild asthma is poor,” Dr. Hardy said. In PRACTICAL, all patients were provided with an asthma action plan but no strategies were offered to improve compliance over those employed in usual practice.

In the open-label Novel START trial, published in 2019 in the New England Journal of Medicine, the question posed was different. In that study, which randomized 675 patients, as-needed budesonide/formoterol was superior to as-needed albuterol for prevention of asthma exacerbations at 52 weeks, the time point employed in all four studies. The results, while confirming the importance of the ICS component, have been generally interpreted as supporting the as-needed therapy in mild asthma.

At the ERS 2019 Congress, one of the moderators of the session in which Dr. Hardy spoke, Guy Brusselle, MD, Ghent (Belgium) University, agreed that the available evidence supports as-needed therapy as a viable strategy in mild asthma, but expressed concern about applying this conclusion to patients who have asthma requiring therapy beyond GINA step 2.

“These data might put patients who need GINA step 3 or 4 therapy at risk of not receiving the maintenance therapy they need for disease control,” Dr. Brusselle said.

In light of the challenge of separating those with moderate from mild asthma, Dr. Brusselle suggested another arm to add to real-world clinical trials attempting to identify the most effective approach.

“The optimal arm might be maintenance budesonide with as-needed ICS/LABA,” Dr. Brusselle said. He explained that even if compliance is low, at least some patients will be receiving a maintenance therapy, and this approach might ultimately offer more benefit than one in which patients do not even consider maintenance.

Dr. Hardy reports no potential conflicts of interest.

MADRID – The serious adverse events faced by asthma patients taking maintenance or rescue oral corticosteroids (OCS) might be avoidable if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.

“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.

In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.

Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.

In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.

On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,

When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.

Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.

“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.

The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.

“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.

In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.

“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”

Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.

Dr. Eger reports no potential conflicts of interest.

MADRID – The serious adverse events faced by asthma patients taking maintenance or rescue oral corticosteroids (OCS) might be avoidable if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.

“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.

In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.

Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.

In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.

On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,

When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.

Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.

“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.

The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.

“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.

In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.

“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”

Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.

Dr. Eger reports no potential conflicts of interest.

MADRID – The serious adverse events faced by asthma patients taking maintenance or rescue oral corticosteroids (OCS) might be avoidable if data from a Dutch study presented at the annual congress of the European Respiratory Society are representative of practice elsewhere.

“The main message from our study is that OCS overuse is common and unnecessary in the majority of asthma patients,” reported Katrien A.B. Eger, MD, Amsterdam University Medical Centre.

In this study, 5,002 patients on high doses of inhaled corticosteroids (ICS), defined as at least 500 mcg/day, were identified in a pharmacy database in the Netherlands. These patients were asked to complete a questionnaire to determine how many had severe asthma and had received rescue or maintenance OCS in the past year.

Drawing from the pharmacy database, it could be determined that 29% of the 2,312 patients who responded to the questionnaire were taking harmfully high doses of OCS as well as high doses of ICS. For this study, harmful exposure was defined as a cumulative intake of 420 mg of prednisone-equivalent OCS over a 1-year period. The median cumulative 1-year exposure, according to Dr. Eger, was 750 mg of prednisone equivalent.

In this population, the investigators then calculated ICS medication adherence based on prescription refills. In addition, a subset of this population was evaluated for inhaler technique.

On the basis of these calculations, 47.4% of patients with harmful OCS exposure were found not to be adherent to their prescribed ICS. Of those who were adherent, 53.9% were found not be taking their inhaled steroids appropriately,

When these numbers are put together, the data suggest “78.1% of high OCS users are either nonadherent or using poor inhalation techniques, which means there is a big potential for treatment optimization,” Dr. Eger said.

Yet even among the 21.9% who were adherent and using good inhaler technique, identifying a group who presumably require OCS for exacerbations, the study found that only 46.1% had been prescribed a biologic, which Dr. Eger considers an important steroid-sparing option. She conceded that many of those not on a biologic might not be candidates, but she believes this is another missed opportunity for reducing OCS exposure.

“In the Netherlands, we have very good access to health care, and biologics are available to anyone who needs them,” said Dr. Eger, explaining that access to these drugs is not a barrier.

The evidence overall is that not enough is being done to ensure that asthma patients are being protected from the risks of OCS, according to Dr. Eger. Citing evidence that adverse events associated with OCS begin with a cumulative lifetime prednisone-equivalent exposure of only 500 mg, she believes that clinicians should be more aggressive in intervening.

“We know that there are both acute and chronic complications associated with OCS that involve a range of organ systems,” Dr. Eger said. She listed osteoporosis, diabetes mellitus, hypertension, and adrenal insufficiency as examples. Rescue OCS, even if used sparingly, can drive risk of OCS complications attributable to the importance of cumulative exposure.

In the session where these data were presented, the moderator, Guy Brusselle, MD, professor of asthma and immunology, Ghent (Belgium) University, labeled them “important.” However, he quibbled with Dr. Eger’s assertion that biologics represent a major opportunity to reduce OCS exposure.

“By suggesting that biologics are not being used often enough, there is an assumption that all of these patients have type 2 inflammatory asthma,” Dr. Brusselle said. “I think it makes more sense to emphasize steroid-sparing strategies, not just biologics.”

Dr. Eger did not disagree, but she emphasized that steroid-sparing alternatives are just one strategy to reduce OCS exposure, and ensuring that patients are adherent to prescribed ICS therapies and are using them correctly might have an even greater impact.

Dr. Eger reports no potential conflicts of interest.

NEW YORK – For unclear reasons, the prevalence of central centrifugal cicatricial alopecia (CCCA), a progressive disease of permanent hair loss, is increasing dramatically among black women, creating an urgent need for early diagnosis and treatment, according to an expert who described this phenomenon at the Skin of Color Update 2019.

Ted Bosworth/MDedge News

“CCCA has reached epidemic proportions,” contended Susan Taylor, MD, director of diversity, department of dermatology, Penn Medicine, Philadelphia.

Published data place prevalence rates of CCCA somewhere in the range of 3% to 6% among black women, but Dr. Taylor reported that she believes the condition is underdiagnosed. “I am seeing far more patients now than I was 30 years ago,” she maintained.

Others participating in the Skin of Color Update 2019 agreed. Heather Woolery-Lloyd, MD, director of ethnic skin care, department of dermatology and cutaneous surgery, University of Miami, also called the rising incidence of CCCA “an epidemic.” She, like Dr. Taylor, emphasized the critical importance of early diagnosis and treatment.

“I tell patients that if we can prevent hair loss over the next 10 years, this is a treatment success,” Dr. Woolery-Lloyd said. Although hair regrowth can be achieved in a minority of patients with treatments such as minoxidil, “the first goal is to prevent hair loss.”

Upon diagnosis, Dr. Woolery-Lloyd recommends treatment with intralesional triamcinolone and topical steroids immediately, adding other agents, such as oral antibiotics, if needed. Even in cases where CCCA has been identified before hair loss is visible, Dr. Woolery-Lloyd advised immediate therapy. Given that CCCA is a disease of reversible hair loss, she said, “do not take a wait-and-see approach.”

One potential obstacle for early diagnosis of CCCA, shared by other types of alopecia that are common in skin of color, is the failure of many clinicians to employ a standardized diagnosis in this patient population.

“If you do not have tightly coiled hair, it does not mean you cannot understand tightly coiled hair, but you have to learn, and you have to let patients know that you understand and have experience,” said Dr. Taylor, emphasizing the role of reassuring patients so they can be confident in the clinical recommendations.

Part of this reassurance will be derived from “interacting with patients in a culturally competent manner,” Dr. Taylor said. Clinicians must develop comfort and confidence in physically examining the hair and scalp, in asking patients to remove weaves or braids for a thorough inspection, and in avoiding comments that might be misinterpreted. Among these, she advised tactful questions about shampooing to avoid any implication that the clinician is implying inadequate hygiene.

When CCCA is suspected, a “biopsy is important” even in circumstances when the diagnosis seems straightforward. For one reason, a substantial proportion of patients may have a concomitant diagnosis. Dr. Taylor cited data from one study in which nearly 20% of CCCA patients also had traction alopecia and more than 10% had androgenic alopecia. Other coexisting problems identified on biopsy, including infection or seborrheic dermatitis, can help clinicians tailor a more effective intervention.

The initial signs of CCCA are typically hair breakage in the vertex of the scalp, which then expands in a central centrifugal pattern, according to Dr. Taylor. Although not all patients have signs of inflammation, such as itching and pustules, inhibition of inflammation represents the first line of therapy.

Relative to hair in the white population, the hair of black individuals grows more slowly and is more fragile, with greater amounts of breakage, said Dr. Taylor, citing published studies that support these differences. To improve early diagnosis of CCCA, understanding the hair in the black population is the first step for spotting problems in routine physical examinations. It may be this lack of familiarity that is contributing to underdiagnosis of CCCA.

“Almost 70% of African-American patients feel that physicians do not understand their hair,” Dr. Taylor said. “Let’s begin to change that.”

Cautioning that it is too often assumed that hairstyles and hair care, such as relaxants or hot combs, are the source of hair loss in black women, Dr. Taylor advised not to jump to conclusions. As an example, she described a case where weaves, braids, and other strategies were employed to mask alopecia after CCCA developed, not before.

“CCCA is the most important cause of scarring alopecia in African-American women,” Dr. Taylor said. Reiterating that hair loss can be prevented or modified with treatment, she added that this places the emphasis on first obtaining an accurate diagnosis.

Dr. Taylor has a financial relationship with Biersdorf; Dr. Woolery-Lloyd has financial relationships with Allergan, Galderma, Ortho Diagnostics, Pfizer, and Somabella Laboratories.

NEW YORK – For unclear reasons, the prevalence of central centrifugal cicatricial alopecia (CCCA), a progressive disease of permanent hair loss, is increasing dramatically among black women, creating an urgent need for early diagnosis and treatment, according to an expert who described this phenomenon at the Skin of Color Update 2019.

Ted Bosworth/MDedge News

“CCCA has reached epidemic proportions,” contended Susan Taylor, MD, director of diversity, department of dermatology, Penn Medicine, Philadelphia.

Published data place prevalence rates of CCCA somewhere in the range of 3% to 6% among black women, but Dr. Taylor reported that she believes the condition is underdiagnosed. “I am seeing far more patients now than I was 30 years ago,” she maintained.

Others participating in the Skin of Color Update 2019 agreed. Heather Woolery-Lloyd, MD, director of ethnic skin care, department of dermatology and cutaneous surgery, University of Miami, also called the rising incidence of CCCA “an epidemic.” She, like Dr. Taylor, emphasized the critical importance of early diagnosis and treatment.

“I tell patients that if we can prevent hair loss over the next 10 years, this is a treatment success,” Dr. Woolery-Lloyd said. Although hair regrowth can be achieved in a minority of patients with treatments such as minoxidil, “the first goal is to prevent hair loss.”

Upon diagnosis, Dr. Woolery-Lloyd recommends treatment with intralesional triamcinolone and topical steroids immediately, adding other agents, such as oral antibiotics, if needed. Even in cases where CCCA has been identified before hair loss is visible, Dr. Woolery-Lloyd advised immediate therapy. Given that CCCA is a disease of reversible hair loss, she said, “do not take a wait-and-see approach.”

One potential obstacle for early diagnosis of CCCA, shared by other types of alopecia that are common in skin of color, is the failure of many clinicians to employ a standardized diagnosis in this patient population.

“If you do not have tightly coiled hair, it does not mean you cannot understand tightly coiled hair, but you have to learn, and you have to let patients know that you understand and have experience,” said Dr. Taylor, emphasizing the role of reassuring patients so they can be confident in the clinical recommendations.

Part of this reassurance will be derived from “interacting with patients in a culturally competent manner,” Dr. Taylor said. Clinicians must develop comfort and confidence in physically examining the hair and scalp, in asking patients to remove weaves or braids for a thorough inspection, and in avoiding comments that might be misinterpreted. Among these, she advised tactful questions about shampooing to avoid any implication that the clinician is implying inadequate hygiene.

When CCCA is suspected, a “biopsy is important” even in circumstances when the diagnosis seems straightforward. For one reason, a substantial proportion of patients may have a concomitant diagnosis. Dr. Taylor cited data from one study in which nearly 20% of CCCA patients also had traction alopecia and more than 10% had androgenic alopecia. Other coexisting problems identified on biopsy, including infection or seborrheic dermatitis, can help clinicians tailor a more effective intervention.

The initial signs of CCCA are typically hair breakage in the vertex of the scalp, which then expands in a central centrifugal pattern, according to Dr. Taylor. Although not all patients have signs of inflammation, such as itching and pustules, inhibition of inflammation represents the first line of therapy.

Relative to hair in the white population, the hair of black individuals grows more slowly and is more fragile, with greater amounts of breakage, said Dr. Taylor, citing published studies that support these differences. To improve early diagnosis of CCCA, understanding the hair in the black population is the first step for spotting problems in routine physical examinations. It may be this lack of familiarity that is contributing to underdiagnosis of CCCA.

“Almost 70% of African-American patients feel that physicians do not understand their hair,” Dr. Taylor said. “Let’s begin to change that.”

Cautioning that it is too often assumed that hairstyles and hair care, such as relaxants or hot combs, are the source of hair loss in black women, Dr. Taylor advised not to jump to conclusions. As an example, she described a case where weaves, braids, and other strategies were employed to mask alopecia after CCCA developed, not before.

“CCCA is the most important cause of scarring alopecia in African-American women,” Dr. Taylor said. Reiterating that hair loss can be prevented or modified with treatment, she added that this places the emphasis on first obtaining an accurate diagnosis.

Dr. Taylor has a financial relationship with Biersdorf; Dr. Woolery-Lloyd has financial relationships with Allergan, Galderma, Ortho Diagnostics, Pfizer, and Somabella Laboratories.

NEW YORK – For unclear reasons, the prevalence of central centrifugal cicatricial alopecia (CCCA), a progressive disease of permanent hair loss, is increasing dramatically among black women, creating an urgent need for early diagnosis and treatment, according to an expert who described this phenomenon at the Skin of Color Update 2019.

Ted Bosworth/MDedge News

“CCCA has reached epidemic proportions,” contended Susan Taylor, MD, director of diversity, department of dermatology, Penn Medicine, Philadelphia.

Published data place prevalence rates of CCCA somewhere in the range of 3% to 6% among black women, but Dr. Taylor reported that she believes the condition is underdiagnosed. “I am seeing far more patients now than I was 30 years ago,” she maintained.

Others participating in the Skin of Color Update 2019 agreed. Heather Woolery-Lloyd, MD, director of ethnic skin care, department of dermatology and cutaneous surgery, University of Miami, also called the rising incidence of CCCA “an epidemic.” She, like Dr. Taylor, emphasized the critical importance of early diagnosis and treatment.

“I tell patients that if we can prevent hair loss over the next 10 years, this is a treatment success,” Dr. Woolery-Lloyd said. Although hair regrowth can be achieved in a minority of patients with treatments such as minoxidil, “the first goal is to prevent hair loss.”

Upon diagnosis, Dr. Woolery-Lloyd recommends treatment with intralesional triamcinolone and topical steroids immediately, adding other agents, such as oral antibiotics, if needed. Even in cases where CCCA has been identified before hair loss is visible, Dr. Woolery-Lloyd advised immediate therapy. Given that CCCA is a disease of reversible hair loss, she said, “do not take a wait-and-see approach.”

One potential obstacle for early diagnosis of CCCA, shared by other types of alopecia that are common in skin of color, is the failure of many clinicians to employ a standardized diagnosis in this patient population.

“If you do not have tightly coiled hair, it does not mean you cannot understand tightly coiled hair, but you have to learn, and you have to let patients know that you understand and have experience,” said Dr. Taylor, emphasizing the role of reassuring patients so they can be confident in the clinical recommendations.

Part of this reassurance will be derived from “interacting with patients in a culturally competent manner,” Dr. Taylor said. Clinicians must develop comfort and confidence in physically examining the hair and scalp, in asking patients to remove weaves or braids for a thorough inspection, and in avoiding comments that might be misinterpreted. Among these, she advised tactful questions about shampooing to avoid any implication that the clinician is implying inadequate hygiene.

When CCCA is suspected, a “biopsy is important” even in circumstances when the diagnosis seems straightforward. For one reason, a substantial proportion of patients may have a concomitant diagnosis. Dr. Taylor cited data from one study in which nearly 20% of CCCA patients also had traction alopecia and more than 10% had androgenic alopecia. Other coexisting problems identified on biopsy, including infection or seborrheic dermatitis, can help clinicians tailor a more effective intervention.

The initial signs of CCCA are typically hair breakage in the vertex of the scalp, which then expands in a central centrifugal pattern, according to Dr. Taylor. Although not all patients have signs of inflammation, such as itching and pustules, inhibition of inflammation represents the first line of therapy.

Relative to hair in the white population, the hair of black individuals grows more slowly and is more fragile, with greater amounts of breakage, said Dr. Taylor, citing published studies that support these differences. To improve early diagnosis of CCCA, understanding the hair in the black population is the first step for spotting problems in routine physical examinations. It may be this lack of familiarity that is contributing to underdiagnosis of CCCA.

“Almost 70% of African-American patients feel that physicians do not understand their hair,” Dr. Taylor said. “Let’s begin to change that.”

Cautioning that it is too often assumed that hairstyles and hair care, such as relaxants or hot combs, are the source of hair loss in black women, Dr. Taylor advised not to jump to conclusions. As an example, she described a case where weaves, braids, and other strategies were employed to mask alopecia after CCCA developed, not before.

“CCCA is the most important cause of scarring alopecia in African-American women,” Dr. Taylor said. Reiterating that hair loss can be prevented or modified with treatment, she added that this places the emphasis on first obtaining an accurate diagnosis.

Dr. Taylor has a financial relationship with Biersdorf; Dr. Woolery-Lloyd has financial relationships with Allergan, Galderma, Ortho Diagnostics, Pfizer, and Somabella Laboratories.

MADRID – Two newly published but previously reported phase 3 trials associated triple therapy in a single inhaler with a 23% reduction (P = .008) in asthma exacerbations relative to a two-drug inhaler, but fresh data from a prespecified analysis presented at the annual congress of the European Respiratory Society has identified those patients most likely to benefit.

Ted Bosworth/MDedge News

“Six easily identifiable factors appear to be associated with the most prominent response to treatment and may help in the treatment step-up decision at the point of care,” reported Dave Singh, MD, professor in the division of infection, immunity, and respiratory medicine, University of Manchester (England).

The six factors associated with a lower relative risk (RR) of severe exacerbations were derived from the phase 3 TRIMARIN and TRIGGER trials. The primary results of these trials were presented several months ago at the 2019 American Thoracic Society (ATS) meeting, but the full data were published on the day that Dr. Singh spoke at the ERS.

To identify predictors of response, the pooled analysis of TRIMARIN and TRIGGER was prespecified. Both of these trials, which were similarly designed, compared a single inhaler of inhaled corticosteroids (ICS), long-acting beta agonist (LABA), and long-acting muscarinic antagonist (LAMA) to a single ICS/LABA inhaler.

On the basis of risk for severe exacerbations, greater protection from triple therapy relative to a conventional ICS/LABA inhaler was identified for those with a high degree of reversibility (defined as greater than 400 mL) relative to those with a lower degree (RR, 0.729; P = .024), those with a body mass index less than 25 kg/m² relative to a higher BMI (RR, 0.570; P = .005), those with only one exacerbation in the previous 12 months relative to those with more (RR, 0.731; P = .009), never-smokers relative to those with smoking history (RR, 0.764; P = .013), those younger than age 65 years relative to older (RR, 0.770; P = .17), and males relative to females (RR, 0.651; P = .009).

“This gives us six factors to consider when you are thinking about stepping up to triple therapy and are trying to determine which patients would benefit the most,” Dr. Singh said.

Both the TRIMARIN and the TRIGGER trials were double blind and placebo controlled. In both, the experimental arm was a single inhaler triple therapy of the ICS beclomethasone, the LABA formoterol, and the LAMA glycopyrronium. The control arm was a single inhaler combination of beclomethasone and formoterol. All inhalers were used twice daily.

TRIMARIN, with 171 participating sites in 16 countries, randomized 1,155 patients to the triple-drug inhaler with a moderate dose of ICS (100 mcg) or to the ICS/LABA inhaler. In TRIGGER, with 221 sites in 17 countries, 1,437 patients were randomized to one of three arms. Both the triple-drug inhaler arm and the ICS/LABA arm contained a higher dose of ICS (200 mcg) than in TRIMARIN. In an open-label third arm, patients also received the higher dose of ICS plus LABA and a second inhaler with tiotropium. The formoterol dose in all arms of both studies was 6 mcg.

As reported at the ATS and now published in the Lancet, the reduction in exacerbations on single inhaler triple therapy relative to ICS/LABA was significant when the data were pooled (even though the reduction in the TRIGGER study fell short of statistical significance). The median improvement in lung function for single inhaler triple therapy relative to ICS/LABA was significant in both TRIMARIN (57 mL; P = .008) and TRIGGER (73 mL; P = .0025).

In discussing the new pooled analysis of response predictors in TRIMARIN/TRIGGER, the ERS-invited discussant, Celeste M. Porsbjerg, MD, Bispebjerg Hospital, Copenhagen, expressed particular interest in reversibility. A positive reversibility test to salbutamol was an entry criterion for both trials, but Dr. Porsbjerg pointed out that a greater response in those with the highest reversibility suggests these patients have a phenotype in which bronchodilation is a more important driver of disease than is inflammation.

While conceding that this was possible, Dr. Singh cautioned that he considers these predictors of response to be “exploratory.” He believes that the TRIMARIN/TRIGGER studies were not designed to tease out the relative importance of mechanisms of asthma in response to the assigned therapies. However, he believes the response predictor analysis is a step in this direction, which might be valuable for better individualizing therapy.

The studies were funded by Chiesi Farmaceutici. Dr. Singh reports no potential conflicts of interest.

Virchow JC et al. Lancet. 2019 Sep 30. doi. org/10.1016/S0140-6736(19)32215-9.

MADRID – Two newly published but previously reported phase 3 trials associated triple therapy in a single inhaler with a 23% reduction (P = .008) in asthma exacerbations relative to a two-drug inhaler, but fresh data from a prespecified analysis presented at the annual congress of the European Respiratory Society has identified those patients most likely to benefit.

Ted Bosworth/MDedge News

“Six easily identifiable factors appear to be associated with the most prominent response to treatment and may help in the treatment step-up decision at the point of care,” reported Dave Singh, MD, professor in the division of infection, immunity, and respiratory medicine, University of Manchester (England).

The six factors associated with a lower relative risk (RR) of severe exacerbations were derived from the phase 3 TRIMARIN and TRIGGER trials. The primary results of these trials were presented several months ago at the 2019 American Thoracic Society (ATS) meeting, but the full data were published on the day that Dr. Singh spoke at the ERS.

To identify predictors of response, the pooled analysis of TRIMARIN and TRIGGER was prespecified. Both of these trials, which were similarly designed, compared a single inhaler of inhaled corticosteroids (ICS), long-acting beta agonist (LABA), and long-acting muscarinic antagonist (LAMA) to a single ICS/LABA inhaler.

On the basis of risk for severe exacerbations, greater protection from triple therapy relative to a conventional ICS/LABA inhaler was identified for those with a high degree of reversibility (defined as greater than 400 mL) relative to those with a lower degree (RR, 0.729; P = .024), those with a body mass index less than 25 kg/m² relative to a higher BMI (RR, 0.570; P = .005), those with only one exacerbation in the previous 12 months relative to those with more (RR, 0.731; P = .009), never-smokers relative to those with smoking history (RR, 0.764; P = .013), those younger than age 65 years relative to older (RR, 0.770; P = .17), and males relative to females (RR, 0.651; P = .009).

“This gives us six factors to consider when you are thinking about stepping up to triple therapy and are trying to determine which patients would benefit the most,” Dr. Singh said.

Both the TRIMARIN and the TRIGGER trials were double blind and placebo controlled. In both, the experimental arm was a single inhaler triple therapy of the ICS beclomethasone, the LABA formoterol, and the LAMA glycopyrronium. The control arm was a single inhaler combination of beclomethasone and formoterol. All inhalers were used twice daily.

TRIMARIN, with 171 participating sites in 16 countries, randomized 1,155 patients to the triple-drug inhaler with a moderate dose of ICS (100 mcg) or to the ICS/LABA inhaler. In TRIGGER, with 221 sites in 17 countries, 1,437 patients were randomized to one of three arms. Both the triple-drug inhaler arm and the ICS/LABA arm contained a higher dose of ICS (200 mcg) than in TRIMARIN. In an open-label third arm, patients also received the higher dose of ICS plus LABA and a second inhaler with tiotropium. The formoterol dose in all arms of both studies was 6 mcg.

As reported at the ATS and now published in the Lancet, the reduction in exacerbations on single inhaler triple therapy relative to ICS/LABA was significant when the data were pooled (even though the reduction in the TRIGGER study fell short of statistical significance). The median improvement in lung function for single inhaler triple therapy relative to ICS/LABA was significant in both TRIMARIN (57 mL; P = .008) and TRIGGER (73 mL; P = .0025).

In discussing the new pooled analysis of response predictors in TRIMARIN/TRIGGER, the ERS-invited discussant, Celeste M. Porsbjerg, MD, Bispebjerg Hospital, Copenhagen, expressed particular interest in reversibility. A positive reversibility test to salbutamol was an entry criterion for both trials, but Dr. Porsbjerg pointed out that a greater response in those with the highest reversibility suggests these patients have a phenotype in which bronchodilation is a more important driver of disease than is inflammation.

While conceding that this was possible, Dr. Singh cautioned that he considers these predictors of response to be “exploratory.” He believes that the TRIMARIN/TRIGGER studies were not designed to tease out the relative importance of mechanisms of asthma in response to the assigned therapies. However, he believes the response predictor analysis is a step in this direction, which might be valuable for better individualizing therapy.

The studies were funded by Chiesi Farmaceutici. Dr. Singh reports no potential conflicts of interest.

Virchow JC et al. Lancet. 2019 Sep 30. doi. org/10.1016/S0140-6736(19)32215-9.

MADRID – Two newly published but previously reported phase 3 trials associated triple therapy in a single inhaler with a 23% reduction (P = .008) in asthma exacerbations relative to a two-drug inhaler, but fresh data from a prespecified analysis presented at the annual congress of the European Respiratory Society has identified those patients most likely to benefit.

Ted Bosworth/MDedge News

“Six easily identifiable factors appear to be associated with the most prominent response to treatment and may help in the treatment step-up decision at the point of care,” reported Dave Singh, MD, professor in the division of infection, immunity, and respiratory medicine, University of Manchester (England).

The six factors associated with a lower relative risk (RR) of severe exacerbations were derived from the phase 3 TRIMARIN and TRIGGER trials. The primary results of these trials were presented several months ago at the 2019 American Thoracic Society (ATS) meeting, but the full data were published on the day that Dr. Singh spoke at the ERS.

To identify predictors of response, the pooled analysis of TRIMARIN and TRIGGER was prespecified. Both of these trials, which were similarly designed, compared a single inhaler of inhaled corticosteroids (ICS), long-acting beta agonist (LABA), and long-acting muscarinic antagonist (LAMA) to a single ICS/LABA inhaler.

On the basis of risk for severe exacerbations, greater protection from triple therapy relative to a conventional ICS/LABA inhaler was identified for those with a high degree of reversibility (defined as greater than 400 mL) relative to those with a lower degree (RR, 0.729; P = .024), those with a body mass index less than 25 kg/m² relative to a higher BMI (RR, 0.570; P = .005), those with only one exacerbation in the previous 12 months relative to those with more (RR, 0.731; P = .009), never-smokers relative to those with smoking history (RR, 0.764; P = .013), those younger than age 65 years relative to older (RR, 0.770; P = .17), and males relative to females (RR, 0.651; P = .009).

“This gives us six factors to consider when you are thinking about stepping up to triple therapy and are trying to determine which patients would benefit the most,” Dr. Singh said.

Both the TRIMARIN and the TRIGGER trials were double blind and placebo controlled. In both, the experimental arm was a single inhaler triple therapy of the ICS beclomethasone, the LABA formoterol, and the LAMA glycopyrronium. The control arm was a single inhaler combination of beclomethasone and formoterol. All inhalers were used twice daily.

TRIMARIN, with 171 participating sites in 16 countries, randomized 1,155 patients to the triple-drug inhaler with a moderate dose of ICS (100 mcg) or to the ICS/LABA inhaler. In TRIGGER, with 221 sites in 17 countries, 1,437 patients were randomized to one of three arms. Both the triple-drug inhaler arm and the ICS/LABA arm contained a higher dose of ICS (200 mcg) than in TRIMARIN. In an open-label third arm, patients also received the higher dose of ICS plus LABA and a second inhaler with tiotropium. The formoterol dose in all arms of both studies was 6 mcg.

As reported at the ATS and now published in the Lancet, the reduction in exacerbations on single inhaler triple therapy relative to ICS/LABA was significant when the data were pooled (even though the reduction in the TRIGGER study fell short of statistical significance). The median improvement in lung function for single inhaler triple therapy relative to ICS/LABA was significant in both TRIMARIN (57 mL; P = .008) and TRIGGER (73 mL; P = .0025).

In discussing the new pooled analysis of response predictors in TRIMARIN/TRIGGER, the ERS-invited discussant, Celeste M. Porsbjerg, MD, Bispebjerg Hospital, Copenhagen, expressed particular interest in reversibility. A positive reversibility test to salbutamol was an entry criterion for both trials, but Dr. Porsbjerg pointed out that a greater response in those with the highest reversibility suggests these patients have a phenotype in which bronchodilation is a more important driver of disease than is inflammation.

While conceding that this was possible, Dr. Singh cautioned that he considers these predictors of response to be “exploratory.” He believes that the TRIMARIN/TRIGGER studies were not designed to tease out the relative importance of mechanisms of asthma in response to the assigned therapies. However, he believes the response predictor analysis is a step in this direction, which might be valuable for better individualizing therapy.

The studies were funded by Chiesi Farmaceutici. Dr. Singh reports no potential conflicts of interest.

Virchow JC et al. Lancet. 2019 Sep 30. doi. org/10.1016/S0140-6736(19)32215-9.

MADRID – Pirfenidone was shown to be effective for slowing decline in lung function among patients with unclassifiable interstitial lung diseases (uILD), according to results of a late breaker, placebo-controlled, multinational trial presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

For preservation of lung function as monitored with forced vital capacity (FVC), pirfenidone provided a large and highly statistically significant advantage over placebo in a phase 2 trial that randomized 253 uILD patients to 2,403 mg pirfenidone or placebo, according to Toby M. Maher, MD, head of the Fibrosis Research Group for the National Heart and Lung Institute, Imperial College, London.

At 24 weeks, FVC lung function declined by just 17.8 mL in the pirfenidone group vs. 113 mL in the placebo group (P = .002). The results, published simultaneously with Dr. Maher’s ERS presentation in The Lancet Respiratory Medicine, are particularly encouraging because there are no currently approved treatments for uILD, according to Dr. Maher.

However, the data from this study, even though it was double blind and involved 70 participating centers in 14 countries, come with an asterisk. The significant FVC advantage was documented with in-hospital measurements, but this was a secondary, not the primary, endpoint. Measurements with hand-held spirometry, which was the primary endpoint, proved to be uninterpretable due to intra-individual variability.

“We had hoped that daily home spirometry would give us more information of the patient’s trajectory over time,” said Dr. Maher, who blames himself for selecting hand-held device measurements as the primary endpoint. In the end, the variability in the home hand-held spirometry data prevented the planned statistical testing.

“There were issues with the hand-held devices we had not anticipated,” Dr. Maher reported. However, hospital-based measurement, which has long been the “regulatory standard” in ILD trials “supports the conclusion that pirfenidone was effective.”

The conclusion is also supported by other secondary outcomes and analyses. For example, the categorical declines in FVC of greater than 5% (37.0% vs. 58.7%; P = .001) and greater than 10% (14.2% vs. 27.9%; P = .011) both favored pirfenidone. There were no between-group differences in progression-free survival at 24 weeks, but events were low in both study arms over this time period.

There was evidence of functional benefit for pirfenidone relative to placebo, such as a smaller decline in the 6-minute walk test (–2 vs. –26.7 M, P = .04). Treatment favoring pirfenidone over placebo was observed across subgroups defined by age, gender, baseline lung function, and presence or absence of interstitial pneumonia with autoimmune features.

Pirfenidone was generally well tolerated with side effects similar to those reported in other studies. The rate of treatment-related discontinuation was 12.6% on pirfenidone versus 0.8% on placebo. The most frequent adverse events, all of which were more common in the pirfenidone group, were gastrointestinal complaints (47.2% vs. 25.8%), rash (10.2% vs. 7.3%), and dizziness (7.9% vs. 0.8%). Rates of photosensitivity were higher in the experimental arm (7.9% vs. 1.8%), but low relative to previous studies, potentially because of greater emphasis on sun protection, Dr. Maher reported.

About 10%-15% of patients with ILD have an unclassifiable type, he noted. Although it is possible for uILD to be a missed diagnosis of an established ILD type, Dr. Maher reported that participating centers for this study were specifically selected for their expertise in ILD. He noted that more than 45% of patients were deemed uILD on the basis of biopsy.

The ERS-invited discussant of this trial, Martin Kolb, MD, professor of respirology, McMaster University, Hamilton, Ont., called the data “strong.” He suggested the data are particularly encouraging in the context of the lack of approved therapies for uILD.

Despite the fact that benefit of pirfenidone was not established on the primary endpoint, Dr. Maher contended that this is a positive study that can be used to design future investigations. “When we use the normal standard endpoint for the study, we see a clear benefit of pirfenidone over placebo.”

Dr. Maher reported no potential conflicts of interest.

SOURCE: Maher TM et al. Lancet Respir Med. 2019 Sep 29. doi: 10.1016/S2213-2600(19)30341-8.

MADRID – Pirfenidone was shown to be effective for slowing decline in lung function among patients with unclassifiable interstitial lung diseases (uILD), according to results of a late breaker, placebo-controlled, multinational trial presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

For preservation of lung function as monitored with forced vital capacity (FVC), pirfenidone provided a large and highly statistically significant advantage over placebo in a phase 2 trial that randomized 253 uILD patients to 2,403 mg pirfenidone or placebo, according to Toby M. Maher, MD, head of the Fibrosis Research Group for the National Heart and Lung Institute, Imperial College, London.

At 24 weeks, FVC lung function declined by just 17.8 mL in the pirfenidone group vs. 113 mL in the placebo group (P = .002). The results, published simultaneously with Dr. Maher’s ERS presentation in The Lancet Respiratory Medicine, are particularly encouraging because there are no currently approved treatments for uILD, according to Dr. Maher.

However, the data from this study, even though it was double blind and involved 70 participating centers in 14 countries, come with an asterisk. The significant FVC advantage was documented with in-hospital measurements, but this was a secondary, not the primary, endpoint. Measurements with hand-held spirometry, which was the primary endpoint, proved to be uninterpretable due to intra-individual variability.

“We had hoped that daily home spirometry would give us more information of the patient’s trajectory over time,” said Dr. Maher, who blames himself for selecting hand-held device measurements as the primary endpoint. In the end, the variability in the home hand-held spirometry data prevented the planned statistical testing.

“There were issues with the hand-held devices we had not anticipated,” Dr. Maher reported. However, hospital-based measurement, which has long been the “regulatory standard” in ILD trials “supports the conclusion that pirfenidone was effective.”

The conclusion is also supported by other secondary outcomes and analyses. For example, the categorical declines in FVC of greater than 5% (37.0% vs. 58.7%; P = .001) and greater than 10% (14.2% vs. 27.9%; P = .011) both favored pirfenidone. There were no between-group differences in progression-free survival at 24 weeks, but events were low in both study arms over this time period.

There was evidence of functional benefit for pirfenidone relative to placebo, such as a smaller decline in the 6-minute walk test (–2 vs. –26.7 M, P = .04). Treatment favoring pirfenidone over placebo was observed across subgroups defined by age, gender, baseline lung function, and presence or absence of interstitial pneumonia with autoimmune features.

Pirfenidone was generally well tolerated with side effects similar to those reported in other studies. The rate of treatment-related discontinuation was 12.6% on pirfenidone versus 0.8% on placebo. The most frequent adverse events, all of which were more common in the pirfenidone group, were gastrointestinal complaints (47.2% vs. 25.8%), rash (10.2% vs. 7.3%), and dizziness (7.9% vs. 0.8%). Rates of photosensitivity were higher in the experimental arm (7.9% vs. 1.8%), but low relative to previous studies, potentially because of greater emphasis on sun protection, Dr. Maher reported.

About 10%-15% of patients with ILD have an unclassifiable type, he noted. Although it is possible for uILD to be a missed diagnosis of an established ILD type, Dr. Maher reported that participating centers for this study were specifically selected for their expertise in ILD. He noted that more than 45% of patients were deemed uILD on the basis of biopsy.

The ERS-invited discussant of this trial, Martin Kolb, MD, professor of respirology, McMaster University, Hamilton, Ont., called the data “strong.” He suggested the data are particularly encouraging in the context of the lack of approved therapies for uILD.

Despite the fact that benefit of pirfenidone was not established on the primary endpoint, Dr. Maher contended that this is a positive study that can be used to design future investigations. “When we use the normal standard endpoint for the study, we see a clear benefit of pirfenidone over placebo.”

Dr. Maher reported no potential conflicts of interest.

SOURCE: Maher TM et al. Lancet Respir Med. 2019 Sep 29. doi: 10.1016/S2213-2600(19)30341-8.

MADRID – Pirfenidone was shown to be effective for slowing decline in lung function among patients with unclassifiable interstitial lung diseases (uILD), according to results of a late breaker, placebo-controlled, multinational trial presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

For preservation of lung function as monitored with forced vital capacity (FVC), pirfenidone provided a large and highly statistically significant advantage over placebo in a phase 2 trial that randomized 253 uILD patients to 2,403 mg pirfenidone or placebo, according to Toby M. Maher, MD, head of the Fibrosis Research Group for the National Heart and Lung Institute, Imperial College, London.

At 24 weeks, FVC lung function declined by just 17.8 mL in the pirfenidone group vs. 113 mL in the placebo group (P = .002). The results, published simultaneously with Dr. Maher’s ERS presentation in The Lancet Respiratory Medicine, are particularly encouraging because there are no currently approved treatments for uILD, according to Dr. Maher.

However, the data from this study, even though it was double blind and involved 70 participating centers in 14 countries, come with an asterisk. The significant FVC advantage was documented with in-hospital measurements, but this was a secondary, not the primary, endpoint. Measurements with hand-held spirometry, which was the primary endpoint, proved to be uninterpretable due to intra-individual variability.

“We had hoped that daily home spirometry would give us more information of the patient’s trajectory over time,” said Dr. Maher, who blames himself for selecting hand-held device measurements as the primary endpoint. In the end, the variability in the home hand-held spirometry data prevented the planned statistical testing.

“There were issues with the hand-held devices we had not anticipated,” Dr. Maher reported. However, hospital-based measurement, which has long been the “regulatory standard” in ILD trials “supports the conclusion that pirfenidone was effective.”

The conclusion is also supported by other secondary outcomes and analyses. For example, the categorical declines in FVC of greater than 5% (37.0% vs. 58.7%; P = .001) and greater than 10% (14.2% vs. 27.9%; P = .011) both favored pirfenidone. There were no between-group differences in progression-free survival at 24 weeks, but events were low in both study arms over this time period.

There was evidence of functional benefit for pirfenidone relative to placebo, such as a smaller decline in the 6-minute walk test (–2 vs. –26.7 M, P = .04). Treatment favoring pirfenidone over placebo was observed across subgroups defined by age, gender, baseline lung function, and presence or absence of interstitial pneumonia with autoimmune features.

Pirfenidone was generally well tolerated with side effects similar to those reported in other studies. The rate of treatment-related discontinuation was 12.6% on pirfenidone versus 0.8% on placebo. The most frequent adverse events, all of which were more common in the pirfenidone group, were gastrointestinal complaints (47.2% vs. 25.8%), rash (10.2% vs. 7.3%), and dizziness (7.9% vs. 0.8%). Rates of photosensitivity were higher in the experimental arm (7.9% vs. 1.8%), but low relative to previous studies, potentially because of greater emphasis on sun protection, Dr. Maher reported.

About 10%-15% of patients with ILD have an unclassifiable type, he noted. Although it is possible for uILD to be a missed diagnosis of an established ILD type, Dr. Maher reported that participating centers for this study were specifically selected for their expertise in ILD. He noted that more than 45% of patients were deemed uILD on the basis of biopsy.

The ERS-invited discussant of this trial, Martin Kolb, MD, professor of respirology, McMaster University, Hamilton, Ont., called the data “strong.” He suggested the data are particularly encouraging in the context of the lack of approved therapies for uILD.

Despite the fact that benefit of pirfenidone was not established on the primary endpoint, Dr. Maher contended that this is a positive study that can be used to design future investigations. “When we use the normal standard endpoint for the study, we see a clear benefit of pirfenidone over placebo.”

Dr. Maher reported no potential conflicts of interest.

SOURCE: Maher TM et al. Lancet Respir Med. 2019 Sep 29. doi: 10.1016/S2213-2600(19)30341-8.

MADRID – In patients with fibrosing lung diseases other than idiopathic pulmonary fibrosis (IPF), nintedanib, a tyrosine kinase inhibitor, substantially reduced the rate of decline in lung function, according to findings from a phase 3, placebo-controlled trial presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

The trial, called INBUILD, enrolled patients who had a progressive lung disease with a fibrosing phenotype, such as interstitial pneumonia with autoimmune features (IPAF) or noninterstitial pneumonia (NSIP), on the premise that these conditions might share a pathology responsive to a common therapy, explained Kevin R. Flaherty, MD, of National Jewish Health, Denver. The INBUILD trial was a randomized, double-blind, placebo-controlled, parallel-group trial conducted at 153 sites in 15 countries. A total of 663 patients underwent randomization and received at least one dose of nintedanib (332) or placebo (331).

Patients with fibrosing lung disease affecting more than 10% of lung volume were randomized to 150 mg twice daily of nintedanib, which inhibits intracellular growth factors implicated in fibrosis and is already indicated for IPF, or matching placebo.

On the primary endpoint of change in forced vital capacity (FVC) at 52 weeks, those in the nintedanib arm lost lung function at a rate that was less than half that of those randomized to placebo (–80.8 vs. –187.8 mL/year; P less than .001).

In a preplanned stratification, the protection from nintedanib against a decline in lung function was found to be at least as good in those with a usual interstitial pneumonia (UIP-like) pattern of fibrosis on baseline imaging (–82.9 vs. –211.1 mL/year), compared with those with other fibrotic patterns (–79.0 vs. –154.2 mL/year). The UIP-like subgroup represented about 60% of those enrolled.

“The relative protection from decline in lung function supports the hypothesis that progressive fibrosing interstitial lung diseases have a similar pathobiologic mechanism,” said Dr. Flaherty. Results from the INBUILD were published simultaneously with his ERS presentation (N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681).

The curves documenting change of lung function in favor of nintedanib relative to placebo separated within 12 weeks of treatment initiation, according to Dr. Flaherty. The ERS-invited discussant, Martin Kolb, MD, PhD, professor of respirology, McMaster University, Hamilton, Ont., called the reductions in loss of lung function “profound” and “very impactful.”

However, despite these reductions, there was no significant difference in quality of life as measured with the King’s Brief Interstitial Lung Disease (KBILD) questionnaire, which was a secondary outcome. The problem was that there was little change in KBILD in either group at 52 weeks, limiting the ability to show differences.

The rates of death were numerically lower at 52 weeks in the nintedanib arm for the study overall (4.8% vs. 5.1%) and for the UIP-like subgroup (5.3% vs. 7.8%), but the differences did not reach statistical significance.

A suggestion of benefit was derived from a design feature of INBUILD that called for patients to remain on blinded therapy until all enrolled patients completed the trial. When the effect of nintedanib was evaluated in this extended analysis, the event curves for the combined endpoint of interstitial lung disease or death separated and approached significance.

In this extended analysis, which suggests that clinical benefit is likely to accrue after longer periods of treatment, “we saw similar trends when we looked at mortality as an independent outcome,” Dr. Flaherty reported.

More patients in the nintedanib group discontinued therapy because of adverse events (19.6% vs. 10.3%), but Dr. Flaherty characterized the rate of serious adverse events as “similar.” He made this statement even though several adverse events, particularly those involving the gastrointestinal tract, such as diarrhea (66.9% vs. 23.9%), nausea (28.9% vs. 9.4%), vomiting (18.4% vs. 5.1%), and abdominal pain (10.2% vs. 2.4%), were higher in the nintedanib arm.

The INBUILD trial demonstrates that nintedanib preserves lung function in fibrosing lung diseases other than IPF. In his review of this paper, Dr. Kolb pointed out that non-IPF etiologies represent about 75% of interstitial lung diseases. For these patients “we have no drugs, so there is a big medical need.”

Dr. Flaherty reports no potential conflicts of interest. The study was funded by Boehringer-Ingelheim, which produces nintedanib.

SOURCE: Flaherty KR et al. N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681.

MADRID – In patients with fibrosing lung diseases other than idiopathic pulmonary fibrosis (IPF), nintedanib, a tyrosine kinase inhibitor, substantially reduced the rate of decline in lung function, according to findings from a phase 3, placebo-controlled trial presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

The trial, called INBUILD, enrolled patients who had a progressive lung disease with a fibrosing phenotype, such as interstitial pneumonia with autoimmune features (IPAF) or noninterstitial pneumonia (NSIP), on the premise that these conditions might share a pathology responsive to a common therapy, explained Kevin R. Flaherty, MD, of National Jewish Health, Denver. The INBUILD trial was a randomized, double-blind, placebo-controlled, parallel-group trial conducted at 153 sites in 15 countries. A total of 663 patients underwent randomization and received at least one dose of nintedanib (332) or placebo (331).

Patients with fibrosing lung disease affecting more than 10% of lung volume were randomized to 150 mg twice daily of nintedanib, which inhibits intracellular growth factors implicated in fibrosis and is already indicated for IPF, or matching placebo.

On the primary endpoint of change in forced vital capacity (FVC) at 52 weeks, those in the nintedanib arm lost lung function at a rate that was less than half that of those randomized to placebo (–80.8 vs. –187.8 mL/year; P less than .001).

In a preplanned stratification, the protection from nintedanib against a decline in lung function was found to be at least as good in those with a usual interstitial pneumonia (UIP-like) pattern of fibrosis on baseline imaging (–82.9 vs. –211.1 mL/year), compared with those with other fibrotic patterns (–79.0 vs. –154.2 mL/year). The UIP-like subgroup represented about 60% of those enrolled.

“The relative protection from decline in lung function supports the hypothesis that progressive fibrosing interstitial lung diseases have a similar pathobiologic mechanism,” said Dr. Flaherty. Results from the INBUILD were published simultaneously with his ERS presentation (N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681).

The curves documenting change of lung function in favor of nintedanib relative to placebo separated within 12 weeks of treatment initiation, according to Dr. Flaherty. The ERS-invited discussant, Martin Kolb, MD, PhD, professor of respirology, McMaster University, Hamilton, Ont., called the reductions in loss of lung function “profound” and “very impactful.”

However, despite these reductions, there was no significant difference in quality of life as measured with the King’s Brief Interstitial Lung Disease (KBILD) questionnaire, which was a secondary outcome. The problem was that there was little change in KBILD in either group at 52 weeks, limiting the ability to show differences.

The rates of death were numerically lower at 52 weeks in the nintedanib arm for the study overall (4.8% vs. 5.1%) and for the UIP-like subgroup (5.3% vs. 7.8%), but the differences did not reach statistical significance.

A suggestion of benefit was derived from a design feature of INBUILD that called for patients to remain on blinded therapy until all enrolled patients completed the trial. When the effect of nintedanib was evaluated in this extended analysis, the event curves for the combined endpoint of interstitial lung disease or death separated and approached significance.

In this extended analysis, which suggests that clinical benefit is likely to accrue after longer periods of treatment, “we saw similar trends when we looked at mortality as an independent outcome,” Dr. Flaherty reported.

More patients in the nintedanib group discontinued therapy because of adverse events (19.6% vs. 10.3%), but Dr. Flaherty characterized the rate of serious adverse events as “similar.” He made this statement even though several adverse events, particularly those involving the gastrointestinal tract, such as diarrhea (66.9% vs. 23.9%), nausea (28.9% vs. 9.4%), vomiting (18.4% vs. 5.1%), and abdominal pain (10.2% vs. 2.4%), were higher in the nintedanib arm.

The INBUILD trial demonstrates that nintedanib preserves lung function in fibrosing lung diseases other than IPF. In his review of this paper, Dr. Kolb pointed out that non-IPF etiologies represent about 75% of interstitial lung diseases. For these patients “we have no drugs, so there is a big medical need.”

Dr. Flaherty reports no potential conflicts of interest. The study was funded by Boehringer-Ingelheim, which produces nintedanib.

SOURCE: Flaherty KR et al. N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681.

MADRID – In patients with fibrosing lung diseases other than idiopathic pulmonary fibrosis (IPF), nintedanib, a tyrosine kinase inhibitor, substantially reduced the rate of decline in lung function, according to findings from a phase 3, placebo-controlled trial presented at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge News

The trial, called INBUILD, enrolled patients who had a progressive lung disease with a fibrosing phenotype, such as interstitial pneumonia with autoimmune features (IPAF) or noninterstitial pneumonia (NSIP), on the premise that these conditions might share a pathology responsive to a common therapy, explained Kevin R. Flaherty, MD, of National Jewish Health, Denver. The INBUILD trial was a randomized, double-blind, placebo-controlled, parallel-group trial conducted at 153 sites in 15 countries. A total of 663 patients underwent randomization and received at least one dose of nintedanib (332) or placebo (331).

Patients with fibrosing lung disease affecting more than 10% of lung volume were randomized to 150 mg twice daily of nintedanib, which inhibits intracellular growth factors implicated in fibrosis and is already indicated for IPF, or matching placebo.

On the primary endpoint of change in forced vital capacity (FVC) at 52 weeks, those in the nintedanib arm lost lung function at a rate that was less than half that of those randomized to placebo (–80.8 vs. –187.8 mL/year; P less than .001).

In a preplanned stratification, the protection from nintedanib against a decline in lung function was found to be at least as good in those with a usual interstitial pneumonia (UIP-like) pattern of fibrosis on baseline imaging (–82.9 vs. –211.1 mL/year), compared with those with other fibrotic patterns (–79.0 vs. –154.2 mL/year). The UIP-like subgroup represented about 60% of those enrolled.

“The relative protection from decline in lung function supports the hypothesis that progressive fibrosing interstitial lung diseases have a similar pathobiologic mechanism,” said Dr. Flaherty. Results from the INBUILD were published simultaneously with his ERS presentation (N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681).

The curves documenting change of lung function in favor of nintedanib relative to placebo separated within 12 weeks of treatment initiation, according to Dr. Flaherty. The ERS-invited discussant, Martin Kolb, MD, PhD, professor of respirology, McMaster University, Hamilton, Ont., called the reductions in loss of lung function “profound” and “very impactful.”

However, despite these reductions, there was no significant difference in quality of life as measured with the King’s Brief Interstitial Lung Disease (KBILD) questionnaire, which was a secondary outcome. The problem was that there was little change in KBILD in either group at 52 weeks, limiting the ability to show differences.

The rates of death were numerically lower at 52 weeks in the nintedanib arm for the study overall (4.8% vs. 5.1%) and for the UIP-like subgroup (5.3% vs. 7.8%), but the differences did not reach statistical significance.

A suggestion of benefit was derived from a design feature of INBUILD that called for patients to remain on blinded therapy until all enrolled patients completed the trial. When the effect of nintedanib was evaluated in this extended analysis, the event curves for the combined endpoint of interstitial lung disease or death separated and approached significance.

In this extended analysis, which suggests that clinical benefit is likely to accrue after longer periods of treatment, “we saw similar trends when we looked at mortality as an independent outcome,” Dr. Flaherty reported.

More patients in the nintedanib group discontinued therapy because of adverse events (19.6% vs. 10.3%), but Dr. Flaherty characterized the rate of serious adverse events as “similar.” He made this statement even though several adverse events, particularly those involving the gastrointestinal tract, such as diarrhea (66.9% vs. 23.9%), nausea (28.9% vs. 9.4%), vomiting (18.4% vs. 5.1%), and abdominal pain (10.2% vs. 2.4%), were higher in the nintedanib arm.

The INBUILD trial demonstrates that nintedanib preserves lung function in fibrosing lung diseases other than IPF. In his review of this paper, Dr. Kolb pointed out that non-IPF etiologies represent about 75% of interstitial lung diseases. For these patients “we have no drugs, so there is a big medical need.”

Dr. Flaherty reports no potential conflicts of interest. The study was funded by Boehringer-Ingelheim, which produces nintedanib.

SOURCE: Flaherty KR et al. N Engl J Med. 2019 Sep 29. doi: 10.1056/NEJMoa1908681.