Key clinical point: Menopause at an early vs usual age (<45 vs ≥45 years) was associated with a higher disease activity and worse patient-reported outcomes in postmenopausal women with rheumatoid arthritis (RA).

Major finding: At baseline, women with early vs usual menopause had significantly higher Disease Activity Score in 28 joints (DAS28; P = .018) and Visual Analogue Scale (VAS) scores for global assessment (P = .016) and fatigue (P = .005), along with worse EuroQol-5D-VAS scores (P = .006). Early menopause was significantly associated with increased DAS28 (regression coefficient [β] 0.178; P = .013) and decreased EuroQol-5D utility values (β −0.033; P = .016) at 5-year follow-up.

Study details: This prospective observational cohort study included 2878 postmenopausal women with RA who had menopause at an early (n = 437) or usual (n = 2441) age.

Disclosures: This study was supported by Chung-Ang University research grants in 2022 and the National Research Foundation of Korea grant funded by the Korean government. The authors did not declare conflicts of interest.

Source: Park EH et al. Impact of early age at menopause on disease outcomes in postmenopausal women with rheumatoid arthritis: A large observational cohort study of Korean patients with rheumatoid arthritis. RMD Open. 2023;9:e002722 (Feb 15). Doi: 10.1136/rmdopen-2022-002722

Key clinical point: Menopause at an early vs usual age (<45 vs ≥45 years) was associated with a higher disease activity and worse patient-reported outcomes in postmenopausal women with rheumatoid arthritis (RA).

Major finding: At baseline, women with early vs usual menopause had significantly higher Disease Activity Score in 28 joints (DAS28; P = .018) and Visual Analogue Scale (VAS) scores for global assessment (P = .016) and fatigue (P = .005), along with worse EuroQol-5D-VAS scores (P = .006). Early menopause was significantly associated with increased DAS28 (regression coefficient [β] 0.178; P = .013) and decreased EuroQol-5D utility values (β −0.033; P = .016) at 5-year follow-up.

Study details: This prospective observational cohort study included 2878 postmenopausal women with RA who had menopause at an early (n = 437) or usual (n = 2441) age.

Disclosures: This study was supported by Chung-Ang University research grants in 2022 and the National Research Foundation of Korea grant funded by the Korean government. The authors did not declare conflicts of interest.

Source: Park EH et al. Impact of early age at menopause on disease outcomes in postmenopausal women with rheumatoid arthritis: A large observational cohort study of Korean patients with rheumatoid arthritis. RMD Open. 2023;9:e002722 (Feb 15). Doi: 10.1136/rmdopen-2022-002722

Key clinical point: Menopause at an early vs usual age (<45 vs ≥45 years) was associated with a higher disease activity and worse patient-reported outcomes in postmenopausal women with rheumatoid arthritis (RA).

Major finding: At baseline, women with early vs usual menopause had significantly higher Disease Activity Score in 28 joints (DAS28; P = .018) and Visual Analogue Scale (VAS) scores for global assessment (P = .016) and fatigue (P = .005), along with worse EuroQol-5D-VAS scores (P = .006). Early menopause was significantly associated with increased DAS28 (regression coefficient [β] 0.178; P = .013) and decreased EuroQol-5D utility values (β −0.033; P = .016) at 5-year follow-up.

Study details: This prospective observational cohort study included 2878 postmenopausal women with RA who had menopause at an early (n = 437) or usual (n = 2441) age.

Disclosures: This study was supported by Chung-Ang University research grants in 2022 and the National Research Foundation of Korea grant funded by the Korean government. The authors did not declare conflicts of interest.

Source: Park EH et al. Impact of early age at menopause on disease outcomes in postmenopausal women with rheumatoid arthritis: A large observational cohort study of Korean patients with rheumatoid arthritis. RMD Open. 2023;9:e002722 (Feb 15). Doi: 10.1136/rmdopen-2022-002722

Key clinical point: Computed tomography (CT) screening before initiating biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) in patients with rheumatoid arthritis (RA) may help in early detection and treatment of malignancies, resulting in a safer and more stable RA treatment course.

Major finding: Malignancy was confirmed in 33 patients; however, only 7 vs 33 cases were detected with regular vs CT screening, respectively. Overall, 6 of 7 cases detected by regular screening were progressed stage malignancies, whereas 19 of 33 cases detected by CT screening were early stage malignancies; 80% of patients diagnosed with early stage malignancy achieved low-disease activity after 1 year of RA treatment.

Study details: This study evaluated 2192 patients with RA who were screened for malignancy using regular physical examination followed by CT before initiating b/tsDMARD.

Disclosures: This study was partly supported by the University of Occupational and Environmental Health, Japan. Five authors declared receiving research grants, consulting fees, lecture fees, speaking fees, or honoraria from various sources.

Source: Miyata H et al. Computed tomography for malignancy screening in patients with rheumatoid arthritis before initiation of disease modifying antirheumatic drug. Rheumatology (Oxford). 2023 (Feb 14). Doi: 10.1093/rheumatology/kead075

Key clinical point: Computed tomography (CT) screening before initiating biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) in patients with rheumatoid arthritis (RA) may help in early detection and treatment of malignancies, resulting in a safer and more stable RA treatment course.

Major finding: Malignancy was confirmed in 33 patients; however, only 7 vs 33 cases were detected with regular vs CT screening, respectively. Overall, 6 of 7 cases detected by regular screening were progressed stage malignancies, whereas 19 of 33 cases detected by CT screening were early stage malignancies; 80% of patients diagnosed with early stage malignancy achieved low-disease activity after 1 year of RA treatment.

Study details: This study evaluated 2192 patients with RA who were screened for malignancy using regular physical examination followed by CT before initiating b/tsDMARD.

Disclosures: This study was partly supported by the University of Occupational and Environmental Health, Japan. Five authors declared receiving research grants, consulting fees, lecture fees, speaking fees, or honoraria from various sources.

Source: Miyata H et al. Computed tomography for malignancy screening in patients with rheumatoid arthritis before initiation of disease modifying antirheumatic drug. Rheumatology (Oxford). 2023 (Feb 14). Doi: 10.1093/rheumatology/kead075

Key clinical point: Computed tomography (CT) screening before initiating biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) in patients with rheumatoid arthritis (RA) may help in early detection and treatment of malignancies, resulting in a safer and more stable RA treatment course.

Major finding: Malignancy was confirmed in 33 patients; however, only 7 vs 33 cases were detected with regular vs CT screening, respectively. Overall, 6 of 7 cases detected by regular screening were progressed stage malignancies, whereas 19 of 33 cases detected by CT screening were early stage malignancies; 80% of patients diagnosed with early stage malignancy achieved low-disease activity after 1 year of RA treatment.

Study details: This study evaluated 2192 patients with RA who were screened for malignancy using regular physical examination followed by CT before initiating b/tsDMARD.

Disclosures: This study was partly supported by the University of Occupational and Environmental Health, Japan. Five authors declared receiving research grants, consulting fees, lecture fees, speaking fees, or honoraria from various sources.

Source: Miyata H et al. Computed tomography for malignancy screening in patients with rheumatoid arthritis before initiation of disease modifying antirheumatic drug. Rheumatology (Oxford). 2023 (Feb 14). Doi: 10.1093/rheumatology/kead075

Key clinical point: Rheumatoid arthritis (RA) reduced survival rates and increased the risk for long-term major adverse cardiovascular events (MACE) in patients with ischemic heart disease who underwent percutaneous coronary intervention (PCI); however, RA had no influence over short-term MACE.

Major finding: Patients with vs without RA who underwent PCI had lower survival rates (log-rank P < .001) and were at a significantly higher risk for long-term MACE (adjusted hazard ratio 1.07; P < .001), although the risk for short-term MACE was not significantly different between both the cohorts (P = .222).

Study details: This retrospective cohort study included 236,134 patients who underwent PCI, of which 34,493 patients had RA.

Disclosures: This study was supported by the Medical Research Promotion Program of Gangneung Asan Hospital, funded by the Asan Foundation, South Korea. The authors declared no conflicts of interest.

Source: Ha SJ et al. Clinical outcomes of patients with rheumatoid arthritis who underwent percutaneous coronary intervention: A Korean nationwide cohort study. PLoS One. 2023;18(2):e0281067 (Feb 14). Doi: 10.1371/journal.pone.0281067

Key clinical point: Rheumatoid arthritis (RA) reduced survival rates and increased the risk for long-term major adverse cardiovascular events (MACE) in patients with ischemic heart disease who underwent percutaneous coronary intervention (PCI); however, RA had no influence over short-term MACE.

Major finding: Patients with vs without RA who underwent PCI had lower survival rates (log-rank P < .001) and were at a significantly higher risk for long-term MACE (adjusted hazard ratio 1.07; P < .001), although the risk for short-term MACE was not significantly different between both the cohorts (P = .222).

Study details: This retrospective cohort study included 236,134 patients who underwent PCI, of which 34,493 patients had RA.

Disclosures: This study was supported by the Medical Research Promotion Program of Gangneung Asan Hospital, funded by the Asan Foundation, South Korea. The authors declared no conflicts of interest.

Source: Ha SJ et al. Clinical outcomes of patients with rheumatoid arthritis who underwent percutaneous coronary intervention: A Korean nationwide cohort study. PLoS One. 2023;18(2):e0281067 (Feb 14). Doi: 10.1371/journal.pone.0281067

Key clinical point: Rheumatoid arthritis (RA) reduced survival rates and increased the risk for long-term major adverse cardiovascular events (MACE) in patients with ischemic heart disease who underwent percutaneous coronary intervention (PCI); however, RA had no influence over short-term MACE.

Major finding: Patients with vs without RA who underwent PCI had lower survival rates (log-rank P < .001) and were at a significantly higher risk for long-term MACE (adjusted hazard ratio 1.07; P < .001), although the risk for short-term MACE was not significantly different between both the cohorts (P = .222).

Study details: This retrospective cohort study included 236,134 patients who underwent PCI, of which 34,493 patients had RA.

Disclosures: This study was supported by the Medical Research Promotion Program of Gangneung Asan Hospital, funded by the Asan Foundation, South Korea. The authors declared no conflicts of interest.

Source: Ha SJ et al. Clinical outcomes of patients with rheumatoid arthritis who underwent percutaneous coronary intervention: A Korean nationwide cohort study. PLoS One. 2023;18(2):e0281067 (Feb 14). Doi: 10.1371/journal.pone.0281067

Key clinical point: Younger patients and patients with higher disability scores at early stages were more likely to develop difficult-to-treat rheumatoid arthritis (RA). Thus focusing on severe disability during initial stages may alter disease course.

Major finding: Elevated initial disability score (odds ratio [OR] 1.89; P = .01) and a younger age at baseline (OR 0.95; P = .01) were associated with an increased risk for difficult-to-treat RA, whereas initial disease activity failed to show any influence.

Study details: The data come from a longitudinal, prospective cohort study including 631 patients with newly diagnosed RA, of which 35 patients developed difficult-to-treat RA.

Disclosures: This study was supported by the Instituto de Salud Carlos III, Spain, and other sources. The authors did not declare any conflicts of interest.

Source: Leon L et al. Difficult-to-treat rheumatoid arthritis (D2T RA): Clinical issues at early stages of disease. RMD Open. 2023;9:e002842 (Mar 8). Doi: 10.1136/rmdopen-2022-002842

Key clinical point: Younger patients and patients with higher disability scores at early stages were more likely to develop difficult-to-treat rheumatoid arthritis (RA). Thus focusing on severe disability during initial stages may alter disease course.

Major finding: Elevated initial disability score (odds ratio [OR] 1.89; P = .01) and a younger age at baseline (OR 0.95; P = .01) were associated with an increased risk for difficult-to-treat RA, whereas initial disease activity failed to show any influence.

Study details: The data come from a longitudinal, prospective cohort study including 631 patients with newly diagnosed RA, of which 35 patients developed difficult-to-treat RA.

Disclosures: This study was supported by the Instituto de Salud Carlos III, Spain, and other sources. The authors did not declare any conflicts of interest.

Source: Leon L et al. Difficult-to-treat rheumatoid arthritis (D2T RA): Clinical issues at early stages of disease. RMD Open. 2023;9:e002842 (Mar 8). Doi: 10.1136/rmdopen-2022-002842

Key clinical point: Younger patients and patients with higher disability scores at early stages were more likely to develop difficult-to-treat rheumatoid arthritis (RA). Thus focusing on severe disability during initial stages may alter disease course.

Major finding: Elevated initial disability score (odds ratio [OR] 1.89; P = .01) and a younger age at baseline (OR 0.95; P = .01) were associated with an increased risk for difficult-to-treat RA, whereas initial disease activity failed to show any influence.

Study details: The data come from a longitudinal, prospective cohort study including 631 patients with newly diagnosed RA, of which 35 patients developed difficult-to-treat RA.

Disclosures: This study was supported by the Instituto de Salud Carlos III, Spain, and other sources. The authors did not declare any conflicts of interest.

Source: Leon L et al. Difficult-to-treat rheumatoid arthritis (D2T RA): Clinical issues at early stages of disease. RMD Open. 2023;9:e002842 (Mar 8). Doi: 10.1136/rmdopen-2022-002842

Key clinical point: A nearly 50% reduction in methotrexate dose at the time of initiating a tumor necrosis factor inhibitor (TNFi) is possible in patients with rheumatoid arthritis (RA) who had an inadequate response to the initial maximum tolerated dose of methotrexate.

Major finding: Reduced-dose methotrexate+adalimumab was noninferior to maximal-dose methotrexate+adalimumab in achieving Simplified Disease Activity Index-based remission at week 48 (adjusted risk difference 6.4%; 90% CI −7.0% to 19.8%) and less frequently caused adverse events after 24 weeks (20% vs 35%). No deaths were reported.

Study details: Findings are from the MIRACLE trial including 291 methotrexate-naive patients with RA and inadequate response to the maximum tolerated methotrexate dose who were randomly assigned to initiate adalimumab in combination with the maximum tolerated dose or a reduced dose of methotrexate.

Disclosures: This study was funded by Eisai. Three authors declared being employees and shareholders of Eisai. Several authors declared receiving speaker honoraria, grants, research support, consulting fees, or royalties from Eisai and other sources.

Source: Tamai H et al and MIRACLE study collaborators. Reduced versus maximum tolerated methotrexate dose concomitant with adalimumab in patients with rheumatoid arthritis (MIRACLE): A randomised, open-label, non-inferiority trial. Lancet Rheumatol. 2023;5(4):E215-E224 (Apr). Doi: 10.1016/S2665-9913(23)00070-X

Key clinical point: A nearly 50% reduction in methotrexate dose at the time of initiating a tumor necrosis factor inhibitor (TNFi) is possible in patients with rheumatoid arthritis (RA) who had an inadequate response to the initial maximum tolerated dose of methotrexate.

Major finding: Reduced-dose methotrexate+adalimumab was noninferior to maximal-dose methotrexate+adalimumab in achieving Simplified Disease Activity Index-based remission at week 48 (adjusted risk difference 6.4%; 90% CI −7.0% to 19.8%) and less frequently caused adverse events after 24 weeks (20% vs 35%). No deaths were reported.

Study details: Findings are from the MIRACLE trial including 291 methotrexate-naive patients with RA and inadequate response to the maximum tolerated methotrexate dose who were randomly assigned to initiate adalimumab in combination with the maximum tolerated dose or a reduced dose of methotrexate.

Disclosures: This study was funded by Eisai. Three authors declared being employees and shareholders of Eisai. Several authors declared receiving speaker honoraria, grants, research support, consulting fees, or royalties from Eisai and other sources.

Source: Tamai H et al and MIRACLE study collaborators. Reduced versus maximum tolerated methotrexate dose concomitant with adalimumab in patients with rheumatoid arthritis (MIRACLE): A randomised, open-label, non-inferiority trial. Lancet Rheumatol. 2023;5(4):E215-E224 (Apr). Doi: 10.1016/S2665-9913(23)00070-X

Key clinical point: A nearly 50% reduction in methotrexate dose at the time of initiating a tumor necrosis factor inhibitor (TNFi) is possible in patients with rheumatoid arthritis (RA) who had an inadequate response to the initial maximum tolerated dose of methotrexate.

Major finding: Reduced-dose methotrexate+adalimumab was noninferior to maximal-dose methotrexate+adalimumab in achieving Simplified Disease Activity Index-based remission at week 48 (adjusted risk difference 6.4%; 90% CI −7.0% to 19.8%) and less frequently caused adverse events after 24 weeks (20% vs 35%). No deaths were reported.

Study details: Findings are from the MIRACLE trial including 291 methotrexate-naive patients with RA and inadequate response to the maximum tolerated methotrexate dose who were randomly assigned to initiate adalimumab in combination with the maximum tolerated dose or a reduced dose of methotrexate.

Disclosures: This study was funded by Eisai. Three authors declared being employees and shareholders of Eisai. Several authors declared receiving speaker honoraria, grants, research support, consulting fees, or royalties from Eisai and other sources.

Source: Tamai H et al and MIRACLE study collaborators. Reduced versus maximum tolerated methotrexate dose concomitant with adalimumab in patients with rheumatoid arthritis (MIRACLE): A randomised, open-label, non-inferiority trial. Lancet Rheumatol. 2023;5(4):E215-E224 (Apr). Doi: 10.1016/S2665-9913(23)00070-X

Anifrolumab appears to improve outcomes in patients with refractory discoid lupus erythematosus (DLE), especially in those with severe or recalcitrant disease, a small retrospective study reports.

DLE, the most common form of chronic cutaneous lupus erythematosus, can permanently scar and disfigure patients, and traditional treatments such as antimalarials, steroid-sparing immunosuppressive agents, thalidomide, retinoids, and lenalidomide don’t consistently improve refractory DLE, the authors noted.

“All patients demonstrated significant improvement in symptomatology and disease activity within 2 months of initiating anifrolumab,” lead study author Katharina Shaw, MD, of the department of dermatology of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues wrote in a research letter published in JAMA Dermatology. “These early results highlight the potential for anifrolumab to be a viable therapeutic option for patients with DLE, particularly those with severe or recalcitrant disease.”

The Food and Drug Administration approved anifrolumab (Saphnelo), a human monoclonal antibody targeting type 1 interferon receptor subunit 1, in 2021 for adults with moderate to severe systemic lupus erythematosus, but it has not been approved for the treatment of DLE.

Dr. Shaw and colleagues queried the medical records from Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, to find all cases of DLE based on biopsy, expert opinion, or both from January 2000 to October 2022.

The researchers identified eight female patients who had received anifrolumab for at least 8 weeks. The women were aged between 19 and 75 years (median, 42.5 years), and all had DLE recalcitrant to standard therapies and had been treated with hydroxychloroquine and between 1 and 10 other drugs, most commonly methotrexate and mycophenolate mofetil (MMF).

The authors looked for improvements in patient-reported symptoms and Cutaneous Lupus Erythematosus Disease Area and Severity Index scores, including CLASI A (activity) score 0-70, and CLASI-D (damage) score 0-56.

All patients showed significantly improved symptoms and disease activity within 2 months of their first infusion of the treatment. The mean decrease and mean percentage decrease in CLASI-A scores were 17.1 and 65.1%, respectively. The mean decrease and mean percentage decrease in CLASI-D scores were 0.5 and 2.9%, respectively.

The rapid clinical improvements with anifrolumab, compared with improvements with traditional medications, were striking, the authors wrote. “Given the risk for permanent scarring, dyspigmentation, and alopecia with poorly controlled DLE, the importance of rapidly mitigating disease activity cannot be overemphasized.”

They acknowledged that the results are limited by the study’s small sample size and retrospective design, and they recommend larger related prospective studies.

Dr. Kaveh Ardalan

Asked to comment on the results, Kaveh Ardalan, MD, MS, assistant professor of pediatrics in the division of pediatric rheumatology at Duke University, Durham, N.C., said that finding new DLE therapeutics is important because of the huge impact of uncontrolled DLE on patients’ quality of life, body image, and social roles.

Dr. Ardalan noted that he sees DLE in his pediatric patients, “either as an isolated finding or in the context of systemic lupus erythematosus. Anifrolumab is not approved by the FDA to treat DLE or children.

“Randomized controlled trials, including the TULIP-1 and TULIP-2 studies of anifrolumab in systemic lupus, have indicated that lupus skin manifestations can improve in patients who receive anifrolumab,” said Dr. Ardalan, who was not involved in the study. “And we know that type I interferons are major drivers of cutaneous disease activity in patients with lupus, so targeting that mechanism with anifrolumab makes biological sense.”

The authors’ use of the validated CLASI classification system to quantify disease activity and damage over time, and their determination of the length of time for the drug to take effect are strengths of the study, he added.

Funding information was not provided. Two authors reported financial relationships with Pfizer, which does not manufacture anifrolumab. Dr. Ardalan reported no conflicts of interest with the study.

Anifrolumab appears to improve outcomes in patients with refractory discoid lupus erythematosus (DLE), especially in those with severe or recalcitrant disease, a small retrospective study reports.

DLE, the most common form of chronic cutaneous lupus erythematosus, can permanently scar and disfigure patients, and traditional treatments such as antimalarials, steroid-sparing immunosuppressive agents, thalidomide, retinoids, and lenalidomide don’t consistently improve refractory DLE, the authors noted.

“All patients demonstrated significant improvement in symptomatology and disease activity within 2 months of initiating anifrolumab,” lead study author Katharina Shaw, MD, of the department of dermatology of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues wrote in a research letter published in JAMA Dermatology. “These early results highlight the potential for anifrolumab to be a viable therapeutic option for patients with DLE, particularly those with severe or recalcitrant disease.”

The Food and Drug Administration approved anifrolumab (Saphnelo), a human monoclonal antibody targeting type 1 interferon receptor subunit 1, in 2021 for adults with moderate to severe systemic lupus erythematosus, but it has not been approved for the treatment of DLE.

Dr. Shaw and colleagues queried the medical records from Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, to find all cases of DLE based on biopsy, expert opinion, or both from January 2000 to October 2022.

The researchers identified eight female patients who had received anifrolumab for at least 8 weeks. The women were aged between 19 and 75 years (median, 42.5 years), and all had DLE recalcitrant to standard therapies and had been treated with hydroxychloroquine and between 1 and 10 other drugs, most commonly methotrexate and mycophenolate mofetil (MMF).

The authors looked for improvements in patient-reported symptoms and Cutaneous Lupus Erythematosus Disease Area and Severity Index scores, including CLASI A (activity) score 0-70, and CLASI-D (damage) score 0-56.

All patients showed significantly improved symptoms and disease activity within 2 months of their first infusion of the treatment. The mean decrease and mean percentage decrease in CLASI-A scores were 17.1 and 65.1%, respectively. The mean decrease and mean percentage decrease in CLASI-D scores were 0.5 and 2.9%, respectively.

The rapid clinical improvements with anifrolumab, compared with improvements with traditional medications, were striking, the authors wrote. “Given the risk for permanent scarring, dyspigmentation, and alopecia with poorly controlled DLE, the importance of rapidly mitigating disease activity cannot be overemphasized.”

They acknowledged that the results are limited by the study’s small sample size and retrospective design, and they recommend larger related prospective studies.

Dr. Kaveh Ardalan

Asked to comment on the results, Kaveh Ardalan, MD, MS, assistant professor of pediatrics in the division of pediatric rheumatology at Duke University, Durham, N.C., said that finding new DLE therapeutics is important because of the huge impact of uncontrolled DLE on patients’ quality of life, body image, and social roles.

Dr. Ardalan noted that he sees DLE in his pediatric patients, “either as an isolated finding or in the context of systemic lupus erythematosus. Anifrolumab is not approved by the FDA to treat DLE or children.

“Randomized controlled trials, including the TULIP-1 and TULIP-2 studies of anifrolumab in systemic lupus, have indicated that lupus skin manifestations can improve in patients who receive anifrolumab,” said Dr. Ardalan, who was not involved in the study. “And we know that type I interferons are major drivers of cutaneous disease activity in patients with lupus, so targeting that mechanism with anifrolumab makes biological sense.”

The authors’ use of the validated CLASI classification system to quantify disease activity and damage over time, and their determination of the length of time for the drug to take effect are strengths of the study, he added.

Funding information was not provided. Two authors reported financial relationships with Pfizer, which does not manufacture anifrolumab. Dr. Ardalan reported no conflicts of interest with the study.

Anifrolumab appears to improve outcomes in patients with refractory discoid lupus erythematosus (DLE), especially in those with severe or recalcitrant disease, a small retrospective study reports.

DLE, the most common form of chronic cutaneous lupus erythematosus, can permanently scar and disfigure patients, and traditional treatments such as antimalarials, steroid-sparing immunosuppressive agents, thalidomide, retinoids, and lenalidomide don’t consistently improve refractory DLE, the authors noted.

“All patients demonstrated significant improvement in symptomatology and disease activity within 2 months of initiating anifrolumab,” lead study author Katharina Shaw, MD, of the department of dermatology of Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues wrote in a research letter published in JAMA Dermatology. “These early results highlight the potential for anifrolumab to be a viable therapeutic option for patients with DLE, particularly those with severe or recalcitrant disease.”

The Food and Drug Administration approved anifrolumab (Saphnelo), a human monoclonal antibody targeting type 1 interferon receptor subunit 1, in 2021 for adults with moderate to severe systemic lupus erythematosus, but it has not been approved for the treatment of DLE.

Dr. Shaw and colleagues queried the medical records from Brigham and Women’s Hospital and Massachusetts General Hospital, Boston, to find all cases of DLE based on biopsy, expert opinion, or both from January 2000 to October 2022.

The researchers identified eight female patients who had received anifrolumab for at least 8 weeks. The women were aged between 19 and 75 years (median, 42.5 years), and all had DLE recalcitrant to standard therapies and had been treated with hydroxychloroquine and between 1 and 10 other drugs, most commonly methotrexate and mycophenolate mofetil (MMF).

The authors looked for improvements in patient-reported symptoms and Cutaneous Lupus Erythematosus Disease Area and Severity Index scores, including CLASI A (activity) score 0-70, and CLASI-D (damage) score 0-56.

All patients showed significantly improved symptoms and disease activity within 2 months of their first infusion of the treatment. The mean decrease and mean percentage decrease in CLASI-A scores were 17.1 and 65.1%, respectively. The mean decrease and mean percentage decrease in CLASI-D scores were 0.5 and 2.9%, respectively.

The rapid clinical improvements with anifrolumab, compared with improvements with traditional medications, were striking, the authors wrote. “Given the risk for permanent scarring, dyspigmentation, and alopecia with poorly controlled DLE, the importance of rapidly mitigating disease activity cannot be overemphasized.”

They acknowledged that the results are limited by the study’s small sample size and retrospective design, and they recommend larger related prospective studies.

Dr. Kaveh Ardalan

Asked to comment on the results, Kaveh Ardalan, MD, MS, assistant professor of pediatrics in the division of pediatric rheumatology at Duke University, Durham, N.C., said that finding new DLE therapeutics is important because of the huge impact of uncontrolled DLE on patients’ quality of life, body image, and social roles.

Dr. Ardalan noted that he sees DLE in his pediatric patients, “either as an isolated finding or in the context of systemic lupus erythematosus. Anifrolumab is not approved by the FDA to treat DLE or children.

“Randomized controlled trials, including the TULIP-1 and TULIP-2 studies of anifrolumab in systemic lupus, have indicated that lupus skin manifestations can improve in patients who receive anifrolumab,” said Dr. Ardalan, who was not involved in the study. “And we know that type I interferons are major drivers of cutaneous disease activity in patients with lupus, so targeting that mechanism with anifrolumab makes biological sense.”

The authors’ use of the validated CLASI classification system to quantify disease activity and damage over time, and their determination of the length of time for the drug to take effect are strengths of the study, he added.

Funding information was not provided. Two authors reported financial relationships with Pfizer, which does not manufacture anifrolumab. Dr. Ardalan reported no conflicts of interest with the study.

NEW ORLEANS – For the treatment of plaque psoriasis, a novel oral phosphodiesterase-4 (PDE4) inhibitor achieved high rates of response, compared with placebo, according to results of a phase 2 clinical trial presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

The phase 2b data, which are prompting a phase 3 trial, suggest that the drug, called orismilast, “is a potential new addition to the psoriasis armamentarium,” reported Lars E. French, MD, professor and chair, department of dermatology, Ludwig Maximilian University of Munich (Germany).

Ted Bowsworth/MDedge News

At the same session, findings from another study supported off-label use of oral roflumilast (Daliresp and generic), a PDE4 inhibitor approved for severe chronic obstructive pulmonary disease (COPD). The only PDE4 inhibitors with an indication for psoriasis are roflumilast, approved as a cream (Zoryve), and apremilast (Otezla), approved as an oral therapy.
 

Phase 2 study of orismilast

In the orismilast trial, Dr. French attributed the efficacy observed  to the potency of orismilast on the B and D subtypes of PDE4 associated with inflammation. One clue is that these specific subtypes are overly expressed in the skin of patients with either psoriasis or atopic dermatitis.

“When compared to apremilast, orismilast is at least two to fivefold more potent on all PDE4 isoforms and up to 39 times more potent on some of the PDE4 B and D isoforms,” said Dr. French, referring to preclinical findings in human whole blood and blood cells and in a mouse model of chronic inflammation.

The efficacy of orismilast in an immediate-release oral formulation was previously demonstrated in a recently published phase 2a trial, but the newest study tested a modified-release formulation of orismilast to test its potential to improve tolerability.

In the study, 202 adult patients with moderate to severe psoriasis (Psoriasis Area Severity Index [PASI] score ≥ 12) were randomly assigned to one of three doses of orismilast or to placebo. Each of the three doses – 20 mg, 30 mg, or 40 mg – were administered twice daily. The primary endpoint was change in PASI score at 16 weeks. Secondary endpoints included PASI 75 responses (signifying 75% clearance) and safety.

Relative to placebo, which was associated with a PASI improvement of 17%, all three of the tested orismilast doses were superior in a dose-dependent manner. The rates of response were 53%, 61%, and 64% for the 20-mg, 30-mg, and 40-mg twice-daily doses, respectively.

The PASI improvements were rapid, Dr. French said. At 4 weeks, PASI scores climbed from baseline by nearly 40% for those on all orismilast doses, which was more than double the improvement in the placebo group.

In the intention-to-treat analysis with missing data counted as nonresponders, the proportion of patients reaching PASI-75 scores at 16 weeks were 39%, 49%, 45%, and 17%, in the 20-mg, 30-mg, 40-mg, and placebo groups, respectively. The proportion of patients experiencing complete or near-complete skin clearance defined by a PASI 90 were 24%, 22%, 28%, and 8%, respectively.

The side-effect profile was consistent with other PDE4 inhibitors. The most common adverse events included gastrointestinal complaints, such as diarrhea and nausea, as well as headache and dizziness. But the majority of these events were of low grade, and they were largely confined to the first 4 weeks of treatment, which is a pattern reported with other PDE4 inhibitors in psoriasis and other chronic inflammatory diseases, such as COPD, according to Dr. French.

“There were no discontinuations for a treatment-related adverse event in the arms receiving either the 20-mg or the 30-mg doses,” Dr. French reported. There were only two serious adverse events, and neither were considered by trial investigators to be related to orismilast.

Based on the limited therapeutic gain but greater risk for adverse events on the 40-mg twice-daily dose, “the question is now whether to move forward with the 20-mg or the 30-mg dose,” said Dr. French, who said planning of a phase 3 trial is underway.
 

Phase 2 study of roflumilast

However, this was not the only set of data on an oral PDE4 inhibitor presented as a late-breaker at the AAD meeting. For clinicians looking for a more immediate and less expensive alternative to apremilast, another study indicated that off-label use of oral roflumilast is an option.

In an investigator-initiated, multicenter, double-blind, placebo-controlled trial conducted in Denmark, the rate of response to oral roflumilast at 24 weeks, including the clear or almost clear response, was on the same general order of magnitude as that seen in the orismilast study, reported Alexander Egeberg, MD, PhD, professor of dermatology, University of Copenhagen.

“At 24 weeks, 21.7% had achieved a PASI 90, and 8.7% achieved a PASI 100,” Dr. Egeberg said.

Oral roflumilast has been available for the treatment of COPD for more than 10 years and is now available in a generic formulation. This study was conducted independent of any pharmaceutical company involvement, and the high rate of response and low risk of adverse events suggests that patients can benefit from a PDE4 inhibitor in a very low-cost form.

“Generic oral roflumilast is cheaper than a Starbucks coffee,” Dr. Egeberg said.

In this trial, 46 patients were randomly assigned to placebo or to the COPD-approved roflumilast dose of 500 mcg once daily. The primary endpoint was change in PASI scores from baseline to week 12, which Dr. Egeberg pointed out is a shorter time frame than the 16 weeks more typical of psoriasis treatment studies.

At week 12, the median improvement in PASI was 34.8% in the roflumilast group versus 0% in the placebo group. Patients were then followed for an additional 12 weeks, but those randomized to placebo were switched to the active treatment. By week 24, the switch patients had largely caught up to those initiated on roflumilast for median PASI improvement (39.1% vs. 43.5%).

Similar to orismilast, roflumilast “was generally well tolerated,” Dr. Egeberg said. The adverse events were consistent with those associated with PDE4 inhibitors in previous trials, whether in psoriasis or COPD. There was only one serious adverse event, and it was not considered treatment related. Discontinuations for adverse events “were very low.”

In a population with a relatively high rate of smoking, Dr. Egeberg further reported, lung function was improved, a remark initially interpreted as a joke by some attending the presentation. However, Dr. Egeberg confirmed that lung function was monitored, and objective improvements were recorded.

By Danish law, the investigators were required to inform the manufacturers of roflumilast. Despite the results of this study, he is not aware of any plans to seek an indication for roflumilast in psoriasis, but he noted that the drug is readily available at a low price.

For those willing to offer this therapy off label, “you can start using it tomorrow if you’d like,” he said.

Dr. French reports financial relationships with Almirall, Amgen, Biotest, Galderma, Janssen Cilag, Leo Pharma, Pincell, Regeneron, UCB, and UNION Therapeutics, which provided funding for this trial. Dr. Egeberg reports financial relationships with Eli Lilly, Galderma, Janssen-Cilag, Novartis, and Pfizer.

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

NEW ORLEANS – For the treatment of plaque psoriasis, a novel oral phosphodiesterase-4 (PDE4) inhibitor achieved high rates of response, compared with placebo, according to results of a phase 2 clinical trial presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

The phase 2b data, which are prompting a phase 3 trial, suggest that the drug, called orismilast, “is a potential new addition to the psoriasis armamentarium,” reported Lars E. French, MD, professor and chair, department of dermatology, Ludwig Maximilian University of Munich (Germany).

Ted Bowsworth/MDedge News

At the same session, findings from another study supported off-label use of oral roflumilast (Daliresp and generic), a PDE4 inhibitor approved for severe chronic obstructive pulmonary disease (COPD). The only PDE4 inhibitors with an indication for psoriasis are roflumilast, approved as a cream (Zoryve), and apremilast (Otezla), approved as an oral therapy.
 

Phase 2 study of orismilast

In the orismilast trial, Dr. French attributed the efficacy observed  to the potency of orismilast on the B and D subtypes of PDE4 associated with inflammation. One clue is that these specific subtypes are overly expressed in the skin of patients with either psoriasis or atopic dermatitis.

“When compared to apremilast, orismilast is at least two to fivefold more potent on all PDE4 isoforms and up to 39 times more potent on some of the PDE4 B and D isoforms,” said Dr. French, referring to preclinical findings in human whole blood and blood cells and in a mouse model of chronic inflammation.

The efficacy of orismilast in an immediate-release oral formulation was previously demonstrated in a recently published phase 2a trial, but the newest study tested a modified-release formulation of orismilast to test its potential to improve tolerability.

In the study, 202 adult patients with moderate to severe psoriasis (Psoriasis Area Severity Index [PASI] score ≥ 12) were randomly assigned to one of three doses of orismilast or to placebo. Each of the three doses – 20 mg, 30 mg, or 40 mg – were administered twice daily. The primary endpoint was change in PASI score at 16 weeks. Secondary endpoints included PASI 75 responses (signifying 75% clearance) and safety.

Relative to placebo, which was associated with a PASI improvement of 17%, all three of the tested orismilast doses were superior in a dose-dependent manner. The rates of response were 53%, 61%, and 64% for the 20-mg, 30-mg, and 40-mg twice-daily doses, respectively.

The PASI improvements were rapid, Dr. French said. At 4 weeks, PASI scores climbed from baseline by nearly 40% for those on all orismilast doses, which was more than double the improvement in the placebo group.

In the intention-to-treat analysis with missing data counted as nonresponders, the proportion of patients reaching PASI-75 scores at 16 weeks were 39%, 49%, 45%, and 17%, in the 20-mg, 30-mg, 40-mg, and placebo groups, respectively. The proportion of patients experiencing complete or near-complete skin clearance defined by a PASI 90 were 24%, 22%, 28%, and 8%, respectively.

The side-effect profile was consistent with other PDE4 inhibitors. The most common adverse events included gastrointestinal complaints, such as diarrhea and nausea, as well as headache and dizziness. But the majority of these events were of low grade, and they were largely confined to the first 4 weeks of treatment, which is a pattern reported with other PDE4 inhibitors in psoriasis and other chronic inflammatory diseases, such as COPD, according to Dr. French.

“There were no discontinuations for a treatment-related adverse event in the arms receiving either the 20-mg or the 30-mg doses,” Dr. French reported. There were only two serious adverse events, and neither were considered by trial investigators to be related to orismilast.

Based on the limited therapeutic gain but greater risk for adverse events on the 40-mg twice-daily dose, “the question is now whether to move forward with the 20-mg or the 30-mg dose,” said Dr. French, who said planning of a phase 3 trial is underway.
 

Phase 2 study of roflumilast

However, this was not the only set of data on an oral PDE4 inhibitor presented as a late-breaker at the AAD meeting. For clinicians looking for a more immediate and less expensive alternative to apremilast, another study indicated that off-label use of oral roflumilast is an option.

In an investigator-initiated, multicenter, double-blind, placebo-controlled trial conducted in Denmark, the rate of response to oral roflumilast at 24 weeks, including the clear or almost clear response, was on the same general order of magnitude as that seen in the orismilast study, reported Alexander Egeberg, MD, PhD, professor of dermatology, University of Copenhagen.

“At 24 weeks, 21.7% had achieved a PASI 90, and 8.7% achieved a PASI 100,” Dr. Egeberg said.

Oral roflumilast has been available for the treatment of COPD for more than 10 years and is now available in a generic formulation. This study was conducted independent of any pharmaceutical company involvement, and the high rate of response and low risk of adverse events suggests that patients can benefit from a PDE4 inhibitor in a very low-cost form.

“Generic oral roflumilast is cheaper than a Starbucks coffee,” Dr. Egeberg said.

In this trial, 46 patients were randomly assigned to placebo or to the COPD-approved roflumilast dose of 500 mcg once daily. The primary endpoint was change in PASI scores from baseline to week 12, which Dr. Egeberg pointed out is a shorter time frame than the 16 weeks more typical of psoriasis treatment studies.

At week 12, the median improvement in PASI was 34.8% in the roflumilast group versus 0% in the placebo group. Patients were then followed for an additional 12 weeks, but those randomized to placebo were switched to the active treatment. By week 24, the switch patients had largely caught up to those initiated on roflumilast for median PASI improvement (39.1% vs. 43.5%).

Similar to orismilast, roflumilast “was generally well tolerated,” Dr. Egeberg said. The adverse events were consistent with those associated with PDE4 inhibitors in previous trials, whether in psoriasis or COPD. There was only one serious adverse event, and it was not considered treatment related. Discontinuations for adverse events “were very low.”

In a population with a relatively high rate of smoking, Dr. Egeberg further reported, lung function was improved, a remark initially interpreted as a joke by some attending the presentation. However, Dr. Egeberg confirmed that lung function was monitored, and objective improvements were recorded.

By Danish law, the investigators were required to inform the manufacturers of roflumilast. Despite the results of this study, he is not aware of any plans to seek an indication for roflumilast in psoriasis, but he noted that the drug is readily available at a low price.

For those willing to offer this therapy off label, “you can start using it tomorrow if you’d like,” he said.

Dr. French reports financial relationships with Almirall, Amgen, Biotest, Galderma, Janssen Cilag, Leo Pharma, Pincell, Regeneron, UCB, and UNION Therapeutics, which provided funding for this trial. Dr. Egeberg reports financial relationships with Eli Lilly, Galderma, Janssen-Cilag, Novartis, and Pfizer.

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

NEW ORLEANS – For the treatment of plaque psoriasis, a novel oral phosphodiesterase-4 (PDE4) inhibitor achieved high rates of response, compared with placebo, according to results of a phase 2 clinical trial presented as a late-breaker at the annual meeting of the American Academy of Dermatology.

The phase 2b data, which are prompting a phase 3 trial, suggest that the drug, called orismilast, “is a potential new addition to the psoriasis armamentarium,” reported Lars E. French, MD, professor and chair, department of dermatology, Ludwig Maximilian University of Munich (Germany).

Ted Bowsworth/MDedge News

At the same session, findings from another study supported off-label use of oral roflumilast (Daliresp and generic), a PDE4 inhibitor approved for severe chronic obstructive pulmonary disease (COPD). The only PDE4 inhibitors with an indication for psoriasis are roflumilast, approved as a cream (Zoryve), and apremilast (Otezla), approved as an oral therapy.
 

Phase 2 study of orismilast

In the orismilast trial, Dr. French attributed the efficacy observed  to the potency of orismilast on the B and D subtypes of PDE4 associated with inflammation. One clue is that these specific subtypes are overly expressed in the skin of patients with either psoriasis or atopic dermatitis.

“When compared to apremilast, orismilast is at least two to fivefold more potent on all PDE4 isoforms and up to 39 times more potent on some of the PDE4 B and D isoforms,” said Dr. French, referring to preclinical findings in human whole blood and blood cells and in a mouse model of chronic inflammation.

The efficacy of orismilast in an immediate-release oral formulation was previously demonstrated in a recently published phase 2a trial, but the newest study tested a modified-release formulation of orismilast to test its potential to improve tolerability.

In the study, 202 adult patients with moderate to severe psoriasis (Psoriasis Area Severity Index [PASI] score ≥ 12) were randomly assigned to one of three doses of orismilast or to placebo. Each of the three doses – 20 mg, 30 mg, or 40 mg – were administered twice daily. The primary endpoint was change in PASI score at 16 weeks. Secondary endpoints included PASI 75 responses (signifying 75% clearance) and safety.

Relative to placebo, which was associated with a PASI improvement of 17%, all three of the tested orismilast doses were superior in a dose-dependent manner. The rates of response were 53%, 61%, and 64% for the 20-mg, 30-mg, and 40-mg twice-daily doses, respectively.

The PASI improvements were rapid, Dr. French said. At 4 weeks, PASI scores climbed from baseline by nearly 40% for those on all orismilast doses, which was more than double the improvement in the placebo group.

In the intention-to-treat analysis with missing data counted as nonresponders, the proportion of patients reaching PASI-75 scores at 16 weeks were 39%, 49%, 45%, and 17%, in the 20-mg, 30-mg, 40-mg, and placebo groups, respectively. The proportion of patients experiencing complete or near-complete skin clearance defined by a PASI 90 were 24%, 22%, 28%, and 8%, respectively.

The side-effect profile was consistent with other PDE4 inhibitors. The most common adverse events included gastrointestinal complaints, such as diarrhea and nausea, as well as headache and dizziness. But the majority of these events were of low grade, and they were largely confined to the first 4 weeks of treatment, which is a pattern reported with other PDE4 inhibitors in psoriasis and other chronic inflammatory diseases, such as COPD, according to Dr. French.

“There were no discontinuations for a treatment-related adverse event in the arms receiving either the 20-mg or the 30-mg doses,” Dr. French reported. There were only two serious adverse events, and neither were considered by trial investigators to be related to orismilast.

Based on the limited therapeutic gain but greater risk for adverse events on the 40-mg twice-daily dose, “the question is now whether to move forward with the 20-mg or the 30-mg dose,” said Dr. French, who said planning of a phase 3 trial is underway.
 

Phase 2 study of roflumilast

However, this was not the only set of data on an oral PDE4 inhibitor presented as a late-breaker at the AAD meeting. For clinicians looking for a more immediate and less expensive alternative to apremilast, another study indicated that off-label use of oral roflumilast is an option.

In an investigator-initiated, multicenter, double-blind, placebo-controlled trial conducted in Denmark, the rate of response to oral roflumilast at 24 weeks, including the clear or almost clear response, was on the same general order of magnitude as that seen in the orismilast study, reported Alexander Egeberg, MD, PhD, professor of dermatology, University of Copenhagen.

“At 24 weeks, 21.7% had achieved a PASI 90, and 8.7% achieved a PASI 100,” Dr. Egeberg said.

Oral roflumilast has been available for the treatment of COPD for more than 10 years and is now available in a generic formulation. This study was conducted independent of any pharmaceutical company involvement, and the high rate of response and low risk of adverse events suggests that patients can benefit from a PDE4 inhibitor in a very low-cost form.

“Generic oral roflumilast is cheaper than a Starbucks coffee,” Dr. Egeberg said.

In this trial, 46 patients were randomly assigned to placebo or to the COPD-approved roflumilast dose of 500 mcg once daily. The primary endpoint was change in PASI scores from baseline to week 12, which Dr. Egeberg pointed out is a shorter time frame than the 16 weeks more typical of psoriasis treatment studies.

At week 12, the median improvement in PASI was 34.8% in the roflumilast group versus 0% in the placebo group. Patients were then followed for an additional 12 weeks, but those randomized to placebo were switched to the active treatment. By week 24, the switch patients had largely caught up to those initiated on roflumilast for median PASI improvement (39.1% vs. 43.5%).

Similar to orismilast, roflumilast “was generally well tolerated,” Dr. Egeberg said. The adverse events were consistent with those associated with PDE4 inhibitors in previous trials, whether in psoriasis or COPD. There was only one serious adverse event, and it was not considered treatment related. Discontinuations for adverse events “were very low.”

In a population with a relatively high rate of smoking, Dr. Egeberg further reported, lung function was improved, a remark initially interpreted as a joke by some attending the presentation. However, Dr. Egeberg confirmed that lung function was monitored, and objective improvements were recorded.

By Danish law, the investigators were required to inform the manufacturers of roflumilast. Despite the results of this study, he is not aware of any plans to seek an indication for roflumilast in psoriasis, but he noted that the drug is readily available at a low price.

For those willing to offer this therapy off label, “you can start using it tomorrow if you’d like,” he said.

Dr. French reports financial relationships with Almirall, Amgen, Biotest, Galderma, Janssen Cilag, Leo Pharma, Pincell, Regeneron, UCB, and UNION Therapeutics, which provided funding for this trial. Dr. Egeberg reports financial relationships with Eli Lilly, Galderma, Janssen-Cilag, Novartis, and Pfizer.

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

Low bone mineral density (BMD), particularly at the femoral neck, emerged as a “robust” risk factor for dementia in older adults in the long-running Rotterdam Study. After adjusting for relevant factors, adults with the lowest versus highest BMD at the femoral neck were 42% more likely to develop dementia over roughly 10 years.

“Our research has found a link between bone loss and dementia, but further studies are needed to better understand this connection between bone density and memory loss,” study investigator Mohammad Arfan Ikram, MD, PhD, with Erasmus University Medical Center in Rotterdam, the Netherlands, said in a statement.

“It’s possible that bone loss may occur already in the earliest phases of dementia, years before any clinical symptoms manifest themselves. If that were the case, bone loss could be an indicator of risk for dementia and people with bone loss could be targeted for screening and improved care,” Dr. Ikram added.

The study was published online in Neurology.


 

Common bedfellows

Low BMD and dementia commonly co-occur in the older population, with bone loss accelerating in dementia patients because of physical inactivity and poor nutrition. However, the extent to which bone loss already exists prior to the onset of dementia remains unclear.

The new findings are based on 3,651 adults (mean age 72 years, 58% women) in the Rotterdam Study who were free of dementia between 2002 and 2005. At that time, BMD at the femoral neck, lumbar spine, and total body were obtained using dual-energy radiography absorptiometry (DXA) and the trabecular bone score, which offers further details such as bone microarchitecture, was calculated. Participants were followed up until Jan. 1, 2020.

Analyses were adjusted for age, sex, education, physical activity, smoking status, body mass index, blood pressure, cholesterol, history of comorbidities (stroke and diabetes), and apolipoprotein E genotype.

During follow-up, 688 (19%) participants developed dementia, mostly Alzheimer’s disease (77%).

Throughout the entire follow-up period, lower BMD at the femoral neck (per standard deviation), but not at other bone sites, correlated with a higher risk for all-cause dementia (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) and Alzheimer’s disease (HR, 1.14; 95% CI, 1.02-1.28).

Within the first 10 years after baseline, the risk for dementia was greatest in individuals with the lowest BMD at the femoral neck (HR, 2.03; 95% CI, 1.39-2.96) and total body (HR, 1.42; 95% CI, 1.01-2.02) and lowest trabecular bone score (HR, 1.59; 95% CI, 1.11-2.28).

Only BMD at the femoral neck was related to incident all-cause dementia in the first 5 years of follow-up (HR, 2.13; 95% CI, 1.28-3.57).

These findings add “extra knowledge to previous findings that associations change with time, with the strength of the effect decreasing with increasing follow-up time,” the investigators noted.

They suggest that total BMD and trabecular bone score might occur as “prodromal features instead of causes of dementia and related toxic protein accumulation in the brain. In other words, persons with subclinical, incipient dementia may have poor bone health due to the dementia process instead of vice versa.”

The investigators noted that further research focusing on the predictive ability of BMD for dementia is necessary. “As an indicator of dementia risk, intervening in BMD may improve clinical care of these persons, especially considering the multicomorbidities and polypharmacy that are highly preventive in this group,” they concluded.
 

Little known bone-brain axis to blame?

In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, noted that “bone health is increasingly becoming front of mind in older adults. This study confirms an association between poor bone health – low bone mineral density and bone scores – and poor brain health.”

However, it’s unclear whether the link is causal – that is, whether poor bone health actually leads to poor brain health, and whether that can be staved off by directly supporting bone density,” Dr. Lakhan said.

“The link may very well be the little known ‘brain-bone axis’ – where our bones actually regulate our brain,” he added.

“Take for example the bone-generated hormone osteocalcin that crosses the blood-brain barrier and regulates brain functions like memory and cognition. Mice who don’t express the osteocalcin gene or are injected with antibodies that block osteocalcin actually have poor memory and worse anxiety,” Dr. Lakhan said.

“In any event, good bone health begins with healthy habits: a diet with plenty of calcium, vitamin D, and protein; a regimen of not just cardio, but also weight-bearing exercises; and staying clear of smoking and heavy alcohol intake,” he concluded.

The study was funded by Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission, and the Municipality of Rotterdam. Dr. Ikram and Dr. Lakhan report no relevant disclosures.

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

Low bone mineral density (BMD), particularly at the femoral neck, emerged as a “robust” risk factor for dementia in older adults in the long-running Rotterdam Study. After adjusting for relevant factors, adults with the lowest versus highest BMD at the femoral neck were 42% more likely to develop dementia over roughly 10 years.

“Our research has found a link between bone loss and dementia, but further studies are needed to better understand this connection between bone density and memory loss,” study investigator Mohammad Arfan Ikram, MD, PhD, with Erasmus University Medical Center in Rotterdam, the Netherlands, said in a statement.

“It’s possible that bone loss may occur already in the earliest phases of dementia, years before any clinical symptoms manifest themselves. If that were the case, bone loss could be an indicator of risk for dementia and people with bone loss could be targeted for screening and improved care,” Dr. Ikram added.

The study was published online in Neurology.


 

Common bedfellows

Low BMD and dementia commonly co-occur in the older population, with bone loss accelerating in dementia patients because of physical inactivity and poor nutrition. However, the extent to which bone loss already exists prior to the onset of dementia remains unclear.

The new findings are based on 3,651 adults (mean age 72 years, 58% women) in the Rotterdam Study who were free of dementia between 2002 and 2005. At that time, BMD at the femoral neck, lumbar spine, and total body were obtained using dual-energy radiography absorptiometry (DXA) and the trabecular bone score, which offers further details such as bone microarchitecture, was calculated. Participants were followed up until Jan. 1, 2020.

Analyses were adjusted for age, sex, education, physical activity, smoking status, body mass index, blood pressure, cholesterol, history of comorbidities (stroke and diabetes), and apolipoprotein E genotype.

During follow-up, 688 (19%) participants developed dementia, mostly Alzheimer’s disease (77%).

Throughout the entire follow-up period, lower BMD at the femoral neck (per standard deviation), but not at other bone sites, correlated with a higher risk for all-cause dementia (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) and Alzheimer’s disease (HR, 1.14; 95% CI, 1.02-1.28).

Within the first 10 years after baseline, the risk for dementia was greatest in individuals with the lowest BMD at the femoral neck (HR, 2.03; 95% CI, 1.39-2.96) and total body (HR, 1.42; 95% CI, 1.01-2.02) and lowest trabecular bone score (HR, 1.59; 95% CI, 1.11-2.28).

Only BMD at the femoral neck was related to incident all-cause dementia in the first 5 years of follow-up (HR, 2.13; 95% CI, 1.28-3.57).

These findings add “extra knowledge to previous findings that associations change with time, with the strength of the effect decreasing with increasing follow-up time,” the investigators noted.

They suggest that total BMD and trabecular bone score might occur as “prodromal features instead of causes of dementia and related toxic protein accumulation in the brain. In other words, persons with subclinical, incipient dementia may have poor bone health due to the dementia process instead of vice versa.”

The investigators noted that further research focusing on the predictive ability of BMD for dementia is necessary. “As an indicator of dementia risk, intervening in BMD may improve clinical care of these persons, especially considering the multicomorbidities and polypharmacy that are highly preventive in this group,” they concluded.
 

Little known bone-brain axis to blame?

In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, noted that “bone health is increasingly becoming front of mind in older adults. This study confirms an association between poor bone health – low bone mineral density and bone scores – and poor brain health.”

However, it’s unclear whether the link is causal – that is, whether poor bone health actually leads to poor brain health, and whether that can be staved off by directly supporting bone density,” Dr. Lakhan said.

“The link may very well be the little known ‘brain-bone axis’ – where our bones actually regulate our brain,” he added.

“Take for example the bone-generated hormone osteocalcin that crosses the blood-brain barrier and regulates brain functions like memory and cognition. Mice who don’t express the osteocalcin gene or are injected with antibodies that block osteocalcin actually have poor memory and worse anxiety,” Dr. Lakhan said.

“In any event, good bone health begins with healthy habits: a diet with plenty of calcium, vitamin D, and protein; a regimen of not just cardio, but also weight-bearing exercises; and staying clear of smoking and heavy alcohol intake,” he concluded.

The study was funded by Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission, and the Municipality of Rotterdam. Dr. Ikram and Dr. Lakhan report no relevant disclosures.

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

Low bone mineral density (BMD), particularly at the femoral neck, emerged as a “robust” risk factor for dementia in older adults in the long-running Rotterdam Study. After adjusting for relevant factors, adults with the lowest versus highest BMD at the femoral neck were 42% more likely to develop dementia over roughly 10 years.

“Our research has found a link between bone loss and dementia, but further studies are needed to better understand this connection between bone density and memory loss,” study investigator Mohammad Arfan Ikram, MD, PhD, with Erasmus University Medical Center in Rotterdam, the Netherlands, said in a statement.

“It’s possible that bone loss may occur already in the earliest phases of dementia, years before any clinical symptoms manifest themselves. If that were the case, bone loss could be an indicator of risk for dementia and people with bone loss could be targeted for screening and improved care,” Dr. Ikram added.

The study was published online in Neurology.


 

Common bedfellows

Low BMD and dementia commonly co-occur in the older population, with bone loss accelerating in dementia patients because of physical inactivity and poor nutrition. However, the extent to which bone loss already exists prior to the onset of dementia remains unclear.

The new findings are based on 3,651 adults (mean age 72 years, 58% women) in the Rotterdam Study who were free of dementia between 2002 and 2005. At that time, BMD at the femoral neck, lumbar spine, and total body were obtained using dual-energy radiography absorptiometry (DXA) and the trabecular bone score, which offers further details such as bone microarchitecture, was calculated. Participants were followed up until Jan. 1, 2020.

Analyses were adjusted for age, sex, education, physical activity, smoking status, body mass index, blood pressure, cholesterol, history of comorbidities (stroke and diabetes), and apolipoprotein E genotype.

During follow-up, 688 (19%) participants developed dementia, mostly Alzheimer’s disease (77%).

Throughout the entire follow-up period, lower BMD at the femoral neck (per standard deviation), but not at other bone sites, correlated with a higher risk for all-cause dementia (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) and Alzheimer’s disease (HR, 1.14; 95% CI, 1.02-1.28).

Within the first 10 years after baseline, the risk for dementia was greatest in individuals with the lowest BMD at the femoral neck (HR, 2.03; 95% CI, 1.39-2.96) and total body (HR, 1.42; 95% CI, 1.01-2.02) and lowest trabecular bone score (HR, 1.59; 95% CI, 1.11-2.28).

Only BMD at the femoral neck was related to incident all-cause dementia in the first 5 years of follow-up (HR, 2.13; 95% CI, 1.28-3.57).

These findings add “extra knowledge to previous findings that associations change with time, with the strength of the effect decreasing with increasing follow-up time,” the investigators noted.

They suggest that total BMD and trabecular bone score might occur as “prodromal features instead of causes of dementia and related toxic protein accumulation in the brain. In other words, persons with subclinical, incipient dementia may have poor bone health due to the dementia process instead of vice versa.”

The investigators noted that further research focusing on the predictive ability of BMD for dementia is necessary. “As an indicator of dementia risk, intervening in BMD may improve clinical care of these persons, especially considering the multicomorbidities and polypharmacy that are highly preventive in this group,” they concluded.
 

Little known bone-brain axis to blame?

In a comment, Shaheen Lakhan, MD, a neurologist and researcher in Boston, noted that “bone health is increasingly becoming front of mind in older adults. This study confirms an association between poor bone health – low bone mineral density and bone scores – and poor brain health.”

However, it’s unclear whether the link is causal – that is, whether poor bone health actually leads to poor brain health, and whether that can be staved off by directly supporting bone density,” Dr. Lakhan said.

“The link may very well be the little known ‘brain-bone axis’ – where our bones actually regulate our brain,” he added.

“Take for example the bone-generated hormone osteocalcin that crosses the blood-brain barrier and regulates brain functions like memory and cognition. Mice who don’t express the osteocalcin gene or are injected with antibodies that block osteocalcin actually have poor memory and worse anxiety,” Dr. Lakhan said.

“In any event, good bone health begins with healthy habits: a diet with plenty of calcium, vitamin D, and protein; a regimen of not just cardio, but also weight-bearing exercises; and staying clear of smoking and heavy alcohol intake,” he concluded.

The study was funded by Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research, the Netherlands Organization for Health Research and Development, the Research Institute for Diseases in the Elderly, the Netherlands Genomics Initiative, the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission, and the Municipality of Rotterdam. Dr. Ikram and Dr. Lakhan report no relevant disclosures.

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

Telomere shortening – a sign of cellular aging – is associated with multiple changes in the brain associated with dementia, whereas longer telomeres associate with better brain health and lower risk for dementia, new research suggests.

“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.

The study was published online in PLOS ONE.
 

UK Biobank cohort

Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.

Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.

Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).

Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.

She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
 

Need for more research

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”

This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.

But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”

“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.

The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.

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

Telomere shortening – a sign of cellular aging – is associated with multiple changes in the brain associated with dementia, whereas longer telomeres associate with better brain health and lower risk for dementia, new research suggests.

“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.

The study was published online in PLOS ONE.
 

UK Biobank cohort

Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.

Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.

Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).

Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.

She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
 

Need for more research

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”

This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.

But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”

“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.

The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.

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

Telomere shortening – a sign of cellular aging – is associated with multiple changes in the brain associated with dementia, whereas longer telomeres associate with better brain health and lower risk for dementia, new research suggests.

“This is the largest and most systematic investigation of telomere length and brain structure and function,” said Anya Topiwala, of the University of Oxford (England). “We found that longer telomeres associated with protection against dementia. The links with brain structure, we think, offer a possible mechanism for this protection. The hope is, by understanding the mechanism, new treatment targets could be uncovered,” Dr. Topiwala said.

The study was published online in PLOS ONE.
 

UK Biobank cohort

Telomeres form protective caps at the ends of chromosomes, and they progressively shorten with age, which may increase susceptibility to age-related diseases including Alzheimer’s disease. The mechanism underlying this risk is unclear and may involve changes in brain structure and function. However, the relationship between telomere length and neuroimaging markers is poorly characterized.

Dr. Topiwala and colleagues compared telomere length in white blood cells to brain MRI and health record data in 31,661 middle-aged and older adults in UK Biobank. They found that longer leucocyte telomere length (LTL) was associated with a larger volume of global and subcortical grey matter and a larger hippocampus – both of which shrink in patients with Alzheimer’s disease. Longer telomeres were also associated with a thicker cerebral cortex, which thins as Alzheimer’s disease progresses.

Longer LTL was also associated with reduced incidence of dementia during follow-up (hazard ratio, 0.93; 95% confidence interval, 0.91-0.96).

Dr. Topiwala noted that many of the factors related to telomere shortening, such as age, genetics, and sex, can’t be changed. However, in a previous study, her team found that drinking alcohol may shorten telomere length. “So by this logic, reducing your alcohol intake could curb the shortening,” Dr. Topiwala said.

She said that a limitation of the study is that telomere length was measured in blood rather than brain and that it’s not clear at present how closely the two relate. Also, UK Biobank participants are generally more healthy than is the general population. Also, though telomere length and brain measures were associated, “we cannot from this study prove one is causing the other,” she added.
 

Need for more research

Commenting on the research, Percy Griffin, PhD, Alzheimer’s Association director of scientific engagement, said that it’s been “known for some time that shortened telomeres – the caps at the end of DNA – are associated with increased aging.”

This new study is “interesting,” said Dr. Percy, in that it shows an association between longer telomere length in white blood cells and healthier brain structures in the areas associated with Alzheimer’s disease. The longer telomeres were also associated with lower incidence of all-cause dementia.

But echoing Dr. Topiwala, “association does not mean causation,” Dr. Griffin said. “More research is needed to understand how diverse mechanisms contributing to Alzheimer’s and other dementia can be targeted.”

“The Alzheimer’s Association is accelerating the discovery of novel therapies through its Part the Cloud funding program, which has invested more than $65 million to accelerate the development of 65 drug development programs,” Dr. Griffin said.

The study had no specific funding. Dr. Topiwala and Dr. Griffin report no relevant disclosures.

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

Recently, Dr. Jeffrey Benabio (I don’t believe we’ve ever met), wrote an enjoyable commentary mourning the loss of letters – the wonderful paper-and-pen documents that were, for the vast majority of human history, the main method of long distance communication. Even today, he notes, there’s something special about a letter, with the time and human effort required to sit down and put pen to paper, seal it into an envelope, and entrust it to the post office.

In his piece, Dr. Benabio describes his work desk as “a small surface, perhaps just enough for the monitor and a mug ... it has no drawers. It is lean and immaculate, but it has no soul.”

With all due respect, I can’t do that. I need a desk to function. A REAL one.

I was 9 when I got my first desk, far more than a 4th-grader needed. My dad was an attorney and had an extra desk from a partner who’d retired. It was big and heavy and made of wood. It had three drawers on each side, one in the middle, and pull-outs on each side in case you needed even more writing space. I loved it. As the years went by I did homework, wrote short stories, and built models on it. I covered the pull-outs with stickers for starship controls, so on a whim I could jump to hyperspace. In 1984 a brand-new Apple Macintosh, with 128K of RAM showed up on it. I began using the computer to write college papers, but most of my work at the desk still involved books and handwriting.

My current home desk has been with me through college, medical school, residency, and fellowship, and it continues with me today.

At my office, though, is my main desk. Before 2013 I was in a small back office, with only room for a tiny three-drawer college desk.

But in 2013 I moved into my own office, for the first time in my career. Now it was time to bring in my real desk, waiting in storage since my Dad had retired.

Dr. Allan M. Block

This is my desk now. It’s huge. It’s heavy. My dad bought it when he started his law practice in 1968. It has eight drawers, and my Dad’s original leather blotter is on top. It came with his chrome and brass letter opener in the top drawer. It has space for my computer, writing pads, exam tools (for people who can’t get on the exam table across the hall), business cards, a few baubles from my kids, stapler, tape dispenser, pen cup, phone, coffee mug, and a million other things.

It takes up a lot of space, but I don’t mind. There’s a human comfort to it and the organized disorder on top of it. I’d much rather have my patients and I talk while sitting across my desk, in comfortable chairs, then in a sterile exam room with them on the exam table and me on a rolling chair trying to balance an iPad on my lap.

Everyone practices medicine differently. What works for me isn’t going to work for another doctor, and definitely not for another specialty.

But here, the big desk is part of my personal style. Sitting there gets me into “doctor mode” each day. I hope the more casual surroundings make it comfortable for patients, too.

It’s part of the soul of my practice, and I wouldn’t have it any other way.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Recently, Dr. Jeffrey Benabio (I don’t believe we’ve ever met), wrote an enjoyable commentary mourning the loss of letters – the wonderful paper-and-pen documents that were, for the vast majority of human history, the main method of long distance communication. Even today, he notes, there’s something special about a letter, with the time and human effort required to sit down and put pen to paper, seal it into an envelope, and entrust it to the post office.

In his piece, Dr. Benabio describes his work desk as “a small surface, perhaps just enough for the monitor and a mug ... it has no drawers. It is lean and immaculate, but it has no soul.”

With all due respect, I can’t do that. I need a desk to function. A REAL one.

I was 9 when I got my first desk, far more than a 4th-grader needed. My dad was an attorney and had an extra desk from a partner who’d retired. It was big and heavy and made of wood. It had three drawers on each side, one in the middle, and pull-outs on each side in case you needed even more writing space. I loved it. As the years went by I did homework, wrote short stories, and built models on it. I covered the pull-outs with stickers for starship controls, so on a whim I could jump to hyperspace. In 1984 a brand-new Apple Macintosh, with 128K of RAM showed up on it. I began using the computer to write college papers, but most of my work at the desk still involved books and handwriting.

My current home desk has been with me through college, medical school, residency, and fellowship, and it continues with me today.

At my office, though, is my main desk. Before 2013 I was in a small back office, with only room for a tiny three-drawer college desk.

But in 2013 I moved into my own office, for the first time in my career. Now it was time to bring in my real desk, waiting in storage since my Dad had retired.

Dr. Allan M. Block

This is my desk now. It’s huge. It’s heavy. My dad bought it when he started his law practice in 1968. It has eight drawers, and my Dad’s original leather blotter is on top. It came with his chrome and brass letter opener in the top drawer. It has space for my computer, writing pads, exam tools (for people who can’t get on the exam table across the hall), business cards, a few baubles from my kids, stapler, tape dispenser, pen cup, phone, coffee mug, and a million other things.

It takes up a lot of space, but I don’t mind. There’s a human comfort to it and the organized disorder on top of it. I’d much rather have my patients and I talk while sitting across my desk, in comfortable chairs, then in a sterile exam room with them on the exam table and me on a rolling chair trying to balance an iPad on my lap.

Everyone practices medicine differently. What works for me isn’t going to work for another doctor, and definitely not for another specialty.

But here, the big desk is part of my personal style. Sitting there gets me into “doctor mode” each day. I hope the more casual surroundings make it comfortable for patients, too.

It’s part of the soul of my practice, and I wouldn’t have it any other way.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Recently, Dr. Jeffrey Benabio (I don’t believe we’ve ever met), wrote an enjoyable commentary mourning the loss of letters – the wonderful paper-and-pen documents that were, for the vast majority of human history, the main method of long distance communication. Even today, he notes, there’s something special about a letter, with the time and human effort required to sit down and put pen to paper, seal it into an envelope, and entrust it to the post office.

In his piece, Dr. Benabio describes his work desk as “a small surface, perhaps just enough for the monitor and a mug ... it has no drawers. It is lean and immaculate, but it has no soul.”

With all due respect, I can’t do that. I need a desk to function. A REAL one.

I was 9 when I got my first desk, far more than a 4th-grader needed. My dad was an attorney and had an extra desk from a partner who’d retired. It was big and heavy and made of wood. It had three drawers on each side, one in the middle, and pull-outs on each side in case you needed even more writing space. I loved it. As the years went by I did homework, wrote short stories, and built models on it. I covered the pull-outs with stickers for starship controls, so on a whim I could jump to hyperspace. In 1984 a brand-new Apple Macintosh, with 128K of RAM showed up on it. I began using the computer to write college papers, but most of my work at the desk still involved books and handwriting.

My current home desk has been with me through college, medical school, residency, and fellowship, and it continues with me today.

At my office, though, is my main desk. Before 2013 I was in a small back office, with only room for a tiny three-drawer college desk.

But in 2013 I moved into my own office, for the first time in my career. Now it was time to bring in my real desk, waiting in storage since my Dad had retired.

Dr. Allan M. Block

This is my desk now. It’s huge. It’s heavy. My dad bought it when he started his law practice in 1968. It has eight drawers, and my Dad’s original leather blotter is on top. It came with his chrome and brass letter opener in the top drawer. It has space for my computer, writing pads, exam tools (for people who can’t get on the exam table across the hall), business cards, a few baubles from my kids, stapler, tape dispenser, pen cup, phone, coffee mug, and a million other things.

It takes up a lot of space, but I don’t mind. There’s a human comfort to it and the organized disorder on top of it. I’d much rather have my patients and I talk while sitting across my desk, in comfortable chairs, then in a sterile exam room with them on the exam table and me on a rolling chair trying to balance an iPad on my lap.

Everyone practices medicine differently. What works for me isn’t going to work for another doctor, and definitely not for another specialty.

But here, the big desk is part of my personal style. Sitting there gets me into “doctor mode” each day. I hope the more casual surroundings make it comfortable for patients, too.

It’s part of the soul of my practice, and I wouldn’t have it any other way.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.