Steve Cimino

A new study has found that although dose escalation is common in RA patients being treated with infliximab, the low price of infliximab biosimilars that are currently commercially available in the United States often outweighs switching to a similarly administered tumor necrosis factor inhibitor with no biosimilar, such as intravenous golimumab (Simponi).

anttohoho/Thinkstock

“Given the 21% lower average sales price [ASP] of biosimilar infliximab-dyyb [Inflectra], as compared to the ASP of bio-originator infliximab, in Q3 2019, even infliximab dose[d] at 8 mg/kg [every] 6 weeks should be approximately neutral or cost saving, compared to golimumab IV,” wrote Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and coauthors. The study was published in Arthritis Research & Therapy.

To determine if and when dose escalation of an infliximab biosimilar might offset the cost savings of its use, the researchers launched a cohort study of Medicare enrollees with RA who began treatment in 2013 (when intravenous golimumab first went on the market) through the end of 2016 (biosimilar infliximab-dyyb was first marketed in the United States in November 2016). They analyzed dose escalations and reimbursement amounts through 78 weeks for 5,174 patients who started infliximab and 2,843 patients who started golimumab. The golimumab patients were slightly older (70 years vs. 68.6 years) and more likely to receive monotherapy.

After 18 months, 5% of golimumab patients increased their dose, compared with 49% of infliximab patients (P less than .0001). Of patients who had no gap in infliximab treatment for greater than 10 weeks (n = 1,380), 72% had their dose escalated. Characteristics associated with dose escalation included being younger, being male, and not having chronic pulmonary disease. Physicians who owned their own infusion centers were 25% more likely to escalate doses of infliximab (adjusted odds ratio, 1.25; 95% confidence interval, 1.09-1.44).

Mean costs paid by Medicare for the first 18 months of treatment were significantly higher for golimumab ($28,146; 95% CI, $27,497-$28,810), compared with infliximab ($21,216; 95% CI, $20,737-$21,706). An analysis of patients who persisted on therapy for all 18 months with no treatment gap greater than 10 weeks revealed an even greater disparity in cost: $43,940 for golimumab (95% CI, $42,849-$45,058) versus $34,671 for infliximab (95% CI, $33,891-$35,470).

According to a sensitivity analysis, 34% of infliximab-treated patients increased their dose to 5 mg/kg, 5% increased their dose to 8 mg/kg, and 4% increased their dose to 10 mg/kg. In a modeling scenario that considered cost, dose, and frequency, infliximab at 8 mg/kg dosed every 6 weeks was cheaper than golimumab with a biosimilar discount of greater than 25%. At 10 mg/kg dosed every 6 weeks, infliximab was cheaper than golimumab with a biosimilar discount of 30% or more.

That said, given comparable clinical outcomes with other RA biologics plus the increased indirect costs and greater risk of serious infections associated with infliximab dose escalation, the researchers noted that “escalation beyond 5 mg/kg is probably not a prudent course of treatment for most RA patients, compared to switching to alternative treatment options.”

Though they emphasized their study’s strengths – including the impressive sample size of older Medicare patients – the authors also acknowledged its limitations, such as a lack of information on the clinical reasons for treatment discontinuation and dose escalation. They also were not able to examine whether safety or tolerability played a role in patients’ treatment decisions.

Two of the four authors reported receiving research grants and consulting fees from various medical and pharmaceutical companies, and one other author reported owning stock in Amgen.

SOURCE: Curtis JR et al. Arthritis Res Ther. 2019 Dec 12. doi: 10.1186/s13075-019-2022-8.

A new study has found that although dose escalation is common in RA patients being treated with infliximab, the low price of infliximab biosimilars that are currently commercially available in the United States often outweighs switching to a similarly administered tumor necrosis factor inhibitor with no biosimilar, such as intravenous golimumab (Simponi).

anttohoho/Thinkstock

“Given the 21% lower average sales price [ASP] of biosimilar infliximab-dyyb [Inflectra], as compared to the ASP of bio-originator infliximab, in Q3 2019, even infliximab dose[d] at 8 mg/kg [every] 6 weeks should be approximately neutral or cost saving, compared to golimumab IV,” wrote Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and coauthors. The study was published in Arthritis Research & Therapy.

To determine if and when dose escalation of an infliximab biosimilar might offset the cost savings of its use, the researchers launched a cohort study of Medicare enrollees with RA who began treatment in 2013 (when intravenous golimumab first went on the market) through the end of 2016 (biosimilar infliximab-dyyb was first marketed in the United States in November 2016). They analyzed dose escalations and reimbursement amounts through 78 weeks for 5,174 patients who started infliximab and 2,843 patients who started golimumab. The golimumab patients were slightly older (70 years vs. 68.6 years) and more likely to receive monotherapy.

After 18 months, 5% of golimumab patients increased their dose, compared with 49% of infliximab patients (P less than .0001). Of patients who had no gap in infliximab treatment for greater than 10 weeks (n = 1,380), 72% had their dose escalated. Characteristics associated with dose escalation included being younger, being male, and not having chronic pulmonary disease. Physicians who owned their own infusion centers were 25% more likely to escalate doses of infliximab (adjusted odds ratio, 1.25; 95% confidence interval, 1.09-1.44).

Mean costs paid by Medicare for the first 18 months of treatment were significantly higher for golimumab ($28,146; 95% CI, $27,497-$28,810), compared with infliximab ($21,216; 95% CI, $20,737-$21,706). An analysis of patients who persisted on therapy for all 18 months with no treatment gap greater than 10 weeks revealed an even greater disparity in cost: $43,940 for golimumab (95% CI, $42,849-$45,058) versus $34,671 for infliximab (95% CI, $33,891-$35,470).

According to a sensitivity analysis, 34% of infliximab-treated patients increased their dose to 5 mg/kg, 5% increased their dose to 8 mg/kg, and 4% increased their dose to 10 mg/kg. In a modeling scenario that considered cost, dose, and frequency, infliximab at 8 mg/kg dosed every 6 weeks was cheaper than golimumab with a biosimilar discount of greater than 25%. At 10 mg/kg dosed every 6 weeks, infliximab was cheaper than golimumab with a biosimilar discount of 30% or more.

That said, given comparable clinical outcomes with other RA biologics plus the increased indirect costs and greater risk of serious infections associated with infliximab dose escalation, the researchers noted that “escalation beyond 5 mg/kg is probably not a prudent course of treatment for most RA patients, compared to switching to alternative treatment options.”

Though they emphasized their study’s strengths – including the impressive sample size of older Medicare patients – the authors also acknowledged its limitations, such as a lack of information on the clinical reasons for treatment discontinuation and dose escalation. They also were not able to examine whether safety or tolerability played a role in patients’ treatment decisions.

Two of the four authors reported receiving research grants and consulting fees from various medical and pharmaceutical companies, and one other author reported owning stock in Amgen.

SOURCE: Curtis JR et al. Arthritis Res Ther. 2019 Dec 12. doi: 10.1186/s13075-019-2022-8.

A new study has found that although dose escalation is common in RA patients being treated with infliximab, the low price of infliximab biosimilars that are currently commercially available in the United States often outweighs switching to a similarly administered tumor necrosis factor inhibitor with no biosimilar, such as intravenous golimumab (Simponi).

anttohoho/Thinkstock

“Given the 21% lower average sales price [ASP] of biosimilar infliximab-dyyb [Inflectra], as compared to the ASP of bio-originator infliximab, in Q3 2019, even infliximab dose[d] at 8 mg/kg [every] 6 weeks should be approximately neutral or cost saving, compared to golimumab IV,” wrote Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and coauthors. The study was published in Arthritis Research & Therapy.

To determine if and when dose escalation of an infliximab biosimilar might offset the cost savings of its use, the researchers launched a cohort study of Medicare enrollees with RA who began treatment in 2013 (when intravenous golimumab first went on the market) through the end of 2016 (biosimilar infliximab-dyyb was first marketed in the United States in November 2016). They analyzed dose escalations and reimbursement amounts through 78 weeks for 5,174 patients who started infliximab and 2,843 patients who started golimumab. The golimumab patients were slightly older (70 years vs. 68.6 years) and more likely to receive monotherapy.

After 18 months, 5% of golimumab patients increased their dose, compared with 49% of infliximab patients (P less than .0001). Of patients who had no gap in infliximab treatment for greater than 10 weeks (n = 1,380), 72% had their dose escalated. Characteristics associated with dose escalation included being younger, being male, and not having chronic pulmonary disease. Physicians who owned their own infusion centers were 25% more likely to escalate doses of infliximab (adjusted odds ratio, 1.25; 95% confidence interval, 1.09-1.44).

Mean costs paid by Medicare for the first 18 months of treatment were significantly higher for golimumab ($28,146; 95% CI, $27,497-$28,810), compared with infliximab ($21,216; 95% CI, $20,737-$21,706). An analysis of patients who persisted on therapy for all 18 months with no treatment gap greater than 10 weeks revealed an even greater disparity in cost: $43,940 for golimumab (95% CI, $42,849-$45,058) versus $34,671 for infliximab (95% CI, $33,891-$35,470).

According to a sensitivity analysis, 34% of infliximab-treated patients increased their dose to 5 mg/kg, 5% increased their dose to 8 mg/kg, and 4% increased their dose to 10 mg/kg. In a modeling scenario that considered cost, dose, and frequency, infliximab at 8 mg/kg dosed every 6 weeks was cheaper than golimumab with a biosimilar discount of greater than 25%. At 10 mg/kg dosed every 6 weeks, infliximab was cheaper than golimumab with a biosimilar discount of 30% or more.

That said, given comparable clinical outcomes with other RA biologics plus the increased indirect costs and greater risk of serious infections associated with infliximab dose escalation, the researchers noted that “escalation beyond 5 mg/kg is probably not a prudent course of treatment for most RA patients, compared to switching to alternative treatment options.”

Though they emphasized their study’s strengths – including the impressive sample size of older Medicare patients – the authors also acknowledged its limitations, such as a lack of information on the clinical reasons for treatment discontinuation and dose escalation. They also were not able to examine whether safety or tolerability played a role in patients’ treatment decisions.

Two of the four authors reported receiving research grants and consulting fees from various medical and pharmaceutical companies, and one other author reported owning stock in Amgen.

SOURCE: Curtis JR et al. Arthritis Res Ther. 2019 Dec 12. doi: 10.1186/s13075-019-2022-8.

Radiation therapy should be the primary treatment for patients with basal cell carcinoma and cutaneous squamous cell carcinoma who are not candidates for surgery, according to a new guideline from an American Society for Radiation Oncology task force.

“We hope that the dermatology community will find this guideline helpful, especially when it comes to defining clinical and pathological characteristics that may necessitate a discussion about the merits of postoperative radiation therapy,” said lead author Anna Likhacheva, MD, of the Sutter Medical Center in Sacramento, Calif., in an email. The guideline was published in Practical Radiation Oncology.

To address five key questions in regard to radiation therapy (RT) for the two most common skin cancers, the American Society for Radiation Oncology convened a task force of radiation, medical, and surgical oncologists; dermatopathologists; a radiation oncology resident; a medical physicist; and a dermatologist. They reviewed studies of adults with nonmetastatic, invasive basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) that were published between May 1998 and June 2018, with the caveat that “there are limited, well-conducted modern randomized trials” in this area. As such, the majority of the recommendations have low to moderate quality of evidence designations.

“The conspicuous lack of prospective and randomized data should serve as a reminder to open clinical trials and collect outcomes data in a prospective fashion,” added Dr. Likhacheva, noting that “improving the quality of data on this topic will ultimately serve our common goal of improving patient outcomes.”

Their first recommendation was to strongly consider definitive RT as an alternative to surgery for BCC and cSCC, especially in areas where a surgical procedure would potentially compromise function or cosmesis. However, they did discourage its use in patients with genetic conditions associated with increased radiosensitivity.

Their second recommendation was to strongly consider postoperative radiation therapy for clinically or radiologically apparent gross perineural spread. They also strongly recommended PORT for cSCC patients with close or positive margins, with T3 or T4 tumors, or with desmoplastic or infiltrative tumors.

Their third recommendation was to strongly consider therapeutic lymphadenectomy followed by adjuvant RT in patients with cSCC or BCC that has metastasized to the regional lymph nodes. They also recommended definitive RT in medically inoperable patients with the same metastasized cSCC or BCC. In addition, patients with BCC or cSCC undergoing adjuvant RT after therapeutic lymphadenectomy were recommended a dose of 6,000-6,600 cGy, while patients with cSCC undergoing elective RT without a lymphadenectomy were recommended a dose of 5,000-5,400 cGy.

Their fourth recommendation focused on techniques and dose-fractionation schedules for RT in the definitive or postoperative setting. For patients with BCC and cSCC receiving definitive RT, the biologically effective dose (BED₁₀) range for conventional fractionation – defined as 180-200 cGy/fraction – should be 70-93.5 and the BED₁₀ range for hypofractionation – defined as 210-500 cGy/fraction – should be 56-88. For patients with BCC and cSCC receiving postoperative RT, the BED₁₀ range for conventional fractionation should be 59.5-79.2 and the BED₁₀ range for hypofractionation should be 56-70.2.

Finally, their fifth recommendation was to not add concurrent carboplatin to adjuvant RT in patients with resected, locally advanced cSCC. They also conditionally recommended adding concurrent drug therapies to definitive RT in patients with unresected, locally advanced cSCC.

Several of the authors reported receiving honoraria and travel expenses from medical and pharmaceutical companies, along with serving on their advisory boards. The others reported no conflicts of interest.

SOURCE: Likhacheva A et al. Pract Radiat Oncol. 2019 Dec 9. doi: 10.1016/j.prro.2019.10.014.

Radiation therapy should be the primary treatment for patients with basal cell carcinoma and cutaneous squamous cell carcinoma who are not candidates for surgery, according to a new guideline from an American Society for Radiation Oncology task force.

“We hope that the dermatology community will find this guideline helpful, especially when it comes to defining clinical and pathological characteristics that may necessitate a discussion about the merits of postoperative radiation therapy,” said lead author Anna Likhacheva, MD, of the Sutter Medical Center in Sacramento, Calif., in an email. The guideline was published in Practical Radiation Oncology.

To address five key questions in regard to radiation therapy (RT) for the two most common skin cancers, the American Society for Radiation Oncology convened a task force of radiation, medical, and surgical oncologists; dermatopathologists; a radiation oncology resident; a medical physicist; and a dermatologist. They reviewed studies of adults with nonmetastatic, invasive basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) that were published between May 1998 and June 2018, with the caveat that “there are limited, well-conducted modern randomized trials” in this area. As such, the majority of the recommendations have low to moderate quality of evidence designations.

“The conspicuous lack of prospective and randomized data should serve as a reminder to open clinical trials and collect outcomes data in a prospective fashion,” added Dr. Likhacheva, noting that “improving the quality of data on this topic will ultimately serve our common goal of improving patient outcomes.”

Their first recommendation was to strongly consider definitive RT as an alternative to surgery for BCC and cSCC, especially in areas where a surgical procedure would potentially compromise function or cosmesis. However, they did discourage its use in patients with genetic conditions associated with increased radiosensitivity.

Their second recommendation was to strongly consider postoperative radiation therapy for clinically or radiologically apparent gross perineural spread. They also strongly recommended PORT for cSCC patients with close or positive margins, with T3 or T4 tumors, or with desmoplastic or infiltrative tumors.

Their third recommendation was to strongly consider therapeutic lymphadenectomy followed by adjuvant RT in patients with cSCC or BCC that has metastasized to the regional lymph nodes. They also recommended definitive RT in medically inoperable patients with the same metastasized cSCC or BCC. In addition, patients with BCC or cSCC undergoing adjuvant RT after therapeutic lymphadenectomy were recommended a dose of 6,000-6,600 cGy, while patients with cSCC undergoing elective RT without a lymphadenectomy were recommended a dose of 5,000-5,400 cGy.

Their fourth recommendation focused on techniques and dose-fractionation schedules for RT in the definitive or postoperative setting. For patients with BCC and cSCC receiving definitive RT, the biologically effective dose (BED₁₀) range for conventional fractionation – defined as 180-200 cGy/fraction – should be 70-93.5 and the BED₁₀ range for hypofractionation – defined as 210-500 cGy/fraction – should be 56-88. For patients with BCC and cSCC receiving postoperative RT, the BED₁₀ range for conventional fractionation should be 59.5-79.2 and the BED₁₀ range for hypofractionation should be 56-70.2.

Finally, their fifth recommendation was to not add concurrent carboplatin to adjuvant RT in patients with resected, locally advanced cSCC. They also conditionally recommended adding concurrent drug therapies to definitive RT in patients with unresected, locally advanced cSCC.

Several of the authors reported receiving honoraria and travel expenses from medical and pharmaceutical companies, along with serving on their advisory boards. The others reported no conflicts of interest.

SOURCE: Likhacheva A et al. Pract Radiat Oncol. 2019 Dec 9. doi: 10.1016/j.prro.2019.10.014.

Radiation therapy should be the primary treatment for patients with basal cell carcinoma and cutaneous squamous cell carcinoma who are not candidates for surgery, according to a new guideline from an American Society for Radiation Oncology task force.

“We hope that the dermatology community will find this guideline helpful, especially when it comes to defining clinical and pathological characteristics that may necessitate a discussion about the merits of postoperative radiation therapy,” said lead author Anna Likhacheva, MD, of the Sutter Medical Center in Sacramento, Calif., in an email. The guideline was published in Practical Radiation Oncology.

To address five key questions in regard to radiation therapy (RT) for the two most common skin cancers, the American Society for Radiation Oncology convened a task force of radiation, medical, and surgical oncologists; dermatopathologists; a radiation oncology resident; a medical physicist; and a dermatologist. They reviewed studies of adults with nonmetastatic, invasive basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) that were published between May 1998 and June 2018, with the caveat that “there are limited, well-conducted modern randomized trials” in this area. As such, the majority of the recommendations have low to moderate quality of evidence designations.

“The conspicuous lack of prospective and randomized data should serve as a reminder to open clinical trials and collect outcomes data in a prospective fashion,” added Dr. Likhacheva, noting that “improving the quality of data on this topic will ultimately serve our common goal of improving patient outcomes.”

Their first recommendation was to strongly consider definitive RT as an alternative to surgery for BCC and cSCC, especially in areas where a surgical procedure would potentially compromise function or cosmesis. However, they did discourage its use in patients with genetic conditions associated with increased radiosensitivity.

Their second recommendation was to strongly consider postoperative radiation therapy for clinically or radiologically apparent gross perineural spread. They also strongly recommended PORT for cSCC patients with close or positive margins, with T3 or T4 tumors, or with desmoplastic or infiltrative tumors.

Their third recommendation was to strongly consider therapeutic lymphadenectomy followed by adjuvant RT in patients with cSCC or BCC that has metastasized to the regional lymph nodes. They also recommended definitive RT in medically inoperable patients with the same metastasized cSCC or BCC. In addition, patients with BCC or cSCC undergoing adjuvant RT after therapeutic lymphadenectomy were recommended a dose of 6,000-6,600 cGy, while patients with cSCC undergoing elective RT without a lymphadenectomy were recommended a dose of 5,000-5,400 cGy.

Their fourth recommendation focused on techniques and dose-fractionation schedules for RT in the definitive or postoperative setting. For patients with BCC and cSCC receiving definitive RT, the biologically effective dose (BED₁₀) range for conventional fractionation – defined as 180-200 cGy/fraction – should be 70-93.5 and the BED₁₀ range for hypofractionation – defined as 210-500 cGy/fraction – should be 56-88. For patients with BCC and cSCC receiving postoperative RT, the BED₁₀ range for conventional fractionation should be 59.5-79.2 and the BED₁₀ range for hypofractionation should be 56-70.2.

Finally, their fifth recommendation was to not add concurrent carboplatin to adjuvant RT in patients with resected, locally advanced cSCC. They also conditionally recommended adding concurrent drug therapies to definitive RT in patients with unresected, locally advanced cSCC.

Several of the authors reported receiving honoraria and travel expenses from medical and pharmaceutical companies, along with serving on their advisory boards. The others reported no conflicts of interest.

SOURCE: Likhacheva A et al. Pract Radiat Oncol. 2019 Dec 9. doi: 10.1016/j.prro.2019.10.014.

A new Norwegian study has identified a high body mass index and lower levels of physical activity as modifiable risk factors for developing psoriatic arthritis (PsA).

“Our study adds to the growing evidence that the risk of PsA is modifiable and highlights the importance of preventive work against obesity as well as encouraging physical activity in order to reduce the incidence of PsA,” wrote Ruth S. Thomsen, MD, of the Norwegian University of Science and Technology, and coauthors. The study was published in Arthritis Care & Research.

To determine the impact that adiposity and body fat distribution have on developing PsA, the researchers analyzed data from 36,626 women and men who participated in two surveys from the longitudinal, population-based Norwegian HUNT Study. All participants did not have diagnosed PsA at baseline in 1995-1997. Variables used in statistical analysis included calculated baseline BMI, waist circumference, waist-hip ratio, and level of physical activity.

Between baseline and follow-up in 2012, 185 new cases of PsA were reported. One standard deviation increase in BMI (4.2 kg/m² for women, 3.5 kg/m² for men) and waist circumstance (10.8 cm for women, 8.6 cm for men) was associated with adjusted hazard ratios of 1.40 (95% confidence interval, 1.24-1.58) and 1.48 (95% CI, 1.31-1.68), accordingly. Obese individuals – defined as BMI of 30 kg/m² or higher – had an adjusted HR of 2.46 (95% CI, 1.65-3.68) when compared with individuals at normal weight.

Compared to individuals with BMI less than 25 kg/m² and a high level of physical activity, individuals with BMI at 25 kg/m² or higher and any lower level of physical activity had an adjusted HR of 2.06 (95% CI, 1.18-3.58). In addition, individuals with a high waist circumference – defined as 81 cm or more in women and 95 cm or more in men – and low physical activity had an adjusted HR of 2.22 (95% CI, 1.37-3.58) in comparison to those with a high waist circumference and high physical activity (adjusted HR, 1.84; 95% CI, 0.97-3.47). Physical activity level was considered low with less than 3 hours of light physical activity and no hard physical activity per week and high with any amount of light activity plus 1 or more hours of hard physical activity.

The authors acknowledged the study’s potential limitations, including the requirement for participants to complete the final two HUNT study surveys and the use of stricter criteria than usual in validating PsA diagnoses.

The study was partially funded by a grant Dr. Thomsen received from the Norwegian Extra Foundation for Health and Rehabilitation. The authors reported no conflicts of interest.

SOURCE: Thomsen RS et al. Arthritis Care Res. 2019 Dec 7. doi: 10.1002/acr.24121.

A new Norwegian study has identified a high body mass index and lower levels of physical activity as modifiable risk factors for developing psoriatic arthritis (PsA).

“Our study adds to the growing evidence that the risk of PsA is modifiable and highlights the importance of preventive work against obesity as well as encouraging physical activity in order to reduce the incidence of PsA,” wrote Ruth S. Thomsen, MD, of the Norwegian University of Science and Technology, and coauthors. The study was published in Arthritis Care & Research.

To determine the impact that adiposity and body fat distribution have on developing PsA, the researchers analyzed data from 36,626 women and men who participated in two surveys from the longitudinal, population-based Norwegian HUNT Study. All participants did not have diagnosed PsA at baseline in 1995-1997. Variables used in statistical analysis included calculated baseline BMI, waist circumference, waist-hip ratio, and level of physical activity.

Between baseline and follow-up in 2012, 185 new cases of PsA were reported. One standard deviation increase in BMI (4.2 kg/m² for women, 3.5 kg/m² for men) and waist circumstance (10.8 cm for women, 8.6 cm for men) was associated with adjusted hazard ratios of 1.40 (95% confidence interval, 1.24-1.58) and 1.48 (95% CI, 1.31-1.68), accordingly. Obese individuals – defined as BMI of 30 kg/m² or higher – had an adjusted HR of 2.46 (95% CI, 1.65-3.68) when compared with individuals at normal weight.

Compared to individuals with BMI less than 25 kg/m² and a high level of physical activity, individuals with BMI at 25 kg/m² or higher and any lower level of physical activity had an adjusted HR of 2.06 (95% CI, 1.18-3.58). In addition, individuals with a high waist circumference – defined as 81 cm or more in women and 95 cm or more in men – and low physical activity had an adjusted HR of 2.22 (95% CI, 1.37-3.58) in comparison to those with a high waist circumference and high physical activity (adjusted HR, 1.84; 95% CI, 0.97-3.47). Physical activity level was considered low with less than 3 hours of light physical activity and no hard physical activity per week and high with any amount of light activity plus 1 or more hours of hard physical activity.

The authors acknowledged the study’s potential limitations, including the requirement for participants to complete the final two HUNT study surveys and the use of stricter criteria than usual in validating PsA diagnoses.

The study was partially funded by a grant Dr. Thomsen received from the Norwegian Extra Foundation for Health and Rehabilitation. The authors reported no conflicts of interest.

SOURCE: Thomsen RS et al. Arthritis Care Res. 2019 Dec 7. doi: 10.1002/acr.24121.

A new Norwegian study has identified a high body mass index and lower levels of physical activity as modifiable risk factors for developing psoriatic arthritis (PsA).

“Our study adds to the growing evidence that the risk of PsA is modifiable and highlights the importance of preventive work against obesity as well as encouraging physical activity in order to reduce the incidence of PsA,” wrote Ruth S. Thomsen, MD, of the Norwegian University of Science and Technology, and coauthors. The study was published in Arthritis Care & Research.

To determine the impact that adiposity and body fat distribution have on developing PsA, the researchers analyzed data from 36,626 women and men who participated in two surveys from the longitudinal, population-based Norwegian HUNT Study. All participants did not have diagnosed PsA at baseline in 1995-1997. Variables used in statistical analysis included calculated baseline BMI, waist circumference, waist-hip ratio, and level of physical activity.

Between baseline and follow-up in 2012, 185 new cases of PsA were reported. One standard deviation increase in BMI (4.2 kg/m² for women, 3.5 kg/m² for men) and waist circumstance (10.8 cm for women, 8.6 cm for men) was associated with adjusted hazard ratios of 1.40 (95% confidence interval, 1.24-1.58) and 1.48 (95% CI, 1.31-1.68), accordingly. Obese individuals – defined as BMI of 30 kg/m² or higher – had an adjusted HR of 2.46 (95% CI, 1.65-3.68) when compared with individuals at normal weight.

Compared to individuals with BMI less than 25 kg/m² and a high level of physical activity, individuals with BMI at 25 kg/m² or higher and any lower level of physical activity had an adjusted HR of 2.06 (95% CI, 1.18-3.58). In addition, individuals with a high waist circumference – defined as 81 cm or more in women and 95 cm or more in men – and low physical activity had an adjusted HR of 2.22 (95% CI, 1.37-3.58) in comparison to those with a high waist circumference and high physical activity (adjusted HR, 1.84; 95% CI, 0.97-3.47). Physical activity level was considered low with less than 3 hours of light physical activity and no hard physical activity per week and high with any amount of light activity plus 1 or more hours of hard physical activity.

The authors acknowledged the study’s potential limitations, including the requirement for participants to complete the final two HUNT study surveys and the use of stricter criteria than usual in validating PsA diagnoses.

The study was partially funded by a grant Dr. Thomsen received from the Norwegian Extra Foundation for Health and Rehabilitation. The authors reported no conflicts of interest.

SOURCE: Thomsen RS et al. Arthritis Care Res. 2019 Dec 7. doi: 10.1002/acr.24121.

A variety of socio-demographic variables – including residing in a lower-income zip code and lacking private insurance – can influence treatment decisions for orthopedic trauma patients, according to a new study on the management of calcaneus fractures.

“While our study demonstrated socio-demographic disparities regarding utilization of open reduction and internal fixation of calcaneus fractures, the exact reasons for these disparities remain unclear,” wrote Boris A. Zelle, MD, of UT Health San Antonio and his coauthors. The study was published in the Journal of Orthopaedic Surgery and Research.

To assess how certain variables might impact how patients manage decisions regarding orthopedic trauma surgery, the researchers identified 17,156 patients with closed calcaneus fractures via the National Inpatient Sample (NIS) and analyzed their treatment and demographic data. The statistical analysis included variables such as age, sex, insurance status, race/ethnicity, income, hospital location, and hospital size. A total of 59% of the patients (n = 10,117) underwent nonoperative management of their calcaneus fracture while 41% (n = 7,039) underwent open reduction and internal fixation. A multivariate logistic regression determined that variables like older age, female gender, being on Medicare, being African American or Hispanic, and having a lower estimated income by zip code were all associated with significantly lower use of surgical treatment (P less than .05). Not surprisingly, clinical comorbidities that were also associated with lower surgical rates included diabetes, peripheral vascular disease, a history of drug and alcohol abuse, and psychosis (P less than .05).

The authors acknowledged their study’s potential limitations, including a lack of research data on why these patients and providers chose surgery or otherwise. In addition, all available patient data came from a multicenter database, which can come with data entry issues. Finally, relying on data from only inpatient admissions “introduces a potential selection bias” by overrepresenting patients with “potentially more comorbidities and social issues.”

One author reported receiving consultant fees, speaker fees, and grant support from several organizations and medical corporations. The other authors reported no potential conflicts of interest.

SOURCE: Zelle BA et al. J Orthop Surg Res. 2019 Nov 12. doi: 10.1186/s13018-019-1402-8.

A variety of socio-demographic variables – including residing in a lower-income zip code and lacking private insurance – can influence treatment decisions for orthopedic trauma patients, according to a new study on the management of calcaneus fractures.

“While our study demonstrated socio-demographic disparities regarding utilization of open reduction and internal fixation of calcaneus fractures, the exact reasons for these disparities remain unclear,” wrote Boris A. Zelle, MD, of UT Health San Antonio and his coauthors. The study was published in the Journal of Orthopaedic Surgery and Research.

To assess how certain variables might impact how patients manage decisions regarding orthopedic trauma surgery, the researchers identified 17,156 patients with closed calcaneus fractures via the National Inpatient Sample (NIS) and analyzed their treatment and demographic data. The statistical analysis included variables such as age, sex, insurance status, race/ethnicity, income, hospital location, and hospital size. A total of 59% of the patients (n = 10,117) underwent nonoperative management of their calcaneus fracture while 41% (n = 7,039) underwent open reduction and internal fixation. A multivariate logistic regression determined that variables like older age, female gender, being on Medicare, being African American or Hispanic, and having a lower estimated income by zip code were all associated with significantly lower use of surgical treatment (P less than .05). Not surprisingly, clinical comorbidities that were also associated with lower surgical rates included diabetes, peripheral vascular disease, a history of drug and alcohol abuse, and psychosis (P less than .05).

The authors acknowledged their study’s potential limitations, including a lack of research data on why these patients and providers chose surgery or otherwise. In addition, all available patient data came from a multicenter database, which can come with data entry issues. Finally, relying on data from only inpatient admissions “introduces a potential selection bias” by overrepresenting patients with “potentially more comorbidities and social issues.”

One author reported receiving consultant fees, speaker fees, and grant support from several organizations and medical corporations. The other authors reported no potential conflicts of interest.

SOURCE: Zelle BA et al. J Orthop Surg Res. 2019 Nov 12. doi: 10.1186/s13018-019-1402-8.

A variety of socio-demographic variables – including residing in a lower-income zip code and lacking private insurance – can influence treatment decisions for orthopedic trauma patients, according to a new study on the management of calcaneus fractures.

“While our study demonstrated socio-demographic disparities regarding utilization of open reduction and internal fixation of calcaneus fractures, the exact reasons for these disparities remain unclear,” wrote Boris A. Zelle, MD, of UT Health San Antonio and his coauthors. The study was published in the Journal of Orthopaedic Surgery and Research.

To assess how certain variables might impact how patients manage decisions regarding orthopedic trauma surgery, the researchers identified 17,156 patients with closed calcaneus fractures via the National Inpatient Sample (NIS) and analyzed their treatment and demographic data. The statistical analysis included variables such as age, sex, insurance status, race/ethnicity, income, hospital location, and hospital size. A total of 59% of the patients (n = 10,117) underwent nonoperative management of their calcaneus fracture while 41% (n = 7,039) underwent open reduction and internal fixation. A multivariate logistic regression determined that variables like older age, female gender, being on Medicare, being African American or Hispanic, and having a lower estimated income by zip code were all associated with significantly lower use of surgical treatment (P less than .05). Not surprisingly, clinical comorbidities that were also associated with lower surgical rates included diabetes, peripheral vascular disease, a history of drug and alcohol abuse, and psychosis (P less than .05).

The authors acknowledged their study’s potential limitations, including a lack of research data on why these patients and providers chose surgery or otherwise. In addition, all available patient data came from a multicenter database, which can come with data entry issues. Finally, relying on data from only inpatient admissions “introduces a potential selection bias” by overrepresenting patients with “potentially more comorbidities and social issues.”

One author reported receiving consultant fees, speaker fees, and grant support from several organizations and medical corporations. The other authors reported no potential conflicts of interest.

SOURCE: Zelle BA et al. J Orthop Surg Res. 2019 Nov 12. doi: 10.1186/s13018-019-1402-8.

While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.

©Thinkstock

“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.

To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).

Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.

Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).

After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.

In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).

Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.

“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.

Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.

The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.

SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.

While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.

©Thinkstock

“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.

To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).

Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.

Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).

After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.

In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).

Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.

“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.

Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.

The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.

SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.

While women were found to be at lower risk of major cardiovascular events than men after non–ST-segment elevation acute coronary syndromes (NSTEACS), a new study has also shown that they remain undertreated with guideline-directed therapies.

©Thinkstock

“These findings underscore the fact that efforts to modify risk factors and implement appropriate treatment strategies in women and men may be a powerful means to further improve outcomes among patients with NSTEACS,” wrote Amy A. Sarma, MD, of Massachusetts General Hospital in Boston and coauthors. The study was published in the Journal of the American College of Cardiology.

To determine if outcomes differed between men and women after NSTEACS, the researchers analyzed 68,730 patients from 10 different clinical trials as part of the Thrombolysis In Myocardial Infarction (TIMI) Study Group. All trials enrolled patients with NSTEACS within 30 days of hospitalization. Across the 10 trials, there were a total of 19,827 women (29%).

Female patients had an average age of 67 years, compared with a mean age of 62 years for men. Women were also more likely to have had hypertension, diabetes, or prior heart failure, though less likely to have had a prior MI. In regard to treatment strategies for NSTEACS, women were less likely to receive aspirin, P2Y12 inhibitors, or statins. Women at high risk were also less likely to receive aspirin, P2Y12 inhibitors, or statins.

Before adjusted analysis, women and men had a similar risk of major adverse cardiovascular events (MACE) – defined as cardiovascular death, MI, or stroke – after NSTEACS (hazard ratio, 1.04; 95% confidence interval, 0.99-1.09; P = .16). However, women were found to be at increased risk of cardiovascular death (HR, 1.16; 95% CI, 1.02-1.32; P = .03), all-cause mortality (HR, 1.12; 95% CI, 1.01-1.24; P = .03), and stroke (HR, 1.19; 95% CI, 1.03-1.37; P = .02).

After adjusting for baseline risk predictors, women were found to have a 7% lower risk of MACE (adjusted HR, 0.93; 95% CI, 0.89-0.98; P = .005), along with a 15% lower risk of cardiovascular death (aHR, 0.85; 95% CI, 0.76-0.96; P = .008) and a 16% lower risk of all-cause death (aHR, 0.84; 95% CI, 0.78-0.90; P less than .0001). Additional adjustments for guideline-based therapies did not significantly alter the risk estimates.

In an accompanying editorial, Michael E. Farkouh, MD, and Wendy Tsang, MD, of the University of Toronto noted that this study from Sarma et al. underlines the “lack of progress made in addressing sex inequality in the care for women with ACS” (J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.10.017).

Though Dr. Farkouh and Dr. Tsang were not surprised that the women in the study were older than the men, as women typically develop cardiovascular disease later, they noted that the women also presented with higher baseline risk. Could this be because of the “persistent perception that coronary disease is a male disease?” They cited the treatment-risk paradox and an emphasis on diagnosing obstructive coronary disease – typically seen in men – as potential contributors to underdiagnosis and undertreatment in at-risk women.

“That this care gap for women with cardiovascular diseases continues to persist, even in well-run contemporary landmark ACS trials, highlights how challenging it is to address,” they wrote.

Dr. Sarma and coauthors acknowledged their study’s potential limitations, including the 10 trials differing in study design, enrollment timing, treatments tested, and follow-up duration. They also noted that the cohort of patients were all at moderate to high risk, which may not make the findings generalizable to the broader NSTEACS patient population.

The study authors reported numerous potential conflicts of interest, including receiving research grants from – and serving as a consultant or on the advisory board of – various pharmaceutical and medical companies. Dr. Farkouh reported receiving research support from Amgen and Novo Nordisk, and Dr. Tsang is supported by a National New Investigator Award from the Heart and Stroke Foundation of Canada.

SOURCE: Sarma AA et al. J Am Coll Cardiol. 2019 Dec 9. doi: 10.1016/j.jacc.2019.09.065.

A molecular analysis of a patient with follicular lymphoma (FL) that became B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) uncovered genetic changes that may improve understanding of this transformation.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

“The study provides new insights into the pathogenesis of FL-B-ALL/LBL transformation and suggests novel, disease biology–based therapeutic approaches to this aggressive and currently incurable disease,” wrote Jonathan Belman, MD, PhD, of the Hospital of the University of Pennsylvania, Philadelphia, and coauthors. Their findings were published in Cold Spring Harbor Molecular Case Studies.

To further understand the rare occasions when FL transforms into a more aggressive form of lymphoma, the researchers investigated a 36-year-old man with low-grade FL that became B-ALL/LBL roughly 1 year after diagnosis. Their analysis included immunoglobulin (Ig) gene rearrangement studies, cytogenetic analysis, and whole exome sequencing of the patient’s FL, B-ALL/LBL, and normal cells.

Next generation sequencing of Ig rearrangements from normal, FL, and B-ALL/LBL specimens revealed considerable somatic hypermutation (SHM) in a single neoplastic clone – IgHV4-34_JH6 – in the FL cells. By comparison, though no dominant clone was found in the B-ALL/LBL specimen, there was even more extensive SHM, along with clones that could be traced to the FL lineage.

In addition, fluorescence in situ hybridization (FISH) studies on the FL specimen were positive for rearrangements of BCL2 and BCL6 genes; a rearrangement of BCL6 is associated with clinical aggressiveness. Those same two rearrangements were found in the B-ALL/LBL specimen, along with a MYC gene rearrangement unseen in the FL.

“MYC translocations are well known to contribute to high aggressiveness of lymphomas, and are hallmark of FL-B-ALL/LBL transformation,” the researchers wrote.

Finally, comparative whole exome sequencing of normal tissue plus the cancerous specimens identified 751 single nucleotide variants. The normal tissue contained 111 of those mutations, while the FL specimens contained 116 mutations – 11 of which were shared solely with B-ALL/LBL – and the B-ALL/LBL specimens contained a striking 575 unique mutations. Notably, a nonsense mutation in the KMT2D gene that was shared by FL and B-ALL/LBL may have contributed to lymphomagenesis.

The study was funded by a grant from the National Institutes of Health, the Abramson Cancer Center Translational Center in Lymphoma, the Daniel B. Allanoff Foundation, and a Hematopathology Divisional Training grant.

SOURCE: Belman JP et al. Cold Spring Harb Mol Case Stud. 2019 Nov 27. doi: 10.1101/mcs.a004614.

A molecular analysis of a patient with follicular lymphoma (FL) that became B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) uncovered genetic changes that may improve understanding of this transformation.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

“The study provides new insights into the pathogenesis of FL-B-ALL/LBL transformation and suggests novel, disease biology–based therapeutic approaches to this aggressive and currently incurable disease,” wrote Jonathan Belman, MD, PhD, of the Hospital of the University of Pennsylvania, Philadelphia, and coauthors. Their findings were published in Cold Spring Harbor Molecular Case Studies.

To further understand the rare occasions when FL transforms into a more aggressive form of lymphoma, the researchers investigated a 36-year-old man with low-grade FL that became B-ALL/LBL roughly 1 year after diagnosis. Their analysis included immunoglobulin (Ig) gene rearrangement studies, cytogenetic analysis, and whole exome sequencing of the patient’s FL, B-ALL/LBL, and normal cells.

Next generation sequencing of Ig rearrangements from normal, FL, and B-ALL/LBL specimens revealed considerable somatic hypermutation (SHM) in a single neoplastic clone – IgHV4-34_JH6 – in the FL cells. By comparison, though no dominant clone was found in the B-ALL/LBL specimen, there was even more extensive SHM, along with clones that could be traced to the FL lineage.

In addition, fluorescence in situ hybridization (FISH) studies on the FL specimen were positive for rearrangements of BCL2 and BCL6 genes; a rearrangement of BCL6 is associated with clinical aggressiveness. Those same two rearrangements were found in the B-ALL/LBL specimen, along with a MYC gene rearrangement unseen in the FL.

“MYC translocations are well known to contribute to high aggressiveness of lymphomas, and are hallmark of FL-B-ALL/LBL transformation,” the researchers wrote.

Finally, comparative whole exome sequencing of normal tissue plus the cancerous specimens identified 751 single nucleotide variants. The normal tissue contained 111 of those mutations, while the FL specimens contained 116 mutations – 11 of which were shared solely with B-ALL/LBL – and the B-ALL/LBL specimens contained a striking 575 unique mutations. Notably, a nonsense mutation in the KMT2D gene that was shared by FL and B-ALL/LBL may have contributed to lymphomagenesis.

The study was funded by a grant from the National Institutes of Health, the Abramson Cancer Center Translational Center in Lymphoma, the Daniel B. Allanoff Foundation, and a Hematopathology Divisional Training grant.

SOURCE: Belman JP et al. Cold Spring Harb Mol Case Stud. 2019 Nov 27. doi: 10.1101/mcs.a004614.

A molecular analysis of a patient with follicular lymphoma (FL) that became B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) uncovered genetic changes that may improve understanding of this transformation.

Patho/Wikimedia Commons/CC BY-SA 3.0(http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons

“The study provides new insights into the pathogenesis of FL-B-ALL/LBL transformation and suggests novel, disease biology–based therapeutic approaches to this aggressive and currently incurable disease,” wrote Jonathan Belman, MD, PhD, of the Hospital of the University of Pennsylvania, Philadelphia, and coauthors. Their findings were published in Cold Spring Harbor Molecular Case Studies.

To further understand the rare occasions when FL transforms into a more aggressive form of lymphoma, the researchers investigated a 36-year-old man with low-grade FL that became B-ALL/LBL roughly 1 year after diagnosis. Their analysis included immunoglobulin (Ig) gene rearrangement studies, cytogenetic analysis, and whole exome sequencing of the patient’s FL, B-ALL/LBL, and normal cells.

Next generation sequencing of Ig rearrangements from normal, FL, and B-ALL/LBL specimens revealed considerable somatic hypermutation (SHM) in a single neoplastic clone – IgHV4-34_JH6 – in the FL cells. By comparison, though no dominant clone was found in the B-ALL/LBL specimen, there was even more extensive SHM, along with clones that could be traced to the FL lineage.

In addition, fluorescence in situ hybridization (FISH) studies on the FL specimen were positive for rearrangements of BCL2 and BCL6 genes; a rearrangement of BCL6 is associated with clinical aggressiveness. Those same two rearrangements were found in the B-ALL/LBL specimen, along with a MYC gene rearrangement unseen in the FL.

“MYC translocations are well known to contribute to high aggressiveness of lymphomas, and are hallmark of FL-B-ALL/LBL transformation,” the researchers wrote.

Finally, comparative whole exome sequencing of normal tissue plus the cancerous specimens identified 751 single nucleotide variants. The normal tissue contained 111 of those mutations, while the FL specimens contained 116 mutations – 11 of which were shared solely with B-ALL/LBL – and the B-ALL/LBL specimens contained a striking 575 unique mutations. Notably, a nonsense mutation in the KMT2D gene that was shared by FL and B-ALL/LBL may have contributed to lymphomagenesis.

The study was funded by a grant from the National Institutes of Health, the Abramson Cancer Center Translational Center in Lymphoma, the Daniel B. Allanoff Foundation, and a Hematopathology Divisional Training grant.

SOURCE: Belman JP et al. Cold Spring Harb Mol Case Stud. 2019 Nov 27. doi: 10.1101/mcs.a004614.

A new study has found that keloid formation may be driven by Th2 pathogenesis and, as such, Th2-targeting dupilumab may be useful in treating chronic keloids.

“This preliminary report demonstrates a novel use of dupilumab for chronic keloids, showing major reductions in skin fibrosis and keloidal scarring,” wrote Aisleen Diaz, from the department of dermatology and laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. The study was published as a letter to the editor in the Journal of the European Academy of Dermatology and Venereology.

The authors described a 53-year-old black male patient with severe atopic dermatitis and two keloids who, after 7 months of treatment with dupilumab for AD, had significant improvements in AD – as well as shrinkage of the larger keloid and “complete disappearance” of the smaller keloid.

As a follow-up, the researchers used real-time polymerase chain reaction testing to monitor Th2 gene expression in lesional and nonlesional keloid skin from three black patients (mean age, 47.3 years) with severe keloids and no AD. Five healthy black controls (mean age, 39.8 years) were also included for comparison. In addition, 6-mm whole-skin biopsy specimens were obtained from all patients.

Interleukin-4 receptors, directly targeted by dupilumab, were highly up-regulated in keloid lesions, compared with controls (P less than .1). The Th2 cytokine IL-13 was significantly increased in lesional and nonlesional keloids, compared with controls (P less than .05), and the TH2 cytokine CCL18 was also highly increased in keloids, chiefly in nonlesional skin (P less than .05).

With regard to genes involved in cartilage and bone development that have been recognized as highly expressed in keloids – such as cadherin 11 and fibrillin 2 – all were increased in keloid lesions, compared with both controls and to nonlesional skin (P less than .05), the researchers reported.

“Dupilumab and other Th2-targeting agents may provide treatment options for patients with severe keloids, warranting further studies,” they commented, adding that the patient they described was the first report of a keloid improving with dupilumab, which “blocks type 2 driven inflammation via IL-4/IL-13 signaling.”

Four authors, including Ms. Diaz, had no disclosures. Two authors reported numerous disclosures, including receiving grants, research funds, and personal and consulting fees, from various pharmaceutical companies, including dupilumab manufacturers Regeneron and/or Sanofi.

SOURCE: Diaz A et al. J Eur Acad Dermatol Venereol. 2019 Nov 20. doi: 10.1111/jdv.16097.

A new study has found that keloid formation may be driven by Th2 pathogenesis and, as such, Th2-targeting dupilumab may be useful in treating chronic keloids.

“This preliminary report demonstrates a novel use of dupilumab for chronic keloids, showing major reductions in skin fibrosis and keloidal scarring,” wrote Aisleen Diaz, from the department of dermatology and laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. The study was published as a letter to the editor in the Journal of the European Academy of Dermatology and Venereology.

The authors described a 53-year-old black male patient with severe atopic dermatitis and two keloids who, after 7 months of treatment with dupilumab for AD, had significant improvements in AD – as well as shrinkage of the larger keloid and “complete disappearance” of the smaller keloid.

As a follow-up, the researchers used real-time polymerase chain reaction testing to monitor Th2 gene expression in lesional and nonlesional keloid skin from three black patients (mean age, 47.3 years) with severe keloids and no AD. Five healthy black controls (mean age, 39.8 years) were also included for comparison. In addition, 6-mm whole-skin biopsy specimens were obtained from all patients.

Interleukin-4 receptors, directly targeted by dupilumab, were highly up-regulated in keloid lesions, compared with controls (P less than .1). The Th2 cytokine IL-13 was significantly increased in lesional and nonlesional keloids, compared with controls (P less than .05), and the TH2 cytokine CCL18 was also highly increased in keloids, chiefly in nonlesional skin (P less than .05).

With regard to genes involved in cartilage and bone development that have been recognized as highly expressed in keloids – such as cadherin 11 and fibrillin 2 – all were increased in keloid lesions, compared with both controls and to nonlesional skin (P less than .05), the researchers reported.

“Dupilumab and other Th2-targeting agents may provide treatment options for patients with severe keloids, warranting further studies,” they commented, adding that the patient they described was the first report of a keloid improving with dupilumab, which “blocks type 2 driven inflammation via IL-4/IL-13 signaling.”

Four authors, including Ms. Diaz, had no disclosures. Two authors reported numerous disclosures, including receiving grants, research funds, and personal and consulting fees, from various pharmaceutical companies, including dupilumab manufacturers Regeneron and/or Sanofi.

SOURCE: Diaz A et al. J Eur Acad Dermatol Venereol. 2019 Nov 20. doi: 10.1111/jdv.16097.

A new study has found that keloid formation may be driven by Th2 pathogenesis and, as such, Th2-targeting dupilumab may be useful in treating chronic keloids.

“This preliminary report demonstrates a novel use of dupilumab for chronic keloids, showing major reductions in skin fibrosis and keloidal scarring,” wrote Aisleen Diaz, from the department of dermatology and laboratory of inflammatory skin diseases at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. The study was published as a letter to the editor in the Journal of the European Academy of Dermatology and Venereology.

The authors described a 53-year-old black male patient with severe atopic dermatitis and two keloids who, after 7 months of treatment with dupilumab for AD, had significant improvements in AD – as well as shrinkage of the larger keloid and “complete disappearance” of the smaller keloid.

As a follow-up, the researchers used real-time polymerase chain reaction testing to monitor Th2 gene expression in lesional and nonlesional keloid skin from three black patients (mean age, 47.3 years) with severe keloids and no AD. Five healthy black controls (mean age, 39.8 years) were also included for comparison. In addition, 6-mm whole-skin biopsy specimens were obtained from all patients.

Interleukin-4 receptors, directly targeted by dupilumab, were highly up-regulated in keloid lesions, compared with controls (P less than .1). The Th2 cytokine IL-13 was significantly increased in lesional and nonlesional keloids, compared with controls (P less than .05), and the TH2 cytokine CCL18 was also highly increased in keloids, chiefly in nonlesional skin (P less than .05).

With regard to genes involved in cartilage and bone development that have been recognized as highly expressed in keloids – such as cadherin 11 and fibrillin 2 – all were increased in keloid lesions, compared with both controls and to nonlesional skin (P less than .05), the researchers reported.

“Dupilumab and other Th2-targeting agents may provide treatment options for patients with severe keloids, warranting further studies,” they commented, adding that the patient they described was the first report of a keloid improving with dupilumab, which “blocks type 2 driven inflammation via IL-4/IL-13 signaling.”

Four authors, including Ms. Diaz, had no disclosures. Two authors reported numerous disclosures, including receiving grants, research funds, and personal and consulting fees, from various pharmaceutical companies, including dupilumab manufacturers Regeneron and/or Sanofi.

SOURCE: Diaz A et al. J Eur Acad Dermatol Venereol. 2019 Nov 20. doi: 10.1111/jdv.16097.

A new study has found that a simple screening tool can identify patients at risk of postoperative delirium (POD) after orthopedic surgery, and a prevention program can help improve staff education and outcomes.

Spotmatik/Thinkstock

“In an aging society, it is very important to develop and implement a strategy for POD prevention to ensure that aging patients are treated as safely and effectively as possible,” wrote Jung-Yeon Choi of Seoul (South Korea) National University Bundang Hospital and coauthors. The study was published in BMC Geriatrics.

To determine how to better identify and treat high-risk patients for POD after orthopedic surgery, the researchers led a retrospective cohort study that included an intervention group of participants who were aged at least 65 years (n = 275) and a control group from a year prior (n = 274). Patients in the intervention group had their risk of delirium assessed and categorized using a simple screening tool, and those deemed at risk were entered into a multicomponent delirium prevention program.

Of the 275 patients in the intervention group, 144 required screening for delirium. Ninety-nine were classified as low risk, 29 were classified as high risk, and 16 missed the screening. Fifty-three additional patients were classified as high risk because they were aged 80 years or older. During the study, 17 participants experienced POD, 16 of whom were classified as high risk. In regard to estimating POD risk, the sensitivity and specificity of the delirium screening tool were 94.1% and 72.7%, respectively. Incidence rates of POD were 10.2% in the control group and 6.2% in the intervention group.

The authors noted their study’s limitations, including its design as a retrospective review of medical records rather than a prospective randomized controlled trial. In addition, because it was conducted in just one teaching hospital, they deemed it “not possible to determine the generalizability and long-term effect of our findings.”

The authors reported no conflicts of interest.

SOURCE: Choi JY et al. BMC Geriatr. 2019 Oct 26. doi: 10.1186/s12877-019-1303-z.

A new study has found that a simple screening tool can identify patients at risk of postoperative delirium (POD) after orthopedic surgery, and a prevention program can help improve staff education and outcomes.

Spotmatik/Thinkstock

“In an aging society, it is very important to develop and implement a strategy for POD prevention to ensure that aging patients are treated as safely and effectively as possible,” wrote Jung-Yeon Choi of Seoul (South Korea) National University Bundang Hospital and coauthors. The study was published in BMC Geriatrics.

To determine how to better identify and treat high-risk patients for POD after orthopedic surgery, the researchers led a retrospective cohort study that included an intervention group of participants who were aged at least 65 years (n = 275) and a control group from a year prior (n = 274). Patients in the intervention group had their risk of delirium assessed and categorized using a simple screening tool, and those deemed at risk were entered into a multicomponent delirium prevention program.

Of the 275 patients in the intervention group, 144 required screening for delirium. Ninety-nine were classified as low risk, 29 were classified as high risk, and 16 missed the screening. Fifty-three additional patients were classified as high risk because they were aged 80 years or older. During the study, 17 participants experienced POD, 16 of whom were classified as high risk. In regard to estimating POD risk, the sensitivity and specificity of the delirium screening tool were 94.1% and 72.7%, respectively. Incidence rates of POD were 10.2% in the control group and 6.2% in the intervention group.

The authors noted their study’s limitations, including its design as a retrospective review of medical records rather than a prospective randomized controlled trial. In addition, because it was conducted in just one teaching hospital, they deemed it “not possible to determine the generalizability and long-term effect of our findings.”

The authors reported no conflicts of interest.

SOURCE: Choi JY et al. BMC Geriatr. 2019 Oct 26. doi: 10.1186/s12877-019-1303-z.

A new study has found that a simple screening tool can identify patients at risk of postoperative delirium (POD) after orthopedic surgery, and a prevention program can help improve staff education and outcomes.

Spotmatik/Thinkstock

“In an aging society, it is very important to develop and implement a strategy for POD prevention to ensure that aging patients are treated as safely and effectively as possible,” wrote Jung-Yeon Choi of Seoul (South Korea) National University Bundang Hospital and coauthors. The study was published in BMC Geriatrics.

To determine how to better identify and treat high-risk patients for POD after orthopedic surgery, the researchers led a retrospective cohort study that included an intervention group of participants who were aged at least 65 years (n = 275) and a control group from a year prior (n = 274). Patients in the intervention group had their risk of delirium assessed and categorized using a simple screening tool, and those deemed at risk were entered into a multicomponent delirium prevention program.

Of the 275 patients in the intervention group, 144 required screening for delirium. Ninety-nine were classified as low risk, 29 were classified as high risk, and 16 missed the screening. Fifty-three additional patients were classified as high risk because they were aged 80 years or older. During the study, 17 participants experienced POD, 16 of whom were classified as high risk. In regard to estimating POD risk, the sensitivity and specificity of the delirium screening tool were 94.1% and 72.7%, respectively. Incidence rates of POD were 10.2% in the control group and 6.2% in the intervention group.

The authors noted their study’s limitations, including its design as a retrospective review of medical records rather than a prospective randomized controlled trial. In addition, because it was conducted in just one teaching hospital, they deemed it “not possible to determine the generalizability and long-term effect of our findings.”

The authors reported no conflicts of interest.

SOURCE: Choi JY et al. BMC Geriatr. 2019 Oct 26. doi: 10.1186/s12877-019-1303-z.

A study has found that consistent occupational exposure to disinfectants is associated with an increased risk of chronic obstructive pulmonary disease (COPD).

“Clinicians should be aware of this new risk factor and systematically look for sources of exposure to cleaning products and disinfectants in addition to other occupational exposures in patients with COPD,” wrote Orianne Dumas, PhD, of the Université de Versailles St-Quentin-en-Yvelines (France) and coauthors. The study was published in JAMA Network Open.

To determine if regular use of disinfectants had a negative impact on respiratory health, the researchers analyzed data from 73,262 active female nurses who had no history of COPD and completed questionnaires every 2 years for the Nurses’ Health Study II. Their mean age at baseline was 54.7. Exposure to commonly used disinfectants was evaluated by a job-task-exposure matrix (JTEM) specific to nurses.

Between 2009 and 2015, 582 nurses reported incident physician-diagnosed COPD. Weekly use of disinfectants was associated with COPD incidence (adjusted hazard ratio 1.35; 95% confidence interval, 1.14-1.59). Additional associations were found in nurses who used disinfectants to clean surfaces (AHR, 1.38; 95% CI, 1.13-1.68) and to clean medical instruments (AHR, 1.31; 95% CI, 1.07-1.61). High-level exposure to certain disinfectants – including glutaraldehyde, bleach, hydrogen peroxide, alcohol, and quaternary ammonium compounds – were significantly associated with increased risk of COPD incidence.

The authors acknowledged their study’s limitations, including the JTEM only assessing exposure to seven of the major cleaning products commonly used in health care. In addition, detailed data on exposure to disinfectants was not available before 2009. However, they added that, because the study has been ongoing since 1989, it could be expected that women who had been nurses for decades had “already accumulated a long history of exposure.”

The study was supported in part by grants from the Centers for Disease Control and Prevention and the National Institutes of Health. Five of the authors reported receiving grants from the CDC’s National Institute for Occupational Safety and Health (NIOSH); one additional author reported being a consultant on a NIOSH grant and receiving personal fees from a health care system. No other conflicts of interest were reported.

SOURCE: Dumas O et al. JAMA Netw Open. 2019 Oct 18. doi: 10.1001/jamanetworkopen.2019.13563.

A study has found that consistent occupational exposure to disinfectants is associated with an increased risk of chronic obstructive pulmonary disease (COPD).

“Clinicians should be aware of this new risk factor and systematically look for sources of exposure to cleaning products and disinfectants in addition to other occupational exposures in patients with COPD,” wrote Orianne Dumas, PhD, of the Université de Versailles St-Quentin-en-Yvelines (France) and coauthors. The study was published in JAMA Network Open.

To determine if regular use of disinfectants had a negative impact on respiratory health, the researchers analyzed data from 73,262 active female nurses who had no history of COPD and completed questionnaires every 2 years for the Nurses’ Health Study II. Their mean age at baseline was 54.7. Exposure to commonly used disinfectants was evaluated by a job-task-exposure matrix (JTEM) specific to nurses.

Between 2009 and 2015, 582 nurses reported incident physician-diagnosed COPD. Weekly use of disinfectants was associated with COPD incidence (adjusted hazard ratio 1.35; 95% confidence interval, 1.14-1.59). Additional associations were found in nurses who used disinfectants to clean surfaces (AHR, 1.38; 95% CI, 1.13-1.68) and to clean medical instruments (AHR, 1.31; 95% CI, 1.07-1.61). High-level exposure to certain disinfectants – including glutaraldehyde, bleach, hydrogen peroxide, alcohol, and quaternary ammonium compounds – were significantly associated with increased risk of COPD incidence.

The authors acknowledged their study’s limitations, including the JTEM only assessing exposure to seven of the major cleaning products commonly used in health care. In addition, detailed data on exposure to disinfectants was not available before 2009. However, they added that, because the study has been ongoing since 1989, it could be expected that women who had been nurses for decades had “already accumulated a long history of exposure.”

The study was supported in part by grants from the Centers for Disease Control and Prevention and the National Institutes of Health. Five of the authors reported receiving grants from the CDC’s National Institute for Occupational Safety and Health (NIOSH); one additional author reported being a consultant on a NIOSH grant and receiving personal fees from a health care system. No other conflicts of interest were reported.

SOURCE: Dumas O et al. JAMA Netw Open. 2019 Oct 18. doi: 10.1001/jamanetworkopen.2019.13563.

A study has found that consistent occupational exposure to disinfectants is associated with an increased risk of chronic obstructive pulmonary disease (COPD).

“Clinicians should be aware of this new risk factor and systematically look for sources of exposure to cleaning products and disinfectants in addition to other occupational exposures in patients with COPD,” wrote Orianne Dumas, PhD, of the Université de Versailles St-Quentin-en-Yvelines (France) and coauthors. The study was published in JAMA Network Open.

To determine if regular use of disinfectants had a negative impact on respiratory health, the researchers analyzed data from 73,262 active female nurses who had no history of COPD and completed questionnaires every 2 years for the Nurses’ Health Study II. Their mean age at baseline was 54.7. Exposure to commonly used disinfectants was evaluated by a job-task-exposure matrix (JTEM) specific to nurses.

Between 2009 and 2015, 582 nurses reported incident physician-diagnosed COPD. Weekly use of disinfectants was associated with COPD incidence (adjusted hazard ratio 1.35; 95% confidence interval, 1.14-1.59). Additional associations were found in nurses who used disinfectants to clean surfaces (AHR, 1.38; 95% CI, 1.13-1.68) and to clean medical instruments (AHR, 1.31; 95% CI, 1.07-1.61). High-level exposure to certain disinfectants – including glutaraldehyde, bleach, hydrogen peroxide, alcohol, and quaternary ammonium compounds – were significantly associated with increased risk of COPD incidence.

The authors acknowledged their study’s limitations, including the JTEM only assessing exposure to seven of the major cleaning products commonly used in health care. In addition, detailed data on exposure to disinfectants was not available before 2009. However, they added that, because the study has been ongoing since 1989, it could be expected that women who had been nurses for decades had “already accumulated a long history of exposure.”

The study was supported in part by grants from the Centers for Disease Control and Prevention and the National Institutes of Health. Five of the authors reported receiving grants from the CDC’s National Institute for Occupational Safety and Health (NIOSH); one additional author reported being a consultant on a NIOSH grant and receiving personal fees from a health care system. No other conflicts of interest were reported.

SOURCE: Dumas O et al. JAMA Netw Open. 2019 Oct 18. doi: 10.1001/jamanetworkopen.2019.13563.

A new study has found that omalizumab (Xolair) reduced severity and improved quality of life in pediatric patients with severe atopic dermatitis.

Michail_Petrov-96/Thinkstock

“Future work with an even larger sample size, a longer duration, and higher-affinity versions of omalizumab would clarify the precise role of anti-IgE therapy and its ideal target population,” wrote Susan Chan, MD, of Guy’s and St. Thomas’ NHS Foundation Trust in London and her coauthors. The study was published in JAMA Pediatrics.

To determine the benefits of omalizumab in reducing immunoglobulin E levels and thereby treating severe childhood eczema, the researchers launched the Atopic Dermatitis Anti-IgE Pediatric Trial (ADAPT). This randomized clinical trial recruited 62 patients between the ages of 4 and 19 years with severe eczema, which was defined as a score over 40 on the objective Scoring Atopic Dermatitis (SCORAD) index. They received 24 weeks of treatment with either omalizumab (n = 30) or placebo (n = 32) followed by 24 weeks of follow-up. Participants had a mean age of 10.3 years.

After 24 weeks, the adjusted mean difference in objective SCORAD index between the two groups was –6.9 (95% confidence interval, –12.2 to –1.5; P = .01) and significantly favored omalizumab therapy. The adjusted mean difference for the Eczema Area and Severity Index (–6.7; 95% CI, –13.2 to –0.1) also favored omalizumab. In regard to quality of life, after 24 weeks the Children’s Dermatology Life Quality Index/Dermatology Life Quality Index favored the omalizumab group with an adjusted mean difference of –3.5 (95% CI, –6.4 to –0.5).

In an accompanying editorial, Ann Chen Wu, MD, of Harvard Medical School in Boston noted that the results of the study from Chan et al. were promising but “more questions need to be answered before the drug can be used to treat atopic dermatitis in clinical practice” (JAMA Pediatr. 2019 Nov. 25. doi: 10.1001/jamapediatrics.2019.4509).

Her initial concern was price; she acknowledged that “omalizumab is a costly intervention” but said atopic dermatitis is also costly, raising the question as to whether the high costs of both justify treatment. In addition, omalizumab as treatment can come with both benefits and harms. Severe atopic dermatitis can decrease quality of life and, though omalizumab appears to be safe, there are adverse effects and logistical burdens to overcome.

More than anything, she recognized the need to prioritize, wondering what level of atopic dermatitis patients would truly benefit from this level of treatment. “Is using a $100,000-per-year medication for an itchy condition an overtreatment,” she asked, “or a lifesaver?”

The study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme and Guy’s and St. Thomas’ Charity. The authors had numerous financial disclosures, including receiving grants from the NIHR EME Programme and Guy’s and St. Thomas’ Charity along with active and placebo drugs from Novartis for use in the study. Dr. Wu reported receiving a grant from GlaxoSmithKline.

SOURCE: Chan S et al. JAMA Pediatr. 2019 Nov 25. doi: 10.1001/jamapediatrics.2019.4476.

A new study has found that omalizumab (Xolair) reduced severity and improved quality of life in pediatric patients with severe atopic dermatitis.

Michail_Petrov-96/Thinkstock

“Future work with an even larger sample size, a longer duration, and higher-affinity versions of omalizumab would clarify the precise role of anti-IgE therapy and its ideal target population,” wrote Susan Chan, MD, of Guy’s and St. Thomas’ NHS Foundation Trust in London and her coauthors. The study was published in JAMA Pediatrics.

To determine the benefits of omalizumab in reducing immunoglobulin E levels and thereby treating severe childhood eczema, the researchers launched the Atopic Dermatitis Anti-IgE Pediatric Trial (ADAPT). This randomized clinical trial recruited 62 patients between the ages of 4 and 19 years with severe eczema, which was defined as a score over 40 on the objective Scoring Atopic Dermatitis (SCORAD) index. They received 24 weeks of treatment with either omalizumab (n = 30) or placebo (n = 32) followed by 24 weeks of follow-up. Participants had a mean age of 10.3 years.

After 24 weeks, the adjusted mean difference in objective SCORAD index between the two groups was –6.9 (95% confidence interval, –12.2 to –1.5; P = .01) and significantly favored omalizumab therapy. The adjusted mean difference for the Eczema Area and Severity Index (–6.7; 95% CI, –13.2 to –0.1) also favored omalizumab. In regard to quality of life, after 24 weeks the Children’s Dermatology Life Quality Index/Dermatology Life Quality Index favored the omalizumab group with an adjusted mean difference of –3.5 (95% CI, –6.4 to –0.5).

In an accompanying editorial, Ann Chen Wu, MD, of Harvard Medical School in Boston noted that the results of the study from Chan et al. were promising but “more questions need to be answered before the drug can be used to treat atopic dermatitis in clinical practice” (JAMA Pediatr. 2019 Nov. 25. doi: 10.1001/jamapediatrics.2019.4509).

Her initial concern was price; she acknowledged that “omalizumab is a costly intervention” but said atopic dermatitis is also costly, raising the question as to whether the high costs of both justify treatment. In addition, omalizumab as treatment can come with both benefits and harms. Severe atopic dermatitis can decrease quality of life and, though omalizumab appears to be safe, there are adverse effects and logistical burdens to overcome.

More than anything, she recognized the need to prioritize, wondering what level of atopic dermatitis patients would truly benefit from this level of treatment. “Is using a $100,000-per-year medication for an itchy condition an overtreatment,” she asked, “or a lifesaver?”

The study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme and Guy’s and St. Thomas’ Charity. The authors had numerous financial disclosures, including receiving grants from the NIHR EME Programme and Guy’s and St. Thomas’ Charity along with active and placebo drugs from Novartis for use in the study. Dr. Wu reported receiving a grant from GlaxoSmithKline.

SOURCE: Chan S et al. JAMA Pediatr. 2019 Nov 25. doi: 10.1001/jamapediatrics.2019.4476.

A new study has found that omalizumab (Xolair) reduced severity and improved quality of life in pediatric patients with severe atopic dermatitis.

Michail_Petrov-96/Thinkstock

“Future work with an even larger sample size, a longer duration, and higher-affinity versions of omalizumab would clarify the precise role of anti-IgE therapy and its ideal target population,” wrote Susan Chan, MD, of Guy’s and St. Thomas’ NHS Foundation Trust in London and her coauthors. The study was published in JAMA Pediatrics.

To determine the benefits of omalizumab in reducing immunoglobulin E levels and thereby treating severe childhood eczema, the researchers launched the Atopic Dermatitis Anti-IgE Pediatric Trial (ADAPT). This randomized clinical trial recruited 62 patients between the ages of 4 and 19 years with severe eczema, which was defined as a score over 40 on the objective Scoring Atopic Dermatitis (SCORAD) index. They received 24 weeks of treatment with either omalizumab (n = 30) or placebo (n = 32) followed by 24 weeks of follow-up. Participants had a mean age of 10.3 years.

After 24 weeks, the adjusted mean difference in objective SCORAD index between the two groups was –6.9 (95% confidence interval, –12.2 to –1.5; P = .01) and significantly favored omalizumab therapy. The adjusted mean difference for the Eczema Area and Severity Index (–6.7; 95% CI, –13.2 to –0.1) also favored omalizumab. In regard to quality of life, after 24 weeks the Children’s Dermatology Life Quality Index/Dermatology Life Quality Index favored the omalizumab group with an adjusted mean difference of –3.5 (95% CI, –6.4 to –0.5).

In an accompanying editorial, Ann Chen Wu, MD, of Harvard Medical School in Boston noted that the results of the study from Chan et al. were promising but “more questions need to be answered before the drug can be used to treat atopic dermatitis in clinical practice” (JAMA Pediatr. 2019 Nov. 25. doi: 10.1001/jamapediatrics.2019.4509).

Her initial concern was price; she acknowledged that “omalizumab is a costly intervention” but said atopic dermatitis is also costly, raising the question as to whether the high costs of both justify treatment. In addition, omalizumab as treatment can come with both benefits and harms. Severe atopic dermatitis can decrease quality of life and, though omalizumab appears to be safe, there are adverse effects and logistical burdens to overcome.

More than anything, she recognized the need to prioritize, wondering what level of atopic dermatitis patients would truly benefit from this level of treatment. “Is using a $100,000-per-year medication for an itchy condition an overtreatment,” she asked, “or a lifesaver?”

The study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation Programme and Guy’s and St. Thomas’ Charity. The authors had numerous financial disclosures, including receiving grants from the NIHR EME Programme and Guy’s and St. Thomas’ Charity along with active and placebo drugs from Novartis for use in the study. Dr. Wu reported receiving a grant from GlaxoSmithKline.

SOURCE: Chan S et al. JAMA Pediatr. 2019 Nov 25. doi: 10.1001/jamapediatrics.2019.4476.