Lupus & Connective Tissue Diseases

Renal transplant is associated with a substantial survival benefit in patients with end-stage renal disease due to lupus nephritis, according to researchers who conducted a nationwide cohort study encompassing nearly all such patients treated in the United States over a 20-year period.

Transplant conferred a 70% reduction in overall death risk in these lupus nephritis end-stage renal disease (ESRD) patients, largely due to reduced deaths caused by infection and cardiovascular disease, according to the researchers, led by April Jorge, MD, and Zachary Wallace, MD, of Massachusetts General Hospital, Harvard Medical School, Boston.

Those findings suggest that patients with lupus nephritis ESRD should routinely be considered for renal transplant in a timely manner, the investigators wrote in Annals of Internal Medicine.

“Improved access to renal transplantation for this population may considerably improve outcomes,” they said.

The study was based on an analysis of 9,659 patients who had lupus nephritis ESRD between 1995 and 2014 and were waitlisted for renal transplant. The data came from the United States Renal Data System, which includes most ESRD patients treated in the country. Of those 9,659 patients, 5,738 (59%) underwent kidney transplant.

Mortality rates were 22.5 per 1,000 person-years for lupus nephritis ESRD patients who underwent transplant, and 56.3 per 1,000 person-years for those patients who did not receive transplant, the investigators found.

Renal transplant reduced risk of death by 70% in results of multivariate analysis (hazard ratio, 0.30; 95% CI, 0.27-0.33).

That lower risk of all-cause mortality was consistent across racial groups and for other characteristics, such as sex, age at ESRD onset, and Medicare enrollment status.

Risk of cardiovascular death was 74% lower with renal transplant (adjusted hazard ratio, 0.26; 95% CI, 0.23-0.30), and risk of death from infection was also markedly lower among those who underwent transplant (adjusted hazard ratio, 0.41; 95% CI, 0.32-0.52), investigators found in a cause-specific mortality analysis.

While transplant has been associated with improved survival in patients with ESRD from all causes, there are “unique concerns” regarding the potential for infections or other post-transplant complications from transplant in lupus nephritis patients with ESRD, Dr. Jorge and colleagues wrote.

“To that end, our study provides evidence for a substantial survival benefit of renal transplant among patients with lupus nephritis ESRD,” they noted.

Dr. Jorge reported grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases during the conduct of the study. One co-author provided additional disclosures related to Teva Pharmaceuticals and Gilead Sciences outside of the study conduct.

SOURCE: Jorge A, et al. Ann Intern Med 2019 Jan 21. doi: 10.7326/M18-1570.

Renal transplant is associated with a substantial survival benefit in patients with end-stage renal disease due to lupus nephritis, according to researchers who conducted a nationwide cohort study encompassing nearly all such patients treated in the United States over a 20-year period.

Transplant conferred a 70% reduction in overall death risk in these lupus nephritis end-stage renal disease (ESRD) patients, largely due to reduced deaths caused by infection and cardiovascular disease, according to the researchers, led by April Jorge, MD, and Zachary Wallace, MD, of Massachusetts General Hospital, Harvard Medical School, Boston.

Those findings suggest that patients with lupus nephritis ESRD should routinely be considered for renal transplant in a timely manner, the investigators wrote in Annals of Internal Medicine.

“Improved access to renal transplantation for this population may considerably improve outcomes,” they said.

The study was based on an analysis of 9,659 patients who had lupus nephritis ESRD between 1995 and 2014 and were waitlisted for renal transplant. The data came from the United States Renal Data System, which includes most ESRD patients treated in the country. Of those 9,659 patients, 5,738 (59%) underwent kidney transplant.

Mortality rates were 22.5 per 1,000 person-years for lupus nephritis ESRD patients who underwent transplant, and 56.3 per 1,000 person-years for those patients who did not receive transplant, the investigators found.

Renal transplant reduced risk of death by 70% in results of multivariate analysis (hazard ratio, 0.30; 95% CI, 0.27-0.33).

That lower risk of all-cause mortality was consistent across racial groups and for other characteristics, such as sex, age at ESRD onset, and Medicare enrollment status.

Risk of cardiovascular death was 74% lower with renal transplant (adjusted hazard ratio, 0.26; 95% CI, 0.23-0.30), and risk of death from infection was also markedly lower among those who underwent transplant (adjusted hazard ratio, 0.41; 95% CI, 0.32-0.52), investigators found in a cause-specific mortality analysis.

While transplant has been associated with improved survival in patients with ESRD from all causes, there are “unique concerns” regarding the potential for infections or other post-transplant complications from transplant in lupus nephritis patients with ESRD, Dr. Jorge and colleagues wrote.

“To that end, our study provides evidence for a substantial survival benefit of renal transplant among patients with lupus nephritis ESRD,” they noted.

Dr. Jorge reported grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases during the conduct of the study. One co-author provided additional disclosures related to Teva Pharmaceuticals and Gilead Sciences outside of the study conduct.

SOURCE: Jorge A, et al. Ann Intern Med 2019 Jan 21. doi: 10.7326/M18-1570.

Renal transplant is associated with a substantial survival benefit in patients with end-stage renal disease due to lupus nephritis, according to researchers who conducted a nationwide cohort study encompassing nearly all such patients treated in the United States over a 20-year period.

Transplant conferred a 70% reduction in overall death risk in these lupus nephritis end-stage renal disease (ESRD) patients, largely due to reduced deaths caused by infection and cardiovascular disease, according to the researchers, led by April Jorge, MD, and Zachary Wallace, MD, of Massachusetts General Hospital, Harvard Medical School, Boston.

Those findings suggest that patients with lupus nephritis ESRD should routinely be considered for renal transplant in a timely manner, the investigators wrote in Annals of Internal Medicine.

“Improved access to renal transplantation for this population may considerably improve outcomes,” they said.

The study was based on an analysis of 9,659 patients who had lupus nephritis ESRD between 1995 and 2014 and were waitlisted for renal transplant. The data came from the United States Renal Data System, which includes most ESRD patients treated in the country. Of those 9,659 patients, 5,738 (59%) underwent kidney transplant.

Mortality rates were 22.5 per 1,000 person-years for lupus nephritis ESRD patients who underwent transplant, and 56.3 per 1,000 person-years for those patients who did not receive transplant, the investigators found.

Renal transplant reduced risk of death by 70% in results of multivariate analysis (hazard ratio, 0.30; 95% CI, 0.27-0.33).

That lower risk of all-cause mortality was consistent across racial groups and for other characteristics, such as sex, age at ESRD onset, and Medicare enrollment status.

Risk of cardiovascular death was 74% lower with renal transplant (adjusted hazard ratio, 0.26; 95% CI, 0.23-0.30), and risk of death from infection was also markedly lower among those who underwent transplant (adjusted hazard ratio, 0.41; 95% CI, 0.32-0.52), investigators found in a cause-specific mortality analysis.

While transplant has been associated with improved survival in patients with ESRD from all causes, there are “unique concerns” regarding the potential for infections or other post-transplant complications from transplant in lupus nephritis patients with ESRD, Dr. Jorge and colleagues wrote.

“To that end, our study provides evidence for a substantial survival benefit of renal transplant among patients with lupus nephritis ESRD,” they noted.

Dr. Jorge reported grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases during the conduct of the study. One co-author provided additional disclosures related to Teva Pharmaceuticals and Gilead Sciences outside of the study conduct.

SOURCE: Jorge A, et al. Ann Intern Med 2019 Jan 21. doi: 10.7326/M18-1570.

Mycophenolate mofetil was noninferior to pulsed cyclophosphamide for remission induction in ANCA-associated vasculitis, but there were more relapses, in a randomized, unblinded trial of 140 patients with non–life-threatening disease.

“Our results demonstrate that MMF [mycophenolate mofetil] represents an alternative to CYC [cyclophosphamide] for remission induction in AAV [ANCA-associated vasculitis],” said investigators led by Rachel B. Jones, MD, of the department of renal medicine at Addenbrooke’s Hospital, Cambridge, England.

“While treatment with MMF may be associated with a higher risk of relapse compared with pulsed CYC, this increased risk may be acceptable to avoid the potential adverse effects of CYC” – infections, malignancies, and infertility – “particularly when the baseline risk of relapse is low,” as with the elderly or myeloperoxidase (MPO)-ANCA disease, “or if rituximab is unavailable,” Dr. Jones and her colleagues wrote in Annals of the Rheumatic Diseases.

Since enrollment began in 2007, they also noted that “it has become common to use rituximab as an alternative to CYC induction therapy ... However, rituximab is expensive, and its use is restricted in many countries ... Alternative effective low-cost induction therapies” – such as MMF – “may be required in some cases.”

The work, which was done on behalf of the European Vasculitis Study Group, was the largest randomized trial to date of MMF for AAV remission induction, and the first to include children; patients were enrolled at 21 sites in Europe, Australia, and New Zealand.

They were randomly assigned to MMF or pulsed CYC, with 66 adults and 4 children ranging in age from 10 to 16 years in each group. In addition to those with life-threatening disease, patients younger than 6 years old and those on dialysis or with an estimated glomerular filtration rate below 15 mL/min/m² were excluded. Following remission, subjects were switched to oral azathioprine and a prednisone taper.

The primary outcome was remission by 6 months, defined as the absence of disease activity on two consecutive occasions at least 1 month apart, plus adherence to the taper. Baseline ANCA subtype, disease activity, and organ involvement were similar between the groups.

Overall, 47 patients in the in the MMF group (67%), including 1 child, reached the primary endpoint, versus 43 patients (61%), again including 1 child, in the CYC group (risk difference = 5.7%; 90% confidence interval, –7.5% to 19%), which established noninferiority. The median time to remission was about 90 days in both arms. “Compliance was a contributory factor to the lower remission rate[s] in children,” the authors noted.

More relapses occurred in the MMF group (33% vs. 19% with CYC). Among MPO-ANCA patients, the relapse rate was 15% versus 12% with CYC. In proteinase 3 (PR3)-ANCA patients, almost half in the MMF group relapsed (48% versus 24%).

There were no significant differences in serious infections (26% with MMF versus 17% with CYC; P = .3), malignancies, thromboembolisms, or death (four CYC patients and five MMF patients at 6 months).

Adult patients in the MMF group received MMF 2 g/day, with dose increases to 3 g/day permitted for uncontrolled disease at 4 weeks. Patients younger than 17 years old were dosed according to body surface area. The CYC group received intravenous pulsed CYC 15 mg/kg every 2-3 weeks with reductions for age and renal function. A total of 58 CYC patients (83%) received at least six pulses.

After remission, azathioprine was dosed at 2 mg/kg per day. Oral prednisolone started at 1 mg/kg per day and was reduced to 5 mg/day by 6 months.

Plasma exchange or additional methylprednisolone were allowed at entry; there were no differences in their use between the groups.

The trial was sponsored by Cambridge University Hospitals NHS Foundation Trust. Vifor Pharma provided a research grant to cover the trial and MMF costs. Dr. Jones and the other investigators reported ties to several companies, including GlaxoSmithKline, Genentech/Roche, ChemoCentryx, and Genzyme/Sanofi. Vifor holds an equity stake in ChemoCentryx.

[email protected]

SOURCE: Jones RB et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214245.

Mycophenolate mofetil was noninferior to pulsed cyclophosphamide for remission induction in ANCA-associated vasculitis, but there were more relapses, in a randomized, unblinded trial of 140 patients with non–life-threatening disease.

“Our results demonstrate that MMF [mycophenolate mofetil] represents an alternative to CYC [cyclophosphamide] for remission induction in AAV [ANCA-associated vasculitis],” said investigators led by Rachel B. Jones, MD, of the department of renal medicine at Addenbrooke’s Hospital, Cambridge, England.

“While treatment with MMF may be associated with a higher risk of relapse compared with pulsed CYC, this increased risk may be acceptable to avoid the potential adverse effects of CYC” – infections, malignancies, and infertility – “particularly when the baseline risk of relapse is low,” as with the elderly or myeloperoxidase (MPO)-ANCA disease, “or if rituximab is unavailable,” Dr. Jones and her colleagues wrote in Annals of the Rheumatic Diseases.

Since enrollment began in 2007, they also noted that “it has become common to use rituximab as an alternative to CYC induction therapy ... However, rituximab is expensive, and its use is restricted in many countries ... Alternative effective low-cost induction therapies” – such as MMF – “may be required in some cases.”

The work, which was done on behalf of the European Vasculitis Study Group, was the largest randomized trial to date of MMF for AAV remission induction, and the first to include children; patients were enrolled at 21 sites in Europe, Australia, and New Zealand.

They were randomly assigned to MMF or pulsed CYC, with 66 adults and 4 children ranging in age from 10 to 16 years in each group. In addition to those with life-threatening disease, patients younger than 6 years old and those on dialysis or with an estimated glomerular filtration rate below 15 mL/min/m² were excluded. Following remission, subjects were switched to oral azathioprine and a prednisone taper.

The primary outcome was remission by 6 months, defined as the absence of disease activity on two consecutive occasions at least 1 month apart, plus adherence to the taper. Baseline ANCA subtype, disease activity, and organ involvement were similar between the groups.

Overall, 47 patients in the in the MMF group (67%), including 1 child, reached the primary endpoint, versus 43 patients (61%), again including 1 child, in the CYC group (risk difference = 5.7%; 90% confidence interval, –7.5% to 19%), which established noninferiority. The median time to remission was about 90 days in both arms. “Compliance was a contributory factor to the lower remission rate[s] in children,” the authors noted.

More relapses occurred in the MMF group (33% vs. 19% with CYC). Among MPO-ANCA patients, the relapse rate was 15% versus 12% with CYC. In proteinase 3 (PR3)-ANCA patients, almost half in the MMF group relapsed (48% versus 24%).

There were no significant differences in serious infections (26% with MMF versus 17% with CYC; P = .3), malignancies, thromboembolisms, or death (four CYC patients and five MMF patients at 6 months).

Adult patients in the MMF group received MMF 2 g/day, with dose increases to 3 g/day permitted for uncontrolled disease at 4 weeks. Patients younger than 17 years old were dosed according to body surface area. The CYC group received intravenous pulsed CYC 15 mg/kg every 2-3 weeks with reductions for age and renal function. A total of 58 CYC patients (83%) received at least six pulses.

After remission, azathioprine was dosed at 2 mg/kg per day. Oral prednisolone started at 1 mg/kg per day and was reduced to 5 mg/day by 6 months.

Plasma exchange or additional methylprednisolone were allowed at entry; there were no differences in their use between the groups.

The trial was sponsored by Cambridge University Hospitals NHS Foundation Trust. Vifor Pharma provided a research grant to cover the trial and MMF costs. Dr. Jones and the other investigators reported ties to several companies, including GlaxoSmithKline, Genentech/Roche, ChemoCentryx, and Genzyme/Sanofi. Vifor holds an equity stake in ChemoCentryx.

[email protected]

SOURCE: Jones RB et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214245.

Mycophenolate mofetil was noninferior to pulsed cyclophosphamide for remission induction in ANCA-associated vasculitis, but there were more relapses, in a randomized, unblinded trial of 140 patients with non–life-threatening disease.

“Our results demonstrate that MMF [mycophenolate mofetil] represents an alternative to CYC [cyclophosphamide] for remission induction in AAV [ANCA-associated vasculitis],” said investigators led by Rachel B. Jones, MD, of the department of renal medicine at Addenbrooke’s Hospital, Cambridge, England.

“While treatment with MMF may be associated with a higher risk of relapse compared with pulsed CYC, this increased risk may be acceptable to avoid the potential adverse effects of CYC” – infections, malignancies, and infertility – “particularly when the baseline risk of relapse is low,” as with the elderly or myeloperoxidase (MPO)-ANCA disease, “or if rituximab is unavailable,” Dr. Jones and her colleagues wrote in Annals of the Rheumatic Diseases.

Since enrollment began in 2007, they also noted that “it has become common to use rituximab as an alternative to CYC induction therapy ... However, rituximab is expensive, and its use is restricted in many countries ... Alternative effective low-cost induction therapies” – such as MMF – “may be required in some cases.”

The work, which was done on behalf of the European Vasculitis Study Group, was the largest randomized trial to date of MMF for AAV remission induction, and the first to include children; patients were enrolled at 21 sites in Europe, Australia, and New Zealand.

They were randomly assigned to MMF or pulsed CYC, with 66 adults and 4 children ranging in age from 10 to 16 years in each group. In addition to those with life-threatening disease, patients younger than 6 years old and those on dialysis or with an estimated glomerular filtration rate below 15 mL/min/m² were excluded. Following remission, subjects were switched to oral azathioprine and a prednisone taper.

The primary outcome was remission by 6 months, defined as the absence of disease activity on two consecutive occasions at least 1 month apart, plus adherence to the taper. Baseline ANCA subtype, disease activity, and organ involvement were similar between the groups.

Overall, 47 patients in the in the MMF group (67%), including 1 child, reached the primary endpoint, versus 43 patients (61%), again including 1 child, in the CYC group (risk difference = 5.7%; 90% confidence interval, –7.5% to 19%), which established noninferiority. The median time to remission was about 90 days in both arms. “Compliance was a contributory factor to the lower remission rate[s] in children,” the authors noted.

More relapses occurred in the MMF group (33% vs. 19% with CYC). Among MPO-ANCA patients, the relapse rate was 15% versus 12% with CYC. In proteinase 3 (PR3)-ANCA patients, almost half in the MMF group relapsed (48% versus 24%).

There were no significant differences in serious infections (26% with MMF versus 17% with CYC; P = .3), malignancies, thromboembolisms, or death (four CYC patients and five MMF patients at 6 months).

Adult patients in the MMF group received MMF 2 g/day, with dose increases to 3 g/day permitted for uncontrolled disease at 4 weeks. Patients younger than 17 years old were dosed according to body surface area. The CYC group received intravenous pulsed CYC 15 mg/kg every 2-3 weeks with reductions for age and renal function. A total of 58 CYC patients (83%) received at least six pulses.

After remission, azathioprine was dosed at 2 mg/kg per day. Oral prednisolone started at 1 mg/kg per day and was reduced to 5 mg/day by 6 months.

Plasma exchange or additional methylprednisolone were allowed at entry; there were no differences in their use between the groups.

The trial was sponsored by Cambridge University Hospitals NHS Foundation Trust. Vifor Pharma provided a research grant to cover the trial and MMF costs. Dr. Jones and the other investigators reported ties to several companies, including GlaxoSmithKline, Genentech/Roche, ChemoCentryx, and Genzyme/Sanofi. Vifor holds an equity stake in ChemoCentryx.

[email protected]

SOURCE: Jones RB et al. Ann Rheum Dis. 2019 Jan 5. doi: 10.1136/annrheumdis-2018-214245.

The use of anticoagulation in patients with comorbid lupus nephritis and thrombotic microangiopathy was linked with a greater rate of clinical response after 12 months of therapy, according to results from a study published in Annals of the Rheumatic Diseases.

copyright HYWARDS/Thinkstock

“The purpose of this multicenter retrospective study was to analyze the impact of anticoagulation (vitamin K antagonists and/or heparins), in addition to conventional immunosuppression on kidney outcomes, according to the Kidney Disease: Improving Global Outcomes guidelines,” wrote first author Savino Sciascia, MD, PhD, of the University of Turin (Italy), along with his colleagues.

The researchers analyzed data from 97 patients with biopsy-confirmed lupus nephritis (LN) and thrombotic microangiopathy (TMA) who were diagnosed during 2007-2017. The entire cohort was administered standard immunosuppressive agents, including corticosteroids, cyclophosphamide, and mycophenolate, among others. After 12 months of therapy, the patients were assessed for degree of clinical response, measured using complete, partial, or no response to therapy.

“Sixty-one patients (62.9%) were [antiphospholipid antibody] positive and 37 (38.1%) of these patients received anticoagulation with a vitamin K antagonist and/or heparins,” the investigators wrote. “Mean duration of anticoagulation therapy after TMA and LN diagnosis was 7.7 months,” they added.

After statistical analysis, the researchers found that patients treated with anticoagulation therapy experienced a greater rate of clinical response, compared with those not treated. The investigators saw a complete response to therapy in 22 (59.5%) patients given anticoagulation, compared with 15 (25.0%) patients without anticoagulation. Partial treatment responses were comparable, occurring in 7 (18.9%) with anticoagulation and 15 (25.0%) without. Without anticoagulation, 30 (50%) had no response to therapy, compared with 8 (21.6%) patients given anticoagulation.

“When limiting the analysis to patients with antiphospholipid antibodies, we observed a rate of any response (either complete response [or] partial response) as high as 66% in patients receiving anticoagulant treatment compared with those receiving immunosuppression alone (34%),” they added.

The authors acknowledged a major limitation of the study was the short duration of follow-up, which limited the ability to evaluate relapse rate.

“Despite its limitations, this study represents the largest available multicenter cohort of real-life systemic lupus erythematosus patients,” said Dr. Sciascia and his colleagues. “The use of anticoagulation appeared protective and warrants further investigation as a therapeutic tool,” they concluded.

The authors reported no conflicts of interest, and no specific study funding was declared.

SOURCE: Sciascia S et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214559.

The use of anticoagulation in patients with comorbid lupus nephritis and thrombotic microangiopathy was linked with a greater rate of clinical response after 12 months of therapy, according to results from a study published in Annals of the Rheumatic Diseases.

copyright HYWARDS/Thinkstock

“The purpose of this multicenter retrospective study was to analyze the impact of anticoagulation (vitamin K antagonists and/or heparins), in addition to conventional immunosuppression on kidney outcomes, according to the Kidney Disease: Improving Global Outcomes guidelines,” wrote first author Savino Sciascia, MD, PhD, of the University of Turin (Italy), along with his colleagues.

The researchers analyzed data from 97 patients with biopsy-confirmed lupus nephritis (LN) and thrombotic microangiopathy (TMA) who were diagnosed during 2007-2017. The entire cohort was administered standard immunosuppressive agents, including corticosteroids, cyclophosphamide, and mycophenolate, among others. After 12 months of therapy, the patients were assessed for degree of clinical response, measured using complete, partial, or no response to therapy.

“Sixty-one patients (62.9%) were [antiphospholipid antibody] positive and 37 (38.1%) of these patients received anticoagulation with a vitamin K antagonist and/or heparins,” the investigators wrote. “Mean duration of anticoagulation therapy after TMA and LN diagnosis was 7.7 months,” they added.

After statistical analysis, the researchers found that patients treated with anticoagulation therapy experienced a greater rate of clinical response, compared with those not treated. The investigators saw a complete response to therapy in 22 (59.5%) patients given anticoagulation, compared with 15 (25.0%) patients without anticoagulation. Partial treatment responses were comparable, occurring in 7 (18.9%) with anticoagulation and 15 (25.0%) without. Without anticoagulation, 30 (50%) had no response to therapy, compared with 8 (21.6%) patients given anticoagulation.

“When limiting the analysis to patients with antiphospholipid antibodies, we observed a rate of any response (either complete response [or] partial response) as high as 66% in patients receiving anticoagulant treatment compared with those receiving immunosuppression alone (34%),” they added.

The authors acknowledged a major limitation of the study was the short duration of follow-up, which limited the ability to evaluate relapse rate.

“Despite its limitations, this study represents the largest available multicenter cohort of real-life systemic lupus erythematosus patients,” said Dr. Sciascia and his colleagues. “The use of anticoagulation appeared protective and warrants further investigation as a therapeutic tool,” they concluded.

The authors reported no conflicts of interest, and no specific study funding was declared.

SOURCE: Sciascia S et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214559.

The use of anticoagulation in patients with comorbid lupus nephritis and thrombotic microangiopathy was linked with a greater rate of clinical response after 12 months of therapy, according to results from a study published in Annals of the Rheumatic Diseases.

copyright HYWARDS/Thinkstock

“The purpose of this multicenter retrospective study was to analyze the impact of anticoagulation (vitamin K antagonists and/or heparins), in addition to conventional immunosuppression on kidney outcomes, according to the Kidney Disease: Improving Global Outcomes guidelines,” wrote first author Savino Sciascia, MD, PhD, of the University of Turin (Italy), along with his colleagues.

The researchers analyzed data from 97 patients with biopsy-confirmed lupus nephritis (LN) and thrombotic microangiopathy (TMA) who were diagnosed during 2007-2017. The entire cohort was administered standard immunosuppressive agents, including corticosteroids, cyclophosphamide, and mycophenolate, among others. After 12 months of therapy, the patients were assessed for degree of clinical response, measured using complete, partial, or no response to therapy.

“Sixty-one patients (62.9%) were [antiphospholipid antibody] positive and 37 (38.1%) of these patients received anticoagulation with a vitamin K antagonist and/or heparins,” the investigators wrote. “Mean duration of anticoagulation therapy after TMA and LN diagnosis was 7.7 months,” they added.

After statistical analysis, the researchers found that patients treated with anticoagulation therapy experienced a greater rate of clinical response, compared with those not treated. The investigators saw a complete response to therapy in 22 (59.5%) patients given anticoagulation, compared with 15 (25.0%) patients without anticoagulation. Partial treatment responses were comparable, occurring in 7 (18.9%) with anticoagulation and 15 (25.0%) without. Without anticoagulation, 30 (50%) had no response to therapy, compared with 8 (21.6%) patients given anticoagulation.

“When limiting the analysis to patients with antiphospholipid antibodies, we observed a rate of any response (either complete response [or] partial response) as high as 66% in patients receiving anticoagulant treatment compared with those receiving immunosuppression alone (34%),” they added.

The authors acknowledged a major limitation of the study was the short duration of follow-up, which limited the ability to evaluate relapse rate.

“Despite its limitations, this study represents the largest available multicenter cohort of real-life systemic lupus erythematosus patients,” said Dr. Sciascia and his colleagues. “The use of anticoagulation appeared protective and warrants further investigation as a therapeutic tool,” they concluded.

The authors reported no conflicts of interest, and no specific study funding was declared.

SOURCE: Sciascia S et al. Ann Rheum Dis. 2018 Dec 14. doi: 10.1136/annrheumdis-2018-214559.

Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.

Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.

The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).

Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.

The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.

Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.

“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.

The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.

The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.

SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.

Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.

Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.

The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).

Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.

The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.

Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.

“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.

The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.

The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.

SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.

Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.

Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.

The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).

Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.

The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.

Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.

“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.

The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.

The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.

SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.

Tofacitinib significantly improved skin lesions associated with cutaneous sarcoidosis, according to a case report published in the New England Journal of Medicine.

Treatment options for cutaneous sarcoidosis are limited, as are data on the effectiveness of alternatives to prednisone, which is often the first choice despite adverse effects, wrote William Damsky, MD, of Yale University in New Haven, Conn., and his colleagues.

Previous studies have suggested involvement of the JAK-STAT pathway in sarcoidosis; therefore, the researchers treated a patient who had refractory cutaneous sarcoidosis with oral tofacitinib. The treatment significantly improved the patient’s skin lesions both clinically and histologically.

The patient was a 48-year-old woman with a history of cutaneous and pulmonary sarcoidosis and treatment-resistant skin lesions. At the time of the case report, she had no pulmonary symptoms and no ophthalmologic issues, but presented with pink-brown indurated papules and plaques, and some alopecia on her scalp (N Engl J Med. 2018;379:2540-6).

The patient had not responded to other medications including glucocorticoids, minocycline, hydroxychloroquine, methotrexate, adalimumab, tacrolimus, and apremilast. With her consent, the patient received off-label tofacitinib at 5 mg twice daily. The lesions began to improve, but treatment was discontinued because of insurance issues. When treatment resumed, the patient’s Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) score, used to assess disease activity, was 85 on a scale of 0 to 165; this score dropped to 53 after 4 months of treatment.

In addition, two samples collected after 10 months of treatment showed histologic resolution of granulomas.

Although the findings must be replicated in other patients, the results suggest that “the dysregulation of JAK-STAT–dependent cytokines (e.g., interferon-gamma) is pathogenically involved in cutaneous sarcoidosis and, probably, in sarcoidosis in general,” the researchers said.

Dr. Damsky disclosed a financial relationship with Eli Lilly, and research funding from the Dermatology Foundation and the National Institutes of Health. The study was supported by the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research, the National Institutes of Health, and the Dermatology Foundation.
 

SOURCE: Damsky W et al. N Engl J Med. 2018;379:2540-6.

Tofacitinib significantly improved skin lesions associated with cutaneous sarcoidosis, according to a case report published in the New England Journal of Medicine.

Treatment options for cutaneous sarcoidosis are limited, as are data on the effectiveness of alternatives to prednisone, which is often the first choice despite adverse effects, wrote William Damsky, MD, of Yale University in New Haven, Conn., and his colleagues.

Previous studies have suggested involvement of the JAK-STAT pathway in sarcoidosis; therefore, the researchers treated a patient who had refractory cutaneous sarcoidosis with oral tofacitinib. The treatment significantly improved the patient’s skin lesions both clinically and histologically.

The patient was a 48-year-old woman with a history of cutaneous and pulmonary sarcoidosis and treatment-resistant skin lesions. At the time of the case report, she had no pulmonary symptoms and no ophthalmologic issues, but presented with pink-brown indurated papules and plaques, and some alopecia on her scalp (N Engl J Med. 2018;379:2540-6).

The patient had not responded to other medications including glucocorticoids, minocycline, hydroxychloroquine, methotrexate, adalimumab, tacrolimus, and apremilast. With her consent, the patient received off-label tofacitinib at 5 mg twice daily. The lesions began to improve, but treatment was discontinued because of insurance issues. When treatment resumed, the patient’s Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) score, used to assess disease activity, was 85 on a scale of 0 to 165; this score dropped to 53 after 4 months of treatment.

In addition, two samples collected after 10 months of treatment showed histologic resolution of granulomas.

Although the findings must be replicated in other patients, the results suggest that “the dysregulation of JAK-STAT–dependent cytokines (e.g., interferon-gamma) is pathogenically involved in cutaneous sarcoidosis and, probably, in sarcoidosis in general,” the researchers said.

Dr. Damsky disclosed a financial relationship with Eli Lilly, and research funding from the Dermatology Foundation and the National Institutes of Health. The study was supported by the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research, the National Institutes of Health, and the Dermatology Foundation.
 

SOURCE: Damsky W et al. N Engl J Med. 2018;379:2540-6.

Tofacitinib significantly improved skin lesions associated with cutaneous sarcoidosis, according to a case report published in the New England Journal of Medicine.

Treatment options for cutaneous sarcoidosis are limited, as are data on the effectiveness of alternatives to prednisone, which is often the first choice despite adverse effects, wrote William Damsky, MD, of Yale University in New Haven, Conn., and his colleagues.

Previous studies have suggested involvement of the JAK-STAT pathway in sarcoidosis; therefore, the researchers treated a patient who had refractory cutaneous sarcoidosis with oral tofacitinib. The treatment significantly improved the patient’s skin lesions both clinically and histologically.

The patient was a 48-year-old woman with a history of cutaneous and pulmonary sarcoidosis and treatment-resistant skin lesions. At the time of the case report, she had no pulmonary symptoms and no ophthalmologic issues, but presented with pink-brown indurated papules and plaques, and some alopecia on her scalp (N Engl J Med. 2018;379:2540-6).

The patient had not responded to other medications including glucocorticoids, minocycline, hydroxychloroquine, methotrexate, adalimumab, tacrolimus, and apremilast. With her consent, the patient received off-label tofacitinib at 5 mg twice daily. The lesions began to improve, but treatment was discontinued because of insurance issues. When treatment resumed, the patient’s Cutaneous Sarcoidosis Activity and Morphology Instrument (CSAMI) score, used to assess disease activity, was 85 on a scale of 0 to 165; this score dropped to 53 after 4 months of treatment.

In addition, two samples collected after 10 months of treatment showed histologic resolution of granulomas.

Although the findings must be replicated in other patients, the results suggest that “the dysregulation of JAK-STAT–dependent cytokines (e.g., interferon-gamma) is pathogenically involved in cutaneous sarcoidosis and, probably, in sarcoidosis in general,” the researchers said.

Dr. Damsky disclosed a financial relationship with Eli Lilly, and research funding from the Dermatology Foundation and the National Institutes of Health. The study was supported by the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research, the National Institutes of Health, and the Dermatology Foundation.
 

SOURCE: Damsky W et al. N Engl J Med. 2018;379:2540-6.

CHICAGO – Patients who meet the criteria for interstitial pneumonia with autoimmune features are more than 14 times more likely to progress to a systemic autoimmune rheumatic disease than are those with idiopathic interstitial lung disease who don’t meet the criteria, Michail Alevizos, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“We think this is a very novel finding. It means that patients with IPAF [interstitial pneumonia with autoimmune features] should be followed and evaluated by rheumatologists over time,” said Dr. Alevizos, who was a rheumatology fellow at Columbia University in New York at the time of the study.

Interstitial pneumonia with autoimmune features (IPAF) is a term proposed by a joint task force of the American Thoracic Society and European Respiratory Society in 2015 to describe patients diagnosed with idiopathic interstitial lung disease who possess some features of autoimmunity without meeting formal criteria for a full-blown rheumatic disease. The designation requires the presence of interstitial lung disease by imaging or biopsy, exclusion of all other etiologies, and at least one feature from within at least two of three domains: clinical, serologic, and morphologic.

The clinical domain includes Raynaud’s, palmar telangiectasias, distal digital tip ulceration, and other entities. The serologic criteria include any of a dozen possible autoantibodies. And the morphologic domain encompasses a radiographic or histopathologic pattern suggestive of organizing pneumonia, nonspecific interstitial pneumonia, or other specific abnormalities (Eur Respir J. 2015 Oct;46[4]:976-87).

The natural history of IPAF is largely unknown, which was the impetus for Dr. Alevizos’ study. He presented a single-center, retrospective study of 697 patients diagnosed with interstitial lung disease, 174 of whom had idiopathic interstitial lung disease at baseline. Fifty of the 174 met criteria for IPAF, while the other 124 did not.

During a median follow-up of 5.2 years, 8 of the 50 patients with IPAF (16%) were diagnosed with a systemic autoimmune rheumatic disease, as were 2 of the 124 non-IPAF group (1.6%). The average time to diagnosis of a formal rheumatic disease was 3.4 years in the IPAF group and 7.8 years in the comparator arm. The rheumatic diseases that arose in the IPAF group consisted of two cases of rheumatoid arthritis, two of antineutrophil cytoplasmic antibody–associated vasculitis, three of systemic sclerosis, and one of polymyositis.

In an analysis adjusted for age, sex, smoking status, and immunosuppressive therapy at baseline, patients with IPAF were 14.1 times more likely to progress to an autoimmune rheumatic disease.

In terms of distinguishing features, the IPAF patients were on average 10 years younger at baseline and more commonly female. On high-resolution CT, 82% of them displayed a pattern of nonspecific interstitial pneumonia, compared with only 15% of the non-IPAF group. Also, 96% of the IPAF patients were on immunosuppressive therapy at baseline, as were 52% of the non-IPAF group. Usual interstitial pneumonia was evident on high-resolution CT in 18% of the IPAF group, compared with 75% of patients with idiopathic interstitial pneumonia without IPAF.

Dr. Alevizos said he hopes to validate these findings in a prospective study. He reported having no financial conflicts regarding the study, which was conducted free of commercial support.

[email protected]

SOURCE: Alevizos M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1305.

CHICAGO – Patients who meet the criteria for interstitial pneumonia with autoimmune features are more than 14 times more likely to progress to a systemic autoimmune rheumatic disease than are those with idiopathic interstitial lung disease who don’t meet the criteria, Michail Alevizos, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“We think this is a very novel finding. It means that patients with IPAF [interstitial pneumonia with autoimmune features] should be followed and evaluated by rheumatologists over time,” said Dr. Alevizos, who was a rheumatology fellow at Columbia University in New York at the time of the study.

Interstitial pneumonia with autoimmune features (IPAF) is a term proposed by a joint task force of the American Thoracic Society and European Respiratory Society in 2015 to describe patients diagnosed with idiopathic interstitial lung disease who possess some features of autoimmunity without meeting formal criteria for a full-blown rheumatic disease. The designation requires the presence of interstitial lung disease by imaging or biopsy, exclusion of all other etiologies, and at least one feature from within at least two of three domains: clinical, serologic, and morphologic.

The clinical domain includes Raynaud’s, palmar telangiectasias, distal digital tip ulceration, and other entities. The serologic criteria include any of a dozen possible autoantibodies. And the morphologic domain encompasses a radiographic or histopathologic pattern suggestive of organizing pneumonia, nonspecific interstitial pneumonia, or other specific abnormalities (Eur Respir J. 2015 Oct;46[4]:976-87).

The natural history of IPAF is largely unknown, which was the impetus for Dr. Alevizos’ study. He presented a single-center, retrospective study of 697 patients diagnosed with interstitial lung disease, 174 of whom had idiopathic interstitial lung disease at baseline. Fifty of the 174 met criteria for IPAF, while the other 124 did not.

During a median follow-up of 5.2 years, 8 of the 50 patients with IPAF (16%) were diagnosed with a systemic autoimmune rheumatic disease, as were 2 of the 124 non-IPAF group (1.6%). The average time to diagnosis of a formal rheumatic disease was 3.4 years in the IPAF group and 7.8 years in the comparator arm. The rheumatic diseases that arose in the IPAF group consisted of two cases of rheumatoid arthritis, two of antineutrophil cytoplasmic antibody–associated vasculitis, three of systemic sclerosis, and one of polymyositis.

In an analysis adjusted for age, sex, smoking status, and immunosuppressive therapy at baseline, patients with IPAF were 14.1 times more likely to progress to an autoimmune rheumatic disease.

In terms of distinguishing features, the IPAF patients were on average 10 years younger at baseline and more commonly female. On high-resolution CT, 82% of them displayed a pattern of nonspecific interstitial pneumonia, compared with only 15% of the non-IPAF group. Also, 96% of the IPAF patients were on immunosuppressive therapy at baseline, as were 52% of the non-IPAF group. Usual interstitial pneumonia was evident on high-resolution CT in 18% of the IPAF group, compared with 75% of patients with idiopathic interstitial pneumonia without IPAF.

Dr. Alevizos said he hopes to validate these findings in a prospective study. He reported having no financial conflicts regarding the study, which was conducted free of commercial support.

[email protected]

SOURCE: Alevizos M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1305.

CHICAGO – Patients who meet the criteria for interstitial pneumonia with autoimmune features are more than 14 times more likely to progress to a systemic autoimmune rheumatic disease than are those with idiopathic interstitial lung disease who don’t meet the criteria, Michail Alevizos, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

“We think this is a very novel finding. It means that patients with IPAF [interstitial pneumonia with autoimmune features] should be followed and evaluated by rheumatologists over time,” said Dr. Alevizos, who was a rheumatology fellow at Columbia University in New York at the time of the study.

Interstitial pneumonia with autoimmune features (IPAF) is a term proposed by a joint task force of the American Thoracic Society and European Respiratory Society in 2015 to describe patients diagnosed with idiopathic interstitial lung disease who possess some features of autoimmunity without meeting formal criteria for a full-blown rheumatic disease. The designation requires the presence of interstitial lung disease by imaging or biopsy, exclusion of all other etiologies, and at least one feature from within at least two of three domains: clinical, serologic, and morphologic.

The clinical domain includes Raynaud’s, palmar telangiectasias, distal digital tip ulceration, and other entities. The serologic criteria include any of a dozen possible autoantibodies. And the morphologic domain encompasses a radiographic or histopathologic pattern suggestive of organizing pneumonia, nonspecific interstitial pneumonia, or other specific abnormalities (Eur Respir J. 2015 Oct;46[4]:976-87).

The natural history of IPAF is largely unknown, which was the impetus for Dr. Alevizos’ study. He presented a single-center, retrospective study of 697 patients diagnosed with interstitial lung disease, 174 of whom had idiopathic interstitial lung disease at baseline. Fifty of the 174 met criteria for IPAF, while the other 124 did not.

During a median follow-up of 5.2 years, 8 of the 50 patients with IPAF (16%) were diagnosed with a systemic autoimmune rheumatic disease, as were 2 of the 124 non-IPAF group (1.6%). The average time to diagnosis of a formal rheumatic disease was 3.4 years in the IPAF group and 7.8 years in the comparator arm. The rheumatic diseases that arose in the IPAF group consisted of two cases of rheumatoid arthritis, two of antineutrophil cytoplasmic antibody–associated vasculitis, three of systemic sclerosis, and one of polymyositis.

In an analysis adjusted for age, sex, smoking status, and immunosuppressive therapy at baseline, patients with IPAF were 14.1 times more likely to progress to an autoimmune rheumatic disease.

In terms of distinguishing features, the IPAF patients were on average 10 years younger at baseline and more commonly female. On high-resolution CT, 82% of them displayed a pattern of nonspecific interstitial pneumonia, compared with only 15% of the non-IPAF group. Also, 96% of the IPAF patients were on immunosuppressive therapy at baseline, as were 52% of the non-IPAF group. Usual interstitial pneumonia was evident on high-resolution CT in 18% of the IPAF group, compared with 75% of patients with idiopathic interstitial pneumonia without IPAF.

Dr. Alevizos said he hopes to validate these findings in a prospective study. He reported having no financial conflicts regarding the study, which was conducted free of commercial support.

[email protected]

SOURCE: Alevizos M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1305.

CHICAGO – Chronic use of proton pump inhibitors is widespread among patients with rheumatoid arthritis or systemic lupus erythematosus, posing a distinct danger of unwelcome drug-drug interactions affecting the rate and extent of absorption of selected oral antirheumatic drugs, Nicholas Jones, PharmD, said at the annual meeting of the American College of Rheumatology.

Of particular interest is the fact that the oral Janus kinase inhibitors – a drug class that’s a red hot research topic now in rheumatology – are weak bases whose absorption can be greatly affected by pH-dependent solubility, according to Dr. Jones, a research scientist at Genentech in South San Francisco.

Other commonly prescribed oral antirheumatic drugs whose solubility is affected by the level of stomach acidity include azathioprine, methotrexate, mycophenolate mofetil, and sulfasalazine. On the other hand, solubility is not pH-dependent for apremilast, chloroquine, cyclophosphamide, cyclosporine, hydroxychloroquine, leflunomide, or tacrolimus.

Dr. Jones presented a retrospective analysis of proton pump inhibitor (PPI) utilization patterns during 2012-2015 in 77,034 rheumatoid arthritis and 2,224 systemic lupus erythematosus (SLE) patients included in the national Truven Health MarketScan database.

Thirty-five percent of the rheumatoid arthritis patients and 34% of SLE patients were chronic users of PPIs as defined by continuous daily use for more than a month during 2 years of follow-up. Among the SLE cohort, chronic utilization of PPIs increased stepwise with disease severity: The rate was 27% in those with mild SLE, 39% with moderate disease, and 54% among those with severe SLE.

Omeprazole was far and away the most widely used PPI. It was the one used by 53% of the RA patients who were chronic users of PPIs, followed by pantoprazole at 20% and esomeprazole at 15%. The PPI distribution pattern closely followed suit in SLE patients who were chronic users.

Esomeprazole is 60% more potent and pantoprazole 77% less potent than omeprazole, Dr. Jones noted. The pharmacokinetic clearance routes for omeprazole and esomeprazole involve CYP2C19 and CYP3A4. Clearance of pantoprazole is by those two mechanisms as well as by CYP2D6 and CYP2C9.

Dr. Jones recommended that physicians who treat rheumatoid arthritis and SLE patients be sure to ask them about concomitant use of PPIs, including OTC formulations. And clinical trialists need to be attentive to PPI usage in potential study participants.

Genentech sponsored the study.

[email protected]

SOURCE: Keebler D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 228

CHICAGO – Chronic use of proton pump inhibitors is widespread among patients with rheumatoid arthritis or systemic lupus erythematosus, posing a distinct danger of unwelcome drug-drug interactions affecting the rate and extent of absorption of selected oral antirheumatic drugs, Nicholas Jones, PharmD, said at the annual meeting of the American College of Rheumatology.

Of particular interest is the fact that the oral Janus kinase inhibitors – a drug class that’s a red hot research topic now in rheumatology – are weak bases whose absorption can be greatly affected by pH-dependent solubility, according to Dr. Jones, a research scientist at Genentech in South San Francisco.

Other commonly prescribed oral antirheumatic drugs whose solubility is affected by the level of stomach acidity include azathioprine, methotrexate, mycophenolate mofetil, and sulfasalazine. On the other hand, solubility is not pH-dependent for apremilast, chloroquine, cyclophosphamide, cyclosporine, hydroxychloroquine, leflunomide, or tacrolimus.

Dr. Jones presented a retrospective analysis of proton pump inhibitor (PPI) utilization patterns during 2012-2015 in 77,034 rheumatoid arthritis and 2,224 systemic lupus erythematosus (SLE) patients included in the national Truven Health MarketScan database.

Thirty-five percent of the rheumatoid arthritis patients and 34% of SLE patients were chronic users of PPIs as defined by continuous daily use for more than a month during 2 years of follow-up. Among the SLE cohort, chronic utilization of PPIs increased stepwise with disease severity: The rate was 27% in those with mild SLE, 39% with moderate disease, and 54% among those with severe SLE.

Omeprazole was far and away the most widely used PPI. It was the one used by 53% of the RA patients who were chronic users of PPIs, followed by pantoprazole at 20% and esomeprazole at 15%. The PPI distribution pattern closely followed suit in SLE patients who were chronic users.

Esomeprazole is 60% more potent and pantoprazole 77% less potent than omeprazole, Dr. Jones noted. The pharmacokinetic clearance routes for omeprazole and esomeprazole involve CYP2C19 and CYP3A4. Clearance of pantoprazole is by those two mechanisms as well as by CYP2D6 and CYP2C9.

Dr. Jones recommended that physicians who treat rheumatoid arthritis and SLE patients be sure to ask them about concomitant use of PPIs, including OTC formulations. And clinical trialists need to be attentive to PPI usage in potential study participants.

Genentech sponsored the study.

[email protected]

SOURCE: Keebler D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 228

CHICAGO – Chronic use of proton pump inhibitors is widespread among patients with rheumatoid arthritis or systemic lupus erythematosus, posing a distinct danger of unwelcome drug-drug interactions affecting the rate and extent of absorption of selected oral antirheumatic drugs, Nicholas Jones, PharmD, said at the annual meeting of the American College of Rheumatology.

Of particular interest is the fact that the oral Janus kinase inhibitors – a drug class that’s a red hot research topic now in rheumatology – are weak bases whose absorption can be greatly affected by pH-dependent solubility, according to Dr. Jones, a research scientist at Genentech in South San Francisco.

Other commonly prescribed oral antirheumatic drugs whose solubility is affected by the level of stomach acidity include azathioprine, methotrexate, mycophenolate mofetil, and sulfasalazine. On the other hand, solubility is not pH-dependent for apremilast, chloroquine, cyclophosphamide, cyclosporine, hydroxychloroquine, leflunomide, or tacrolimus.

Dr. Jones presented a retrospective analysis of proton pump inhibitor (PPI) utilization patterns during 2012-2015 in 77,034 rheumatoid arthritis and 2,224 systemic lupus erythematosus (SLE) patients included in the national Truven Health MarketScan database.

Thirty-five percent of the rheumatoid arthritis patients and 34% of SLE patients were chronic users of PPIs as defined by continuous daily use for more than a month during 2 years of follow-up. Among the SLE cohort, chronic utilization of PPIs increased stepwise with disease severity: The rate was 27% in those with mild SLE, 39% with moderate disease, and 54% among those with severe SLE.

Omeprazole was far and away the most widely used PPI. It was the one used by 53% of the RA patients who were chronic users of PPIs, followed by pantoprazole at 20% and esomeprazole at 15%. The PPI distribution pattern closely followed suit in SLE patients who were chronic users.

Esomeprazole is 60% more potent and pantoprazole 77% less potent than omeprazole, Dr. Jones noted. The pharmacokinetic clearance routes for omeprazole and esomeprazole involve CYP2C19 and CYP3A4. Clearance of pantoprazole is by those two mechanisms as well as by CYP2D6 and CYP2C9.

Dr. Jones recommended that physicians who treat rheumatoid arthritis and SLE patients be sure to ask them about concomitant use of PPIs, including OTC formulations. And clinical trialists need to be attentive to PPI usage in potential study participants.

Genentech sponsored the study.

[email protected]

SOURCE: Keebler D et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 228

CHICAGO – A simple new classification scheme that combines autoantibody specificity and extent of skin involvement could improve risk stratification of patients with systemic sclerosis, according to researchers at University College London.

“The Le Roy et al. classification of SSc [systemic sclerosis] into limited and diffuse cutaneous subtype remains the most commonly used classification system for systemic sclerosis, but autoantibodies are much better predictors of organ involvement, and while more sophisticated approaches exist, this proposed simple classification using antibodies and skin subset is relevant to clinical practice and could help risk stratification,” Svetlana I. Nihtyanova, MD, said at the annual meeting of the American College of Rheumatology.

Dr. Nihtyanova, a clinical research fellow at University College London, reported how she and her colleagues at UCL divided 1,025 SSc patients into 12 subgroups based on skin subset and autoantibodies and then conducted Kaplan-Meier estimates of survival and cumulative incidence of organ complications to rank these 12 subgroups by endpoint estimates. They merged subgroups with similar ranking in multiple endpoints, ending up with seven groups in the final classification.

Group 1 comprised anti–centromere antibody–positive limited cutaneous SSc (lcSSc) patients and accounted for 29% of patients.

“This was the subgroup with the highest survival (72%) and the lowest incidence of pulmonary fibrosis (13%) and scleroderma renal crisis (no cases) at 20 years from onset,” she said, noting that the incidence of pulmonary hypertension in this group was similar to the average for the whole cohort.

Group 2 comprised all anti–RNA polymerase antibody–positive subjects and accounted for 11% of patients. This group had the highest incidence of scleroderma renal crisis (SRC; 32% at 20 years), but other organ complications and survival were similar to the cohort average.


Group 3 comprised Scl-70–positive lcSSc patients, and accounted for 11% of patients.

“Although incidence of pulmonary fibrosis in this group was the second highest (69% at 20 years), other complications were rare,” Dr. Nihtyanova said, adding that this group had the lowest incidence of pulmonary hypertension (6%) and the second lowest incidence of SRC (3%) at 20 years.

Group 4, conversely, included Scl-70–positive dcSSc patients and accounted for 11% of patients, who had a very poor prognosis; they had the highest incidence of pulmonary fibrosis (91%) and cardiac scleroderma (14%), and the worst survival (41%) at 20 years, she said.

Group 5 included all U3 RNP–positive patients, accounting for 5% of patients.

“Although survival in this group was not bad (70% at 20 years), the group had the highest pulmonary hypertension incidence (40%) and the second highest incidence of cardiac SSc (11%) at 20 years,” she noted.

Groups 6 and 7 (comprising 22% and 11% of study subjects, respectively) included lcSSc and diffuse cutaneous SSc (dcSSc) patients with other antibody specificities. Group 6 had low overall SRC and cardiac SSc risk, while other outcomes were similar to the cohort average. Group 7, however, had poor prognosis, with the second lowest survival (42% at 20 years) and above average rates of organ disease, particularly pulmonary fibrosis and SRC, she said.

Overall, estimated survival for the entire cohort was 60% at 20 years from onset, and in that time frame 44% developed significant pulmonary fibrosis, 25% pulmonary hypertension, 7% SRC, and 6% cardiac SSc. The patients had a mean age of 47 years at disease onset, and 16% were men. Diffuse cutaneous SSc was diagnosed in 35% of the subjects, she noted.

Dr. Nihtyanova reported having no disclosures.

[email protected]

SOURCE: Nihtyanova S et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2935.

CHICAGO – A simple new classification scheme that combines autoantibody specificity and extent of skin involvement could improve risk stratification of patients with systemic sclerosis, according to researchers at University College London.

“The Le Roy et al. classification of SSc [systemic sclerosis] into limited and diffuse cutaneous subtype remains the most commonly used classification system for systemic sclerosis, but autoantibodies are much better predictors of organ involvement, and while more sophisticated approaches exist, this proposed simple classification using antibodies and skin subset is relevant to clinical practice and could help risk stratification,” Svetlana I. Nihtyanova, MD, said at the annual meeting of the American College of Rheumatology.

Dr. Nihtyanova, a clinical research fellow at University College London, reported how she and her colleagues at UCL divided 1,025 SSc patients into 12 subgroups based on skin subset and autoantibodies and then conducted Kaplan-Meier estimates of survival and cumulative incidence of organ complications to rank these 12 subgroups by endpoint estimates. They merged subgroups with similar ranking in multiple endpoints, ending up with seven groups in the final classification.

Group 1 comprised anti–centromere antibody–positive limited cutaneous SSc (lcSSc) patients and accounted for 29% of patients.

“This was the subgroup with the highest survival (72%) and the lowest incidence of pulmonary fibrosis (13%) and scleroderma renal crisis (no cases) at 20 years from onset,” she said, noting that the incidence of pulmonary hypertension in this group was similar to the average for the whole cohort.

Group 2 comprised all anti–RNA polymerase antibody–positive subjects and accounted for 11% of patients. This group had the highest incidence of scleroderma renal crisis (SRC; 32% at 20 years), but other organ complications and survival were similar to the cohort average.


Group 3 comprised Scl-70–positive lcSSc patients, and accounted for 11% of patients.

“Although incidence of pulmonary fibrosis in this group was the second highest (69% at 20 years), other complications were rare,” Dr. Nihtyanova said, adding that this group had the lowest incidence of pulmonary hypertension (6%) and the second lowest incidence of SRC (3%) at 20 years.

Group 4, conversely, included Scl-70–positive dcSSc patients and accounted for 11% of patients, who had a very poor prognosis; they had the highest incidence of pulmonary fibrosis (91%) and cardiac scleroderma (14%), and the worst survival (41%) at 20 years, she said.

Group 5 included all U3 RNP–positive patients, accounting for 5% of patients.

“Although survival in this group was not bad (70% at 20 years), the group had the highest pulmonary hypertension incidence (40%) and the second highest incidence of cardiac SSc (11%) at 20 years,” she noted.

Groups 6 and 7 (comprising 22% and 11% of study subjects, respectively) included lcSSc and diffuse cutaneous SSc (dcSSc) patients with other antibody specificities. Group 6 had low overall SRC and cardiac SSc risk, while other outcomes were similar to the cohort average. Group 7, however, had poor prognosis, with the second lowest survival (42% at 20 years) and above average rates of organ disease, particularly pulmonary fibrosis and SRC, she said.

Overall, estimated survival for the entire cohort was 60% at 20 years from onset, and in that time frame 44% developed significant pulmonary fibrosis, 25% pulmonary hypertension, 7% SRC, and 6% cardiac SSc. The patients had a mean age of 47 years at disease onset, and 16% were men. Diffuse cutaneous SSc was diagnosed in 35% of the subjects, she noted.

Dr. Nihtyanova reported having no disclosures.

[email protected]

SOURCE: Nihtyanova S et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2935.

CHICAGO – A simple new classification scheme that combines autoantibody specificity and extent of skin involvement could improve risk stratification of patients with systemic sclerosis, according to researchers at University College London.

“The Le Roy et al. classification of SSc [systemic sclerosis] into limited and diffuse cutaneous subtype remains the most commonly used classification system for systemic sclerosis, but autoantibodies are much better predictors of organ involvement, and while more sophisticated approaches exist, this proposed simple classification using antibodies and skin subset is relevant to clinical practice and could help risk stratification,” Svetlana I. Nihtyanova, MD, said at the annual meeting of the American College of Rheumatology.

Dr. Nihtyanova, a clinical research fellow at University College London, reported how she and her colleagues at UCL divided 1,025 SSc patients into 12 subgroups based on skin subset and autoantibodies and then conducted Kaplan-Meier estimates of survival and cumulative incidence of organ complications to rank these 12 subgroups by endpoint estimates. They merged subgroups with similar ranking in multiple endpoints, ending up with seven groups in the final classification.

Group 1 comprised anti–centromere antibody–positive limited cutaneous SSc (lcSSc) patients and accounted for 29% of patients.

“This was the subgroup with the highest survival (72%) and the lowest incidence of pulmonary fibrosis (13%) and scleroderma renal crisis (no cases) at 20 years from onset,” she said, noting that the incidence of pulmonary hypertension in this group was similar to the average for the whole cohort.

Group 2 comprised all anti–RNA polymerase antibody–positive subjects and accounted for 11% of patients. This group had the highest incidence of scleroderma renal crisis (SRC; 32% at 20 years), but other organ complications and survival were similar to the cohort average.


Group 3 comprised Scl-70–positive lcSSc patients, and accounted for 11% of patients.

“Although incidence of pulmonary fibrosis in this group was the second highest (69% at 20 years), other complications were rare,” Dr. Nihtyanova said, adding that this group had the lowest incidence of pulmonary hypertension (6%) and the second lowest incidence of SRC (3%) at 20 years.

Group 4, conversely, included Scl-70–positive dcSSc patients and accounted for 11% of patients, who had a very poor prognosis; they had the highest incidence of pulmonary fibrosis (91%) and cardiac scleroderma (14%), and the worst survival (41%) at 20 years, she said.

Group 5 included all U3 RNP–positive patients, accounting for 5% of patients.

“Although survival in this group was not bad (70% at 20 years), the group had the highest pulmonary hypertension incidence (40%) and the second highest incidence of cardiac SSc (11%) at 20 years,” she noted.

Groups 6 and 7 (comprising 22% and 11% of study subjects, respectively) included lcSSc and diffuse cutaneous SSc (dcSSc) patients with other antibody specificities. Group 6 had low overall SRC and cardiac SSc risk, while other outcomes were similar to the cohort average. Group 7, however, had poor prognosis, with the second lowest survival (42% at 20 years) and above average rates of organ disease, particularly pulmonary fibrosis and SRC, she said.

Overall, estimated survival for the entire cohort was 60% at 20 years from onset, and in that time frame 44% developed significant pulmonary fibrosis, 25% pulmonary hypertension, 7% SRC, and 6% cardiac SSc. The patients had a mean age of 47 years at disease onset, and 16% were men. Diffuse cutaneous SSc was diagnosed in 35% of the subjects, she noted.

Dr. Nihtyanova reported having no disclosures.

[email protected]

SOURCE: Nihtyanova S et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2935.

The increased risk of cancer associated with anti-TIF1-Ab-positive dermatomyositis is limited almost exclusively to 3 years on either side of the onset of dermatomyositis, new research suggests.

Idiopathic inflammatory myopathy have been associated with malignancy, in particular dermatomyositis (DM) and the DM-specific antitranscriptional intermediary factor 1 antibody (anti-TIF1-Ab).

Around one-fifth of the 236 patients diagnosed with DM in the current study, published online Dec. 7 in Rheumatology, were anti-TIF1-Ab positive, and these patients had a more than threefold higher risk of developing cancer comapared with patients who were anti-TIF1-Ab negative (hazard ratio = 3.4, 95% confidence interval, 2.2-5.4; P less than .01).

Overall, 38% of patients in the anti-TIF1-Ab-positive group developed cancer during the 10-year follow-up, compared with 15% of patients with anti-TIF1-Ab-negative DM.

However, all the cancers in the anti-TIF1-Ab-positive group occurred within the 3 years before the onset of DM or within 2.5 years after onset. No anti-TIF1-Ab-positive patients developed cancers after this time, but some patients in the anti-TIF1-Ab-negative group did.

“This finding is not likely to be due to a disparity in follow-up time between anti-TIF1-Ab-positive and -negative cases, as the median follow-up times were similar for both groups: 10 years and 12 years, respectively,” wrote Alexander Oldroyd, MBChB, a clinical research fellow in the Centre for Musculoskeletal Research at the University of Manchester (England), and his coauthors. “Further, this finding is unlikely to be due to differences in cancer detection methods, as both cohorts’ cancer diagnoses were identified through HSCIC [U.K. Health and Social Care Information Centre] data, ensuring capture of all incident cancers during the follow-up period.”

Anti-TIF1-Ab-positive patients were more likely to develop cancer if they were older. None of the 15 anti-TIF1-Ab-positive patients who were aged under 39 when they developed DM went on to develop cancer. But cancer developed in around half of the anti-TIF1-Ab-positive patients who were aged 39 years or older when their DM began.


The anti-TIF1 antibody is commonly found in juvenile DM, but previous research has not found an association with an increased risk of cancer in this younger patient population.

“Our findings add strength to the hypothesis that there exists a subset of young adult anti-TIF1-Ab-positive cases who do not have a discernible increased risk of cancer, similar to that observed in TIF1-Ab-positive juvenile DM,” the authors wrote. They suggested that given the increased risk of malignancy in older patients who were anti-TIF1-Ab positive, this group should be subject to more detailed cancer screening.

Breast cancer was the most common malignancy among both anti-TIF1-Ab-positive and anti-TIF1-Ab-negative patients (33% and 25%, respectively). However, ovarian cancer was significantly more common among the anti-TIF1-Ab-positive patients than among the anti-TIF1-Ab-negative patients (19% vs. 2%; P less than .05); four of the five ovarian cancers in the entire cohort occurred in the anti-TIF1-Ab-positive group.

The authors noted that this confirmed the finding of a number of previous studies suggesting an increased risk of ovarian cancer with DM.

“However, this is the first large study to identify that ovarian cancer is overrepresented in anti-TIF1-Ab-positive individuals, suggesting that the true association between DM and ovarian cancer may be through possession of anti-TIF1-Abs,” they noted.

The authors wrote that they had aimed to inform cancer screening strategies among patients with DM.

“It may be that a focus on screening for cancer within the first 3 years after DM onset and particularly screening for ovarian cancer in anti-TIF1-Ab-positive female patients may be required,” they wrote. “Our findings also strengthen the hypothesis that inflammatory myopathies represent a paraneoplastic reaction initiated by attempted immune-mediated clearance of a cancer.”

The study was supported by Arthritis Research UK, Myositis UK, the European Science Foundation for EuMyoNet, Association Francaise Contre Les Myopathies, the Medical Research Council, and the Manchester Academic Health Science Centre. No conflicts of interest were declared.

SOURCE: Oldroyd A et al. Rheumatology. 2018 Dec 7. doi: 10.1093/rheumatology/key357.

The increased risk of cancer associated with anti-TIF1-Ab-positive dermatomyositis is limited almost exclusively to 3 years on either side of the onset of dermatomyositis, new research suggests.

Idiopathic inflammatory myopathy have been associated with malignancy, in particular dermatomyositis (DM) and the DM-specific antitranscriptional intermediary factor 1 antibody (anti-TIF1-Ab).

Around one-fifth of the 236 patients diagnosed with DM in the current study, published online Dec. 7 in Rheumatology, were anti-TIF1-Ab positive, and these patients had a more than threefold higher risk of developing cancer comapared with patients who were anti-TIF1-Ab negative (hazard ratio = 3.4, 95% confidence interval, 2.2-5.4; P less than .01).

Overall, 38% of patients in the anti-TIF1-Ab-positive group developed cancer during the 10-year follow-up, compared with 15% of patients with anti-TIF1-Ab-negative DM.

However, all the cancers in the anti-TIF1-Ab-positive group occurred within the 3 years before the onset of DM or within 2.5 years after onset. No anti-TIF1-Ab-positive patients developed cancers after this time, but some patients in the anti-TIF1-Ab-negative group did.

“This finding is not likely to be due to a disparity in follow-up time between anti-TIF1-Ab-positive and -negative cases, as the median follow-up times were similar for both groups: 10 years and 12 years, respectively,” wrote Alexander Oldroyd, MBChB, a clinical research fellow in the Centre for Musculoskeletal Research at the University of Manchester (England), and his coauthors. “Further, this finding is unlikely to be due to differences in cancer detection methods, as both cohorts’ cancer diagnoses were identified through HSCIC [U.K. Health and Social Care Information Centre] data, ensuring capture of all incident cancers during the follow-up period.”

Anti-TIF1-Ab-positive patients were more likely to develop cancer if they were older. None of the 15 anti-TIF1-Ab-positive patients who were aged under 39 when they developed DM went on to develop cancer. But cancer developed in around half of the anti-TIF1-Ab-positive patients who were aged 39 years or older when their DM began.


The anti-TIF1 antibody is commonly found in juvenile DM, but previous research has not found an association with an increased risk of cancer in this younger patient population.

“Our findings add strength to the hypothesis that there exists a subset of young adult anti-TIF1-Ab-positive cases who do not have a discernible increased risk of cancer, similar to that observed in TIF1-Ab-positive juvenile DM,” the authors wrote. They suggested that given the increased risk of malignancy in older patients who were anti-TIF1-Ab positive, this group should be subject to more detailed cancer screening.

Breast cancer was the most common malignancy among both anti-TIF1-Ab-positive and anti-TIF1-Ab-negative patients (33% and 25%, respectively). However, ovarian cancer was significantly more common among the anti-TIF1-Ab-positive patients than among the anti-TIF1-Ab-negative patients (19% vs. 2%; P less than .05); four of the five ovarian cancers in the entire cohort occurred in the anti-TIF1-Ab-positive group.

The authors noted that this confirmed the finding of a number of previous studies suggesting an increased risk of ovarian cancer with DM.

“However, this is the first large study to identify that ovarian cancer is overrepresented in anti-TIF1-Ab-positive individuals, suggesting that the true association between DM and ovarian cancer may be through possession of anti-TIF1-Abs,” they noted.

The authors wrote that they had aimed to inform cancer screening strategies among patients with DM.

“It may be that a focus on screening for cancer within the first 3 years after DM onset and particularly screening for ovarian cancer in anti-TIF1-Ab-positive female patients may be required,” they wrote. “Our findings also strengthen the hypothesis that inflammatory myopathies represent a paraneoplastic reaction initiated by attempted immune-mediated clearance of a cancer.”

The study was supported by Arthritis Research UK, Myositis UK, the European Science Foundation for EuMyoNet, Association Francaise Contre Les Myopathies, the Medical Research Council, and the Manchester Academic Health Science Centre. No conflicts of interest were declared.

SOURCE: Oldroyd A et al. Rheumatology. 2018 Dec 7. doi: 10.1093/rheumatology/key357.

The increased risk of cancer associated with anti-TIF1-Ab-positive dermatomyositis is limited almost exclusively to 3 years on either side of the onset of dermatomyositis, new research suggests.

Idiopathic inflammatory myopathy have been associated with malignancy, in particular dermatomyositis (DM) and the DM-specific antitranscriptional intermediary factor 1 antibody (anti-TIF1-Ab).

Around one-fifth of the 236 patients diagnosed with DM in the current study, published online Dec. 7 in Rheumatology, were anti-TIF1-Ab positive, and these patients had a more than threefold higher risk of developing cancer comapared with patients who were anti-TIF1-Ab negative (hazard ratio = 3.4, 95% confidence interval, 2.2-5.4; P less than .01).

Overall, 38% of patients in the anti-TIF1-Ab-positive group developed cancer during the 10-year follow-up, compared with 15% of patients with anti-TIF1-Ab-negative DM.

However, all the cancers in the anti-TIF1-Ab-positive group occurred within the 3 years before the onset of DM or within 2.5 years after onset. No anti-TIF1-Ab-positive patients developed cancers after this time, but some patients in the anti-TIF1-Ab-negative group did.

“This finding is not likely to be due to a disparity in follow-up time between anti-TIF1-Ab-positive and -negative cases, as the median follow-up times were similar for both groups: 10 years and 12 years, respectively,” wrote Alexander Oldroyd, MBChB, a clinical research fellow in the Centre for Musculoskeletal Research at the University of Manchester (England), and his coauthors. “Further, this finding is unlikely to be due to differences in cancer detection methods, as both cohorts’ cancer diagnoses were identified through HSCIC [U.K. Health and Social Care Information Centre] data, ensuring capture of all incident cancers during the follow-up period.”

Anti-TIF1-Ab-positive patients were more likely to develop cancer if they were older. None of the 15 anti-TIF1-Ab-positive patients who were aged under 39 when they developed DM went on to develop cancer. But cancer developed in around half of the anti-TIF1-Ab-positive patients who were aged 39 years or older when their DM began.


The anti-TIF1 antibody is commonly found in juvenile DM, but previous research has not found an association with an increased risk of cancer in this younger patient population.

“Our findings add strength to the hypothesis that there exists a subset of young adult anti-TIF1-Ab-positive cases who do not have a discernible increased risk of cancer, similar to that observed in TIF1-Ab-positive juvenile DM,” the authors wrote. They suggested that given the increased risk of malignancy in older patients who were anti-TIF1-Ab positive, this group should be subject to more detailed cancer screening.

Breast cancer was the most common malignancy among both anti-TIF1-Ab-positive and anti-TIF1-Ab-negative patients (33% and 25%, respectively). However, ovarian cancer was significantly more common among the anti-TIF1-Ab-positive patients than among the anti-TIF1-Ab-negative patients (19% vs. 2%; P less than .05); four of the five ovarian cancers in the entire cohort occurred in the anti-TIF1-Ab-positive group.

The authors noted that this confirmed the finding of a number of previous studies suggesting an increased risk of ovarian cancer with DM.

“However, this is the first large study to identify that ovarian cancer is overrepresented in anti-TIF1-Ab-positive individuals, suggesting that the true association between DM and ovarian cancer may be through possession of anti-TIF1-Abs,” they noted.

The authors wrote that they had aimed to inform cancer screening strategies among patients with DM.

“It may be that a focus on screening for cancer within the first 3 years after DM onset and particularly screening for ovarian cancer in anti-TIF1-Ab-positive female patients may be required,” they wrote. “Our findings also strengthen the hypothesis that inflammatory myopathies represent a paraneoplastic reaction initiated by attempted immune-mediated clearance of a cancer.”

The study was supported by Arthritis Research UK, Myositis UK, the European Science Foundation for EuMyoNet, Association Francaise Contre Les Myopathies, the Medical Research Council, and the Manchester Academic Health Science Centre. No conflicts of interest were declared.

SOURCE: Oldroyd A et al. Rheumatology. 2018 Dec 7. doi: 10.1093/rheumatology/key357.

CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

[email protected]

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.

CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

[email protected]

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.

CHICAGO – Early treatment with combined high-dose glucocorticoids, tacrolimus, and intravenous cyclophosphamide therapy significantly improves survival vs. step-up therapy in interstitial lung disease patients with anti–melanoma differentiation–associated gene 5 (anti-MDA5)–positive dermatomyositis, according to findings from a prospective, multicenter study.

However, the combination therapy was associated with a high risk of cytomegalovirus reactivation and other opportunistic infections that warrants careful monitoring of treated patients, Hideaki Tsuji, MD, reported at the annual meeting of the American College of Rheumatology.

ILD accompanied by anti-MDA5–positive dermatomyositis (DM) is often intractable and associated with high mortality in Japanese patients. Case reports have suggested improved outcomes with combined immunosuppressive therapy, but a standard treatment has not been established, said Dr. Tsuji of Kyoto University.

“Therefore, we evaluated the efficacy and safety of combined immunosuppressive therapy for anti-MDA5–positive DM with ILD in a prospective single-arm study,” he said, adding that early administration, a short interval of intravenous cyclophosphamide, use of plasmapheresis as an additional therapy, and control of opportunistic infections may contribute to the improved outcomes seen with the regimen in this study.

The primary endpoint of 6-month survival was reached by 24 (89%) of 27 patients treated with the combination regimen for 52 weeks, compared with 5 (33%) of 15 historical controls who received high-dose glucocorticoids followed by step-wise addition of immunosuppressants. At 12 months, the survival rates were 85% and 33%, respectively, Dr. Tsuji said.

Additionally, anti-MDA5 titer, serum ferritin level, C-reactive protein level, lactate dehydrogenase, and KL-6 level gradually decreased over the 52 months, and percent vital capacity increased with combination vs. step-up therapy, he noted.

Cytomegalovirus reactivation occurred in 90% of combination regimen patients vs. 33% of controls over the 52-week study period, he said, adding that pneumocystic pneumonia and sepsis also occurred in combination regimen group patients, and were associated with death in four patients.

When the 23 surviving patients in the combination regimen group were compared with the 4 in the group who died, it was noted that the deceased patients were significantly more likely to have cutaneous ulcers (75% vs. 13%), higher mean C-reactive protein level (2.7 vs. 0.77 mg/dL), and higher creatine kinase level (644.3 vs. 219.3 IU/L), respectively, before treatment, he said.

Study subjects were Japanese adults with new-onset anti-MDA5–positive dermatomyositis with interstitial lung disease (ILD) who were enrolled between July 2014 and September 2017.

They were treated with 1 mg/kg/day of prednisolone for 4 weeks with reduced doses thereafter, 500-1,000 mg/m² of IV cyclophosphamide every 2 weeks for six cycles then every 4 weeks for up to a total of 10-15 treatments, and 10-12 ng/mL of tacrolimus (12-hour trough). Plasmapheresis was allowed in patients who progressed and needed oxygenation after the regimen was initiated, and it was administered in nine patients (31%) in the combination regimen group vs. one (7%) of the historical controls.

Given the different frequencies of rapidly progressive ILD in Asian vs. Western countries (39%-71% vs. 22%-57%, respectively), it is unclear whether the results seen in this study can be extrapolated to patients from the United States and Europe. Therefore, it is necessary to analyze the efficacy of the regimen in those patient populations, Dr. Tsuji said, also noting that future studies should evaluate risk-based modifications of the regimen to identify the optimal treatment for individuals based on factors such as age, respiratory dysfunction, hyperferritinemia, and treatment delay.

Dr. Tsuji reported having no disclosures.

[email protected]

SOURCE: Tsuji H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 838.