ACR Annual Meeting 2018

CHICAGO – Etanercept monotherapy showed greater efficacy, compared with methotrexate monotherapy for the treatment of psoriatic arthritis, and combining the two agents provided no benefit over etanercept alone for most outcomes in the randomized, controlled, international, phase 3 SEAM-PsA study.

A 20% improvement in American College of Rheumatology criteria at week 24 – the primary endpoint of the study – was significantly greater in 284 patients treated with etanercept monotherapy and in 283 patients treated with combination etanercept and methotrexate than in 284 patients treated with methotrexate monotherapy (60.9% and 65.0% vs. 50.7%, respectively), Philip J. Mease, MD, of the Swedish Medical Center and the University of Washington, Seattle, and his colleagues reported in a late-breaking poster on the SEAM-PsA (Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) study at the annual meeting of the American College of Rheumatology.

The key secondary endpoint of minimal disease activity response at week 24 also was significantly greater in the etanercept monotherapy and combination groups than in the methotrexate monotherapy group (35.9% and 35.7% vs. 22.9%, respectively), the investigators noted.

Additionally, at week 48, the etanercept monotherapy group and combination group both showed less radiographic progression than did the methotrexate monotherapy arm (mean change in modified total Sharp score from baseline, –0.04 and –0.01 vs. 0.08).


Overall, the etanercept monotherapy group and combination therapy group had similar results, with some differences in skin outcomes. Treatment was well tolerated, and except for more nausea occurring with methotrexate, adverse event rates were similar in the three study arms. No new safety signals were observed.

“The most common serious adverse events were infections and infestations, which occurred in 1.1% of patients in the methotrexate monotherapy arm, 2.8% of patients in the etanercept monotherapy arm, and 2.5% of patients in the combination therapy arm,” they wrote.

Study participants were biologic-naive adults with active PsA and no prior methotrexate treatment for their disease. They had a mean age of 48.4 years, most were white, and median disease duration was 0.6 years.

They were randomized to receive either 50 mg subcutaneous injections of etanercept plus oral placebo weekly, 50 mg subcutaneous etanercept plus 20 mg oral methotrexate weekly, or 20 mg oral methotrexate plus placebo injections weekly; the groups were well balanced with respect to baseline characteristics, the investigators said.

Rescue therapy of etanercept plus methotrexate was given after 24 weeks in patients with less than 20% improvement in tender joint counts and swollen joint counts from baseline.

“Agents used to treat PsA include disease-modifying antirheumatic drugs such as methotrexate and tumor necrosis factor inhibitors, but how to optimally use these agents to treat PsA is unknown,” they wrote, explaining that while methotrexate is widely used in this setting, little clinical evidence exists to guide its use, and that while tumor necrosis factor inhibitors have shown efficacy in PsA, the benefit of adding methotrexate remains unclear.

The current findings, however, demonstrate that adding methotrexate does not appear to increase the efficacy of etanercept monotherapy for most outcomes.

An exception was with combination therapy for some skin-related outcomes, including percent improvement in psoriasis-affected body surface area and percentage of patients with “status clear or almost clear,” they said.

Further, methotrexate monotherapy in this study appeared to have some “meaningful efficacy for both articular and nonarticular PsA symptoms,” the investigators noted.

“These results provide information of practical value for clinical practice when considering treatment option for PsA,” they concluded.

The study was supported by Amgen. Dr. Mease reported receiving research grants, speaker fees, and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Genentech, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, and UCB.

[email protected]

SOURCE: Mease PJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L11.

CHICAGO – Etanercept monotherapy showed greater efficacy, compared with methotrexate monotherapy for the treatment of psoriatic arthritis, and combining the two agents provided no benefit over etanercept alone for most outcomes in the randomized, controlled, international, phase 3 SEAM-PsA study.

A 20% improvement in American College of Rheumatology criteria at week 24 – the primary endpoint of the study – was significantly greater in 284 patients treated with etanercept monotherapy and in 283 patients treated with combination etanercept and methotrexate than in 284 patients treated with methotrexate monotherapy (60.9% and 65.0% vs. 50.7%, respectively), Philip J. Mease, MD, of the Swedish Medical Center and the University of Washington, Seattle, and his colleagues reported in a late-breaking poster on the SEAM-PsA (Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) study at the annual meeting of the American College of Rheumatology.

The key secondary endpoint of minimal disease activity response at week 24 also was significantly greater in the etanercept monotherapy and combination groups than in the methotrexate monotherapy group (35.9% and 35.7% vs. 22.9%, respectively), the investigators noted.

Additionally, at week 48, the etanercept monotherapy group and combination group both showed less radiographic progression than did the methotrexate monotherapy arm (mean change in modified total Sharp score from baseline, –0.04 and –0.01 vs. 0.08).


Overall, the etanercept monotherapy group and combination therapy group had similar results, with some differences in skin outcomes. Treatment was well tolerated, and except for more nausea occurring with methotrexate, adverse event rates were similar in the three study arms. No new safety signals were observed.

“The most common serious adverse events were infections and infestations, which occurred in 1.1% of patients in the methotrexate monotherapy arm, 2.8% of patients in the etanercept monotherapy arm, and 2.5% of patients in the combination therapy arm,” they wrote.

Study participants were biologic-naive adults with active PsA and no prior methotrexate treatment for their disease. They had a mean age of 48.4 years, most were white, and median disease duration was 0.6 years.

They were randomized to receive either 50 mg subcutaneous injections of etanercept plus oral placebo weekly, 50 mg subcutaneous etanercept plus 20 mg oral methotrexate weekly, or 20 mg oral methotrexate plus placebo injections weekly; the groups were well balanced with respect to baseline characteristics, the investigators said.

Rescue therapy of etanercept plus methotrexate was given after 24 weeks in patients with less than 20% improvement in tender joint counts and swollen joint counts from baseline.

“Agents used to treat PsA include disease-modifying antirheumatic drugs such as methotrexate and tumor necrosis factor inhibitors, but how to optimally use these agents to treat PsA is unknown,” they wrote, explaining that while methotrexate is widely used in this setting, little clinical evidence exists to guide its use, and that while tumor necrosis factor inhibitors have shown efficacy in PsA, the benefit of adding methotrexate remains unclear.

The current findings, however, demonstrate that adding methotrexate does not appear to increase the efficacy of etanercept monotherapy for most outcomes.

An exception was with combination therapy for some skin-related outcomes, including percent improvement in psoriasis-affected body surface area and percentage of patients with “status clear or almost clear,” they said.

Further, methotrexate monotherapy in this study appeared to have some “meaningful efficacy for both articular and nonarticular PsA symptoms,” the investigators noted.

“These results provide information of practical value for clinical practice when considering treatment option for PsA,” they concluded.

The study was supported by Amgen. Dr. Mease reported receiving research grants, speaker fees, and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Genentech, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, and UCB.

[email protected]

SOURCE: Mease PJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L11.

CHICAGO – Etanercept monotherapy showed greater efficacy, compared with methotrexate monotherapy for the treatment of psoriatic arthritis, and combining the two agents provided no benefit over etanercept alone for most outcomes in the randomized, controlled, international, phase 3 SEAM-PsA study.

A 20% improvement in American College of Rheumatology criteria at week 24 – the primary endpoint of the study – was significantly greater in 284 patients treated with etanercept monotherapy and in 283 patients treated with combination etanercept and methotrexate than in 284 patients treated with methotrexate monotherapy (60.9% and 65.0% vs. 50.7%, respectively), Philip J. Mease, MD, of the Swedish Medical Center and the University of Washington, Seattle, and his colleagues reported in a late-breaking poster on the SEAM-PsA (Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) study at the annual meeting of the American College of Rheumatology.

The key secondary endpoint of minimal disease activity response at week 24 also was significantly greater in the etanercept monotherapy and combination groups than in the methotrexate monotherapy group (35.9% and 35.7% vs. 22.9%, respectively), the investigators noted.

Additionally, at week 48, the etanercept monotherapy group and combination group both showed less radiographic progression than did the methotrexate monotherapy arm (mean change in modified total Sharp score from baseline, –0.04 and –0.01 vs. 0.08).


Overall, the etanercept monotherapy group and combination therapy group had similar results, with some differences in skin outcomes. Treatment was well tolerated, and except for more nausea occurring with methotrexate, adverse event rates were similar in the three study arms. No new safety signals were observed.

“The most common serious adverse events were infections and infestations, which occurred in 1.1% of patients in the methotrexate monotherapy arm, 2.8% of patients in the etanercept monotherapy arm, and 2.5% of patients in the combination therapy arm,” they wrote.

Study participants were biologic-naive adults with active PsA and no prior methotrexate treatment for their disease. They had a mean age of 48.4 years, most were white, and median disease duration was 0.6 years.

They were randomized to receive either 50 mg subcutaneous injections of etanercept plus oral placebo weekly, 50 mg subcutaneous etanercept plus 20 mg oral methotrexate weekly, or 20 mg oral methotrexate plus placebo injections weekly; the groups were well balanced with respect to baseline characteristics, the investigators said.

Rescue therapy of etanercept plus methotrexate was given after 24 weeks in patients with less than 20% improvement in tender joint counts and swollen joint counts from baseline.

“Agents used to treat PsA include disease-modifying antirheumatic drugs such as methotrexate and tumor necrosis factor inhibitors, but how to optimally use these agents to treat PsA is unknown,” they wrote, explaining that while methotrexate is widely used in this setting, little clinical evidence exists to guide its use, and that while tumor necrosis factor inhibitors have shown efficacy in PsA, the benefit of adding methotrexate remains unclear.

The current findings, however, demonstrate that adding methotrexate does not appear to increase the efficacy of etanercept monotherapy for most outcomes.

An exception was with combination therapy for some skin-related outcomes, including percent improvement in psoriasis-affected body surface area and percentage of patients with “status clear or almost clear,” they said.

Further, methotrexate monotherapy in this study appeared to have some “meaningful efficacy for both articular and nonarticular PsA symptoms,” the investigators noted.

“These results provide information of practical value for clinical practice when considering treatment option for PsA,” they concluded.

The study was supported by Amgen. Dr. Mease reported receiving research grants, speaker fees, and/or consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Galapagos, Genentech, Janssen Pharmaceuticals, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, and UCB.

[email protected]

SOURCE: Mease PJ et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L11.

CHICAGO – Women who self-reported a high level of physical and emotional abuse as children had a nearly three-fold increased incidence of systemic lupus erythematosus during adulthood, in a study of more than 67,000 American nurses.

The results also suggested that development of depression and post-traumatic stress disorder (PTSD) may have been intermediary steps between episodes of childhood abuse and later development of systemic lupus erythematosus (SLE), Candace H. Feldman, MD, said at the annual meeting of the American College of Rheumatology.

These findings suggest the “importance of screening for childhood abuse exposures as well as for depression and PTSD in routine practice,” although Dr. Feldman acknowledged that interventions aimed at treating depression and PTSD have as of now no proven role for mitigating SLE.

The analysis Dr. Feldman and her associates ran on data collected in the Nurses Health Study II also documented a “striking” number of the enrolled women who completed the survey in 2001 and reported a history of abuse when they were 11 years old or younger: 30% of the 67,516 respondents reported a moderate level of abuse, and 24% reported a high level of abuse. An additional 22% reported either no or a very low level of abuse. These numbers suggest that abuse of girls “is very common and probably underreported,” she said in a video interview.

The Nurses Health Study II enrolled more than 116,429 U.S. women in 1989 who were 25-42 years old and had no history of SLE. Recording of incident SLE cases began in 1991 and for this analysis continued for 24 years, through 2015, during which time 94 women developed SLE that was confirmed in a review by two rheumatologists applying the 1997 SLE classification criteria (Arthritis Rheum. 1997 Sept;40[9]:1725. The incidence of SLE was 2.57-fold more common among women who reported a high level of abuse, compared with those who had no or very low abuse, after adjustment for several demographic and clinical confounders, reported Dr. Feldman, a rheumatologist at Brigham and Women’s Hospital in Boston.

“To our knowledge this is the first study to prospectively look at exposure to different forms of childhood abuse and SLE incidence in a general population of women,” she said.

To make the analysis more prospective the researchers also ran a calculation that considered only SLE cases that appeared after completion of the 2001 abuse survey. Using this criterion the incidence was 3.11-fold higher among women who reported a high level of childhood abuse. Further analyses showed that statistically a diagnosis of PTSD accounted for about 23% of the risk for developing SLE, and depression appeared responsible for about 17% of the risk. The analysis also showed no statistically significant link between sexual abuse in childhood or as a teenager and later onset of SLE.

The findings are consistent with prior reports that linked stress to development of various autoimmune diseases, Dr. Feldman noted. She speculated that high childhood stress could cause changes in inflammation, immune function, epigenetics, the autonomic nervous system, and endocrine pathways that could play a role in triggering depression or PTSD, and eventually SLE.
 

[email protected]

On Twitter @mitchelzoler

SOURCE:Feldman C et al. Arthritis Rheumatol. 2018;70(suppl 10) Abstract 2807.

CHICAGO – Women who self-reported a high level of physical and emotional abuse as children had a nearly three-fold increased incidence of systemic lupus erythematosus during adulthood, in a study of more than 67,000 American nurses.

The results also suggested that development of depression and post-traumatic stress disorder (PTSD) may have been intermediary steps between episodes of childhood abuse and later development of systemic lupus erythematosus (SLE), Candace H. Feldman, MD, said at the annual meeting of the American College of Rheumatology.

These findings suggest the “importance of screening for childhood abuse exposures as well as for depression and PTSD in routine practice,” although Dr. Feldman acknowledged that interventions aimed at treating depression and PTSD have as of now no proven role for mitigating SLE.

The analysis Dr. Feldman and her associates ran on data collected in the Nurses Health Study II also documented a “striking” number of the enrolled women who completed the survey in 2001 and reported a history of abuse when they were 11 years old or younger: 30% of the 67,516 respondents reported a moderate level of abuse, and 24% reported a high level of abuse. An additional 22% reported either no or a very low level of abuse. These numbers suggest that abuse of girls “is very common and probably underreported,” she said in a video interview.

The Nurses Health Study II enrolled more than 116,429 U.S. women in 1989 who were 25-42 years old and had no history of SLE. Recording of incident SLE cases began in 1991 and for this analysis continued for 24 years, through 2015, during which time 94 women developed SLE that was confirmed in a review by two rheumatologists applying the 1997 SLE classification criteria (Arthritis Rheum. 1997 Sept;40[9]:1725. The incidence of SLE was 2.57-fold more common among women who reported a high level of abuse, compared with those who had no or very low abuse, after adjustment for several demographic and clinical confounders, reported Dr. Feldman, a rheumatologist at Brigham and Women’s Hospital in Boston.

“To our knowledge this is the first study to prospectively look at exposure to different forms of childhood abuse and SLE incidence in a general population of women,” she said.

To make the analysis more prospective the researchers also ran a calculation that considered only SLE cases that appeared after completion of the 2001 abuse survey. Using this criterion the incidence was 3.11-fold higher among women who reported a high level of childhood abuse. Further analyses showed that statistically a diagnosis of PTSD accounted for about 23% of the risk for developing SLE, and depression appeared responsible for about 17% of the risk. The analysis also showed no statistically significant link between sexual abuse in childhood or as a teenager and later onset of SLE.

The findings are consistent with prior reports that linked stress to development of various autoimmune diseases, Dr. Feldman noted. She speculated that high childhood stress could cause changes in inflammation, immune function, epigenetics, the autonomic nervous system, and endocrine pathways that could play a role in triggering depression or PTSD, and eventually SLE.
 

[email protected]

On Twitter @mitchelzoler

SOURCE:Feldman C et al. Arthritis Rheumatol. 2018;70(suppl 10) Abstract 2807.

CHICAGO – Women who self-reported a high level of physical and emotional abuse as children had a nearly three-fold increased incidence of systemic lupus erythematosus during adulthood, in a study of more than 67,000 American nurses.

The results also suggested that development of depression and post-traumatic stress disorder (PTSD) may have been intermediary steps between episodes of childhood abuse and later development of systemic lupus erythematosus (SLE), Candace H. Feldman, MD, said at the annual meeting of the American College of Rheumatology.

These findings suggest the “importance of screening for childhood abuse exposures as well as for depression and PTSD in routine practice,” although Dr. Feldman acknowledged that interventions aimed at treating depression and PTSD have as of now no proven role for mitigating SLE.

The analysis Dr. Feldman and her associates ran on data collected in the Nurses Health Study II also documented a “striking” number of the enrolled women who completed the survey in 2001 and reported a history of abuse when they were 11 years old or younger: 30% of the 67,516 respondents reported a moderate level of abuse, and 24% reported a high level of abuse. An additional 22% reported either no or a very low level of abuse. These numbers suggest that abuse of girls “is very common and probably underreported,” she said in a video interview.

The Nurses Health Study II enrolled more than 116,429 U.S. women in 1989 who were 25-42 years old and had no history of SLE. Recording of incident SLE cases began in 1991 and for this analysis continued for 24 years, through 2015, during which time 94 women developed SLE that was confirmed in a review by two rheumatologists applying the 1997 SLE classification criteria (Arthritis Rheum. 1997 Sept;40[9]:1725. The incidence of SLE was 2.57-fold more common among women who reported a high level of abuse, compared with those who had no or very low abuse, after adjustment for several demographic and clinical confounders, reported Dr. Feldman, a rheumatologist at Brigham and Women’s Hospital in Boston.

“To our knowledge this is the first study to prospectively look at exposure to different forms of childhood abuse and SLE incidence in a general population of women,” she said.

To make the analysis more prospective the researchers also ran a calculation that considered only SLE cases that appeared after completion of the 2001 abuse survey. Using this criterion the incidence was 3.11-fold higher among women who reported a high level of childhood abuse. Further analyses showed that statistically a diagnosis of PTSD accounted for about 23% of the risk for developing SLE, and depression appeared responsible for about 17% of the risk. The analysis also showed no statistically significant link between sexual abuse in childhood or as a teenager and later onset of SLE.

The findings are consistent with prior reports that linked stress to development of various autoimmune diseases, Dr. Feldman noted. She speculated that high childhood stress could cause changes in inflammation, immune function, epigenetics, the autonomic nervous system, and endocrine pathways that could play a role in triggering depression or PTSD, and eventually SLE.
 

[email protected]

On Twitter @mitchelzoler

SOURCE:Feldman C et al. Arthritis Rheumatol. 2018;70(suppl 10) Abstract 2807.

CHICAGO – Vascular ultrasound showed high sensitivity and specificity for diagnosing large-vessel giant-cell arteritis (LV-GCA) in a prospective study of patients with suspected new-onset disease.

Sharon Worcester/MDedge News

The findings highlight the value of vascular ultrasound – in the hands of experienced sonographers – as a first-line imaging test in this setting, Berit Dalsgaard Nielsen, MD, reported at the annual meeting of the American College of Rheumatology.

Of 41 control subjects without LV-GCA, none had a positive ultrasound, whereas 36 of 45 LV-GCA patients had a positive ultrasound, which gives the test a specificity of 100% and sensitivity of 80%, Dr. Nielsen of Aarhus (Denmark) University Hospital said during a press briefing at the meeting.

Ultrasound was performed on the carotid artery in the neck and axillary arteries under the arm, which are easily accessible by ultrasound.

“These patients also had temporal arteries evaluated, and if we included this evaluation in the diagnostic performance, it showed a sensitivity of 91%,” she noted, explaining that temporal artery ultrasound alone conferred 71% sensitivity. “So it actually helped us identify more GCA patients.”

The study subjects were adults with suspected GCA. Inclusion criteria included age of at least 50 years, C-reactive protein of more than 15 mg/L or erythrocyte sedimentation rate of more than 40 mm, and either cranial symptoms, new-onset limb claudication, protracted constitutional symptoms, or polymyalgia rheumatica (PMR) symptoms. Patients were excluded if they had recent or ongoing glucocorticoid or disease-modifying antirheumatic drug treatment, a previous GCA or PMR diagnosis, or a large vessel inflammation that mimicked LV-GCA.

Clinical evaluations and imaging tests were performed prior to treatment initiation. The reference diagnosis was a clinical diagnosis of GCA and a positive 18F-FDG PET/CT scan, Dr Nielsen said, adding that ultrasound examinations were performed by experienced sonographers who were blinded to the PET/CT results.

Of the 86 patients included, 45 had LV-GCA with or without concomitant cranial GCA, 10 had isolated cranial GCA, 21 had PMR, and 10 were diagnosed with other diseases. The patients found to not have LV-GCA were considered control subjects.

The findings are notable because, while PET is considered the gold standard, it is very expensive and not always readily available, Dr. Nielsen said.

Additionally, while cranial-GCA patients generally present with symptoms such as headache, jaw claudication, and visual disturbances that are considered typical for GCA, LV-GCA patients rarely present with these symptoms.

Rather, these LV-GCA patients tend to present with constitutional symptoms mimicking infection or cancer, and they undergo extensive examination programs before the diagnosis is established. For this reason, diagnosis is often delayed for several months in LV-GCA patients until late in the disease course.

“During this time they often experience a decline in physical ability,” she said. “So in this disease subset of patients with GCA, there’s an unmet need for earlier recognition and earlier diagnosis.”

New recommendations from the European League Against Rheumatism call for early diagnostic imaging in all cases of suspected GCA, she added, noting that, for cranial-GCA symptoms, temporal artery ultrasound is recommended first line, but for those who present without cranial symptoms, no particular imaging modality is recommended because of a lack of comparative and diagnostic accuracy data in LV-GCA.

Biopsy has traditionally been used in these cases, but now imaging can be substituted – and vascular ultrasound is an attractive first-line option given its affordability and availability.

Indeed, the current findings support its use in this setting, she said.

“We think that these results indicate that ultrasound should not only be the first-line imaging test in patients presenting with cranial symptoms, but also in patients suspected of GCA presenting with constitutional symptoms, and if this examination is included in the standard examinations in fast-track clinics, it may overcome the delay in diagnosis and the patients can be treated earlier. It may also spare the unneeded examinations performed in these patients,” she concluded.

Dr. Nielsen disclosed a relationship with Roche.

[email protected]

SOURCE: Nielsen B et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2905.

CHICAGO – Vascular ultrasound showed high sensitivity and specificity for diagnosing large-vessel giant-cell arteritis (LV-GCA) in a prospective study of patients with suspected new-onset disease.

Sharon Worcester/MDedge News

The findings highlight the value of vascular ultrasound – in the hands of experienced sonographers – as a first-line imaging test in this setting, Berit Dalsgaard Nielsen, MD, reported at the annual meeting of the American College of Rheumatology.

Of 41 control subjects without LV-GCA, none had a positive ultrasound, whereas 36 of 45 LV-GCA patients had a positive ultrasound, which gives the test a specificity of 100% and sensitivity of 80%, Dr. Nielsen of Aarhus (Denmark) University Hospital said during a press briefing at the meeting.

Ultrasound was performed on the carotid artery in the neck and axillary arteries under the arm, which are easily accessible by ultrasound.

“These patients also had temporal arteries evaluated, and if we included this evaluation in the diagnostic performance, it showed a sensitivity of 91%,” she noted, explaining that temporal artery ultrasound alone conferred 71% sensitivity. “So it actually helped us identify more GCA patients.”

The study subjects were adults with suspected GCA. Inclusion criteria included age of at least 50 years, C-reactive protein of more than 15 mg/L or erythrocyte sedimentation rate of more than 40 mm, and either cranial symptoms, new-onset limb claudication, protracted constitutional symptoms, or polymyalgia rheumatica (PMR) symptoms. Patients were excluded if they had recent or ongoing glucocorticoid or disease-modifying antirheumatic drug treatment, a previous GCA or PMR diagnosis, or a large vessel inflammation that mimicked LV-GCA.

Clinical evaluations and imaging tests were performed prior to treatment initiation. The reference diagnosis was a clinical diagnosis of GCA and a positive 18F-FDG PET/CT scan, Dr Nielsen said, adding that ultrasound examinations were performed by experienced sonographers who were blinded to the PET/CT results.

Of the 86 patients included, 45 had LV-GCA with or without concomitant cranial GCA, 10 had isolated cranial GCA, 21 had PMR, and 10 were diagnosed with other diseases. The patients found to not have LV-GCA were considered control subjects.

The findings are notable because, while PET is considered the gold standard, it is very expensive and not always readily available, Dr. Nielsen said.

Additionally, while cranial-GCA patients generally present with symptoms such as headache, jaw claudication, and visual disturbances that are considered typical for GCA, LV-GCA patients rarely present with these symptoms.

Rather, these LV-GCA patients tend to present with constitutional symptoms mimicking infection or cancer, and they undergo extensive examination programs before the diagnosis is established. For this reason, diagnosis is often delayed for several months in LV-GCA patients until late in the disease course.

“During this time they often experience a decline in physical ability,” she said. “So in this disease subset of patients with GCA, there’s an unmet need for earlier recognition and earlier diagnosis.”

New recommendations from the European League Against Rheumatism call for early diagnostic imaging in all cases of suspected GCA, she added, noting that, for cranial-GCA symptoms, temporal artery ultrasound is recommended first line, but for those who present without cranial symptoms, no particular imaging modality is recommended because of a lack of comparative and diagnostic accuracy data in LV-GCA.

Biopsy has traditionally been used in these cases, but now imaging can be substituted – and vascular ultrasound is an attractive first-line option given its affordability and availability.

Indeed, the current findings support its use in this setting, she said.

“We think that these results indicate that ultrasound should not only be the first-line imaging test in patients presenting with cranial symptoms, but also in patients suspected of GCA presenting with constitutional symptoms, and if this examination is included in the standard examinations in fast-track clinics, it may overcome the delay in diagnosis and the patients can be treated earlier. It may also spare the unneeded examinations performed in these patients,” she concluded.

Dr. Nielsen disclosed a relationship with Roche.

[email protected]

SOURCE: Nielsen B et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2905.

CHICAGO – Vascular ultrasound showed high sensitivity and specificity for diagnosing large-vessel giant-cell arteritis (LV-GCA) in a prospective study of patients with suspected new-onset disease.

Sharon Worcester/MDedge News

The findings highlight the value of vascular ultrasound – in the hands of experienced sonographers – as a first-line imaging test in this setting, Berit Dalsgaard Nielsen, MD, reported at the annual meeting of the American College of Rheumatology.

Of 41 control subjects without LV-GCA, none had a positive ultrasound, whereas 36 of 45 LV-GCA patients had a positive ultrasound, which gives the test a specificity of 100% and sensitivity of 80%, Dr. Nielsen of Aarhus (Denmark) University Hospital said during a press briefing at the meeting.

Ultrasound was performed on the carotid artery in the neck and axillary arteries under the arm, which are easily accessible by ultrasound.

“These patients also had temporal arteries evaluated, and if we included this evaluation in the diagnostic performance, it showed a sensitivity of 91%,” she noted, explaining that temporal artery ultrasound alone conferred 71% sensitivity. “So it actually helped us identify more GCA patients.”

The study subjects were adults with suspected GCA. Inclusion criteria included age of at least 50 years, C-reactive protein of more than 15 mg/L or erythrocyte sedimentation rate of more than 40 mm, and either cranial symptoms, new-onset limb claudication, protracted constitutional symptoms, or polymyalgia rheumatica (PMR) symptoms. Patients were excluded if they had recent or ongoing glucocorticoid or disease-modifying antirheumatic drug treatment, a previous GCA or PMR diagnosis, or a large vessel inflammation that mimicked LV-GCA.

Clinical evaluations and imaging tests were performed prior to treatment initiation. The reference diagnosis was a clinical diagnosis of GCA and a positive 18F-FDG PET/CT scan, Dr Nielsen said, adding that ultrasound examinations were performed by experienced sonographers who were blinded to the PET/CT results.

Of the 86 patients included, 45 had LV-GCA with or without concomitant cranial GCA, 10 had isolated cranial GCA, 21 had PMR, and 10 were diagnosed with other diseases. The patients found to not have LV-GCA were considered control subjects.

The findings are notable because, while PET is considered the gold standard, it is very expensive and not always readily available, Dr. Nielsen said.

Additionally, while cranial-GCA patients generally present with symptoms such as headache, jaw claudication, and visual disturbances that are considered typical for GCA, LV-GCA patients rarely present with these symptoms.

Rather, these LV-GCA patients tend to present with constitutional symptoms mimicking infection or cancer, and they undergo extensive examination programs before the diagnosis is established. For this reason, diagnosis is often delayed for several months in LV-GCA patients until late in the disease course.

“During this time they often experience a decline in physical ability,” she said. “So in this disease subset of patients with GCA, there’s an unmet need for earlier recognition and earlier diagnosis.”

New recommendations from the European League Against Rheumatism call for early diagnostic imaging in all cases of suspected GCA, she added, noting that, for cranial-GCA symptoms, temporal artery ultrasound is recommended first line, but for those who present without cranial symptoms, no particular imaging modality is recommended because of a lack of comparative and diagnostic accuracy data in LV-GCA.

Biopsy has traditionally been used in these cases, but now imaging can be substituted – and vascular ultrasound is an attractive first-line option given its affordability and availability.

Indeed, the current findings support its use in this setting, she said.

“We think that these results indicate that ultrasound should not only be the first-line imaging test in patients presenting with cranial symptoms, but also in patients suspected of GCA presenting with constitutional symptoms, and if this examination is included in the standard examinations in fast-track clinics, it may overcome the delay in diagnosis and the patients can be treated earlier. It may also spare the unneeded examinations performed in these patients,” she concluded.

Dr. Nielsen disclosed a relationship with Roche.

[email protected]

SOURCE: Nielsen B et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 2905.

CHICAGO – Combination therapy with leflunomide and hydroxychloroquine met all goals for efficacy, safety, and tolerability among patients with primary Sjögren’s syndrome in a randomized, placebo-controlled pilot study, lending support to evidence suggesting the two drugs have additive benefits.

Sharon Worcester/MDedge News

The combined treatment was associated with a statistically significant decrease in the EULAR Sjögren’s syndrome disease activity index (ESSDAI) over 24 weeks – the primary endpoint of the study – in 21 patients in the treatment group. The ESSDAI score on combination treatment dropped from about 10 at baseline to about 6 at 24 weeks, compared with no change from a baseline of about 10 in eight patients in the placebo group. An ESSDAI decrease of 3 or more points occurred in 11 patients in the combination therapy group, compared with none in the placebo group, Joel A.G. van Roon, PhD, a researcher in the Laboratory of Translational Immunology at the University Medical Center Utrecht, the Netherlands, reported in a late-breaking poster at the annual meeting of the American College of Rheumatology.

Both leflunomide and hydroxychloroquine have been shown to inhibit B-cell hyperactivity, but the clinical benefits have been modest and not statistically significant. Since the two agents have complementary inhibitory properties on different immune cells – including B and T cells and plasmacytoid dendritic cells, and based on in vitro findings of additive benefits with respect to inhibition of T- and B-cell activation and CXCL13 production, Dr. van Roon and his colleagues conducted this double-blind, single-center, proof-of-concept pilot study (REPURpSS-1) to assess the efficacy, safety, and tolerability of combined treatment in primary Sjögren’s syndrome.

In all, 29 patients with clinically active disease, defined by ESSDAI of 5 or greater, were randomized 2:1 to receive either 20 mg of leflunomide daily plus 400 mg of hydroxychloroquine daily or placebo/placebo for 24 weeks.

Secondary endpoints such as oral dryness also improved significantly in the treatment group versus the placebo group. Stimulated whole saliva flow increased from about 800 mcL/5 min to about 1,400 mcL/5 min and decreased from about 1,250 to about 1,000 mcL/5 min in the groups, respectively. Median EULAR Sjögren’s syndrome patient reported index (ESSPRI), ESSPRI pain, and ESSPRI fatigue scores, as well as Physician’s and Patient’s Global Assessment scores each improved significantly in the treatment group (at least P less than .05 in all cases) but not in the placebo groups, said Dr. van Roon.

Additionally, serum IgG, IgM rheumatoid factor, and chemokine CXCL13 – a marker for lymphoid neogenesis – decreased significantly, and complement components 3 and 4 (C3 and C4) increased significantly by 24 weeks in the treatment group, but not in the placebo group. B-cell hyperactivity as measured by serum IgG decreased from about 20 g/L to about 14 g/L versus no change from about 15 g/L at baseline in the placebo group, he noted.

“Overall, combination leflunomide and hydroxychloroquine was safe and well tolerated, but larger randomized, controlled trials are needed to confirm the observed effects and to identify potential biomarkers for response,” he concluded.

This study was supported by ZonMw (the Netherlands Organization for Health Research and Development). Dr. van Roon reported having no relevant disclosures.

[email protected]

SOURCE: van Roon JAG et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L10.

CHICAGO – Combination therapy with leflunomide and hydroxychloroquine met all goals for efficacy, safety, and tolerability among patients with primary Sjögren’s syndrome in a randomized, placebo-controlled pilot study, lending support to evidence suggesting the two drugs have additive benefits.

Sharon Worcester/MDedge News

The combined treatment was associated with a statistically significant decrease in the EULAR Sjögren’s syndrome disease activity index (ESSDAI) over 24 weeks – the primary endpoint of the study – in 21 patients in the treatment group. The ESSDAI score on combination treatment dropped from about 10 at baseline to about 6 at 24 weeks, compared with no change from a baseline of about 10 in eight patients in the placebo group. An ESSDAI decrease of 3 or more points occurred in 11 patients in the combination therapy group, compared with none in the placebo group, Joel A.G. van Roon, PhD, a researcher in the Laboratory of Translational Immunology at the University Medical Center Utrecht, the Netherlands, reported in a late-breaking poster at the annual meeting of the American College of Rheumatology.

Both leflunomide and hydroxychloroquine have been shown to inhibit B-cell hyperactivity, but the clinical benefits have been modest and not statistically significant. Since the two agents have complementary inhibitory properties on different immune cells – including B and T cells and plasmacytoid dendritic cells, and based on in vitro findings of additive benefits with respect to inhibition of T- and B-cell activation and CXCL13 production, Dr. van Roon and his colleagues conducted this double-blind, single-center, proof-of-concept pilot study (REPURpSS-1) to assess the efficacy, safety, and tolerability of combined treatment in primary Sjögren’s syndrome.

In all, 29 patients with clinically active disease, defined by ESSDAI of 5 or greater, were randomized 2:1 to receive either 20 mg of leflunomide daily plus 400 mg of hydroxychloroquine daily or placebo/placebo for 24 weeks.

Secondary endpoints such as oral dryness also improved significantly in the treatment group versus the placebo group. Stimulated whole saliva flow increased from about 800 mcL/5 min to about 1,400 mcL/5 min and decreased from about 1,250 to about 1,000 mcL/5 min in the groups, respectively. Median EULAR Sjögren’s syndrome patient reported index (ESSPRI), ESSPRI pain, and ESSPRI fatigue scores, as well as Physician’s and Patient’s Global Assessment scores each improved significantly in the treatment group (at least P less than .05 in all cases) but not in the placebo groups, said Dr. van Roon.

Additionally, serum IgG, IgM rheumatoid factor, and chemokine CXCL13 – a marker for lymphoid neogenesis – decreased significantly, and complement components 3 and 4 (C3 and C4) increased significantly by 24 weeks in the treatment group, but not in the placebo group. B-cell hyperactivity as measured by serum IgG decreased from about 20 g/L to about 14 g/L versus no change from about 15 g/L at baseline in the placebo group, he noted.

“Overall, combination leflunomide and hydroxychloroquine was safe and well tolerated, but larger randomized, controlled trials are needed to confirm the observed effects and to identify potential biomarkers for response,” he concluded.

This study was supported by ZonMw (the Netherlands Organization for Health Research and Development). Dr. van Roon reported having no relevant disclosures.

[email protected]

SOURCE: van Roon JAG et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L10.

CHICAGO – Combination therapy with leflunomide and hydroxychloroquine met all goals for efficacy, safety, and tolerability among patients with primary Sjögren’s syndrome in a randomized, placebo-controlled pilot study, lending support to evidence suggesting the two drugs have additive benefits.

Sharon Worcester/MDedge News

The combined treatment was associated with a statistically significant decrease in the EULAR Sjögren’s syndrome disease activity index (ESSDAI) over 24 weeks – the primary endpoint of the study – in 21 patients in the treatment group. The ESSDAI score on combination treatment dropped from about 10 at baseline to about 6 at 24 weeks, compared with no change from a baseline of about 10 in eight patients in the placebo group. An ESSDAI decrease of 3 or more points occurred in 11 patients in the combination therapy group, compared with none in the placebo group, Joel A.G. van Roon, PhD, a researcher in the Laboratory of Translational Immunology at the University Medical Center Utrecht, the Netherlands, reported in a late-breaking poster at the annual meeting of the American College of Rheumatology.

Both leflunomide and hydroxychloroquine have been shown to inhibit B-cell hyperactivity, but the clinical benefits have been modest and not statistically significant. Since the two agents have complementary inhibitory properties on different immune cells – including B and T cells and plasmacytoid dendritic cells, and based on in vitro findings of additive benefits with respect to inhibition of T- and B-cell activation and CXCL13 production, Dr. van Roon and his colleagues conducted this double-blind, single-center, proof-of-concept pilot study (REPURpSS-1) to assess the efficacy, safety, and tolerability of combined treatment in primary Sjögren’s syndrome.

In all, 29 patients with clinically active disease, defined by ESSDAI of 5 or greater, were randomized 2:1 to receive either 20 mg of leflunomide daily plus 400 mg of hydroxychloroquine daily or placebo/placebo for 24 weeks.

Secondary endpoints such as oral dryness also improved significantly in the treatment group versus the placebo group. Stimulated whole saliva flow increased from about 800 mcL/5 min to about 1,400 mcL/5 min and decreased from about 1,250 to about 1,000 mcL/5 min in the groups, respectively. Median EULAR Sjögren’s syndrome patient reported index (ESSPRI), ESSPRI pain, and ESSPRI fatigue scores, as well as Physician’s and Patient’s Global Assessment scores each improved significantly in the treatment group (at least P less than .05 in all cases) but not in the placebo groups, said Dr. van Roon.

Additionally, serum IgG, IgM rheumatoid factor, and chemokine CXCL13 – a marker for lymphoid neogenesis – decreased significantly, and complement components 3 and 4 (C3 and C4) increased significantly by 24 weeks in the treatment group, but not in the placebo group. B-cell hyperactivity as measured by serum IgG decreased from about 20 g/L to about 14 g/L versus no change from about 15 g/L at baseline in the placebo group, he noted.

“Overall, combination leflunomide and hydroxychloroquine was safe and well tolerated, but larger randomized, controlled trials are needed to confirm the observed effects and to identify potential biomarkers for response,” he concluded.

This study was supported by ZonMw (the Netherlands Organization for Health Research and Development). Dr. van Roon reported having no relevant disclosures.

[email protected]

SOURCE: van Roon JAG et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract L10.

CHICAGO – Encouraging patients with knee osteoarthritis to engage in brisk walking for at least 5 minutes per day pays big dividends in terms of reduced risk of total knee replacement, according to a new analysis of data from the National Institutes of Health-sponsored Osteoarthritis Initiative.
 

Vidyard Video

Whether walking increases or decreases the risk of structural deterioration and total knee replacement (TKR) in patients with knee osteoarthritis has been a controversial topic marked by conflicting data. That’s probably because prior studies haven’t taken into account walking intensity, Hiral Master said at the annual meeting of the American College of Rheumatology.

Ms. Master, a PhD candidate in physical therapy at the University of Delaware, Newark, presented a study of 1,854 patients with knee osteoarthritis who participated in the Osteoarthritis Initiative, all of whom had worn an accelerometer. This permitted calculation of time spent walking at various intensities. Subjects spent an average of 459 minutes per day not walking and 8 minutes walking at moderate to vigorous intensity, defined as a cadence of more than 100 steps per minute.


During 5 years of follow-up, the incidence of TKR was 6%. In this video interview, Ms. Master explains that patients who replaced 5 minutes of not walking with 5 minutes of brisk walking daily had an adjusted 14% reduction in the risk of TKR. A dose-response was evident, with more minutes of moderate to vigorous walking being associated with progressively larger reductions in the risk of this major surgery. Walking at a cadence of less than 100 steps per minute, regardless of duration, was nonprotective.

[email protected]

SOURCE: Master H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1166.

CHICAGO – Encouraging patients with knee osteoarthritis to engage in brisk walking for at least 5 minutes per day pays big dividends in terms of reduced risk of total knee replacement, according to a new analysis of data from the National Institutes of Health-sponsored Osteoarthritis Initiative.
 

Vidyard Video

Whether walking increases or decreases the risk of structural deterioration and total knee replacement (TKR) in patients with knee osteoarthritis has been a controversial topic marked by conflicting data. That’s probably because prior studies haven’t taken into account walking intensity, Hiral Master said at the annual meeting of the American College of Rheumatology.

Ms. Master, a PhD candidate in physical therapy at the University of Delaware, Newark, presented a study of 1,854 patients with knee osteoarthritis who participated in the Osteoarthritis Initiative, all of whom had worn an accelerometer. This permitted calculation of time spent walking at various intensities. Subjects spent an average of 459 minutes per day not walking and 8 minutes walking at moderate to vigorous intensity, defined as a cadence of more than 100 steps per minute.


During 5 years of follow-up, the incidence of TKR was 6%. In this video interview, Ms. Master explains that patients who replaced 5 minutes of not walking with 5 minutes of brisk walking daily had an adjusted 14% reduction in the risk of TKR. A dose-response was evident, with more minutes of moderate to vigorous walking being associated with progressively larger reductions in the risk of this major surgery. Walking at a cadence of less than 100 steps per minute, regardless of duration, was nonprotective.

[email protected]

SOURCE: Master H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1166.

CHICAGO – Encouraging patients with knee osteoarthritis to engage in brisk walking for at least 5 minutes per day pays big dividends in terms of reduced risk of total knee replacement, according to a new analysis of data from the National Institutes of Health-sponsored Osteoarthritis Initiative.
 

Vidyard Video

Whether walking increases or decreases the risk of structural deterioration and total knee replacement (TKR) in patients with knee osteoarthritis has been a controversial topic marked by conflicting data. That’s probably because prior studies haven’t taken into account walking intensity, Hiral Master said at the annual meeting of the American College of Rheumatology.

Ms. Master, a PhD candidate in physical therapy at the University of Delaware, Newark, presented a study of 1,854 patients with knee osteoarthritis who participated in the Osteoarthritis Initiative, all of whom had worn an accelerometer. This permitted calculation of time spent walking at various intensities. Subjects spent an average of 459 minutes per day not walking and 8 minutes walking at moderate to vigorous intensity, defined as a cadence of more than 100 steps per minute.


During 5 years of follow-up, the incidence of TKR was 6%. In this video interview, Ms. Master explains that patients who replaced 5 minutes of not walking with 5 minutes of brisk walking daily had an adjusted 14% reduction in the risk of TKR. A dose-response was evident, with more minutes of moderate to vigorous walking being associated with progressively larger reductions in the risk of this major surgery. Walking at a cadence of less than 100 steps per minute, regardless of duration, was nonprotective.

[email protected]

SOURCE: Master H et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1166.

CHICAGO – Patients with a first MI were nearly nine times more likely to have detectable IgG antiphospholipid antibodies than were matched controls in a cross-sectional cohort study, Elisabet Svenungsson, MD, PhD, reported at the annual meeting of the American College of Rheumatology.
 

Her case-control study included 805 Swedish patients tested for antiphospholipid antibodies 6-10 weeks after experiencing their first MI and an equal number of age-, sex-, and location-matched controls. Prior to their MIs, none of the patients had been diagnosed with antiphospholipid syndrome, which requires both positive antiphospholipid antibodies and a vascular thrombotic event or obstetric morbidity.

A positive test for IgG anti-cardiolipin antibody was present in 10.9% of the first-MI patients, compared with 0.9% of controls. Similarly, 10.4% of acute MI patients and 0.9% of controls were positive for anti-beta2-glycoprotein-1 antibodies. Most patients who tested positive for one were positive for both. Thus, it’s possible that IgG antiphospholipid antibody positivity is an important silent risk factor that’s present in 1 in 10 MI patients, according to Dr. Svenungsson, professor of rheumatology at the Karolinska Institute in Stockholm.

If these results are confirmed and expanded upon in additional studies, testing for antiphospholipid antibodies could become part of the routine care in patients with an acute MI. Those who test positive would meet the criteria for antiphospholipid syndrome and qualify for long-term oral anticoagulation to reduce their elevated risk of further vascular events, she explained in this video interview.

The study was published in Annals of Internal Medicine simultaneously with the presentation at the ACR annual meeting (Ann Int Med. 2018 Oct 23. doi: 10.7326/M18-2130).

[email protected]

SOURCE: Grosso G et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 855.

CHICAGO – Patients with a first MI were nearly nine times more likely to have detectable IgG antiphospholipid antibodies than were matched controls in a cross-sectional cohort study, Elisabet Svenungsson, MD, PhD, reported at the annual meeting of the American College of Rheumatology.
 

Her case-control study included 805 Swedish patients tested for antiphospholipid antibodies 6-10 weeks after experiencing their first MI and an equal number of age-, sex-, and location-matched controls. Prior to their MIs, none of the patients had been diagnosed with antiphospholipid syndrome, which requires both positive antiphospholipid antibodies and a vascular thrombotic event or obstetric morbidity.

A positive test for IgG anti-cardiolipin antibody was present in 10.9% of the first-MI patients, compared with 0.9% of controls. Similarly, 10.4% of acute MI patients and 0.9% of controls were positive for anti-beta2-glycoprotein-1 antibodies. Most patients who tested positive for one were positive for both. Thus, it’s possible that IgG antiphospholipid antibody positivity is an important silent risk factor that’s present in 1 in 10 MI patients, according to Dr. Svenungsson, professor of rheumatology at the Karolinska Institute in Stockholm.

If these results are confirmed and expanded upon in additional studies, testing for antiphospholipid antibodies could become part of the routine care in patients with an acute MI. Those who test positive would meet the criteria for antiphospholipid syndrome and qualify for long-term oral anticoagulation to reduce their elevated risk of further vascular events, she explained in this video interview.

The study was published in Annals of Internal Medicine simultaneously with the presentation at the ACR annual meeting (Ann Int Med. 2018 Oct 23. doi: 10.7326/M18-2130).

[email protected]

SOURCE: Grosso G et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 855.

CHICAGO – Patients with a first MI were nearly nine times more likely to have detectable IgG antiphospholipid antibodies than were matched controls in a cross-sectional cohort study, Elisabet Svenungsson, MD, PhD, reported at the annual meeting of the American College of Rheumatology.
 

Her case-control study included 805 Swedish patients tested for antiphospholipid antibodies 6-10 weeks after experiencing their first MI and an equal number of age-, sex-, and location-matched controls. Prior to their MIs, none of the patients had been diagnosed with antiphospholipid syndrome, which requires both positive antiphospholipid antibodies and a vascular thrombotic event or obstetric morbidity.

A positive test for IgG anti-cardiolipin antibody was present in 10.9% of the first-MI patients, compared with 0.9% of controls. Similarly, 10.4% of acute MI patients and 0.9% of controls were positive for anti-beta2-glycoprotein-1 antibodies. Most patients who tested positive for one were positive for both. Thus, it’s possible that IgG antiphospholipid antibody positivity is an important silent risk factor that’s present in 1 in 10 MI patients, according to Dr. Svenungsson, professor of rheumatology at the Karolinska Institute in Stockholm.

If these results are confirmed and expanded upon in additional studies, testing for antiphospholipid antibodies could become part of the routine care in patients with an acute MI. Those who test positive would meet the criteria for antiphospholipid syndrome and qualify for long-term oral anticoagulation to reduce their elevated risk of further vascular events, she explained in this video interview.

The study was published in Annals of Internal Medicine simultaneously with the presentation at the ACR annual meeting (Ann Int Med. 2018 Oct 23. doi: 10.7326/M18-2130).

[email protected]

SOURCE: Grosso G et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 855.

CHICAGO – Treatment with transcutaneous electrical nerve stimulation led to a significant cut in pain during movement in women with fibromyalgia in a randomized, controlled trial with 301 patients at two U.S. centers.

Mitchel L. Zoler/MDedge News

The findings showed that, among patients assigned to self-administered transcutaneous electrical nerve stimulation (TENS) for at least 2 hours daily for 4 weeks, 44% had at least a 30% reduction in their pain with movement while on treatment, compared with 22% of patients reporting this level of improvement in the group that received mock TENS, Leslie J. Crofford, MD, reported at the annual meeting of the American College of Rheumatology. In addition, 29% of women who received active TENS reported at least a 20% drop in fatigue plus at least a 30% cut in pain, compared with their baseline levels, whereas this level of response occurred in just 13% of women who self-administered mock TENS.

The findings showed that “TENS can safely be used in addition to other treatment to improve pain and fatigue in women with fibromyalgia,” said Dr. Crofford, professor of medicine and director of rheumatology and immunology at Vanderbilt University, Nashville, Tenn. A total of 70% of women in the actively treated group reported they felt better on a global rating of change after 4 weeks of self-treatment, compared with 30% of women in the mock-control arm.


TENS, which uses a U.S.-approved device to deliver a defined series of electrical pulses to, in this case, the cervical and lumbar spine regions during activity, also showed no signs of inducing tolerance in the study and in fact produced results suggesting cumulative benefit with chronic use while causing “minimal” adverse effects, Dr. Crofford said.

“We did this study because we thought that previous studies of TENS had been inadequate,” she explained.

“Until now, most studies of TENS have been null. This was a uniquely positive trial,” commented David T. Felson, MD, professor of medicine at Boston University.

“The size, rigor, patient selection, and the TENS parameters may have been important” for the positive results, Dr. Crofford suggested. The 300-patient study was roughly 10 times larger than prior studies of TENS, and the current study used a “very vigorous placebo,” a TENS device that delivered a mock electrical stimulus. The electrical pulses used during TENS can vary by amplitude, duration, frequency, and pattern, and the settings for each of these parameters used in the trial came from prior clinical and animal studies of TENS.

“Once our study is reviewed and published, we will post our effective TENS parameters on our website. Most TENS units are adjustable” for these parameters, Dr. Crofford said. “Some of the parameters are probably important for avoiding tolerance, so it’s important to use the parameters that we’ve shown are effective.”

TENS “is available, safe, and very well tolerated. It has the potential to change practice immediately. If you look at the effect size and number of responders, TENS treatment is comparable to drug treatment,” Dr. Crofford said in an interview. A quarter of the patients in the study were on opioids at baseline, and the effect in this subgroup was similar to the overall findings. The women in the study were an average age of 46 years and had been diagnosed with fibromyalgia for an average of 7 years. Their average body mass index was 34 kg/m².

The FAST (Fibromyalgia Activity Study with TENS) trial enrolled women aged 18-70 years who met the 1990 criteria for fibromyalgia (Arthritis Rheum. 1990 Feb;33[2]:160-72) who had not received TENS during at least the prior 5 years and scored at least 4 on pain rating during the prior week. The study randomized 103 women to receive active TENS, 99 to receive mock TENS, and 99 to receive no TENS. Patients in the TENS arms received instructions to use it for at least 2 hours a day when they were active. The study’s primary endpoint was the between-group difference in pain during a 6-min walk during TENS treatment. When measured after 4 weeks of at-home treatment, patients on active TENS had an average pain level of about 4.5 on a scale of 0-10, compared with an average score of about 5.5 among the mock-TENS group, a statistically significant difference. Both groups had essentially identical pain scores of about 6.5 at baseline.

FAST did not receive commercial funding. Dr. Crofford and Dr. Felson had no disclosures.

[email protected]

SOURCE: Crofford LJ et al. ACR Annual Meeting, Abstract LB19.

CHICAGO – Treatment with transcutaneous electrical nerve stimulation led to a significant cut in pain during movement in women with fibromyalgia in a randomized, controlled trial with 301 patients at two U.S. centers.

Mitchel L. Zoler/MDedge News

The findings showed that, among patients assigned to self-administered transcutaneous electrical nerve stimulation (TENS) for at least 2 hours daily for 4 weeks, 44% had at least a 30% reduction in their pain with movement while on treatment, compared with 22% of patients reporting this level of improvement in the group that received mock TENS, Leslie J. Crofford, MD, reported at the annual meeting of the American College of Rheumatology. In addition, 29% of women who received active TENS reported at least a 20% drop in fatigue plus at least a 30% cut in pain, compared with their baseline levels, whereas this level of response occurred in just 13% of women who self-administered mock TENS.

The findings showed that “TENS can safely be used in addition to other treatment to improve pain and fatigue in women with fibromyalgia,” said Dr. Crofford, professor of medicine and director of rheumatology and immunology at Vanderbilt University, Nashville, Tenn. A total of 70% of women in the actively treated group reported they felt better on a global rating of change after 4 weeks of self-treatment, compared with 30% of women in the mock-control arm.


TENS, which uses a U.S.-approved device to deliver a defined series of electrical pulses to, in this case, the cervical and lumbar spine regions during activity, also showed no signs of inducing tolerance in the study and in fact produced results suggesting cumulative benefit with chronic use while causing “minimal” adverse effects, Dr. Crofford said.

“We did this study because we thought that previous studies of TENS had been inadequate,” she explained.

“Until now, most studies of TENS have been null. This was a uniquely positive trial,” commented David T. Felson, MD, professor of medicine at Boston University.

“The size, rigor, patient selection, and the TENS parameters may have been important” for the positive results, Dr. Crofford suggested. The 300-patient study was roughly 10 times larger than prior studies of TENS, and the current study used a “very vigorous placebo,” a TENS device that delivered a mock electrical stimulus. The electrical pulses used during TENS can vary by amplitude, duration, frequency, and pattern, and the settings for each of these parameters used in the trial came from prior clinical and animal studies of TENS.

“Once our study is reviewed and published, we will post our effective TENS parameters on our website. Most TENS units are adjustable” for these parameters, Dr. Crofford said. “Some of the parameters are probably important for avoiding tolerance, so it’s important to use the parameters that we’ve shown are effective.”

TENS “is available, safe, and very well tolerated. It has the potential to change practice immediately. If you look at the effect size and number of responders, TENS treatment is comparable to drug treatment,” Dr. Crofford said in an interview. A quarter of the patients in the study were on opioids at baseline, and the effect in this subgroup was similar to the overall findings. The women in the study were an average age of 46 years and had been diagnosed with fibromyalgia for an average of 7 years. Their average body mass index was 34 kg/m².

The FAST (Fibromyalgia Activity Study with TENS) trial enrolled women aged 18-70 years who met the 1990 criteria for fibromyalgia (Arthritis Rheum. 1990 Feb;33[2]:160-72) who had not received TENS during at least the prior 5 years and scored at least 4 on pain rating during the prior week. The study randomized 103 women to receive active TENS, 99 to receive mock TENS, and 99 to receive no TENS. Patients in the TENS arms received instructions to use it for at least 2 hours a day when they were active. The study’s primary endpoint was the between-group difference in pain during a 6-min walk during TENS treatment. When measured after 4 weeks of at-home treatment, patients on active TENS had an average pain level of about 4.5 on a scale of 0-10, compared with an average score of about 5.5 among the mock-TENS group, a statistically significant difference. Both groups had essentially identical pain scores of about 6.5 at baseline.

FAST did not receive commercial funding. Dr. Crofford and Dr. Felson had no disclosures.

[email protected]

SOURCE: Crofford LJ et al. ACR Annual Meeting, Abstract LB19.

CHICAGO – Treatment with transcutaneous electrical nerve stimulation led to a significant cut in pain during movement in women with fibromyalgia in a randomized, controlled trial with 301 patients at two U.S. centers.

Mitchel L. Zoler/MDedge News

The findings showed that, among patients assigned to self-administered transcutaneous electrical nerve stimulation (TENS) for at least 2 hours daily for 4 weeks, 44% had at least a 30% reduction in their pain with movement while on treatment, compared with 22% of patients reporting this level of improvement in the group that received mock TENS, Leslie J. Crofford, MD, reported at the annual meeting of the American College of Rheumatology. In addition, 29% of women who received active TENS reported at least a 20% drop in fatigue plus at least a 30% cut in pain, compared with their baseline levels, whereas this level of response occurred in just 13% of women who self-administered mock TENS.

The findings showed that “TENS can safely be used in addition to other treatment to improve pain and fatigue in women with fibromyalgia,” said Dr. Crofford, professor of medicine and director of rheumatology and immunology at Vanderbilt University, Nashville, Tenn. A total of 70% of women in the actively treated group reported they felt better on a global rating of change after 4 weeks of self-treatment, compared with 30% of women in the mock-control arm.


TENS, which uses a U.S.-approved device to deliver a defined series of electrical pulses to, in this case, the cervical and lumbar spine regions during activity, also showed no signs of inducing tolerance in the study and in fact produced results suggesting cumulative benefit with chronic use while causing “minimal” adverse effects, Dr. Crofford said.

“We did this study because we thought that previous studies of TENS had been inadequate,” she explained.

“Until now, most studies of TENS have been null. This was a uniquely positive trial,” commented David T. Felson, MD, professor of medicine at Boston University.

“The size, rigor, patient selection, and the TENS parameters may have been important” for the positive results, Dr. Crofford suggested. The 300-patient study was roughly 10 times larger than prior studies of TENS, and the current study used a “very vigorous placebo,” a TENS device that delivered a mock electrical stimulus. The electrical pulses used during TENS can vary by amplitude, duration, frequency, and pattern, and the settings for each of these parameters used in the trial came from prior clinical and animal studies of TENS.

“Once our study is reviewed and published, we will post our effective TENS parameters on our website. Most TENS units are adjustable” for these parameters, Dr. Crofford said. “Some of the parameters are probably important for avoiding tolerance, so it’s important to use the parameters that we’ve shown are effective.”

TENS “is available, safe, and very well tolerated. It has the potential to change practice immediately. If you look at the effect size and number of responders, TENS treatment is comparable to drug treatment,” Dr. Crofford said in an interview. A quarter of the patients in the study were on opioids at baseline, and the effect in this subgroup was similar to the overall findings. The women in the study were an average age of 46 years and had been diagnosed with fibromyalgia for an average of 7 years. Their average body mass index was 34 kg/m².

The FAST (Fibromyalgia Activity Study with TENS) trial enrolled women aged 18-70 years who met the 1990 criteria for fibromyalgia (Arthritis Rheum. 1990 Feb;33[2]:160-72) who had not received TENS during at least the prior 5 years and scored at least 4 on pain rating during the prior week. The study randomized 103 women to receive active TENS, 99 to receive mock TENS, and 99 to receive no TENS. Patients in the TENS arms received instructions to use it for at least 2 hours a day when they were active. The study’s primary endpoint was the between-group difference in pain during a 6-min walk during TENS treatment. When measured after 4 weeks of at-home treatment, patients on active TENS had an average pain level of about 4.5 on a scale of 0-10, compared with an average score of about 5.5 among the mock-TENS group, a statistically significant difference. Both groups had essentially identical pain scores of about 6.5 at baseline.

FAST did not receive commercial funding. Dr. Crofford and Dr. Felson had no disclosures.

[email protected]

SOURCE: Crofford LJ et al. ACR Annual Meeting, Abstract LB19.

CHICAGO – Researchers have derived and validated a 10-item formula to estimate a patient’s risk for developing a major adverse event while on NSAID treatment.

Mitchel L. Zoler/MDedge News

The calculator could “help guide use of NSAIDs in clinical practice,” said Daniel H. Solomon, MD, at the annual meeting of the American College of Rheumatology. Although he called for further validation of the risk-score formula using other databases, he noted that it uses readily available data and could easily be calculated with standard inputs in an electronic medical record. The formula predicts the risk for a major adverse effect during 1 year of daily NSAID use.

Dr. Solomon and his associates devised the risk-score calculator with data collected in the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) trial, a safety study designed to test whether treatment with celecoxib was noninferior to treatment with naproxen or ibuprofen for producing cardiovascular adverse events, a hypothesis proven by the study’s results (N Engl J Med. 2016 Dec 29;375[26]:2519-29). They had full data available for 23,950 of the more than 24,000 enrolled patients. The patients averaged 63 years old, just over a third were men, their average body mass index was 31 kg/m², and 90% had osteoarthritis and 10% had rheumatoid arthritis. The study enrolled patients with an elevated risk for a cardiovascular event, so 63% had hypertension and 36% had diabetes.

The adverse events included as possible outcomes estimated by the formula were all-cause death, major adverse cardiovascular events, clinically significant GI events, or renal insufficiency or failure. The investigators used data from more than 15,000 patients enrolled during the first 4 years of the study to derive the risk-score formula, and data from the nearly 9,000 patients enrolled during the next 5 years to validate it.

The analysis identified and validated 10 baseline items that, when plugged into the formula, calculated a predicted rate for the subsequent development of a major averse event during 1 year of NSAID treatment. The 10 parameters are: age, sex, known cardiovascular disease, hypertension, diabetes, current cigarette use, on treatment with a statin, baseline serum creatinine level, rheumatoid arthritis, and hematocrit.

As examples of the accuracy of the prediction score, Dr. Solomon reported that, among the patients with a predicted risk for a major adverse event of less than 1%, the observed rate was 0.4%; among people with a predicted rate of 1%-4%, the observed rate was 1.7%; and among those with a predicted risk of more than 4% the observed rate was 5.6%. Major cardiovascular events were the most common type of adverse events observed among the nearly 24,000 patients enrolled in PRECISION. A total of 5% of the patients fell into the lowest risk category, with a risk of less than 1%; 70% were in the intermediate risk category, with a predicted risk of 1%-4%; and 25% had a predicted risk of more than 4%, reported Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital in Boston.

Age is a major driver of risk, he noted. A patient who is at least 65 years old would have a greater than 1% risk for an adverse event regardless of the other nine risk factors in the scoring formula.

PRECISION was funded by Pfizer. Dr. Solomon has received research funding from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Pfizer.

[email protected]

SOURCE: Solomon D et al. ACR Annual Meeting, Abstract 2952. Arthritis Rheumatol. 2018;70(Suppl 10).

CHICAGO – Researchers have derived and validated a 10-item formula to estimate a patient’s risk for developing a major adverse event while on NSAID treatment.

Mitchel L. Zoler/MDedge News

The calculator could “help guide use of NSAIDs in clinical practice,” said Daniel H. Solomon, MD, at the annual meeting of the American College of Rheumatology. Although he called for further validation of the risk-score formula using other databases, he noted that it uses readily available data and could easily be calculated with standard inputs in an electronic medical record. The formula predicts the risk for a major adverse effect during 1 year of daily NSAID use.

Dr. Solomon and his associates devised the risk-score calculator with data collected in the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) trial, a safety study designed to test whether treatment with celecoxib was noninferior to treatment with naproxen or ibuprofen for producing cardiovascular adverse events, a hypothesis proven by the study’s results (N Engl J Med. 2016 Dec 29;375[26]:2519-29). They had full data available for 23,950 of the more than 24,000 enrolled patients. The patients averaged 63 years old, just over a third were men, their average body mass index was 31 kg/m², and 90% had osteoarthritis and 10% had rheumatoid arthritis. The study enrolled patients with an elevated risk for a cardiovascular event, so 63% had hypertension and 36% had diabetes.

The adverse events included as possible outcomes estimated by the formula were all-cause death, major adverse cardiovascular events, clinically significant GI events, or renal insufficiency or failure. The investigators used data from more than 15,000 patients enrolled during the first 4 years of the study to derive the risk-score formula, and data from the nearly 9,000 patients enrolled during the next 5 years to validate it.

The analysis identified and validated 10 baseline items that, when plugged into the formula, calculated a predicted rate for the subsequent development of a major averse event during 1 year of NSAID treatment. The 10 parameters are: age, sex, known cardiovascular disease, hypertension, diabetes, current cigarette use, on treatment with a statin, baseline serum creatinine level, rheumatoid arthritis, and hematocrit.

As examples of the accuracy of the prediction score, Dr. Solomon reported that, among the patients with a predicted risk for a major adverse event of less than 1%, the observed rate was 0.4%; among people with a predicted rate of 1%-4%, the observed rate was 1.7%; and among those with a predicted risk of more than 4% the observed rate was 5.6%. Major cardiovascular events were the most common type of adverse events observed among the nearly 24,000 patients enrolled in PRECISION. A total of 5% of the patients fell into the lowest risk category, with a risk of less than 1%; 70% were in the intermediate risk category, with a predicted risk of 1%-4%; and 25% had a predicted risk of more than 4%, reported Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital in Boston.

Age is a major driver of risk, he noted. A patient who is at least 65 years old would have a greater than 1% risk for an adverse event regardless of the other nine risk factors in the scoring formula.

PRECISION was funded by Pfizer. Dr. Solomon has received research funding from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Pfizer.

[email protected]

SOURCE: Solomon D et al. ACR Annual Meeting, Abstract 2952. Arthritis Rheumatol. 2018;70(Suppl 10).

CHICAGO – Researchers have derived and validated a 10-item formula to estimate a patient’s risk for developing a major adverse event while on NSAID treatment.

Mitchel L. Zoler/MDedge News

The calculator could “help guide use of NSAIDs in clinical practice,” said Daniel H. Solomon, MD, at the annual meeting of the American College of Rheumatology. Although he called for further validation of the risk-score formula using other databases, he noted that it uses readily available data and could easily be calculated with standard inputs in an electronic medical record. The formula predicts the risk for a major adverse effect during 1 year of daily NSAID use.

Dr. Solomon and his associates devised the risk-score calculator with data collected in the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen) trial, a safety study designed to test whether treatment with celecoxib was noninferior to treatment with naproxen or ibuprofen for producing cardiovascular adverse events, a hypothesis proven by the study’s results (N Engl J Med. 2016 Dec 29;375[26]:2519-29). They had full data available for 23,950 of the more than 24,000 enrolled patients. The patients averaged 63 years old, just over a third were men, their average body mass index was 31 kg/m², and 90% had osteoarthritis and 10% had rheumatoid arthritis. The study enrolled patients with an elevated risk for a cardiovascular event, so 63% had hypertension and 36% had diabetes.

The adverse events included as possible outcomes estimated by the formula were all-cause death, major adverse cardiovascular events, clinically significant GI events, or renal insufficiency or failure. The investigators used data from more than 15,000 patients enrolled during the first 4 years of the study to derive the risk-score formula, and data from the nearly 9,000 patients enrolled during the next 5 years to validate it.

The analysis identified and validated 10 baseline items that, when plugged into the formula, calculated a predicted rate for the subsequent development of a major averse event during 1 year of NSAID treatment. The 10 parameters are: age, sex, known cardiovascular disease, hypertension, diabetes, current cigarette use, on treatment with a statin, baseline serum creatinine level, rheumatoid arthritis, and hematocrit.

As examples of the accuracy of the prediction score, Dr. Solomon reported that, among the patients with a predicted risk for a major adverse event of less than 1%, the observed rate was 0.4%; among people with a predicted rate of 1%-4%, the observed rate was 1.7%; and among those with a predicted risk of more than 4% the observed rate was 5.6%. Major cardiovascular events were the most common type of adverse events observed among the nearly 24,000 patients enrolled in PRECISION. A total of 5% of the patients fell into the lowest risk category, with a risk of less than 1%; 70% were in the intermediate risk category, with a predicted risk of 1%-4%; and 25% had a predicted risk of more than 4%, reported Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital in Boston.

Age is a major driver of risk, he noted. A patient who is at least 65 years old would have a greater than 1% risk for an adverse event regardless of the other nine risk factors in the scoring formula.

PRECISION was funded by Pfizer. Dr. Solomon has received research funding from AbbVie, Amgen, Bristol-Myers Squibb, Genentech, and Pfizer.

[email protected]

SOURCE: Solomon D et al. ACR Annual Meeting, Abstract 2952. Arthritis Rheumatol. 2018;70(Suppl 10).

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

[email protected]

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

[email protected]

CHICAGO – Help is on the way for rheumatologists who may feel out of their depth regarding reproductive health issues in their patients.

Bruce Jancin/MDedge News

“Our patients, fortunately, are pursuing pregnancy more often now than in years past. One of the key messages of the guidelines is that patients really do want to discuss these topics with their rheumatologist, even though that often does not happen now. What patients told us [in the guideline-development process] is their rheumatologist knows them better than their gynecologist or any of their other doctors because we have followed them for a long period of time and we understand their disease and their symptoms. They really want our input on questions about contraception, when to plan a pregnancy, and medication use,” said Dr. Sammaritano of the Hospital for Special Surgery and Cornell University in New York.

The guidelines were created over the course of a year and a half with extensive input from ob.gyns., as well as a patient panel. The project included a systematic review of more than 300 published studies in which guideline panelists attempt to find answers to an initial list of 370 questions. Dr. Sammaritano predicted that the guidelines will prove to be useful not only for rheumatologists, but for their colleagues in ob.gyn. as well. Just as rheumatologists likely haven’t kept up with the sea changes that have occurred in ob.gyn. since their medical school days, most ob.gyns. know little about rheumatic diseases.

“There’s room for education on both sides,” she observed in an interview. “I have had to write letters to gynecologists to get them to put my patients with antiphospholipid antibodies on a contraceptive that includes a progestin because the labeling says, ‘May increase risk of thrombosis.’ And yet if you look at the literature, most of the progestins do not increase the risk of thrombosis, even in patients who are already at increased risk because of a genetic prothrombotic abnormality. I practically had to sign my life away to get a gynecologist to put a progestin-containing IUD in my patient, whereas the risk of thrombosis to my patient with an unplanned pregnancy would have been 10-fold or 100-fold higher. Unplanned pregnancy is dangerous for patients with our diseases.”

And yet, she noted, half of all pregnancies in the United States are unplanned. Among women with rheumatic diseases, the proportion may well be even higher in light of their documented low rate of utilization of effective contraception.

A publication date for the guidelines won’t be set until the review is completed, but the plan is to issue three separate documents. One will address reproductive health outside of pregnancy, with key topics to include contraception, fertility preservation, menopause, and hormone replacement therapy. The second document will focus on pregnancy management, with special attention devoted to women with lupus or antiphospholipid antibodies because they are at particularly high risk of adverse pregnancy outcomes. The third document will be devoted to medications, covering issues including which medications can be continued during pregnancy and when to safely stop the ones that can’t. This section will address both maternal and paternal use of rheumatologic medications, the latter being a topic below the radar of ob.gyns.

The three medications whose paternal use in pregnancy generate the most questions in clinical practice are methotrexate, cyclophosphamide, and sulfasalazine.

“I cannot tell you how many times I’ve been asked whether male patients with rheumatic diseases need to stop their methotrexate before they plan to father a child – that’s been a big one. The answer is they don’t need to stop, but that’s a conditional recommendation because the product label still says to stop it 3 months before. But that’s based on theoretical concerns, and all the data support a lack of teratogenicity for men using methotrexate prior to and during pregnancy,” Dr. Sammaritano said.

Men on cyclophosphamide absolutely have to stop the drug 3 months before pregnancy because the drug causes DNA fragmentation in the sperm. Sulfasalazine is known to impair male fertility. The ACR guidelines will recommend that men continue the drug, but if pregnancy doesn’t occur within a reasonable time, then it’s appropriate to get a semen analysis rather than stopping sulfasalazine unnecessarily.

American College of Obstetricians and Gynecologists guidelines now recommend long-acting reversible contraception, including IUDs and progestin implants, as first-line contraception for all women. The ACR draft guidelines strongly recommend the same.

“That is new. The use of this form of contraception in women with rheumatic diseases is quite low. In general, our patients don’t use contraception as often as other women, and when they do, they don’t use effective contraception. There are many theories as to why that may be: perhaps it’s a focus on the more immediate issues of their rheumatic disease that doesn’t allow their rheumatologist to get to the point of discussing contraception,” according to Dr. Sammaritano.

Many rheumatologists will be pleasantly surprised to learn that the problem of increased risk of pelvic inflammatory disease associated with earlier-generation IUDs is no longer an issue with the current devices. And contrary to a misconception among some ob.gyns., autoimmune disease will not cause a woman to reject her IUD.

The ACR guidelines recommend continuing hydroxychloroquine in lupus patients during pregnancy – and considering starting the drug in those not already on it – because of strong evidence supporting both safety and benefit for mother and baby.

“We are recommending the use of low-dose aspirin for patients with lupus and antiphospholipid antibodies because those two conditions increase the risk for preeclampsia, and the ob.gyns. routinely use low-dose aspirin starting toward the end of the first trimester as preventive therapy. Large studies show that it reduces the risk,” she continued.

Dr. Sammaritano cautioned that the literature on the use of rheumatologic medications in pregnancy and breast feeding is generally weak – and in the case of the new oral small molecule JAK inhibitors, essentially nonexistent.

“A lot of our recommendations are conditional because we did not feel that the data support a strong recommendation. But you have to do something. As long as you communicate the idea that we’re doing the best we can with what information is available, I think patients will respond to that,” the rheumatologist said.

She reported having no financial conflicts regarding her presentation.

[email protected]

CHICAGO – Results of the landmark PEXIVAS study – far and away the largest randomized trial ever done in ANCA-associated vasculitis – will likely change treatment in a couple of major ways.

Bruce Jancin/MDedge News

“I think this trial will have an impact on care. Based on these findings, physicians should strongly reconsider the utility of plasma exchange as a treatment for AAV [antineutrophil cytoplasmic antibody–associated vasculitis] patients and should now consider using lower cumulative doses of glucocorticoids for the treatment of severe AAV,” PEXIVAS coprincipal investigator Peter A. Merkel, MD, said at the annual meeting of the American College of Rheumatology.

That’s because the trial demonstrated that plasma exchange neither saved lives nor avoided end-stage renal disease, while utilization of oral glucocorticoids in doses substantially lower than the high-dose current standard significantly reduced the serious infection rate without causing less effective disease control, according to Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania in Philadelphia.

PEXIVAS comprised 704 patients with severe granulomatosis with polyangiitis or microscopic polyangiitis, making it more than twice as large as any other trial in AAV. This was a multicenter, international, open-label, randomized trial with a 2-by-2 factorial design. To qualify as having severe AAV, participants had to have an estimated glomerular filtration rate below 50 mL/min per 1.73 m² and/or lung hemorrhage.

“This was in essence two trials embedded within one protocol in the factorial design,” he explained.

The impetus for this major clinical trial was a recognition that mortality due to AAV remains high, especially in the first year, with a clear unmet need for better, less toxic therapies. Indeed, it’s estimated that only 29% of deaths in the first year after diagnosis are due to the vasculitis disease itself, while over 50% of the mortality is caused by infection, much of it collateral damage from immunosuppressive therapies.

Dr. Merkel, who heads the National Institutes of Health–supported Vasculitis Clinical Research Consortium, said the time was right for a clinical trial aimed at improving patient management: “Clinical equipoise exists for the efficacy of both plasma exchange and reduced-dose glucocorticoids in ANCA-associated vasculitis.”

The patients underwent induction therapy with cyclophosphamide or rituximab (Rituxan) plus IV methylprednisolone. Then they were randomized to seven plasma exchange sessions in 14 days or no plasma exchange, and further randomized to conventional weight-based, high-dose oral glucocorticoids or a lower-dose regimen. Those on the reduced-dose regimen received 54% of the cumulative amount of glucocorticoids used in the standard-dose group through the first 3 months, and 61% over the course of 6 months. By week 4, those on the reduced-dose regimen were on an average of 25 mg/day, while those on standard therapy were on 50 mg/day. Adherence to assigned study arms exceeded 90%. Patients were followed prospectively for 1-7 years.

The primary endpoint, a composite of all-cause mortality or development of end-stage renal disease, occurred in 28% of patients on plasma exchange and 31% of those who did not undergo plasma exchange, a nonsignificant difference indicative of a lack of benefit for the intervention. No differential effect was seen in prespecified subgroups based on age, creatinine clearance, ANCA type, form of immunosuppression, or presence or absence of lung hemorrhage.

Further, the primary endpoint occurred in 28% of patients on reduced-dose glucocorticoids, compared with 26% on full-dose therapy; again, a nonsignificant difference, meaning lower-dose therapy didn’t result in less effective disease control. But it did result in a significant reduction in the prespecified endpoint of serious infections in the first year: 27% versus 33% with full-dose therapy, representing a 30% relative risk reduction.

Audience members wanted to know if there are any circumstances at all in which Dr. Merkel would now consider resorting to plasma exchange, such as maybe in AAV patients at the most extreme end of the severity spectrum.

“I’m not sure I should be the one dictating that; I think the world needs to see the data,” he replied.

That being said, he added, “I think these data are incredibly helpful to physicians and patients as they face this decision. I think plasma exchange is an expensive therapy and somewhat invasive. I think our results indicate that the benefit that we may have thought was there is not there.”

The study was sponsored by the National Institutes of Health, the Food and Drug Administration, the U.K. Medical Research Council and the National Institute for Health Research, the Canadian Institutes of Health Research, and the governments of France, Australia, and New Zealand. The presenter reported receiving research funding from the ACR, EULAR, FDA, NIH, Patient-Centered Outcomes Research Institute, and the Vasculitis Foundation. He also receives research funding from and/or serves as a consultant to more than a dozen pharmaceutical companies.

[email protected]

SOURCE: Merkel PA et al. Arthritis Rheumatol. 2018;70(Suppl 10):Abstract 2788.

CHICAGO – Results of the landmark PEXIVAS study – far and away the largest randomized trial ever done in ANCA-associated vasculitis – will likely change treatment in a couple of major ways.

Bruce Jancin/MDedge News

“I think this trial will have an impact on care. Based on these findings, physicians should strongly reconsider the utility of plasma exchange as a treatment for AAV [antineutrophil cytoplasmic antibody–associated vasculitis] patients and should now consider using lower cumulative doses of glucocorticoids for the treatment of severe AAV,” PEXIVAS coprincipal investigator Peter A. Merkel, MD, said at the annual meeting of the American College of Rheumatology.

That’s because the trial demonstrated that plasma exchange neither saved lives nor avoided end-stage renal disease, while utilization of oral glucocorticoids in doses substantially lower than the high-dose current standard significantly reduced the serious infection rate without causing less effective disease control, according to Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania in Philadelphia.

PEXIVAS comprised 704 patients with severe granulomatosis with polyangiitis or microscopic polyangiitis, making it more than twice as large as any other trial in AAV. This was a multicenter, international, open-label, randomized trial with a 2-by-2 factorial design. To qualify as having severe AAV, participants had to have an estimated glomerular filtration rate below 50 mL/min per 1.73 m² and/or lung hemorrhage.

“This was in essence two trials embedded within one protocol in the factorial design,” he explained.

The impetus for this major clinical trial was a recognition that mortality due to AAV remains high, especially in the first year, with a clear unmet need for better, less toxic therapies. Indeed, it’s estimated that only 29% of deaths in the first year after diagnosis are due to the vasculitis disease itself, while over 50% of the mortality is caused by infection, much of it collateral damage from immunosuppressive therapies.

Dr. Merkel, who heads the National Institutes of Health–supported Vasculitis Clinical Research Consortium, said the time was right for a clinical trial aimed at improving patient management: “Clinical equipoise exists for the efficacy of both plasma exchange and reduced-dose glucocorticoids in ANCA-associated vasculitis.”

The patients underwent induction therapy with cyclophosphamide or rituximab (Rituxan) plus IV methylprednisolone. Then they were randomized to seven plasma exchange sessions in 14 days or no plasma exchange, and further randomized to conventional weight-based, high-dose oral glucocorticoids or a lower-dose regimen. Those on the reduced-dose regimen received 54% of the cumulative amount of glucocorticoids used in the standard-dose group through the first 3 months, and 61% over the course of 6 months. By week 4, those on the reduced-dose regimen were on an average of 25 mg/day, while those on standard therapy were on 50 mg/day. Adherence to assigned study arms exceeded 90%. Patients were followed prospectively for 1-7 years.

The primary endpoint, a composite of all-cause mortality or development of end-stage renal disease, occurred in 28% of patients on plasma exchange and 31% of those who did not undergo plasma exchange, a nonsignificant difference indicative of a lack of benefit for the intervention. No differential effect was seen in prespecified subgroups based on age, creatinine clearance, ANCA type, form of immunosuppression, or presence or absence of lung hemorrhage.

Further, the primary endpoint occurred in 28% of patients on reduced-dose glucocorticoids, compared with 26% on full-dose therapy; again, a nonsignificant difference, meaning lower-dose therapy didn’t result in less effective disease control. But it did result in a significant reduction in the prespecified endpoint of serious infections in the first year: 27% versus 33% with full-dose therapy, representing a 30% relative risk reduction.

Audience members wanted to know if there are any circumstances at all in which Dr. Merkel would now consider resorting to plasma exchange, such as maybe in AAV patients at the most extreme end of the severity spectrum.

“I’m not sure I should be the one dictating that; I think the world needs to see the data,” he replied.

That being said, he added, “I think these data are incredibly helpful to physicians and patients as they face this decision. I think plasma exchange is an expensive therapy and somewhat invasive. I think our results indicate that the benefit that we may have thought was there is not there.”

The study was sponsored by the National Institutes of Health, the Food and Drug Administration, the U.K. Medical Research Council and the National Institute for Health Research, the Canadian Institutes of Health Research, and the governments of France, Australia, and New Zealand. The presenter reported receiving research funding from the ACR, EULAR, FDA, NIH, Patient-Centered Outcomes Research Institute, and the Vasculitis Foundation. He also receives research funding from and/or serves as a consultant to more than a dozen pharmaceutical companies.

[email protected]

SOURCE: Merkel PA et al. Arthritis Rheumatol. 2018;70(Suppl 10):Abstract 2788.

CHICAGO – Results of the landmark PEXIVAS study – far and away the largest randomized trial ever done in ANCA-associated vasculitis – will likely change treatment in a couple of major ways.

Bruce Jancin/MDedge News

“I think this trial will have an impact on care. Based on these findings, physicians should strongly reconsider the utility of plasma exchange as a treatment for AAV [antineutrophil cytoplasmic antibody–associated vasculitis] patients and should now consider using lower cumulative doses of glucocorticoids for the treatment of severe AAV,” PEXIVAS coprincipal investigator Peter A. Merkel, MD, said at the annual meeting of the American College of Rheumatology.

That’s because the trial demonstrated that plasma exchange neither saved lives nor avoided end-stage renal disease, while utilization of oral glucocorticoids in doses substantially lower than the high-dose current standard significantly reduced the serious infection rate without causing less effective disease control, according to Dr. Merkel, chief of rheumatology and professor of medicine and epidemiology at the University of Pennsylvania in Philadelphia.

PEXIVAS comprised 704 patients with severe granulomatosis with polyangiitis or microscopic polyangiitis, making it more than twice as large as any other trial in AAV. This was a multicenter, international, open-label, randomized trial with a 2-by-2 factorial design. To qualify as having severe AAV, participants had to have an estimated glomerular filtration rate below 50 mL/min per 1.73 m² and/or lung hemorrhage.

“This was in essence two trials embedded within one protocol in the factorial design,” he explained.

The impetus for this major clinical trial was a recognition that mortality due to AAV remains high, especially in the first year, with a clear unmet need for better, less toxic therapies. Indeed, it’s estimated that only 29% of deaths in the first year after diagnosis are due to the vasculitis disease itself, while over 50% of the mortality is caused by infection, much of it collateral damage from immunosuppressive therapies.

Dr. Merkel, who heads the National Institutes of Health–supported Vasculitis Clinical Research Consortium, said the time was right for a clinical trial aimed at improving patient management: “Clinical equipoise exists for the efficacy of both plasma exchange and reduced-dose glucocorticoids in ANCA-associated vasculitis.”

The patients underwent induction therapy with cyclophosphamide or rituximab (Rituxan) plus IV methylprednisolone. Then they were randomized to seven plasma exchange sessions in 14 days or no plasma exchange, and further randomized to conventional weight-based, high-dose oral glucocorticoids or a lower-dose regimen. Those on the reduced-dose regimen received 54% of the cumulative amount of glucocorticoids used in the standard-dose group through the first 3 months, and 61% over the course of 6 months. By week 4, those on the reduced-dose regimen were on an average of 25 mg/day, while those on standard therapy were on 50 mg/day. Adherence to assigned study arms exceeded 90%. Patients were followed prospectively for 1-7 years.

The primary endpoint, a composite of all-cause mortality or development of end-stage renal disease, occurred in 28% of patients on plasma exchange and 31% of those who did not undergo plasma exchange, a nonsignificant difference indicative of a lack of benefit for the intervention. No differential effect was seen in prespecified subgroups based on age, creatinine clearance, ANCA type, form of immunosuppression, or presence or absence of lung hemorrhage.

Further, the primary endpoint occurred in 28% of patients on reduced-dose glucocorticoids, compared with 26% on full-dose therapy; again, a nonsignificant difference, meaning lower-dose therapy didn’t result in less effective disease control. But it did result in a significant reduction in the prespecified endpoint of serious infections in the first year: 27% versus 33% with full-dose therapy, representing a 30% relative risk reduction.

Audience members wanted to know if there are any circumstances at all in which Dr. Merkel would now consider resorting to plasma exchange, such as maybe in AAV patients at the most extreme end of the severity spectrum.

“I’m not sure I should be the one dictating that; I think the world needs to see the data,” he replied.

That being said, he added, “I think these data are incredibly helpful to physicians and patients as they face this decision. I think plasma exchange is an expensive therapy and somewhat invasive. I think our results indicate that the benefit that we may have thought was there is not there.”

The study was sponsored by the National Institutes of Health, the Food and Drug Administration, the U.K. Medical Research Council and the National Institute for Health Research, the Canadian Institutes of Health Research, and the governments of France, Australia, and New Zealand. The presenter reported receiving research funding from the ACR, EULAR, FDA, NIH, Patient-Centered Outcomes Research Institute, and the Vasculitis Foundation. He also receives research funding from and/or serves as a consultant to more than a dozen pharmaceutical companies.

[email protected]

SOURCE: Merkel PA et al. Arthritis Rheumatol. 2018;70(Suppl 10):Abstract 2788.