Steve Cimino

A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.

“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.

To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.

Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).

When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.

“The self-testing kits targeting individuals at high risk of acquiring HIV complement the use of PrEP,” they added, “and are another way to accelerate the end of the epidemic.”

The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.

SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.

A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.

“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.

To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.

Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).

When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.

“The self-testing kits targeting individuals at high risk of acquiring HIV complement the use of PrEP,” they added, “and are another way to accelerate the end of the epidemic.”

The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.

SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.

A new study has found that distributing HIV self-tests to at-risk groups such as men who have sex with men can increase testing frequency and uncover more previously undiagnosed infections.

“Based on these findings, HIV prevention programs might consider adding an HIV self-testing mail distribution component to their portfolio of HIV prevention services for high-risk populations,” wrote Robin J. MacGowan, MPH, of the Centers for Disease Control and Prevention and coauthors. The study was published in JAMA Internal Medicine.

To assess the potential benefits of expanded HIV self-testing, the CDC sponsored a 12-month randomized clinical trial called the Evaluation of Rapid HIV Self-testing Among MSM Project (eSTAMP). Participants were recruited via social media, music and dating websites; criteria included being aged at least 18 years, never having tested positive for HIV, and having engaged in anal sex with at least one man in the past year. The 2,665 participants were assigned to either the self-testing (ST) group (n = 1,325) or the control group (n = 1,340); the ST group received four self-tests in the mail with the option for more each quarter. All participants were asked to complete follow-up surveys every 3 months.

Of all participants, 1,991 (74.7%) initiated at least one follow-up survey. Participants in the ST group reported testing more frequently than those in the control group (an average of 5.3 tests vs. 1.5 tests; P less than .001). In addition, a much higher percentage of ST participants tested at least three times in 12 months (777 of 1014 [76.6%]), compared with controls (215 of 977 [22.0%]). A total of 36 participants tested newly positive for HIV during the study; over the first 3 months, 12 of the 14 infections were identified in the ST group (P less than .007). Over 12 months, 25 of the infections came from the ST group, compared with 11 in the control group (P = .02).

When HIV tests are free and convenient, members of high-risk populations will use them, wrote Julia M. Janssen, MD, of the University of California, San Francisco, and Mitchell H. Katz, MD, of New York City Health and Hospitals in an accompanying editorial (JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5442). But tests are not enough; the authors noted the role of primary care physicians in prescribing pre-exposure prophylaxis (PrEP) for at-risk patients as key in decreasing rates of new HIV diagnoses.

“The self-testing kits targeting individuals at high risk of acquiring HIV complement the use of PrEP,” they added, “and are another way to accelerate the end of the epidemic.”

The study was funded by the CDC. One author reported receiving grants and fees from the CDC and the National Institutes of Health, along with personal fees from Elsevier and the Ontario HIV Treatment Network. Dr. Katz reported receiving royalties for a chapter on HIV in Lange’s Current Medicine and Diagnostic Testing.

SOURCE: MacGowan RJ et al. JAMA Intern Med. 2019 Nov 18. doi: 10.1001/jamainternmed.2019.5222.

A new study has found that neither vitamin D nor omega-3 fatty acids are significantly more beneficial than placebo for prevention and treatment of chronic kidney disease in patients with type 2 diabetes, according to Ian H. de Boer, MD, of the University of Washington, Seattle, and coauthors.

Findings of the study were presented at Kidney Week 2019, sponsored the American Society of Nephrology, and published simultaneously in JAMA.

To determine the benefits of either vitamin D or omega-3 fatty acids in regard to kidney function, the researchers conducted a randomized clinical trial of 1,312 patients with type 2 diabetes. The trial was designed to accompany the Vitamin D and Omega-3 Trial (VITAL), which enrolled 25,871 patients to test the two supplements in the prevention of cardiovascular disease and cancer.

Participants in this study – known as VITAL–Diabetic Kidney Disease, designed as an ancillary to VITAL – were assigned to one of four groups: vitamin D plus omega-3 fatty acids (n = 370), vitamin D plus placebo (n = 333), omega-3 fatty acids plus placebo (n = 289), or both placebos (n = 320). The goal was to assess changes in in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) after 5 years.

Of the initial 1,312 participants, 934 (71%) finished the study. At 5-year follow-up, patients taking vitamin D had a mean change in eGFR of −12.3 mL/min per 1.73 m² (95% confidence interval, −13.4 to −11.2), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −11.9) with placebo. Patients taking omega-3 fatty acids had a mean eGFR change of −12.2 mL/min per 1.73 m² (95% CI, −13.3 to −11.1), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −12.0) with placebo.

The authors noted that the modest number of measurements collected per participant limited the evaluation and analyses. In addition, the study focused broadly on the type 2 diabetes population and not on subgroups, “who may derive more benefit from the study interventions.”

In an accompanying editorial, authors Anika Lucas, MD and Myles Wolf, MD, of Duke University in Durham, N.C., said multiple clinical trials, including this latest study from de Boer and colleagues on kidney function, have failed to reinforce the previously reported benefits of vitamin D.

“The VITAL-DKD study population had nearly normal mean 25-hydroxyvitamin D levels at baseline, leaving open the question of whether the results would have differed had recruitment been restricted to patients with moderate or severe vitamin D deficiency,” they wrote (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17302).

Nevertheless, it seems safe to conclude that the previous associations between vitamin D deficiency and adverse health were “driven by unmeasured residual confounding or reverse causality.

“Without certainty about the ideal approach to vitamin D treatment in advanced CKD, a randomized trial that compared cholecalciferol, exogenous 25-hydroxyvitamin D, and an activated vitamin D analogue vs. placebo could definitively lay to rest multiple remaining questions in the area,” they suggested.

The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, and equipment and supplies from various pharmaceutical companies and the National Institutes of Health. Dr. Wolf reported having served as a consultant for Akebia, AMAG, Amgen, Ardelyx, Diasorin, and Pharmacosmos. No other disclosures were reported.

SOURCE: de Boer IH et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17380.

A new study has found that neither vitamin D nor omega-3 fatty acids are significantly more beneficial than placebo for prevention and treatment of chronic kidney disease in patients with type 2 diabetes, according to Ian H. de Boer, MD, of the University of Washington, Seattle, and coauthors.

Findings of the study were presented at Kidney Week 2019, sponsored the American Society of Nephrology, and published simultaneously in JAMA.

To determine the benefits of either vitamin D or omega-3 fatty acids in regard to kidney function, the researchers conducted a randomized clinical trial of 1,312 patients with type 2 diabetes. The trial was designed to accompany the Vitamin D and Omega-3 Trial (VITAL), which enrolled 25,871 patients to test the two supplements in the prevention of cardiovascular disease and cancer.

Participants in this study – known as VITAL–Diabetic Kidney Disease, designed as an ancillary to VITAL – were assigned to one of four groups: vitamin D plus omega-3 fatty acids (n = 370), vitamin D plus placebo (n = 333), omega-3 fatty acids plus placebo (n = 289), or both placebos (n = 320). The goal was to assess changes in in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) after 5 years.

Of the initial 1,312 participants, 934 (71%) finished the study. At 5-year follow-up, patients taking vitamin D had a mean change in eGFR of −12.3 mL/min per 1.73 m² (95% confidence interval, −13.4 to −11.2), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −11.9) with placebo. Patients taking omega-3 fatty acids had a mean eGFR change of −12.2 mL/min per 1.73 m² (95% CI, −13.3 to −11.1), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −12.0) with placebo.

The authors noted that the modest number of measurements collected per participant limited the evaluation and analyses. In addition, the study focused broadly on the type 2 diabetes population and not on subgroups, “who may derive more benefit from the study interventions.”

In an accompanying editorial, authors Anika Lucas, MD and Myles Wolf, MD, of Duke University in Durham, N.C., said multiple clinical trials, including this latest study from de Boer and colleagues on kidney function, have failed to reinforce the previously reported benefits of vitamin D.

“The VITAL-DKD study population had nearly normal mean 25-hydroxyvitamin D levels at baseline, leaving open the question of whether the results would have differed had recruitment been restricted to patients with moderate or severe vitamin D deficiency,” they wrote (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17302).

Nevertheless, it seems safe to conclude that the previous associations between vitamin D deficiency and adverse health were “driven by unmeasured residual confounding or reverse causality.

“Without certainty about the ideal approach to vitamin D treatment in advanced CKD, a randomized trial that compared cholecalciferol, exogenous 25-hydroxyvitamin D, and an activated vitamin D analogue vs. placebo could definitively lay to rest multiple remaining questions in the area,” they suggested.

The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, and equipment and supplies from various pharmaceutical companies and the National Institutes of Health. Dr. Wolf reported having served as a consultant for Akebia, AMAG, Amgen, Ardelyx, Diasorin, and Pharmacosmos. No other disclosures were reported.

SOURCE: de Boer IH et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17380.

A new study has found that neither vitamin D nor omega-3 fatty acids are significantly more beneficial than placebo for prevention and treatment of chronic kidney disease in patients with type 2 diabetes, according to Ian H. de Boer, MD, of the University of Washington, Seattle, and coauthors.

Findings of the study were presented at Kidney Week 2019, sponsored the American Society of Nephrology, and published simultaneously in JAMA.

To determine the benefits of either vitamin D or omega-3 fatty acids in regard to kidney function, the researchers conducted a randomized clinical trial of 1,312 patients with type 2 diabetes. The trial was designed to accompany the Vitamin D and Omega-3 Trial (VITAL), which enrolled 25,871 patients to test the two supplements in the prevention of cardiovascular disease and cancer.

Participants in this study – known as VITAL–Diabetic Kidney Disease, designed as an ancillary to VITAL – were assigned to one of four groups: vitamin D plus omega-3 fatty acids (n = 370), vitamin D plus placebo (n = 333), omega-3 fatty acids plus placebo (n = 289), or both placebos (n = 320). The goal was to assess changes in in glomerular filtration rate estimated from serum creatinine and cystatin C (eGFR) after 5 years.

Of the initial 1,312 participants, 934 (71%) finished the study. At 5-year follow-up, patients taking vitamin D had a mean change in eGFR of −12.3 mL/min per 1.73 m² (95% confidence interval, −13.4 to −11.2), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −11.9) with placebo. Patients taking omega-3 fatty acids had a mean eGFR change of −12.2 mL/min per 1.73 m² (95% CI, −13.3 to −11.1), compared with −13.1 mL/min per 1.73 m² (95% CI, −14.2 to −12.0) with placebo.

The authors noted that the modest number of measurements collected per participant limited the evaluation and analyses. In addition, the study focused broadly on the type 2 diabetes population and not on subgroups, “who may derive more benefit from the study interventions.”

In an accompanying editorial, authors Anika Lucas, MD and Myles Wolf, MD, of Duke University in Durham, N.C., said multiple clinical trials, including this latest study from de Boer and colleagues on kidney function, have failed to reinforce the previously reported benefits of vitamin D.

“The VITAL-DKD study population had nearly normal mean 25-hydroxyvitamin D levels at baseline, leaving open the question of whether the results would have differed had recruitment been restricted to patients with moderate or severe vitamin D deficiency,” they wrote (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17302).

Nevertheless, it seems safe to conclude that the previous associations between vitamin D deficiency and adverse health were “driven by unmeasured residual confounding or reverse causality.

“Without certainty about the ideal approach to vitamin D treatment in advanced CKD, a randomized trial that compared cholecalciferol, exogenous 25-hydroxyvitamin D, and an activated vitamin D analogue vs. placebo could definitively lay to rest multiple remaining questions in the area,” they suggested.

The National Institute of Diabetes and Digestive and Kidney Diseases funded the study. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, and equipment and supplies from various pharmaceutical companies and the National Institutes of Health. Dr. Wolf reported having served as a consultant for Akebia, AMAG, Amgen, Ardelyx, Diasorin, and Pharmacosmos. No other disclosures were reported.

SOURCE: de Boer IH et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17380.

Though survival rates of patients with metastatic breast cancer (MBC) have increased over the last 2 decades, a new study has indicated disparities exist across regions and by variables like age and race.

“It appears from these results that we may be at a crossroads for MBC treatment and survival,” wrote Judith A. Malmgren, PhD, of the University of Washington and her coauthors. The study was published in Cancer. “Access to appropriate, timely, and up‐to‐date diagnosis, care, treatment, and surveillance could turn this fatal disease into a chronic and treatable phenomenon, depending on patient factors, molecular subtype, and insurance capacity to pay for treatment,” they said.

To determine how breast cancer outcomes might vary across regions, the researchers compared breast cancer–specific survival rates (BCSS) from Surveillance, Epidemiology, and End Results-9 (SEER-9) registry data minus a regional subset from the Seattle-Puget Sound (S-PS) region (n = 12,121) to patients from that S-PS region (n = 1,931) and to an individual cohort in that area (n = 261). Five-year BCSS rates were calculated for three time periods: 1990‐1998, 1999‐2004, and 2005‐2011.

All analyzed patients were diagnosed with a first primary, de novo, stage IV breast cancer between the ages of 25 and 84 years from 1990 to 2011. Patients in the SEER-9 group and the S-PS region had a mean age of 61 years, compared with the individual cohort’s mean age of 55 years. Patients in the individual cohort were more likely to reside in a major metropolitan area of over 1 million people, compared with the SEER group and the S-PS region (86% versus 61% and 58%, respectively).

Patients in the SEER-9 group had improved BCSS rates over the study period, from 19% in 1990-1998 (95% confidence interval, 18%-21%; P less than .001) to 26% in 2005-2011 (95% CI, 24%-27%; P less than .001). Patients in the S-PS region saw even greater improvements in BCSS rates, from 21% in 1990-1998 (95% CI, 18%-24%; P less than .001) to 35% in 2005-2011 (95% CI, 32%-39%; P less than .001). But the largest improvement in survival rates came from patients in the individual cohort, who went from 29% in 1990-1998 (95% CI, 18%-37%; P less than .001) to 56% in 2005-2011 (95% CI, 45%-65%; P = .004).

In a proportional hazards model for breast cancer–specific death, reduced hazard in the SEER-9 group was associated with surgery (hazard ratio, 0.58; 95% CI, 0.55-0.61; P less than .001), an age less than 70 (HR, 0.77; 95% CI, 0.73-0.82; P less than .001) and white race (HR, 0.84; 95% CI, 0.79-0.89; P less than .001). Similar associations were seen in the S-PS region with surgery (HR, 0.57; 95% CI, 0.50-0.66; P less than .001) and an age less than 70 (HR, 0.72; 95% CI, 0.62-0.84; P less than .001), but not white race.

The study results “indicate that the stage IV population that is living longer may be benefiting from many of the same therapies used to treat early breast cancer, especially for patients who are able to handle adjuvant chemotherapy treatment and are HR‐positive,” the researchers said. “However, the lag in survival improvement across different population‐based, geographic regions suggests that some groups and regions may benefit unequally from treatment advances as well as timely diagnosis.”

The study was funded by the Kaplan Cancer Research Fund, the Metastatic Breast Cancer Alliance, and the Surveillance, Epidemiology, and End Results Cancer Surveillance System program of the National Cancer Institute. The authors reported no conflicts of interest.

SOURCE: Malmgren JA et al. Cancer. 2019 Oct 22. doi: 10.1002/cncr.32531.

Though survival rates of patients with metastatic breast cancer (MBC) have increased over the last 2 decades, a new study has indicated disparities exist across regions and by variables like age and race.

“It appears from these results that we may be at a crossroads for MBC treatment and survival,” wrote Judith A. Malmgren, PhD, of the University of Washington and her coauthors. The study was published in Cancer. “Access to appropriate, timely, and up‐to‐date diagnosis, care, treatment, and surveillance could turn this fatal disease into a chronic and treatable phenomenon, depending on patient factors, molecular subtype, and insurance capacity to pay for treatment,” they said.

To determine how breast cancer outcomes might vary across regions, the researchers compared breast cancer–specific survival rates (BCSS) from Surveillance, Epidemiology, and End Results-9 (SEER-9) registry data minus a regional subset from the Seattle-Puget Sound (S-PS) region (n = 12,121) to patients from that S-PS region (n = 1,931) and to an individual cohort in that area (n = 261). Five-year BCSS rates were calculated for three time periods: 1990‐1998, 1999‐2004, and 2005‐2011.

All analyzed patients were diagnosed with a first primary, de novo, stage IV breast cancer between the ages of 25 and 84 years from 1990 to 2011. Patients in the SEER-9 group and the S-PS region had a mean age of 61 years, compared with the individual cohort’s mean age of 55 years. Patients in the individual cohort were more likely to reside in a major metropolitan area of over 1 million people, compared with the SEER group and the S-PS region (86% versus 61% and 58%, respectively).

Patients in the SEER-9 group had improved BCSS rates over the study period, from 19% in 1990-1998 (95% confidence interval, 18%-21%; P less than .001) to 26% in 2005-2011 (95% CI, 24%-27%; P less than .001). Patients in the S-PS region saw even greater improvements in BCSS rates, from 21% in 1990-1998 (95% CI, 18%-24%; P less than .001) to 35% in 2005-2011 (95% CI, 32%-39%; P less than .001). But the largest improvement in survival rates came from patients in the individual cohort, who went from 29% in 1990-1998 (95% CI, 18%-37%; P less than .001) to 56% in 2005-2011 (95% CI, 45%-65%; P = .004).

In a proportional hazards model for breast cancer–specific death, reduced hazard in the SEER-9 group was associated with surgery (hazard ratio, 0.58; 95% CI, 0.55-0.61; P less than .001), an age less than 70 (HR, 0.77; 95% CI, 0.73-0.82; P less than .001) and white race (HR, 0.84; 95% CI, 0.79-0.89; P less than .001). Similar associations were seen in the S-PS region with surgery (HR, 0.57; 95% CI, 0.50-0.66; P less than .001) and an age less than 70 (HR, 0.72; 95% CI, 0.62-0.84; P less than .001), but not white race.

The study results “indicate that the stage IV population that is living longer may be benefiting from many of the same therapies used to treat early breast cancer, especially for patients who are able to handle adjuvant chemotherapy treatment and are HR‐positive,” the researchers said. “However, the lag in survival improvement across different population‐based, geographic regions suggests that some groups and regions may benefit unequally from treatment advances as well as timely diagnosis.”

The study was funded by the Kaplan Cancer Research Fund, the Metastatic Breast Cancer Alliance, and the Surveillance, Epidemiology, and End Results Cancer Surveillance System program of the National Cancer Institute. The authors reported no conflicts of interest.

SOURCE: Malmgren JA et al. Cancer. 2019 Oct 22. doi: 10.1002/cncr.32531.

Though survival rates of patients with metastatic breast cancer (MBC) have increased over the last 2 decades, a new study has indicated disparities exist across regions and by variables like age and race.

“It appears from these results that we may be at a crossroads for MBC treatment and survival,” wrote Judith A. Malmgren, PhD, of the University of Washington and her coauthors. The study was published in Cancer. “Access to appropriate, timely, and up‐to‐date diagnosis, care, treatment, and surveillance could turn this fatal disease into a chronic and treatable phenomenon, depending on patient factors, molecular subtype, and insurance capacity to pay for treatment,” they said.

To determine how breast cancer outcomes might vary across regions, the researchers compared breast cancer–specific survival rates (BCSS) from Surveillance, Epidemiology, and End Results-9 (SEER-9) registry data minus a regional subset from the Seattle-Puget Sound (S-PS) region (n = 12,121) to patients from that S-PS region (n = 1,931) and to an individual cohort in that area (n = 261). Five-year BCSS rates were calculated for three time periods: 1990‐1998, 1999‐2004, and 2005‐2011.

All analyzed patients were diagnosed with a first primary, de novo, stage IV breast cancer between the ages of 25 and 84 years from 1990 to 2011. Patients in the SEER-9 group and the S-PS region had a mean age of 61 years, compared with the individual cohort’s mean age of 55 years. Patients in the individual cohort were more likely to reside in a major metropolitan area of over 1 million people, compared with the SEER group and the S-PS region (86% versus 61% and 58%, respectively).

Patients in the SEER-9 group had improved BCSS rates over the study period, from 19% in 1990-1998 (95% confidence interval, 18%-21%; P less than .001) to 26% in 2005-2011 (95% CI, 24%-27%; P less than .001). Patients in the S-PS region saw even greater improvements in BCSS rates, from 21% in 1990-1998 (95% CI, 18%-24%; P less than .001) to 35% in 2005-2011 (95% CI, 32%-39%; P less than .001). But the largest improvement in survival rates came from patients in the individual cohort, who went from 29% in 1990-1998 (95% CI, 18%-37%; P less than .001) to 56% in 2005-2011 (95% CI, 45%-65%; P = .004).

In a proportional hazards model for breast cancer–specific death, reduced hazard in the SEER-9 group was associated with surgery (hazard ratio, 0.58; 95% CI, 0.55-0.61; P less than .001), an age less than 70 (HR, 0.77; 95% CI, 0.73-0.82; P less than .001) and white race (HR, 0.84; 95% CI, 0.79-0.89; P less than .001). Similar associations were seen in the S-PS region with surgery (HR, 0.57; 95% CI, 0.50-0.66; P less than .001) and an age less than 70 (HR, 0.72; 95% CI, 0.62-0.84; P less than .001), but not white race.

The study results “indicate that the stage IV population that is living longer may be benefiting from many of the same therapies used to treat early breast cancer, especially for patients who are able to handle adjuvant chemotherapy treatment and are HR‐positive,” the researchers said. “However, the lag in survival improvement across different population‐based, geographic regions suggests that some groups and regions may benefit unequally from treatment advances as well as timely diagnosis.”

The study was funded by the Kaplan Cancer Research Fund, the Metastatic Breast Cancer Alliance, and the Surveillance, Epidemiology, and End Results Cancer Surveillance System program of the National Cancer Institute. The authors reported no conflicts of interest.

SOURCE: Malmgren JA et al. Cancer. 2019 Oct 22. doi: 10.1002/cncr.32531.

When it comes to repairing knee cartilage, a new study found no significant differences between autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation with a collagen membrane (ACI-C) as treatment options.

“If the conclusion of the present study stands and is confirmed by further clinical trials, AMIC could be considered an equal alternative to techniques based on chondrocyte transplantation for treatment of cartilage defects of the knee,” wrote Vegard Fossum, MD, of University Hospital of North Norway, Tromsø, and coauthors, adding that cost and comparative ease might actually make AMIC the preferred choice. The study was published in the Orthopaedic Journal of Sports Medicine.

To evaluate outcomes of the two procedures, the researchers initiated a clinical trial of 41 patients with at least one chondral or osteochondral defect of the distal femur or patella. They were split into two groups: those treated with ACI-C (n = 21) and those treated with AMIC (n = 20). At 1- and 2-year follow-up, patients were assessed via improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS), compared with baseline, along with Lysholm and visual analog scale (VAS) pain scores.

After 1 and 2 years, both groups saw improvements from baseline. At 2 years, the AMIC group had an 18.1 change in KOOS, compared with 10.3 in the ACI-C group (P = .17). Two-year improvements on the Lysholm score (19.7 in AMIC, compared with 17.0 in ACI-C, P = .66) and VAS pain score (30.6 in AMIC versus 19.6 in ACI-C, P = .19) were not significantly different. Two patients in the AMIC group had undergone total knee replacement after 2 years, compared with zero in the ACI-C group.

The authors noted their study’s potential limitations, including the small number of patients in each group – the initial plan was to include 80 total – and its broad inclusion criteria. However, since the aim was to compare treatment results and not evaluate effectiveness, they did not consider the broad criteria “a major limitation.”

The authors reported no conflicts of interest.

SOURCE: Fossum V et al. Orthop J Sports Med. 2019 Sept 17. doi: 10.1177/2325967119868212.

When it comes to repairing knee cartilage, a new study found no significant differences between autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation with a collagen membrane (ACI-C) as treatment options.

“If the conclusion of the present study stands and is confirmed by further clinical trials, AMIC could be considered an equal alternative to techniques based on chondrocyte transplantation for treatment of cartilage defects of the knee,” wrote Vegard Fossum, MD, of University Hospital of North Norway, Tromsø, and coauthors, adding that cost and comparative ease might actually make AMIC the preferred choice. The study was published in the Orthopaedic Journal of Sports Medicine.

To evaluate outcomes of the two procedures, the researchers initiated a clinical trial of 41 patients with at least one chondral or osteochondral defect of the distal femur or patella. They were split into two groups: those treated with ACI-C (n = 21) and those treated with AMIC (n = 20). At 1- and 2-year follow-up, patients were assessed via improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS), compared with baseline, along with Lysholm and visual analog scale (VAS) pain scores.

After 1 and 2 years, both groups saw improvements from baseline. At 2 years, the AMIC group had an 18.1 change in KOOS, compared with 10.3 in the ACI-C group (P = .17). Two-year improvements on the Lysholm score (19.7 in AMIC, compared with 17.0 in ACI-C, P = .66) and VAS pain score (30.6 in AMIC versus 19.6 in ACI-C, P = .19) were not significantly different. Two patients in the AMIC group had undergone total knee replacement after 2 years, compared with zero in the ACI-C group.

The authors noted their study’s potential limitations, including the small number of patients in each group – the initial plan was to include 80 total – and its broad inclusion criteria. However, since the aim was to compare treatment results and not evaluate effectiveness, they did not consider the broad criteria “a major limitation.”

The authors reported no conflicts of interest.

SOURCE: Fossum V et al. Orthop J Sports Med. 2019 Sept 17. doi: 10.1177/2325967119868212.

When it comes to repairing knee cartilage, a new study found no significant differences between autologous matrix-induced chondrogenesis (AMIC) and autologous chondrocyte implantation with a collagen membrane (ACI-C) as treatment options.

“If the conclusion of the present study stands and is confirmed by further clinical trials, AMIC could be considered an equal alternative to techniques based on chondrocyte transplantation for treatment of cartilage defects of the knee,” wrote Vegard Fossum, MD, of University Hospital of North Norway, Tromsø, and coauthors, adding that cost and comparative ease might actually make AMIC the preferred choice. The study was published in the Orthopaedic Journal of Sports Medicine.

To evaluate outcomes of the two procedures, the researchers initiated a clinical trial of 41 patients with at least one chondral or osteochondral defect of the distal femur or patella. They were split into two groups: those treated with ACI-C (n = 21) and those treated with AMIC (n = 20). At 1- and 2-year follow-up, patients were assessed via improvements in Knee Injury and Osteoarthritis Outcome Score (KOOS), compared with baseline, along with Lysholm and visual analog scale (VAS) pain scores.

After 1 and 2 years, both groups saw improvements from baseline. At 2 years, the AMIC group had an 18.1 change in KOOS, compared with 10.3 in the ACI-C group (P = .17). Two-year improvements on the Lysholm score (19.7 in AMIC, compared with 17.0 in ACI-C, P = .66) and VAS pain score (30.6 in AMIC versus 19.6 in ACI-C, P = .19) were not significantly different. Two patients in the AMIC group had undergone total knee replacement after 2 years, compared with zero in the ACI-C group.

The authors noted their study’s potential limitations, including the small number of patients in each group – the initial plan was to include 80 total – and its broad inclusion criteria. However, since the aim was to compare treatment results and not evaluate effectiveness, they did not consider the broad criteria “a major limitation.”

The authors reported no conflicts of interest.

SOURCE: Fossum V et al. Orthop J Sports Med. 2019 Sept 17. doi: 10.1177/2325967119868212.

A new study has uncovered how the measles virus (MeV) can induce immunosuppression by delaying the reconstitution of B cells.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

“Our findings provide a biological explanation for the observed increase in childhood mortality and secondary infections several years after an episode of measles,” said Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors. The study was published in Science Immunology.

To determine if B-cell impairment can lead to measles-associated immunosuppression, the researchers investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IGHV-J) gene frequencies across time periods (R² = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B cell frequencies in measles patients recovered to levels before infection, they had significant changes in IGHV-J gene frequencies (P = .01) and decreased correlation in gene expression (R² = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IGHV genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IGHV genes, Dr. Petrova and associates said.

Finally, the researchers confirmed a hypothesis about the depletion of B memory cell clones during measles and a repopulation of new cells with less clonal expansion. The frequency of individual IGHV-J gene combinations before infection was correlated with a reduction after infection, “with the most frequent combinations undergoing the most marked depletion” and the result being an increase in genetic diversity.

To further test their findings, the researchers vaccinated two groups of four ferrets with live-attenuated influenza vaccine (LAIV) and at 4 weeks infected one of the groups with canine distemper virus (CDV), a surrogate for MeV. At 14 weeks after vaccination, the uninfected group maintained high levels of influenza-specific neutralizing antibodies while the infected group saw impaired B cells and a subsequent reduction in neutralizing antibodies.
 

Understanding the impact of measles on the immune system

“How measles infection has such a long-lasting deleterious effect on the immune system while allowing robust immunity against itself has been a burning immunological question,” Duane R. Wesemann, MD, PhD, of Brigham and Women’s Hospital in Boston, said in an accompanying editorial. The research from Petrova et al. begins to answer that question.

Among the observations he found most interesting was how “post-measles memory cells were more diverse than the pre-measles memory pool,” despite expectations that measles immunity would be dominant. He speculated that the void in memory cells is filled by a set of clones binding to unidentified or nonnative antigens, which may bring polyclonal diversity into B memory cells.

More research is needed to determine just what these findings mean, including looking beyond memory cell depletion and focusing on the impact of immature immunoglobulin repertoires in naive cells. But his broad takeaway is that measles remains both a public health concern and an opportunity to understand how the human body counters disease.

“The unique relationship measles has with the human immune system,” he said, “can illuminate aspects of its inner workings.”

The study was funded by grants to the investigators the Indonesian Endowment Fund for Education, the Wellcome Trust, the German Centre for Infection Research, the Collaborative Research Centre of the German Research Foundation, the German Ministry of Health, and the Royal Society. The authors declared no conflicts of interest. Dr. Wesemann reported receiving support from National Institutes of Health grants and an award from the Burroughs Wellcome Fund; he also reports being a consultant for OpenBiome.

SOURCE: Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125; Wesemann DR. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aaz4195.

A new study has uncovered how the measles virus (MeV) can induce immunosuppression by delaying the reconstitution of B cells.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

“Our findings provide a biological explanation for the observed increase in childhood mortality and secondary infections several years after an episode of measles,” said Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors. The study was published in Science Immunology.

To determine if B-cell impairment can lead to measles-associated immunosuppression, the researchers investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IGHV-J) gene frequencies across time periods (R² = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B cell frequencies in measles patients recovered to levels before infection, they had significant changes in IGHV-J gene frequencies (P = .01) and decreased correlation in gene expression (R² = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IGHV genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IGHV genes, Dr. Petrova and associates said.

Finally, the researchers confirmed a hypothesis about the depletion of B memory cell clones during measles and a repopulation of new cells with less clonal expansion. The frequency of individual IGHV-J gene combinations before infection was correlated with a reduction after infection, “with the most frequent combinations undergoing the most marked depletion” and the result being an increase in genetic diversity.

To further test their findings, the researchers vaccinated two groups of four ferrets with live-attenuated influenza vaccine (LAIV) and at 4 weeks infected one of the groups with canine distemper virus (CDV), a surrogate for MeV. At 14 weeks after vaccination, the uninfected group maintained high levels of influenza-specific neutralizing antibodies while the infected group saw impaired B cells and a subsequent reduction in neutralizing antibodies.
 

Understanding the impact of measles on the immune system

“How measles infection has such a long-lasting deleterious effect on the immune system while allowing robust immunity against itself has been a burning immunological question,” Duane R. Wesemann, MD, PhD, of Brigham and Women’s Hospital in Boston, said in an accompanying editorial. The research from Petrova et al. begins to answer that question.

Among the observations he found most interesting was how “post-measles memory cells were more diverse than the pre-measles memory pool,” despite expectations that measles immunity would be dominant. He speculated that the void in memory cells is filled by a set of clones binding to unidentified or nonnative antigens, which may bring polyclonal diversity into B memory cells.

More research is needed to determine just what these findings mean, including looking beyond memory cell depletion and focusing on the impact of immature immunoglobulin repertoires in naive cells. But his broad takeaway is that measles remains both a public health concern and an opportunity to understand how the human body counters disease.

“The unique relationship measles has with the human immune system,” he said, “can illuminate aspects of its inner workings.”

The study was funded by grants to the investigators the Indonesian Endowment Fund for Education, the Wellcome Trust, the German Centre for Infection Research, the Collaborative Research Centre of the German Research Foundation, the German Ministry of Health, and the Royal Society. The authors declared no conflicts of interest. Dr. Wesemann reported receiving support from National Institutes of Health grants and an award from the Burroughs Wellcome Fund; he also reports being a consultant for OpenBiome.

SOURCE: Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125; Wesemann DR. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aaz4195.

A new study has uncovered how the measles virus (MeV) can induce immunosuppression by delaying the reconstitution of B cells.

CDC/ Cynthia S. Goldsmith; William Bellini, Ph.D.

“Our findings provide a biological explanation for the observed increase in childhood mortality and secondary infections several years after an episode of measles,” said Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors. The study was published in Science Immunology.

To determine if B-cell impairment can lead to measles-associated immunosuppression, the researchers investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IGHV-J) gene frequencies across time periods (R² = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B cell frequencies in measles patients recovered to levels before infection, they had significant changes in IGHV-J gene frequencies (P = .01) and decreased correlation in gene expression (R² = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IGHV genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IGHV genes, Dr. Petrova and associates said.

Finally, the researchers confirmed a hypothesis about the depletion of B memory cell clones during measles and a repopulation of new cells with less clonal expansion. The frequency of individual IGHV-J gene combinations before infection was correlated with a reduction after infection, “with the most frequent combinations undergoing the most marked depletion” and the result being an increase in genetic diversity.

To further test their findings, the researchers vaccinated two groups of four ferrets with live-attenuated influenza vaccine (LAIV) and at 4 weeks infected one of the groups with canine distemper virus (CDV), a surrogate for MeV. At 14 weeks after vaccination, the uninfected group maintained high levels of influenza-specific neutralizing antibodies while the infected group saw impaired B cells and a subsequent reduction in neutralizing antibodies.
 

Understanding the impact of measles on the immune system

“How measles infection has such a long-lasting deleterious effect on the immune system while allowing robust immunity against itself has been a burning immunological question,” Duane R. Wesemann, MD, PhD, of Brigham and Women’s Hospital in Boston, said in an accompanying editorial. The research from Petrova et al. begins to answer that question.

Among the observations he found most interesting was how “post-measles memory cells were more diverse than the pre-measles memory pool,” despite expectations that measles immunity would be dominant. He speculated that the void in memory cells is filled by a set of clones binding to unidentified or nonnative antigens, which may bring polyclonal diversity into B memory cells.

More research is needed to determine just what these findings mean, including looking beyond memory cell depletion and focusing on the impact of immature immunoglobulin repertoires in naive cells. But his broad takeaway is that measles remains both a public health concern and an opportunity to understand how the human body counters disease.

“The unique relationship measles has with the human immune system,” he said, “can illuminate aspects of its inner workings.”

The study was funded by grants to the investigators the Indonesian Endowment Fund for Education, the Wellcome Trust, the German Centre for Infection Research, the Collaborative Research Centre of the German Research Foundation, the German Ministry of Health, and the Royal Society. The authors declared no conflicts of interest. Dr. Wesemann reported receiving support from National Institutes of Health grants and an award from the Burroughs Wellcome Fund; he also reports being a consultant for OpenBiome.

SOURCE: Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125; Wesemann DR. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aaz4195.

Reinforcing previous findings, a new study has determined that the next-generation corrector elexacaftor, in combination with tezacaftor and ivacaftor, can effectively treat patients with Phe508del-minimal function genotypes who did not respond to previous cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimens.

“These results provide evidence that elexacaftor-tezacaftor-ivacaftor can modulate a single Phe508del allele in people with cystic fibrosis, thus addressing the underlying cause of disease in the large majority of patients,” wrote Peter G. Middleton, PhD, of the University of Sydney (Australia) and his coauthors. The study was published in the New England Journal of Medicine.

To further determine if the elexacaftor-tezacaftor-ivacaftor regimen was effective and safe, the researchers launched a randomized, placebo-controlled phase 3 trial of 403 cystic fibrosis patients age 12 or older who had a single Phe508del allele. Patients in the combination group (n = 200) received 200 mg of elexacaftor once daily, 100 mg of tezacaftor once daily, and 150 mg of ivacaftor every 12 hours for 24 weeks. Patients in the other group (n = 203) received matched placebos.

At 14 weeks, patients in the combination group had a change in percentage of predicted forced expiratory volume in 1 second (FEV₁) that was 13.8 points higher than the placebo group (95% confidence interval, 12.1-15.4, P less than .001). At 24 weeks, the combination group had a predicted FEV₁ difference that was 14.3 percentage points higher (95% confidence interval, 12.7-15.8, P less than .001). The rate of pulmonary exacerbations was 63% lower (rate ratio 0.37; 95% CI, 0.25-0.55, P less than .001) and sweat chloride concentration was 41.8 mmol/L lower (95% CI, –44.4 to –39.3, P less than .001) in the combination group through 24 weeks.

At least one adverse event occurred in 93.1% of patients in the combination group and 96% of patients in the placebo group. Serious adverse events occurred in 28 patients (13.9%) in the combination group and 42 patients (20.9%) in the placebo group. There were no deaths in either group.

The study was funded by Vertex Pharmaceuticals. The authors had disclosures, including receiving personal fees and grants from various pharmaceutical companies and being on the advisory board, owning stock, or being an employee of Vertex Pharmaceuticals.

SOURCE: Middleton PG et al. 2019 Oct 31. N Engl J Med. doi: 10.1056/NEJMoa1908639.

Reinforcing previous findings, a new study has determined that the next-generation corrector elexacaftor, in combination with tezacaftor and ivacaftor, can effectively treat patients with Phe508del-minimal function genotypes who did not respond to previous cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimens.

“These results provide evidence that elexacaftor-tezacaftor-ivacaftor can modulate a single Phe508del allele in people with cystic fibrosis, thus addressing the underlying cause of disease in the large majority of patients,” wrote Peter G. Middleton, PhD, of the University of Sydney (Australia) and his coauthors. The study was published in the New England Journal of Medicine.

To further determine if the elexacaftor-tezacaftor-ivacaftor regimen was effective and safe, the researchers launched a randomized, placebo-controlled phase 3 trial of 403 cystic fibrosis patients age 12 or older who had a single Phe508del allele. Patients in the combination group (n = 200) received 200 mg of elexacaftor once daily, 100 mg of tezacaftor once daily, and 150 mg of ivacaftor every 12 hours for 24 weeks. Patients in the other group (n = 203) received matched placebos.

At 14 weeks, patients in the combination group had a change in percentage of predicted forced expiratory volume in 1 second (FEV₁) that was 13.8 points higher than the placebo group (95% confidence interval, 12.1-15.4, P less than .001). At 24 weeks, the combination group had a predicted FEV₁ difference that was 14.3 percentage points higher (95% confidence interval, 12.7-15.8, P less than .001). The rate of pulmonary exacerbations was 63% lower (rate ratio 0.37; 95% CI, 0.25-0.55, P less than .001) and sweat chloride concentration was 41.8 mmol/L lower (95% CI, –44.4 to –39.3, P less than .001) in the combination group through 24 weeks.

At least one adverse event occurred in 93.1% of patients in the combination group and 96% of patients in the placebo group. Serious adverse events occurred in 28 patients (13.9%) in the combination group and 42 patients (20.9%) in the placebo group. There were no deaths in either group.

The study was funded by Vertex Pharmaceuticals. The authors had disclosures, including receiving personal fees and grants from various pharmaceutical companies and being on the advisory board, owning stock, or being an employee of Vertex Pharmaceuticals.

SOURCE: Middleton PG et al. 2019 Oct 31. N Engl J Med. doi: 10.1056/NEJMoa1908639.

Reinforcing previous findings, a new study has determined that the next-generation corrector elexacaftor, in combination with tezacaftor and ivacaftor, can effectively treat patients with Phe508del-minimal function genotypes who did not respond to previous cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimens.

“These results provide evidence that elexacaftor-tezacaftor-ivacaftor can modulate a single Phe508del allele in people with cystic fibrosis, thus addressing the underlying cause of disease in the large majority of patients,” wrote Peter G. Middleton, PhD, of the University of Sydney (Australia) and his coauthors. The study was published in the New England Journal of Medicine.

To further determine if the elexacaftor-tezacaftor-ivacaftor regimen was effective and safe, the researchers launched a randomized, placebo-controlled phase 3 trial of 403 cystic fibrosis patients age 12 or older who had a single Phe508del allele. Patients in the combination group (n = 200) received 200 mg of elexacaftor once daily, 100 mg of tezacaftor once daily, and 150 mg of ivacaftor every 12 hours for 24 weeks. Patients in the other group (n = 203) received matched placebos.

At 14 weeks, patients in the combination group had a change in percentage of predicted forced expiratory volume in 1 second (FEV₁) that was 13.8 points higher than the placebo group (95% confidence interval, 12.1-15.4, P less than .001). At 24 weeks, the combination group had a predicted FEV₁ difference that was 14.3 percentage points higher (95% confidence interval, 12.7-15.8, P less than .001). The rate of pulmonary exacerbations was 63% lower (rate ratio 0.37; 95% CI, 0.25-0.55, P less than .001) and sweat chloride concentration was 41.8 mmol/L lower (95% CI, –44.4 to –39.3, P less than .001) in the combination group through 24 weeks.

At least one adverse event occurred in 93.1% of patients in the combination group and 96% of patients in the placebo group. Serious adverse events occurred in 28 patients (13.9%) in the combination group and 42 patients (20.9%) in the placebo group. There were no deaths in either group.

The study was funded by Vertex Pharmaceuticals. The authors had disclosures, including receiving personal fees and grants from various pharmaceutical companies and being on the advisory board, owning stock, or being an employee of Vertex Pharmaceuticals.

SOURCE: Middleton PG et al. 2019 Oct 31. N Engl J Med. doi: 10.1056/NEJMoa1908639.

A new study has indicated that tailoring dosage of infliximab based on serum levels of tumor necrosis factor–alpha did not increase the sustained remission rate in rheumatoid arthritis patients.

“The results did not support our initial hypothesis that deep remission and subsequent sustained discontinuation of infliximab can be achieved by intensive and finely tuned treatments with appropriate doses of TNF [tumor necrosis factor] inhibitors,” wrote Yoshiya Tanaka, MD, PhD, of the University of Occupational and Environmental Health, Kitakyushu, Japan. The study was published in Annals of the Rheumatic Diseases.

To determine if levels of TNF-alpha should initiate an increase in infliximab dosage, the researchers launched a multicenter, randomized trial of 337 patients with infliximab-naive RA. Patients were assigned to two groups: standard infliximab treatment of 3 mg/kg at weeks 0, 2, 6, and then every 8 weeks (n = 167) or programmed infliximab treatment (n = 170) in which the dose was adjusted at week 14 based on low, intermediate, or high levels of baseline TNF-alpha.

Patients with low levels (below 0.55 pg/mL) continued receiving 3 mg/kg every 8 weeks. Intermediate levels (between 0.55 and 1.65 pg/mL) meant an increase to 6 mg/kg every 8 weeks. High levels (1.65 pg/mL or higher) meant an increase to 6 mg/kg at week 14 and to 10 mg/kg at week 22 and every 8 weeks afterward. The goal was to discontinue infliximab at 54 weeks and reassess 1 year later.

After 54 weeks, 39.4% of patients in the programmed group and 32.3% of patients in the standard group achieved remission, defined as a Simplified Disease Activity Index (SDAI) score of 3.3 or lower. After 106 weeks, 23.5% of the programmed group and 21.6% of the standard group had maintained discontinuation of infliximab (–2.2% difference; 95% confidence interval, –6.6% to 11.0%; P = .631). After analysis, the most significant predictor of sustained discontinuation was a baseline SDAI less than 26.

The authors acknowledged their study’s limitations, including the initial version of the study not being double blinded. In addition, they noted that the short length of treatment and the low dosage overall “might not be intense enough to achieve differences in disease control between the two groups.”

The study was supported by a research grant from the Ministry of Health, Labor and Welfare of Japan. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, speaking fees, and/or honoraria from various medical and pharmaceutical companies.

SOURCE: Tanaka Y et al. Ann Rheum Dis. 2019 Oct 19. doi: 10.1136/annrheumdis-2019-216169.

A new study has indicated that tailoring dosage of infliximab based on serum levels of tumor necrosis factor–alpha did not increase the sustained remission rate in rheumatoid arthritis patients.

“The results did not support our initial hypothesis that deep remission and subsequent sustained discontinuation of infliximab can be achieved by intensive and finely tuned treatments with appropriate doses of TNF [tumor necrosis factor] inhibitors,” wrote Yoshiya Tanaka, MD, PhD, of the University of Occupational and Environmental Health, Kitakyushu, Japan. The study was published in Annals of the Rheumatic Diseases.

To determine if levels of TNF-alpha should initiate an increase in infliximab dosage, the researchers launched a multicenter, randomized trial of 337 patients with infliximab-naive RA. Patients were assigned to two groups: standard infliximab treatment of 3 mg/kg at weeks 0, 2, 6, and then every 8 weeks (n = 167) or programmed infliximab treatment (n = 170) in which the dose was adjusted at week 14 based on low, intermediate, or high levels of baseline TNF-alpha.

Patients with low levels (below 0.55 pg/mL) continued receiving 3 mg/kg every 8 weeks. Intermediate levels (between 0.55 and 1.65 pg/mL) meant an increase to 6 mg/kg every 8 weeks. High levels (1.65 pg/mL or higher) meant an increase to 6 mg/kg at week 14 and to 10 mg/kg at week 22 and every 8 weeks afterward. The goal was to discontinue infliximab at 54 weeks and reassess 1 year later.

After 54 weeks, 39.4% of patients in the programmed group and 32.3% of patients in the standard group achieved remission, defined as a Simplified Disease Activity Index (SDAI) score of 3.3 or lower. After 106 weeks, 23.5% of the programmed group and 21.6% of the standard group had maintained discontinuation of infliximab (–2.2% difference; 95% confidence interval, –6.6% to 11.0%; P = .631). After analysis, the most significant predictor of sustained discontinuation was a baseline SDAI less than 26.

The authors acknowledged their study’s limitations, including the initial version of the study not being double blinded. In addition, they noted that the short length of treatment and the low dosage overall “might not be intense enough to achieve differences in disease control between the two groups.”

The study was supported by a research grant from the Ministry of Health, Labor and Welfare of Japan. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, speaking fees, and/or honoraria from various medical and pharmaceutical companies.

SOURCE: Tanaka Y et al. Ann Rheum Dis. 2019 Oct 19. doi: 10.1136/annrheumdis-2019-216169.

A new study has indicated that tailoring dosage of infliximab based on serum levels of tumor necrosis factor–alpha did not increase the sustained remission rate in rheumatoid arthritis patients.

“The results did not support our initial hypothesis that deep remission and subsequent sustained discontinuation of infliximab can be achieved by intensive and finely tuned treatments with appropriate doses of TNF [tumor necrosis factor] inhibitors,” wrote Yoshiya Tanaka, MD, PhD, of the University of Occupational and Environmental Health, Kitakyushu, Japan. The study was published in Annals of the Rheumatic Diseases.

To determine if levels of TNF-alpha should initiate an increase in infliximab dosage, the researchers launched a multicenter, randomized trial of 337 patients with infliximab-naive RA. Patients were assigned to two groups: standard infliximab treatment of 3 mg/kg at weeks 0, 2, 6, and then every 8 weeks (n = 167) or programmed infliximab treatment (n = 170) in which the dose was adjusted at week 14 based on low, intermediate, or high levels of baseline TNF-alpha.

Patients with low levels (below 0.55 pg/mL) continued receiving 3 mg/kg every 8 weeks. Intermediate levels (between 0.55 and 1.65 pg/mL) meant an increase to 6 mg/kg every 8 weeks. High levels (1.65 pg/mL or higher) meant an increase to 6 mg/kg at week 14 and to 10 mg/kg at week 22 and every 8 weeks afterward. The goal was to discontinue infliximab at 54 weeks and reassess 1 year later.

After 54 weeks, 39.4% of patients in the programmed group and 32.3% of patients in the standard group achieved remission, defined as a Simplified Disease Activity Index (SDAI) score of 3.3 or lower. After 106 weeks, 23.5% of the programmed group and 21.6% of the standard group had maintained discontinuation of infliximab (–2.2% difference; 95% confidence interval, –6.6% to 11.0%; P = .631). After analysis, the most significant predictor of sustained discontinuation was a baseline SDAI less than 26.

The authors acknowledged their study’s limitations, including the initial version of the study not being double blinded. In addition, they noted that the short length of treatment and the low dosage overall “might not be intense enough to achieve differences in disease control between the two groups.”

The study was supported by a research grant from the Ministry of Health, Labor and Welfare of Japan. The authors reported numerous potential conflicts of interest, including receiving grants, consulting fees, speaking fees, and/or honoraria from various medical and pharmaceutical companies.

SOURCE: Tanaka Y et al. Ann Rheum Dis. 2019 Oct 19. doi: 10.1136/annrheumdis-2019-216169.

Despite an increasingly diverse workforce, a new study has found that many patients remain biased toward certain physicians, which can produce substantial negative – and occasionally positive – effects.

“Addressing demeaning behavior from patients will require a concerted effort from medical schools and hospital leadership to create an environment that respects the diversity of patients and physicians alike,” wrote Margaret Wheeler, MD, of the University of California, San Francisco (UCSF) and her coauthors. The study was published in JAMA Internal Medicine.

To determine the perspectives of physicians and trainees in regard to patient bias, along with potential barriers to responding effectively, the researchers led 13 focus groups attended by internal 11 medicine hospitalist physicians, 26 internal medicine residents, and 13 medical students affiliated with the UCSF School of Medicine. In terms of gender, 26 participants identified as women, 22 as men, and 2 as gender nonconforming. In terms of racial and ethnic diversity, 26 were white, 8 were Latinx, 7 were Asian, 3 were South Asian, 1 was Middle Eastern, and 5 were black.

In describing biased and demeaning patient behavior, the participants recalled remarks that ranged from refusal of care and questioning the clinician’s role to ethnic jokes, questions as to their ethnic backgrounds, inappropriate flirtations or compliments. The effects of these behaviors on the participants included negative responses like carrying an emotional burden and withdrawing from work, along with positive responses like an increased desire for self-growth and to pursue leadership opportunities.

Barriers to addressing these behaviors included a lack of support, uncertainty as to the appropriate response, and a fear of being perceived as unprofessional. Deciding how to respond – or to respond at all – was often dictated by the level of support from colleagues, a professional responsibility to peers, and the presence of a positive role model who would’ve done the same.

The authors acknowledged their study’s limitations, including only knowing the views of those who were interviewed. In addition, all participants came from a medical school located in a diverse city that embraces different cultures, meaning their findings “may not reflect the experiences of physicians in other geographic regions.”

The study was supported by the Greenwall Foundation. The authors reported no conflicts of interest.

SOURCE: Wheeler M et al. JAMA Intern Med. 2019 Oct 28. doi: 10.1001/jamainternmed.2019.4122.

Despite an increasingly diverse workforce, a new study has found that many patients remain biased toward certain physicians, which can produce substantial negative – and occasionally positive – effects.

“Addressing demeaning behavior from patients will require a concerted effort from medical schools and hospital leadership to create an environment that respects the diversity of patients and physicians alike,” wrote Margaret Wheeler, MD, of the University of California, San Francisco (UCSF) and her coauthors. The study was published in JAMA Internal Medicine.

To determine the perspectives of physicians and trainees in regard to patient bias, along with potential barriers to responding effectively, the researchers led 13 focus groups attended by internal 11 medicine hospitalist physicians, 26 internal medicine residents, and 13 medical students affiliated with the UCSF School of Medicine. In terms of gender, 26 participants identified as women, 22 as men, and 2 as gender nonconforming. In terms of racial and ethnic diversity, 26 were white, 8 were Latinx, 7 were Asian, 3 were South Asian, 1 was Middle Eastern, and 5 were black.

In describing biased and demeaning patient behavior, the participants recalled remarks that ranged from refusal of care and questioning the clinician’s role to ethnic jokes, questions as to their ethnic backgrounds, inappropriate flirtations or compliments. The effects of these behaviors on the participants included negative responses like carrying an emotional burden and withdrawing from work, along with positive responses like an increased desire for self-growth and to pursue leadership opportunities.

Barriers to addressing these behaviors included a lack of support, uncertainty as to the appropriate response, and a fear of being perceived as unprofessional. Deciding how to respond – or to respond at all – was often dictated by the level of support from colleagues, a professional responsibility to peers, and the presence of a positive role model who would’ve done the same.

The authors acknowledged their study’s limitations, including only knowing the views of those who were interviewed. In addition, all participants came from a medical school located in a diverse city that embraces different cultures, meaning their findings “may not reflect the experiences of physicians in other geographic regions.”

The study was supported by the Greenwall Foundation. The authors reported no conflicts of interest.

SOURCE: Wheeler M et al. JAMA Intern Med. 2019 Oct 28. doi: 10.1001/jamainternmed.2019.4122.

Despite an increasingly diverse workforce, a new study has found that many patients remain biased toward certain physicians, which can produce substantial negative – and occasionally positive – effects.

“Addressing demeaning behavior from patients will require a concerted effort from medical schools and hospital leadership to create an environment that respects the diversity of patients and physicians alike,” wrote Margaret Wheeler, MD, of the University of California, San Francisco (UCSF) and her coauthors. The study was published in JAMA Internal Medicine.

To determine the perspectives of physicians and trainees in regard to patient bias, along with potential barriers to responding effectively, the researchers led 13 focus groups attended by internal 11 medicine hospitalist physicians, 26 internal medicine residents, and 13 medical students affiliated with the UCSF School of Medicine. In terms of gender, 26 participants identified as women, 22 as men, and 2 as gender nonconforming. In terms of racial and ethnic diversity, 26 were white, 8 were Latinx, 7 were Asian, 3 were South Asian, 1 was Middle Eastern, and 5 were black.

In describing biased and demeaning patient behavior, the participants recalled remarks that ranged from refusal of care and questioning the clinician’s role to ethnic jokes, questions as to their ethnic backgrounds, inappropriate flirtations or compliments. The effects of these behaviors on the participants included negative responses like carrying an emotional burden and withdrawing from work, along with positive responses like an increased desire for self-growth and to pursue leadership opportunities.

Barriers to addressing these behaviors included a lack of support, uncertainty as to the appropriate response, and a fear of being perceived as unprofessional. Deciding how to respond – or to respond at all – was often dictated by the level of support from colleagues, a professional responsibility to peers, and the presence of a positive role model who would’ve done the same.

The authors acknowledged their study’s limitations, including only knowing the views of those who were interviewed. In addition, all participants came from a medical school located in a diverse city that embraces different cultures, meaning their findings “may not reflect the experiences of physicians in other geographic regions.”

The study was supported by the Greenwall Foundation. The authors reported no conflicts of interest.

SOURCE: Wheeler M et al. JAMA Intern Med. 2019 Oct 28. doi: 10.1001/jamainternmed.2019.4122.

A new study has found that beta-blocker treatment did not prevent exacerbations in patients with moderate or severe chronic obstructive pulmonary disease (COPD).

decade3d/Thinkstock

“These results differ from previously reported findings from observational studies suggesting that beta-blockers reduce the risks of exacerbation and death from any cause in patients with COPD,” wrote Mark T. Dransfield, MD, of the University of Alabama at Birmingham and coauthors. Their findings were presented at the annual meeting of the American College of Chest Physicians and also were published simultaneously in the New England Journal of Medicine.

To determine the value of beta-blockers as a potential treatment for COPD, the researchers launched a prospective randomized trial called BLOCK COPD, consisting of 532 patients with moderate or severe COPD. They were assigned to two groups: those receiving extended-release metoprolol (n = 268) and those receiving placebo (n = 264). The mean age of all patients was 65 years.

The groups saw no significant difference in median time until the first exacerbation, which was 202 days (95% confidence interval, 162-282) in the metoprolol group and 222 days (95% CI, 189-295) in the placebo group (hazard ratio, 1.05; 95% CI, 0.84-1.32; P = .66). Metoprolol was associated with a higher risk of severe or very severe exacerbations leading to hospitalization (HR, 1.91; 95% CI, 1.29-2.83). During treatment, there were 11 deaths in the metoprolol group and 5 deaths in the placebo group.

Though there was no evidence of increases in patient-reported adverse events related to metoprolol, more discontinuations did occur in the metoprolol group compared with placebo (11.2% vs. 6.1%).

The authors acknowledged their study’s limitations, chiefly including the fact that the trial was ended early “on the basis of the conditional power analyses and concern about safety.” In addition, the reduction of heart rate and blood pressure in the metoprolol group made it impossible to fully blind the study. Finally, many patients in the trial had already suffered the effects of moderate to severe COPD, including previous hospitalization and the need for supplemental oxygen, leading to uncertainty as to “whether our results would apply to patients with mild airflow obstruction or a lower exacerbation risk.”

The study was supported by a grant from the Department of Defense. The authors reported numerous potential conflicts of interest, including receiving grants, personal fees and research funds from various pharmaceutical companies and government entities.
 

SOURCE: Dransfield MT et al. CHEST 2019. 2019 Oct 20. doi: 10.1056/NEJMoa1908142.

A new study has found that beta-blocker treatment did not prevent exacerbations in patients with moderate or severe chronic obstructive pulmonary disease (COPD).

decade3d/Thinkstock

“These results differ from previously reported findings from observational studies suggesting that beta-blockers reduce the risks of exacerbation and death from any cause in patients with COPD,” wrote Mark T. Dransfield, MD, of the University of Alabama at Birmingham and coauthors. Their findings were presented at the annual meeting of the American College of Chest Physicians and also were published simultaneously in the New England Journal of Medicine.

To determine the value of beta-blockers as a potential treatment for COPD, the researchers launched a prospective randomized trial called BLOCK COPD, consisting of 532 patients with moderate or severe COPD. They were assigned to two groups: those receiving extended-release metoprolol (n = 268) and those receiving placebo (n = 264). The mean age of all patients was 65 years.

The groups saw no significant difference in median time until the first exacerbation, which was 202 days (95% confidence interval, 162-282) in the metoprolol group and 222 days (95% CI, 189-295) in the placebo group (hazard ratio, 1.05; 95% CI, 0.84-1.32; P = .66). Metoprolol was associated with a higher risk of severe or very severe exacerbations leading to hospitalization (HR, 1.91; 95% CI, 1.29-2.83). During treatment, there were 11 deaths in the metoprolol group and 5 deaths in the placebo group.

Though there was no evidence of increases in patient-reported adverse events related to metoprolol, more discontinuations did occur in the metoprolol group compared with placebo (11.2% vs. 6.1%).

The authors acknowledged their study’s limitations, chiefly including the fact that the trial was ended early “on the basis of the conditional power analyses and concern about safety.” In addition, the reduction of heart rate and blood pressure in the metoprolol group made it impossible to fully blind the study. Finally, many patients in the trial had already suffered the effects of moderate to severe COPD, including previous hospitalization and the need for supplemental oxygen, leading to uncertainty as to “whether our results would apply to patients with mild airflow obstruction or a lower exacerbation risk.”

The study was supported by a grant from the Department of Defense. The authors reported numerous potential conflicts of interest, including receiving grants, personal fees and research funds from various pharmaceutical companies and government entities.
 

SOURCE: Dransfield MT et al. CHEST 2019. 2019 Oct 20. doi: 10.1056/NEJMoa1908142.

A new study has found that beta-blocker treatment did not prevent exacerbations in patients with moderate or severe chronic obstructive pulmonary disease (COPD).

decade3d/Thinkstock

“These results differ from previously reported findings from observational studies suggesting that beta-blockers reduce the risks of exacerbation and death from any cause in patients with COPD,” wrote Mark T. Dransfield, MD, of the University of Alabama at Birmingham and coauthors. Their findings were presented at the annual meeting of the American College of Chest Physicians and also were published simultaneously in the New England Journal of Medicine.

To determine the value of beta-blockers as a potential treatment for COPD, the researchers launched a prospective randomized trial called BLOCK COPD, consisting of 532 patients with moderate or severe COPD. They were assigned to two groups: those receiving extended-release metoprolol (n = 268) and those receiving placebo (n = 264). The mean age of all patients was 65 years.

The groups saw no significant difference in median time until the first exacerbation, which was 202 days (95% confidence interval, 162-282) in the metoprolol group and 222 days (95% CI, 189-295) in the placebo group (hazard ratio, 1.05; 95% CI, 0.84-1.32; P = .66). Metoprolol was associated with a higher risk of severe or very severe exacerbations leading to hospitalization (HR, 1.91; 95% CI, 1.29-2.83). During treatment, there were 11 deaths in the metoprolol group and 5 deaths in the placebo group.

Though there was no evidence of increases in patient-reported adverse events related to metoprolol, more discontinuations did occur in the metoprolol group compared with placebo (11.2% vs. 6.1%).

The authors acknowledged their study’s limitations, chiefly including the fact that the trial was ended early “on the basis of the conditional power analyses and concern about safety.” In addition, the reduction of heart rate and blood pressure in the metoprolol group made it impossible to fully blind the study. Finally, many patients in the trial had already suffered the effects of moderate to severe COPD, including previous hospitalization and the need for supplemental oxygen, leading to uncertainty as to “whether our results would apply to patients with mild airflow obstruction or a lower exacerbation risk.”

The study was supported by a grant from the Department of Defense. The authors reported numerous potential conflicts of interest, including receiving grants, personal fees and research funds from various pharmaceutical companies and government entities.
 

SOURCE: Dransfield MT et al. CHEST 2019. 2019 Oct 20. doi: 10.1056/NEJMoa1908142.

An investigation into a potential biomarker for response to methotrexate found that changes in DNA methylation at 4 weeks were associated with improvements in rheumatoid arthritis (RA) patients at 6 months.

Zffoto/Thinkstock

“The findings in the current study are promising and appear to identify methylation patterns that are predictive of improvement of SJC [swollen joint count] and CRP [C-reactive protein],” wrote Nisha Nair, PhD, of the University of Manchester (England) and her coauthors. The study was published in Rheumatology.

The investigators analyzed DNA samples taken from patients recruited into the Rheumatoid Arthritis Medication Study (RAMS) who had RA or inflammatory polyarthritis and were beginning methotrexate for the first time. The samples were collected at baseline and at 4 weeks from patients who were classified as having good (n = 34) or poor (n = 34) responses to methotrexate after 6 months according to European League Against Rheumatism response criteria, in which good response was defined as having a 28-joint disease activity score (DAS28) of 3.2 or less and a 1.2-point improvement in DAS28 at 6 months, and poor response was defined as having DAS28 higher than 5.1 and improvement of 0.6 points or less at 6 months.

After analysis, two differentially methylated positions that differed between good and poor responders were identified in samples taken at the 4-week mark (P less than 1 × 10^–6). Four CpG (cytosine-phosphate-guanine) sites also predicted improvements in RA patients at 6 months: Two sites associated increased methylation in good responders at 4 weeks with long-term SJC improvement, while two others associated increased methylation at baseline and in good responders at 4 weeks with improvement of CRP levels.

The authors acknowledged their study’s limitations, including the fact that the relapsing nature of RA could have contributed to natural variance in DAS28. In addition, the study’s lack of a control group does not allow for separating prognostic from theranostic biomarkers, although they added that “in terms of selecting treatments that will be effective, that may not necessarily matter in the clinical setting.”

The study was funded by the Medical Research Council and Versus Arthritis. The authors reported no conflicts of interest.
 

SOURCE: Nair N et al. Rheumatology. 2019 Oct 10. doi: 10.1093/rheumatology/kez411

An investigation into a potential biomarker for response to methotrexate found that changes in DNA methylation at 4 weeks were associated with improvements in rheumatoid arthritis (RA) patients at 6 months.

Zffoto/Thinkstock

“The findings in the current study are promising and appear to identify methylation patterns that are predictive of improvement of SJC [swollen joint count] and CRP [C-reactive protein],” wrote Nisha Nair, PhD, of the University of Manchester (England) and her coauthors. The study was published in Rheumatology.

The investigators analyzed DNA samples taken from patients recruited into the Rheumatoid Arthritis Medication Study (RAMS) who had RA or inflammatory polyarthritis and were beginning methotrexate for the first time. The samples were collected at baseline and at 4 weeks from patients who were classified as having good (n = 34) or poor (n = 34) responses to methotrexate after 6 months according to European League Against Rheumatism response criteria, in which good response was defined as having a 28-joint disease activity score (DAS28) of 3.2 or less and a 1.2-point improvement in DAS28 at 6 months, and poor response was defined as having DAS28 higher than 5.1 and improvement of 0.6 points or less at 6 months.

After analysis, two differentially methylated positions that differed between good and poor responders were identified in samples taken at the 4-week mark (P less than 1 × 10^–6). Four CpG (cytosine-phosphate-guanine) sites also predicted improvements in RA patients at 6 months: Two sites associated increased methylation in good responders at 4 weeks with long-term SJC improvement, while two others associated increased methylation at baseline and in good responders at 4 weeks with improvement of CRP levels.

The authors acknowledged their study’s limitations, including the fact that the relapsing nature of RA could have contributed to natural variance in DAS28. In addition, the study’s lack of a control group does not allow for separating prognostic from theranostic biomarkers, although they added that “in terms of selecting treatments that will be effective, that may not necessarily matter in the clinical setting.”

The study was funded by the Medical Research Council and Versus Arthritis. The authors reported no conflicts of interest.
 

SOURCE: Nair N et al. Rheumatology. 2019 Oct 10. doi: 10.1093/rheumatology/kez411

An investigation into a potential biomarker for response to methotrexate found that changes in DNA methylation at 4 weeks were associated with improvements in rheumatoid arthritis (RA) patients at 6 months.

Zffoto/Thinkstock

“The findings in the current study are promising and appear to identify methylation patterns that are predictive of improvement of SJC [swollen joint count] and CRP [C-reactive protein],” wrote Nisha Nair, PhD, of the University of Manchester (England) and her coauthors. The study was published in Rheumatology.

The investigators analyzed DNA samples taken from patients recruited into the Rheumatoid Arthritis Medication Study (RAMS) who had RA or inflammatory polyarthritis and were beginning methotrexate for the first time. The samples were collected at baseline and at 4 weeks from patients who were classified as having good (n = 34) or poor (n = 34) responses to methotrexate after 6 months according to European League Against Rheumatism response criteria, in which good response was defined as having a 28-joint disease activity score (DAS28) of 3.2 or less and a 1.2-point improvement in DAS28 at 6 months, and poor response was defined as having DAS28 higher than 5.1 and improvement of 0.6 points or less at 6 months.

After analysis, two differentially methylated positions that differed between good and poor responders were identified in samples taken at the 4-week mark (P less than 1 × 10^–6). Four CpG (cytosine-phosphate-guanine) sites also predicted improvements in RA patients at 6 months: Two sites associated increased methylation in good responders at 4 weeks with long-term SJC improvement, while two others associated increased methylation at baseline and in good responders at 4 weeks with improvement of CRP levels.

The authors acknowledged their study’s limitations, including the fact that the relapsing nature of RA could have contributed to natural variance in DAS28. In addition, the study’s lack of a control group does not allow for separating prognostic from theranostic biomarkers, although they added that “in terms of selecting treatments that will be effective, that may not necessarily matter in the clinical setting.”

The study was funded by the Medical Research Council and Versus Arthritis. The authors reported no conflicts of interest.
 

SOURCE: Nair N et al. Rheumatology. 2019 Oct 10. doi: 10.1093/rheumatology/kez411