ACR Annual Meeting 2018

CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.

The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
 

Upadacitinib

SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.

Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.

“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.

The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.

“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”

The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.

Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.

As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.

The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”

Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.

“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.

Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.

Peficitinib

Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.

Which oral JAKi to use?

Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.

“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”

Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”

If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.

Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.

“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.

Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”

The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.

[email protected]

CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.

The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
 

Upadacitinib

SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.

Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.

“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.

The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.

“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”

The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.

Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.

As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.

The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”

Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.

“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.

Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.

Peficitinib

Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.

Which oral JAKi to use?

Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.

“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”

Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”

If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.

Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.

“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.

Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”

The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.

[email protected]

CHICAGO – A measure of clarity regarding how the emerging class of oral Janus kinase inhibitors might fit into clinical practice for treatment of rheumatoid arthritis was supplied by a fusillade of five consecutive strongly positive phase 3 trials presented during a single session at the annual meeting of the American College of Rheumatology.

The session featured three randomized, double-blind, phase 3 trials of the Janus kinase inhibitor (JAKi) upadacitinib in more than 3,200 participants in three different clinical scenarios, known as the SELECT-COMPARE, SELECT-EARLY, and SELECT-MONOTHERAPY trials, along with two Japanese phase 3 trials of peficitinib, a JAK1 and -3 inhibitor, in a total of more than 1,000 rheumatoid arthritis patients.
 

Upadacitinib

SELECT-COMPARE: Roy M. Fleischmann, MD, presented the findings of this trial in which 1,629 patients with active RA inadequately responsive to methotrexate were randomized 2:2:1 to 26 weeks of once-daily oral upadacitinib at 15 mg, placebo, or 40 mg of adalimumab (Humira) by subcutaneous injection every 2 weeks, all on top of background stable doses of methotrexate.

Upadacitinib, a JAK1 selective agent, was the clear winner, trouncing placebo, unsurprisingly, but more importantly also proving statistically superior to adalimumab – the current go-to drug in patients with an insufficient response to methotrexate – in terms of across-the-board improvement in RA signs and symptoms, quality-of-life measures, and physical function. This result, coupled with the similarly positive findings of a trial of oral baricitinib (Olumiant) versus adalimumab in inadequate responders to methotrexate alone, and a third positive trial of oral tofacitinib (Xeljanz), have altered Dr. Fleischmann’s treatment philosophy.

“I think that these studies have changed the treatment paradigm. And I think if access – that is, costs – were the same, given a choice, if it were me, I would actually use a JAK inhibitor before I would use adalimumab, based on the results of these multiple studies in different populations,” said Dr. Fleischmann, a rheumatologist at the University of Texas Southwestern Medical Center, Dallas.

The two coprimary endpoints in SELECT-COMPARE were the week 12 American College of Rheumatology–defined 20% level of response (ACR 20) and a 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The ACR 20 response rate was 70.5% with upadacitinib 15 mg, significantly better than the 63% rate with adalimumab and the 36.4% rate with placebo. Similarly, the ACR 50 rate at 12 weeks was 45.2% with upadacitinib versus 29.1% with adalimumab, and ACR 70 rates were 24.9% and 13.5%, respectively.

“These are not small differences,” the rheumatologist observed. “That ACR 70 rate is almost doubled with upadacitinib.”

The rate for DAS28-CRP less than 2.6 at week 12 was 28.7% with upadacitinib, compared with 18% with adalimumab.

Improvements in pain scores and the Health Assessment Questionnaire Disability Index were also significantly greater with the JAKi, both at weeks 12 and 26.

As in the other two SELECT phase 3 trials presented at the meeting, the response to upadacitinib was quick: The JAKi was superior to placebo on the efficacy endpoints by week 2, and superior to adalimumab by week 4.

The week-12 Boolean remission rate, a stringent measure, was 9.8% in the upadacitinib group, more than twice the 4% rate with adalimumab. At week 26, the rates were 18.1% and 9.8%, respectively, a finding Dr. Fleischmann deemed “very impressive.”

Radiographic disease progression as measured by change in modified total Sharp score (mTSS) at week 26 was 0.92 with placebo, 0.24 with upadacitinib, and slightly better at 0.1 with adalimumab. Adalimumab was also slightly better than baricitinib by this metric in a separate randomized trial. But that’s not a deal breaker for Dr. Fleischmann.

“It’s a 0.1–Sharp unit difference over 6 months. So by the time a patient would be able to tell the difference clinically, if my calculation is correct they’ll be 712 years old,” he quipped.

Serious infection rates through 26 weeks were similar in the upadacitinib and adalimumab study arms, with both being higher than placebo. Venous thromboembolism occurred in one patient on placebo, two on upadacitinib, and three on adalimumab.

Peficitinib

Yoshiya Tanaka, MD, PhD, professor and chairman of the department of internal medicine at the University of Occupational and Environmental Health in Kitakyushu, Japan, presented the findings of two pivotal phase 3, placebo-controlled, double-blind clinical trials of peficitinib at 100 or 150 mg once daily in 1,025 Asian patients with active RA insufficiently responsive to methotrexate or other disease-modifying antirheumatic drugs. Both studies were positive for all the key endpoints. Based upon these results, the drug’s developer, Astellas Pharma, has filed for Japanese regulatory approval of peficitinib.

Which oral JAKi to use?

Some audience members, numbed by the parade of positive results, asked the investigators for guidance as to which JAKi to choose, and when.

“The upadacitinib dataset mirrors the two approved oral JAKis. The data all look very similar,” said Stanley B. Cohen, MD, codirector of the division of rheumatology at Presbyterian Hospital in Dallas and a former ACR president. “All the JAKis are effective; the safety profiles are similar. Can you help clinicians know what differentiates them? Why should I choose one or the other?”

Dr. Tanaka replied that, although much gets made of the between-agent differences in selectivity for JAK1, 2, and/or 3 inhibition, “In the human body we cannot see much difference in safety and efficacy.”

If indeed such differences exist, head-to-head randomized trials will be required to ferret them out, noted Dr. Fleischmann.

Dr. Smolen indicated rheumatologists ought to rejoice in the looming prospect of a fistful of JAKis to choose from.

“I always wondered which beta-blocker to use, and I always wondered which cholesterol-lowering drug to use, and which NSAID to use – and interestingly enough, one NSAID will work in you but not in me, and another will work in me but not in you. So I think we should be pleased that we will have several oral JAKis to choose from,” he said.

Dr. Fleischmann got in the final word: “The answer to your question is the way we always answer it in the office. It’s access. Whichever one has the best access for the patient is the one you would select.”

The SELECT trials were sponsored by AbbVie, and all the upadacitinib investigators reported receiving research funds from and serving as paid consultants to that company and numerous others. Dr. Tanaka reported receiving research grants from and serving as a paid consultant to Astellas Pharma and close to a dozen other pharmaceutical companies.

[email protected]

CHICAGO – A specific type of natural killer cell has for the first time been implicated as playing a key contributory role in the development of psoriatic arthritis in patients with psoriasis.

Bruce Jancin/MDedge News

This natural killer cell interacts with the CD94/NKG2A receptor, part of a system believed to have been in place in humans for more than 90 million years.

“We believe there is a possible role for the innate immune system in the development of psoriatic arthritis and its distinction from psoriasis,” Vinod Chandran, MD, PhD, declared at the annual meeting of the American College of Rheumatology.

Dr. Chandran, of the University of Toronto, presented an analysis of a discovery cohort comprising 1,155 patients with dermatologist-diagnosed psoriasis of greater than 10 years duration, 664 rheumatologist-diagnosed psoriatic arthritis patients, and 3,118 controls, all participants in the International Psoriasis and Arthritis Research Team program. These findings were then independently confirmed in a separate University of Toronto replication cohort of 659 psoriasis patients, 1,177 psoriatic arthritis patients of European ancestry, and 1,096 controls.

By way of background, the rheumatologist explained that psoriasis and psoriatic arthritis are known to differ in terms of their genetic architecture, the biggest difference being in the HLA class I region, where HLA-C predominates in psoriasis and HLA-B in psoriatic arthritis. These structurally unrelated forms of HLA class I are known to educate natural killer cells and shape their function. Dr. Chandran and his coinvestigators were eager to shed new light on the mechanisms by which this leads to rheumatic disease.

Humans can be divided into three groups based upon whether they are HLA-B21 methionine/methionine (M/M), HLA-B21 M/threonine (T), or HLA-B21 T/T. The B21 M types educate CD94/NKG2A-positive natural killer cells by delivering functional peptides to the CD94/NKG2A receptor, while the B21 T/T version does not.

In the discovery cohort, individuals with psoriatic arthritis turned out to be 36% more likely to be HLA-B21 M/M or HLA-B21 M/T than were the psoriasis patients, while the psoriasis patients were 22% less likely to be B21 M–positive than controls. These relationships were confirmed in the replication cohort, where psoriatic arthritis patients were 40% more likely to be B21 M–positive than psoriasis patients, and psoriasis patients were 18% less likely to be B21 M–positive than controls, with all of these differences being statistically significant.

While this is translational science, Dr. Chandran explained that it has important clinical implications. He and his coinvestigators are developing a genetic marker panel to differentiate psoriatic arthritis from psoriasis, as are other research groups. And the Toronto investigators are now convinced that including HLA-B21 M/M and HLA-B21 M/T in their evolving genetic test is worthwhile in terms of boosting the test’s predictive power. The 36%-40% increased risk of psoriatic arthritis associated with B21 M–positivity isn’t sufficiently large for it to serve as a standalone test, but when the genetic test panel is finalized and the investigators can evaluate its positive and negative predictive value, it will be clear that the B21 M component will provide added value, he predicted.

Because psoriatic arthritis can take on a variety of disparate forms clinically, Dr. Chandran and his coworkers believe their genetic test will prove most useful for nonrheumatologists, especially dermatologists and primary care physicians.

He reported having no relevant financial relationships regarding this study, funded by the Canadian Institutes of Health Research, the Krembil Foundation, and the Arthritis Foundation.

[email protected]

SOURCE: Chandran V et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 2787.

CHICAGO – A specific type of natural killer cell has for the first time been implicated as playing a key contributory role in the development of psoriatic arthritis in patients with psoriasis.

Bruce Jancin/MDedge News

This natural killer cell interacts with the CD94/NKG2A receptor, part of a system believed to have been in place in humans for more than 90 million years.

“We believe there is a possible role for the innate immune system in the development of psoriatic arthritis and its distinction from psoriasis,” Vinod Chandran, MD, PhD, declared at the annual meeting of the American College of Rheumatology.

Dr. Chandran, of the University of Toronto, presented an analysis of a discovery cohort comprising 1,155 patients with dermatologist-diagnosed psoriasis of greater than 10 years duration, 664 rheumatologist-diagnosed psoriatic arthritis patients, and 3,118 controls, all participants in the International Psoriasis and Arthritis Research Team program. These findings were then independently confirmed in a separate University of Toronto replication cohort of 659 psoriasis patients, 1,177 psoriatic arthritis patients of European ancestry, and 1,096 controls.

By way of background, the rheumatologist explained that psoriasis and psoriatic arthritis are known to differ in terms of their genetic architecture, the biggest difference being in the HLA class I region, where HLA-C predominates in psoriasis and HLA-B in psoriatic arthritis. These structurally unrelated forms of HLA class I are known to educate natural killer cells and shape their function. Dr. Chandran and his coinvestigators were eager to shed new light on the mechanisms by which this leads to rheumatic disease.

Humans can be divided into three groups based upon whether they are HLA-B21 methionine/methionine (M/M), HLA-B21 M/threonine (T), or HLA-B21 T/T. The B21 M types educate CD94/NKG2A-positive natural killer cells by delivering functional peptides to the CD94/NKG2A receptor, while the B21 T/T version does not.

In the discovery cohort, individuals with psoriatic arthritis turned out to be 36% more likely to be HLA-B21 M/M or HLA-B21 M/T than were the psoriasis patients, while the psoriasis patients were 22% less likely to be B21 M–positive than controls. These relationships were confirmed in the replication cohort, where psoriatic arthritis patients were 40% more likely to be B21 M–positive than psoriasis patients, and psoriasis patients were 18% less likely to be B21 M–positive than controls, with all of these differences being statistically significant.

While this is translational science, Dr. Chandran explained that it has important clinical implications. He and his coinvestigators are developing a genetic marker panel to differentiate psoriatic arthritis from psoriasis, as are other research groups. And the Toronto investigators are now convinced that including HLA-B21 M/M and HLA-B21 M/T in their evolving genetic test is worthwhile in terms of boosting the test’s predictive power. The 36%-40% increased risk of psoriatic arthritis associated with B21 M–positivity isn’t sufficiently large for it to serve as a standalone test, but when the genetic test panel is finalized and the investigators can evaluate its positive and negative predictive value, it will be clear that the B21 M component will provide added value, he predicted.

Because psoriatic arthritis can take on a variety of disparate forms clinically, Dr. Chandran and his coworkers believe their genetic test will prove most useful for nonrheumatologists, especially dermatologists and primary care physicians.

He reported having no relevant financial relationships regarding this study, funded by the Canadian Institutes of Health Research, the Krembil Foundation, and the Arthritis Foundation.

[email protected]

SOURCE: Chandran V et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 2787.

CHICAGO – A specific type of natural killer cell has for the first time been implicated as playing a key contributory role in the development of psoriatic arthritis in patients with psoriasis.

Bruce Jancin/MDedge News

This natural killer cell interacts with the CD94/NKG2A receptor, part of a system believed to have been in place in humans for more than 90 million years.

“We believe there is a possible role for the innate immune system in the development of psoriatic arthritis and its distinction from psoriasis,” Vinod Chandran, MD, PhD, declared at the annual meeting of the American College of Rheumatology.

Dr. Chandran, of the University of Toronto, presented an analysis of a discovery cohort comprising 1,155 patients with dermatologist-diagnosed psoriasis of greater than 10 years duration, 664 rheumatologist-diagnosed psoriatic arthritis patients, and 3,118 controls, all participants in the International Psoriasis and Arthritis Research Team program. These findings were then independently confirmed in a separate University of Toronto replication cohort of 659 psoriasis patients, 1,177 psoriatic arthritis patients of European ancestry, and 1,096 controls.

By way of background, the rheumatologist explained that psoriasis and psoriatic arthritis are known to differ in terms of their genetic architecture, the biggest difference being in the HLA class I region, where HLA-C predominates in psoriasis and HLA-B in psoriatic arthritis. These structurally unrelated forms of HLA class I are known to educate natural killer cells and shape their function. Dr. Chandran and his coinvestigators were eager to shed new light on the mechanisms by which this leads to rheumatic disease.

Humans can be divided into three groups based upon whether they are HLA-B21 methionine/methionine (M/M), HLA-B21 M/threonine (T), or HLA-B21 T/T. The B21 M types educate CD94/NKG2A-positive natural killer cells by delivering functional peptides to the CD94/NKG2A receptor, while the B21 T/T version does not.

In the discovery cohort, individuals with psoriatic arthritis turned out to be 36% more likely to be HLA-B21 M/M or HLA-B21 M/T than were the psoriasis patients, while the psoriasis patients were 22% less likely to be B21 M–positive than controls. These relationships were confirmed in the replication cohort, where psoriatic arthritis patients were 40% more likely to be B21 M–positive than psoriasis patients, and psoriasis patients were 18% less likely to be B21 M–positive than controls, with all of these differences being statistically significant.

While this is translational science, Dr. Chandran explained that it has important clinical implications. He and his coinvestigators are developing a genetic marker panel to differentiate psoriatic arthritis from psoriasis, as are other research groups. And the Toronto investigators are now convinced that including HLA-B21 M/M and HLA-B21 M/T in their evolving genetic test is worthwhile in terms of boosting the test’s predictive power. The 36%-40% increased risk of psoriatic arthritis associated with B21 M–positivity isn’t sufficiently large for it to serve as a standalone test, but when the genetic test panel is finalized and the investigators can evaluate its positive and negative predictive value, it will be clear that the B21 M component will provide added value, he predicted.

Because psoriatic arthritis can take on a variety of disparate forms clinically, Dr. Chandran and his coworkers believe their genetic test will prove most useful for nonrheumatologists, especially dermatologists and primary care physicians.

He reported having no relevant financial relationships regarding this study, funded by the Canadian Institutes of Health Research, the Krembil Foundation, and the Arthritis Foundation.

[email protected]

SOURCE: Chandran V et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 2787.

CHICAGO – Canakinumab, a human monoclonal antibody targeting interleukin-1 beta, was associated with an eye-popping 45% relative risk reduction in the rate of total knee or hip replacement in a prespecified secondary analysis of the landmark CANTOS trial, Matthias Schieker, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

For the broader composite endpoint of all osteoarthritis-related adverse events, including new-onset OA or worsening of symptoms in those with OA at baseline, the relative risk reduction was 23% in patients randomized to canakinumab rather than placebo. For CANTOS participants who already had OA at baseline, the relative risk reduction was 31%, according to Dr. Schieker, who is head of the joint, bone, and tendon disease group at the Novartis Institute for Biomedical Research in Basel, Switzerland, and professor of regenerative medicine at the University of Munich.

CANTOS (the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) was designed as a massive phase 3 secondary cardiovascular prevention trial. It included 10,061 patients with a history of acute MI and an elevated high-sensitivity C-reactive protein (hsCRP) level of 2 mg/L or more who were randomized double blind to subcutaneous canakinumab at 50, 150, or 300 mg or placebo given once every 3 months. During a median 3.7 years of prospective follow-up, patients in the 150-mg group had a highly significant 17% reduction relative to placebo in the risk of the composite efficacy endpoint comprising cardiovascular death, MI, stroke, or hospitalization for unstable angina resulting in urgent coronary revascularization (N Engl J Med. 2017 Sep 21;377[12]:1119-31).

Since this result was achieved with a 39% reduction in CRP, compared with placebo, and involved no lipid-lowering effect, it was hailed in the cardiology world as the long-awaited proof of the inflammatory hypothesis of atherosclerotic cardiovascular disease.

CANTOS has proved to be the gift that keeps on giving. Secondary analyses of the study data have found statistically significant reductions in the incidence of and mortality caused by lung cancer in the coronary disease patients on canakinumab, as well as a decreased risk of developing gout. Moreover, the CANTOS investigators, well aware that there are no approved therapies to prevent disease progression in OA, had the foresight to prospectively collect data on OA-related symptoms and outcomes.

At baseline, 15.6% of CANTOS participants had a history of OA. During follow-up, patients in that subgroup had a 3.4% incidence of total knee replacement or total hip replacement if they had been assigned to canakinumab, compared with a 6.3% incidence if they got placebo. In the full 10,000-plus CANTOS cohort, the arthroplasty rates were 0.8% and 1.4%, respectively.

The combined rate of OA-related adverse events in the full CANTOS cohort was 5.4% with canakinumab and 7.0% with placebo. In the subgroup with baseline OA, the rates were 14.5% and 20.8%.

Canakinumab is marketed by Novartis as Ilaris and is already approved for cryopyrin-associated periodic syndromes, familial Mediterranean fever, juvenile idiopathic arthritis, and other rare autoimmune inflammatory diseases. Based upon the positive primary outcomes of the CANTOS trial, Novartis applied to the Food and Drug Administration for a major expanded indication of the IL-1B inhibitor for cardiovascular risk reduction. However, the regulatory agency has turned down that bid.

Although the CANTOS OA-related outcomes data caused quite a stir at the meeting, Dr. Schieker said in an interview that the impressive findings didn’t really come as a surprise to him.

“I think everyone in the field has assumed that IL-1 plays a role in OA. That idea has been around for quite a long time, but until now no effects could be shown in OA. We were lucky to have an enriched population with elevated hsCRP that was so large and followed for so long that we could finally show these relative risk reductions,” he explained.

[email protected]

SOURCE: Schieker M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 445.

CHICAGO – Canakinumab, a human monoclonal antibody targeting interleukin-1 beta, was associated with an eye-popping 45% relative risk reduction in the rate of total knee or hip replacement in a prespecified secondary analysis of the landmark CANTOS trial, Matthias Schieker, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

For the broader composite endpoint of all osteoarthritis-related adverse events, including new-onset OA or worsening of symptoms in those with OA at baseline, the relative risk reduction was 23% in patients randomized to canakinumab rather than placebo. For CANTOS participants who already had OA at baseline, the relative risk reduction was 31%, according to Dr. Schieker, who is head of the joint, bone, and tendon disease group at the Novartis Institute for Biomedical Research in Basel, Switzerland, and professor of regenerative medicine at the University of Munich.

CANTOS (the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) was designed as a massive phase 3 secondary cardiovascular prevention trial. It included 10,061 patients with a history of acute MI and an elevated high-sensitivity C-reactive protein (hsCRP) level of 2 mg/L or more who were randomized double blind to subcutaneous canakinumab at 50, 150, or 300 mg or placebo given once every 3 months. During a median 3.7 years of prospective follow-up, patients in the 150-mg group had a highly significant 17% reduction relative to placebo in the risk of the composite efficacy endpoint comprising cardiovascular death, MI, stroke, or hospitalization for unstable angina resulting in urgent coronary revascularization (N Engl J Med. 2017 Sep 21;377[12]:1119-31).

Since this result was achieved with a 39% reduction in CRP, compared with placebo, and involved no lipid-lowering effect, it was hailed in the cardiology world as the long-awaited proof of the inflammatory hypothesis of atherosclerotic cardiovascular disease.

CANTOS has proved to be the gift that keeps on giving. Secondary analyses of the study data have found statistically significant reductions in the incidence of and mortality caused by lung cancer in the coronary disease patients on canakinumab, as well as a decreased risk of developing gout. Moreover, the CANTOS investigators, well aware that there are no approved therapies to prevent disease progression in OA, had the foresight to prospectively collect data on OA-related symptoms and outcomes.

At baseline, 15.6% of CANTOS participants had a history of OA. During follow-up, patients in that subgroup had a 3.4% incidence of total knee replacement or total hip replacement if they had been assigned to canakinumab, compared with a 6.3% incidence if they got placebo. In the full 10,000-plus CANTOS cohort, the arthroplasty rates were 0.8% and 1.4%, respectively.

The combined rate of OA-related adverse events in the full CANTOS cohort was 5.4% with canakinumab and 7.0% with placebo. In the subgroup with baseline OA, the rates were 14.5% and 20.8%.

Canakinumab is marketed by Novartis as Ilaris and is already approved for cryopyrin-associated periodic syndromes, familial Mediterranean fever, juvenile idiopathic arthritis, and other rare autoimmune inflammatory diseases. Based upon the positive primary outcomes of the CANTOS trial, Novartis applied to the Food and Drug Administration for a major expanded indication of the IL-1B inhibitor for cardiovascular risk reduction. However, the regulatory agency has turned down that bid.

Although the CANTOS OA-related outcomes data caused quite a stir at the meeting, Dr. Schieker said in an interview that the impressive findings didn’t really come as a surprise to him.

“I think everyone in the field has assumed that IL-1 plays a role in OA. That idea has been around for quite a long time, but until now no effects could be shown in OA. We were lucky to have an enriched population with elevated hsCRP that was so large and followed for so long that we could finally show these relative risk reductions,” he explained.

[email protected]

SOURCE: Schieker M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 445.

CHICAGO – Canakinumab, a human monoclonal antibody targeting interleukin-1 beta, was associated with an eye-popping 45% relative risk reduction in the rate of total knee or hip replacement in a prespecified secondary analysis of the landmark CANTOS trial, Matthias Schieker, MD, reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

For the broader composite endpoint of all osteoarthritis-related adverse events, including new-onset OA or worsening of symptoms in those with OA at baseline, the relative risk reduction was 23% in patients randomized to canakinumab rather than placebo. For CANTOS participants who already had OA at baseline, the relative risk reduction was 31%, according to Dr. Schieker, who is head of the joint, bone, and tendon disease group at the Novartis Institute for Biomedical Research in Basel, Switzerland, and professor of regenerative medicine at the University of Munich.

CANTOS (the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) was designed as a massive phase 3 secondary cardiovascular prevention trial. It included 10,061 patients with a history of acute MI and an elevated high-sensitivity C-reactive protein (hsCRP) level of 2 mg/L or more who were randomized double blind to subcutaneous canakinumab at 50, 150, or 300 mg or placebo given once every 3 months. During a median 3.7 years of prospective follow-up, patients in the 150-mg group had a highly significant 17% reduction relative to placebo in the risk of the composite efficacy endpoint comprising cardiovascular death, MI, stroke, or hospitalization for unstable angina resulting in urgent coronary revascularization (N Engl J Med. 2017 Sep 21;377[12]:1119-31).

Since this result was achieved with a 39% reduction in CRP, compared with placebo, and involved no lipid-lowering effect, it was hailed in the cardiology world as the long-awaited proof of the inflammatory hypothesis of atherosclerotic cardiovascular disease.

CANTOS has proved to be the gift that keeps on giving. Secondary analyses of the study data have found statistically significant reductions in the incidence of and mortality caused by lung cancer in the coronary disease patients on canakinumab, as well as a decreased risk of developing gout. Moreover, the CANTOS investigators, well aware that there are no approved therapies to prevent disease progression in OA, had the foresight to prospectively collect data on OA-related symptoms and outcomes.

At baseline, 15.6% of CANTOS participants had a history of OA. During follow-up, patients in that subgroup had a 3.4% incidence of total knee replacement or total hip replacement if they had been assigned to canakinumab, compared with a 6.3% incidence if they got placebo. In the full 10,000-plus CANTOS cohort, the arthroplasty rates were 0.8% and 1.4%, respectively.

The combined rate of OA-related adverse events in the full CANTOS cohort was 5.4% with canakinumab and 7.0% with placebo. In the subgroup with baseline OA, the rates were 14.5% and 20.8%.

Canakinumab is marketed by Novartis as Ilaris and is already approved for cryopyrin-associated periodic syndromes, familial Mediterranean fever, juvenile idiopathic arthritis, and other rare autoimmune inflammatory diseases. Based upon the positive primary outcomes of the CANTOS trial, Novartis applied to the Food and Drug Administration for a major expanded indication of the IL-1B inhibitor for cardiovascular risk reduction. However, the regulatory agency has turned down that bid.

Although the CANTOS OA-related outcomes data caused quite a stir at the meeting, Dr. Schieker said in an interview that the impressive findings didn’t really come as a surprise to him.

“I think everyone in the field has assumed that IL-1 plays a role in OA. That idea has been around for quite a long time, but until now no effects could be shown in OA. We were lucky to have an enriched population with elevated hsCRP that was so large and followed for so long that we could finally show these relative risk reductions,” he explained.

[email protected]

SOURCE: Schieker M et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 445.

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

Bruce Jancin/MDedge News

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

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

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

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

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

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

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

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

[email protected]

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

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

Bruce Jancin/MDedge News

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

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

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

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

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

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

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

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

[email protected]

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

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

Bruce Jancin/MDedge News

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

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

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

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

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

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

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

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

[email protected]

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

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

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

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

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

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

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

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

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

Genentech sponsored the study.

[email protected]

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

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

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

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

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

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

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

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

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

Genentech sponsored the study.

[email protected]

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

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

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

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

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

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

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

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

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

Genentech sponsored the study.

[email protected]

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

CHICAGO – A physician’s baseline opioid prescribing rate strongly predicts future chronic opioid use in rheumatoid arthritis patients, an analysis of data from the Consortium of Rheumatology Researchers of North America (Corrona) Rheumatoid Arthritis Registry suggests.

sdominick/iStock/Getty Images

The baseline 12-month opioid prescribing rate of 148 physicians in the initial cohort varied widely from 0% to 70% (median, 27%), and among 9,337 patients in the registry beyond the baseline 12 months, physician opioid prescribing rates during the baseline period were significantly associated with risk for chronic opioid use, Yvonne C. Lee, MD, reported at the annual meeting of the American College of Rheumatology. She and her colleagues defined chronic opioid use as any opioid use during at least two consecutive study visits.

“It is important to understand the relative contributions of patient vs. physician characteristics on chronic opioid use,” said Dr. Lee of Northwestern University, Chicago. She that the goals of the current study were to identify the extent to which rheumatologists in the United States varied in baseline opioid prescribing rates and to determine the implications of baseline prescribing rates with respect to future chronic opioid use.

Compared with the lowest quartile of baseline opioid prescribing (rate of 18% or less), the second, third, and fourth quartiles of prescribing were associated with increasing odds of chronic opioid use (odds ratios of 1.16, 1.89, and 2.01 for the quartiles, respectively) during the study period, she said.

The researchers saw similar relationships when they used a stricter definition of opioid use and when they extended the cutoff between the baseline and study periods to 18 months. The relationships persisted after adjusting for numerous patient characteristics, such as age, sex, race, insurance status, RA duration, and treatments used, she said.

Subgroup analyses were also conducted to examine heterogeneity across clinical characteristics, including Clinical Disease Activity Index score (10 or less vs. greater than 10), pain intensity (scores of 40 or less, greater than 40 to 60, and greater than 60 out of 100), and use vs. nonuse of antidepressant medication. The relationships between physician baseline prescribing and chronic opioid use were similar across subgroups, she noted.

The findings help to characterize the role of rheumatologists’ prescribing rates in the ongoing opioid crisis even though the conclusions that can be reached are limited by the fact that some patients may receive opioid prescriptions from physicians outside the registry, by a lack of data on specific opioid types and doses, and by a lack of detailed information about physician characteristics, Dr. Lee said.

Physicians were included in the analysis only if they had contributed at least 10 RA patients to the registry within their first year of participation, and patients were included if they were patients of those physicians, if they had at least 12 months of follow-up data available, and if they were not prevalent opioid users at study entry.

A long-term goal is to target interventions to appropriate subgroups, she said, noting that 21%-29% of patients who are prescribed opioids for chronic pain misuse them, and more than 33,000 Americans die of opioid overdoses each year.

“Implications [of the findings] are that, in addition to targeting patients, we may also really want to consider interventions that target high-intensity prescribers. This may be useful for helping to decrease chronic opioid use in patients,” she concluded.

Dr. Lee has an investigator-initiated grant from Pfizer and owns stock in Express Scripts.

[email protected]

SOURCE: Lee Y et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1917

CHICAGO – A physician’s baseline opioid prescribing rate strongly predicts future chronic opioid use in rheumatoid arthritis patients, an analysis of data from the Consortium of Rheumatology Researchers of North America (Corrona) Rheumatoid Arthritis Registry suggests.

sdominick/iStock/Getty Images

The baseline 12-month opioid prescribing rate of 148 physicians in the initial cohort varied widely from 0% to 70% (median, 27%), and among 9,337 patients in the registry beyond the baseline 12 months, physician opioid prescribing rates during the baseline period were significantly associated with risk for chronic opioid use, Yvonne C. Lee, MD, reported at the annual meeting of the American College of Rheumatology. She and her colleagues defined chronic opioid use as any opioid use during at least two consecutive study visits.

“It is important to understand the relative contributions of patient vs. physician characteristics on chronic opioid use,” said Dr. Lee of Northwestern University, Chicago. She that the goals of the current study were to identify the extent to which rheumatologists in the United States varied in baseline opioid prescribing rates and to determine the implications of baseline prescribing rates with respect to future chronic opioid use.

Compared with the lowest quartile of baseline opioid prescribing (rate of 18% or less), the second, third, and fourth quartiles of prescribing were associated with increasing odds of chronic opioid use (odds ratios of 1.16, 1.89, and 2.01 for the quartiles, respectively) during the study period, she said.

The researchers saw similar relationships when they used a stricter definition of opioid use and when they extended the cutoff between the baseline and study periods to 18 months. The relationships persisted after adjusting for numerous patient characteristics, such as age, sex, race, insurance status, RA duration, and treatments used, she said.

Subgroup analyses were also conducted to examine heterogeneity across clinical characteristics, including Clinical Disease Activity Index score (10 or less vs. greater than 10), pain intensity (scores of 40 or less, greater than 40 to 60, and greater than 60 out of 100), and use vs. nonuse of antidepressant medication. The relationships between physician baseline prescribing and chronic opioid use were similar across subgroups, she noted.

The findings help to characterize the role of rheumatologists’ prescribing rates in the ongoing opioid crisis even though the conclusions that can be reached are limited by the fact that some patients may receive opioid prescriptions from physicians outside the registry, by a lack of data on specific opioid types and doses, and by a lack of detailed information about physician characteristics, Dr. Lee said.

Physicians were included in the analysis only if they had contributed at least 10 RA patients to the registry within their first year of participation, and patients were included if they were patients of those physicians, if they had at least 12 months of follow-up data available, and if they were not prevalent opioid users at study entry.

A long-term goal is to target interventions to appropriate subgroups, she said, noting that 21%-29% of patients who are prescribed opioids for chronic pain misuse them, and more than 33,000 Americans die of opioid overdoses each year.

“Implications [of the findings] are that, in addition to targeting patients, we may also really want to consider interventions that target high-intensity prescribers. This may be useful for helping to decrease chronic opioid use in patients,” she concluded.

Dr. Lee has an investigator-initiated grant from Pfizer and owns stock in Express Scripts.

[email protected]

SOURCE: Lee Y et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1917

CHICAGO – A physician’s baseline opioid prescribing rate strongly predicts future chronic opioid use in rheumatoid arthritis patients, an analysis of data from the Consortium of Rheumatology Researchers of North America (Corrona) Rheumatoid Arthritis Registry suggests.

sdominick/iStock/Getty Images

The baseline 12-month opioid prescribing rate of 148 physicians in the initial cohort varied widely from 0% to 70% (median, 27%), and among 9,337 patients in the registry beyond the baseline 12 months, physician opioid prescribing rates during the baseline period were significantly associated with risk for chronic opioid use, Yvonne C. Lee, MD, reported at the annual meeting of the American College of Rheumatology. She and her colleagues defined chronic opioid use as any opioid use during at least two consecutive study visits.

“It is important to understand the relative contributions of patient vs. physician characteristics on chronic opioid use,” said Dr. Lee of Northwestern University, Chicago. She that the goals of the current study were to identify the extent to which rheumatologists in the United States varied in baseline opioid prescribing rates and to determine the implications of baseline prescribing rates with respect to future chronic opioid use.

Compared with the lowest quartile of baseline opioid prescribing (rate of 18% or less), the second, third, and fourth quartiles of prescribing were associated with increasing odds of chronic opioid use (odds ratios of 1.16, 1.89, and 2.01 for the quartiles, respectively) during the study period, she said.

The researchers saw similar relationships when they used a stricter definition of opioid use and when they extended the cutoff between the baseline and study periods to 18 months. The relationships persisted after adjusting for numerous patient characteristics, such as age, sex, race, insurance status, RA duration, and treatments used, she said.

Subgroup analyses were also conducted to examine heterogeneity across clinical characteristics, including Clinical Disease Activity Index score (10 or less vs. greater than 10), pain intensity (scores of 40 or less, greater than 40 to 60, and greater than 60 out of 100), and use vs. nonuse of antidepressant medication. The relationships between physician baseline prescribing and chronic opioid use were similar across subgroups, she noted.

The findings help to characterize the role of rheumatologists’ prescribing rates in the ongoing opioid crisis even though the conclusions that can be reached are limited by the fact that some patients may receive opioid prescriptions from physicians outside the registry, by a lack of data on specific opioid types and doses, and by a lack of detailed information about physician characteristics, Dr. Lee said.

Physicians were included in the analysis only if they had contributed at least 10 RA patients to the registry within their first year of participation, and patients were included if they were patients of those physicians, if they had at least 12 months of follow-up data available, and if they were not prevalent opioid users at study entry.

A long-term goal is to target interventions to appropriate subgroups, she said, noting that 21%-29% of patients who are prescribed opioids for chronic pain misuse them, and more than 33,000 Americans die of opioid overdoses each year.

“Implications [of the findings] are that, in addition to targeting patients, we may also really want to consider interventions that target high-intensity prescribers. This may be useful for helping to decrease chronic opioid use in patients,” she concluded.

Dr. Lee has an investigator-initiated grant from Pfizer and owns stock in Express Scripts.

[email protected]

SOURCE: Lee Y et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 1917

CHICAGO – Fibromyalgia assessment screening tool (FAST) indices derived from the Multidimensional Health Assessment Questionnaire (MDHAQ) provide a simple and effective method for identifying fibromyalgia in routine care, according to findings from a series of more than 500 patients.

Sharon Worcester/MDedge News

The indices are as accurate as the existing – and more complex – diagnostic criteria for fibromyalgia, Juan Schmukler, MD, reported at the annual meeting of the American College of Rheumatology.

For example, three FAST indices developed in the course of the study had better performance versus existing diagnostic criteria than did certain individual MDHAQ scales alone (area under the curve range, 0.924-0.937 vs. 0.829-0.889, respectively), said Dr. Schmukler, who conducted the research as a medical student at Rush Medical College, Chicago, and is now a rheumatology fellow at Mount Sinai Hospital in Chicago.

The findings are notable, because the two-page MDHAQ and a summary index (the RAPID3) derived from three of the MDHAQ scales are already used routinely in clinical care for diagnosing rheumatic diseases, and the new indices could easily – and with minimal work flow disruption – also be incorporated for each patient at each visit.

“Fibromyalgia is common in the general population and it is believed to be more common in patients with other rheumatic diagnoses,” Dr. Schmukler said. “Fibromyalgia may be easily recognized in many cases, but it can also be very subtle, particularly in patients who have other rheumatic diseases.”

ACR fibromyalgia classification criteria published in 1990 were based on tender point examination and non-ACR diagnostic criteria as revised in 2011 are based entirely on patient self-report.


A one-page fibromyalgia criteria questionnaire is available and is useful in clinical trials and other research, but is “rarely, if ever” used in routine care, he said, explaining that the questionnaire contains two domains: a symptom severity score (0-12 scale) and a widespread pain index (0-19 scale).

The MDHAQ/RAPID3 is informative in RA, and has also been shown to be “useful in all rheumatic diseases in which it has been studied,” and at least three prior reports have suggested that the MDHAQ may also provide clues to the presence of fibromyalgia, Dr. Schmukler said.

“And we know from prior reports that patients with fibromyalgia reported the highest RAPID3 scores, compared to other rheumatic disease,” he added, explaining that the goal of the present study was to develop FAST cumulative indices based on the routine MDHAQ scales and using the 2011 diagnostic criteria as a reference standard.

All patients with all diagnoses seen at the Rush Medical College rheumatology clinic in Chicago complete the MDHAQ at all visits in routine care, and between April and July 2017, the fibromyalgia criteria questionnaire was also administered in 502 consecutive patients.

Of those patients, 131 met the 2011 fibromyalgia diagnostic criteria.

MDHAQ scores were analyzed for agreement with the fibromyalgia criteria questionnaire according to receiver operator characteristic curves for AUC and were compiled into three different FAST indices that included various combinations of either three or four of the MDHAQ measures that had the best agreement with the diagnostic criteria questionnaire as identified by the highest AUC values. Those were the 60-symptom checklist (AUC, 0.889), painful joint count (AUC, 0.870), fatigue visual analog scale (VAS; AUC, 0.860), and pain VAS (AUC, 0.829), Dr. Schmukler said.

Proposed cut points that reflected the optimal trade-off between specificity and sensitivity for each of the scales were scores of 6 or greater for the pain VAS and fatigue VAS, and scores of 16 or greater for the symptom checklist and painful joint count measure.

In addition to the better performance of each FAST index versus the 2011 criteria, their performance was also better than that of the RAPID3 versus the 2011 criteria (AUC, 0.848), which many clinicians use in practice without using the full MDHAQ for patient assessment, he said.

Further, the “very easily calculated” FAST indices performed as well as a “very difficult to calculate” polysymptomatic distress continuous scale derived from the fibromyalgia questionnaire to assess the degree of fibromyalgia symptoms, which had an AUC of 0.929 versus the 2011 criteria. The latter index requires complex mathematical calculations for scale conversion and thus is impractical in clinical practice, he noted.

The FAST indices also performed comparably with physician diagnoses as indicated in patient charts and with diagnoses based on tender point count as shown in prior studies.

The FAST index with the greatest sensitivity (85.5% at a cut point of 2 or greater on a scale of 1-3) was the FAST3-P, which includes pain VAS score of 6 or greater, symptom checklist score of 16 or greater, and painful joint count of 16 or greater. The FAST index with the greatest specificity (90.3% at a cut point of score of 3 or greater on a scale of 1-4) was the FAST4 index, which includes a pain VAS score of 6 or greater, fatigue VAS score of 6 or greater, symptom checklist score of 16 or greater, and painful joint count of 16 or greater.

Although the findings are limited by the lack of a gold standard for fibromyalgia diagnosis, changing diagnostic criteria, and a need for physician input for a fibromyalgia diagnosis, the study provides useful real-world data and supports findings from some prior studies with respect to the benefit of using these tools in routine practice.

With minimal extra physician time – if the MDHAQ is completed by patients at the time of registration – this approach can be used in all rheumatology patients to help identify fibromyalgia, he concluded.

Dr. Schmukler reported having no disclosures. One of his coauthors at Rush, Ted Pincus, MD, receives royalties and license fees for the copyright and trademark for the MDHAQ and RAPID3, all of which go to support clinical research.

[email protected]

SOURCE: Schmukler J et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 839.

CHICAGO – Fibromyalgia assessment screening tool (FAST) indices derived from the Multidimensional Health Assessment Questionnaire (MDHAQ) provide a simple and effective method for identifying fibromyalgia in routine care, according to findings from a series of more than 500 patients.

Sharon Worcester/MDedge News

The indices are as accurate as the existing – and more complex – diagnostic criteria for fibromyalgia, Juan Schmukler, MD, reported at the annual meeting of the American College of Rheumatology.

For example, three FAST indices developed in the course of the study had better performance versus existing diagnostic criteria than did certain individual MDHAQ scales alone (area under the curve range, 0.924-0.937 vs. 0.829-0.889, respectively), said Dr. Schmukler, who conducted the research as a medical student at Rush Medical College, Chicago, and is now a rheumatology fellow at Mount Sinai Hospital in Chicago.

The findings are notable, because the two-page MDHAQ and a summary index (the RAPID3) derived from three of the MDHAQ scales are already used routinely in clinical care for diagnosing rheumatic diseases, and the new indices could easily – and with minimal work flow disruption – also be incorporated for each patient at each visit.

“Fibromyalgia is common in the general population and it is believed to be more common in patients with other rheumatic diagnoses,” Dr. Schmukler said. “Fibromyalgia may be easily recognized in many cases, but it can also be very subtle, particularly in patients who have other rheumatic diseases.”

ACR fibromyalgia classification criteria published in 1990 were based on tender point examination and non-ACR diagnostic criteria as revised in 2011 are based entirely on patient self-report.


A one-page fibromyalgia criteria questionnaire is available and is useful in clinical trials and other research, but is “rarely, if ever” used in routine care, he said, explaining that the questionnaire contains two domains: a symptom severity score (0-12 scale) and a widespread pain index (0-19 scale).

The MDHAQ/RAPID3 is informative in RA, and has also been shown to be “useful in all rheumatic diseases in which it has been studied,” and at least three prior reports have suggested that the MDHAQ may also provide clues to the presence of fibromyalgia, Dr. Schmukler said.

“And we know from prior reports that patients with fibromyalgia reported the highest RAPID3 scores, compared to other rheumatic disease,” he added, explaining that the goal of the present study was to develop FAST cumulative indices based on the routine MDHAQ scales and using the 2011 diagnostic criteria as a reference standard.

All patients with all diagnoses seen at the Rush Medical College rheumatology clinic in Chicago complete the MDHAQ at all visits in routine care, and between April and July 2017, the fibromyalgia criteria questionnaire was also administered in 502 consecutive patients.

Of those patients, 131 met the 2011 fibromyalgia diagnostic criteria.

MDHAQ scores were analyzed for agreement with the fibromyalgia criteria questionnaire according to receiver operator characteristic curves for AUC and were compiled into three different FAST indices that included various combinations of either three or four of the MDHAQ measures that had the best agreement with the diagnostic criteria questionnaire as identified by the highest AUC values. Those were the 60-symptom checklist (AUC, 0.889), painful joint count (AUC, 0.870), fatigue visual analog scale (VAS; AUC, 0.860), and pain VAS (AUC, 0.829), Dr. Schmukler said.

Proposed cut points that reflected the optimal trade-off between specificity and sensitivity for each of the scales were scores of 6 or greater for the pain VAS and fatigue VAS, and scores of 16 or greater for the symptom checklist and painful joint count measure.

In addition to the better performance of each FAST index versus the 2011 criteria, their performance was also better than that of the RAPID3 versus the 2011 criteria (AUC, 0.848), which many clinicians use in practice without using the full MDHAQ for patient assessment, he said.

Further, the “very easily calculated” FAST indices performed as well as a “very difficult to calculate” polysymptomatic distress continuous scale derived from the fibromyalgia questionnaire to assess the degree of fibromyalgia symptoms, which had an AUC of 0.929 versus the 2011 criteria. The latter index requires complex mathematical calculations for scale conversion and thus is impractical in clinical practice, he noted.

The FAST indices also performed comparably with physician diagnoses as indicated in patient charts and with diagnoses based on tender point count as shown in prior studies.

The FAST index with the greatest sensitivity (85.5% at a cut point of 2 or greater on a scale of 1-3) was the FAST3-P, which includes pain VAS score of 6 or greater, symptom checklist score of 16 or greater, and painful joint count of 16 or greater. The FAST index with the greatest specificity (90.3% at a cut point of score of 3 or greater on a scale of 1-4) was the FAST4 index, which includes a pain VAS score of 6 or greater, fatigue VAS score of 6 or greater, symptom checklist score of 16 or greater, and painful joint count of 16 or greater.

Although the findings are limited by the lack of a gold standard for fibromyalgia diagnosis, changing diagnostic criteria, and a need for physician input for a fibromyalgia diagnosis, the study provides useful real-world data and supports findings from some prior studies with respect to the benefit of using these tools in routine practice.

With minimal extra physician time – if the MDHAQ is completed by patients at the time of registration – this approach can be used in all rheumatology patients to help identify fibromyalgia, he concluded.

Dr. Schmukler reported having no disclosures. One of his coauthors at Rush, Ted Pincus, MD, receives royalties and license fees for the copyright and trademark for the MDHAQ and RAPID3, all of which go to support clinical research.

[email protected]

SOURCE: Schmukler J et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 839.

CHICAGO – Fibromyalgia assessment screening tool (FAST) indices derived from the Multidimensional Health Assessment Questionnaire (MDHAQ) provide a simple and effective method for identifying fibromyalgia in routine care, according to findings from a series of more than 500 patients.

Sharon Worcester/MDedge News

The indices are as accurate as the existing – and more complex – diagnostic criteria for fibromyalgia, Juan Schmukler, MD, reported at the annual meeting of the American College of Rheumatology.

For example, three FAST indices developed in the course of the study had better performance versus existing diagnostic criteria than did certain individual MDHAQ scales alone (area under the curve range, 0.924-0.937 vs. 0.829-0.889, respectively), said Dr. Schmukler, who conducted the research as a medical student at Rush Medical College, Chicago, and is now a rheumatology fellow at Mount Sinai Hospital in Chicago.

The findings are notable, because the two-page MDHAQ and a summary index (the RAPID3) derived from three of the MDHAQ scales are already used routinely in clinical care for diagnosing rheumatic diseases, and the new indices could easily – and with minimal work flow disruption – also be incorporated for each patient at each visit.

“Fibromyalgia is common in the general population and it is believed to be more common in patients with other rheumatic diagnoses,” Dr. Schmukler said. “Fibromyalgia may be easily recognized in many cases, but it can also be very subtle, particularly in patients who have other rheumatic diseases.”

ACR fibromyalgia classification criteria published in 1990 were based on tender point examination and non-ACR diagnostic criteria as revised in 2011 are based entirely on patient self-report.


A one-page fibromyalgia criteria questionnaire is available and is useful in clinical trials and other research, but is “rarely, if ever” used in routine care, he said, explaining that the questionnaire contains two domains: a symptom severity score (0-12 scale) and a widespread pain index (0-19 scale).

The MDHAQ/RAPID3 is informative in RA, and has also been shown to be “useful in all rheumatic diseases in which it has been studied,” and at least three prior reports have suggested that the MDHAQ may also provide clues to the presence of fibromyalgia, Dr. Schmukler said.

“And we know from prior reports that patients with fibromyalgia reported the highest RAPID3 scores, compared to other rheumatic disease,” he added, explaining that the goal of the present study was to develop FAST cumulative indices based on the routine MDHAQ scales and using the 2011 diagnostic criteria as a reference standard.

All patients with all diagnoses seen at the Rush Medical College rheumatology clinic in Chicago complete the MDHAQ at all visits in routine care, and between April and July 2017, the fibromyalgia criteria questionnaire was also administered in 502 consecutive patients.

Of those patients, 131 met the 2011 fibromyalgia diagnostic criteria.

MDHAQ scores were analyzed for agreement with the fibromyalgia criteria questionnaire according to receiver operator characteristic curves for AUC and were compiled into three different FAST indices that included various combinations of either three or four of the MDHAQ measures that had the best agreement with the diagnostic criteria questionnaire as identified by the highest AUC values. Those were the 60-symptom checklist (AUC, 0.889), painful joint count (AUC, 0.870), fatigue visual analog scale (VAS; AUC, 0.860), and pain VAS (AUC, 0.829), Dr. Schmukler said.

Proposed cut points that reflected the optimal trade-off between specificity and sensitivity for each of the scales were scores of 6 or greater for the pain VAS and fatigue VAS, and scores of 16 or greater for the symptom checklist and painful joint count measure.

In addition to the better performance of each FAST index versus the 2011 criteria, their performance was also better than that of the RAPID3 versus the 2011 criteria (AUC, 0.848), which many clinicians use in practice without using the full MDHAQ for patient assessment, he said.

Further, the “very easily calculated” FAST indices performed as well as a “very difficult to calculate” polysymptomatic distress continuous scale derived from the fibromyalgia questionnaire to assess the degree of fibromyalgia symptoms, which had an AUC of 0.929 versus the 2011 criteria. The latter index requires complex mathematical calculations for scale conversion and thus is impractical in clinical practice, he noted.

The FAST indices also performed comparably with physician diagnoses as indicated in patient charts and with diagnoses based on tender point count as shown in prior studies.

The FAST index with the greatest sensitivity (85.5% at a cut point of 2 or greater on a scale of 1-3) was the FAST3-P, which includes pain VAS score of 6 or greater, symptom checklist score of 16 or greater, and painful joint count of 16 or greater. The FAST index with the greatest specificity (90.3% at a cut point of score of 3 or greater on a scale of 1-4) was the FAST4 index, which includes a pain VAS score of 6 or greater, fatigue VAS score of 6 or greater, symptom checklist score of 16 or greater, and painful joint count of 16 or greater.

Although the findings are limited by the lack of a gold standard for fibromyalgia diagnosis, changing diagnostic criteria, and a need for physician input for a fibromyalgia diagnosis, the study provides useful real-world data and supports findings from some prior studies with respect to the benefit of using these tools in routine practice.

With minimal extra physician time – if the MDHAQ is completed by patients at the time of registration – this approach can be used in all rheumatology patients to help identify fibromyalgia, he concluded.

Dr. Schmukler reported having no disclosures. One of his coauthors at Rush, Ted Pincus, MD, receives royalties and license fees for the copyright and trademark for the MDHAQ and RAPID3, all of which go to support clinical research.

[email protected]

SOURCE: Schmukler J et al. Arthritis Rheumatol. 2018;70(Suppl 10), Abstract 839.

CHICAGO – After 52 weeks of blinded adalimumab, a switch to 48 weeks of unblinded baricitinib without an adalimumab washout period resulted in an uptick in rheumatoid arthritis control with no flares and no increase in serious adverse events in the phase 3 RA-BEYOND baricitinib long-term extension study, Michael E. Weinblatt, MD, reported at the annual meeting of the American College of Rheumatology. 

That’s information of practical clinical utility now that baricitinib, an oral inhibitor of Janus kinase subtypes 1 and 2, is approved as Olumiant for the treatment of moderate to severely active rheumatoid arthritis (RA). Perhaps even more interesting, however, is the way RA-BEYOND shined a spotlight on the high placebo response rate endemic to RA clinical trials, according to Dr. Weinblatt, professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital, Boston.

He presented an analysis of two patient groups: 381 RA patients with moderately to severely active RA at baseline who were randomized to 52 weeks of double-blind baricitinib at 4 mg once daily in the previously reported phase 3 RA-BEAM trial (N Engl J Med. 2017 Feb 16;376[7]:652-62), after which they immediately enrolled in RA-BEYOND and were switched to 48 weeks of open-label, unblinded baricitinib; and 238 RA patients who were randomized to double-blind subcutaneous adalimumab (Humira) at 40 mg every 2 weeks in RA-BEAM before being switched to unblinded baricitinib in RA-BEYOND. All participants were on background oral methotrexate throughout.

Here’s the finding that captured Dr. Weinblatt’s attention: At the time of the switch, 28.2% of patients who’d been on blinded baricitinib for 52 weeks were nonresponders to the drug, meaning that after a full year of treatment they had a Clinical Disease Activity Index (CDAI) score greater than 10. Yet after a mere additional 4 weeks on the same drug in RA-BEYOND – this time unblinded as to their treatment – 23.4% of this group were transformed into responders, with low disease activity as defined by a CDAI of 10 or less. This finding speaks eloquently as to the power of the placebo effect. It’s a real issue for clinical trialists, the rheumatologist observed.

In the adalimumab-to-baricitinib group, 31.1% of patients were nonresponders to 52 weeks of blinded adalimumab. Four weeks after switching to open-label baricitinib, 29.7% of this group had a CDAI of 10 or less.

At week 48 of open-label baricitinib in RA-BEYOND, 54.2% of nonresponders to the 52 weeks of blinded baricitinib had become responders, as did 50% of nonresponders to a year of blinded adalimumab.

Taking a step back to describe the primary outcomes in RA-BEYOND, Dr. Weinblatt noted that at enrollment in RA-BEYOND, after 52 weeks on double-blind baricitinib, 71.8% of patients had a CDAI of 10 or less and 27% were in remission as defined by a CDAI of 2.8 or less. Subsequently, after 48 weeks on unblinded baricitinib, these rates climbed to 78.2% and 31.6%, respectively.

Similarly, in the adalimumab-to-baricitinib study arm, the low disease activity and remission rates at enrollment in RA-BEYOND were 68.9% and 24.4%, improving to 73.5% and 28.2% after 48 weeks on open-label baricitinib.

Scores on the SDAI (Simplified Disease Activity Index) and DAS28-ESR (Disease Activity Score based on 28 joints with erythrocyte sedimentation rate) followed suit in both groups.

During the 48 weeks of open-label baricitinib in RA-BEYOND, the incidence of herpes zoster was roughly 2.2% in both study arms, and the rate of adverse events leading to permanent drug discontinuation was 2.7%. During RA-BEYOND, serious infections occurred in 3.8% of the baricitinib-to-baricitinib group and 2.2% of the adalimumab-to-baricitinib group.

Dr. Weinblatt drew attention to the fact that the dose of baricitinib employed in RA-BEAM and RA-BEYOND was 4 mg/day, whereas the dose approved by the Food and Drug Administration is 2 mg/day.

The RA-BEAM and RA-BEYOND trials were sponsored by Eli Lilly. Dr. Weinblatt reported serving as a paid consultant to that pharmaceutical company and more than a dozen others.

[email protected]

SOURCE: Weinblatt ME et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 886.

CHICAGO – After 52 weeks of blinded adalimumab, a switch to 48 weeks of unblinded baricitinib without an adalimumab washout period resulted in an uptick in rheumatoid arthritis control with no flares and no increase in serious adverse events in the phase 3 RA-BEYOND baricitinib long-term extension study, Michael E. Weinblatt, MD, reported at the annual meeting of the American College of Rheumatology. 

That’s information of practical clinical utility now that baricitinib, an oral inhibitor of Janus kinase subtypes 1 and 2, is approved as Olumiant for the treatment of moderate to severely active rheumatoid arthritis (RA). Perhaps even more interesting, however, is the way RA-BEYOND shined a spotlight on the high placebo response rate endemic to RA clinical trials, according to Dr. Weinblatt, professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital, Boston.

He presented an analysis of two patient groups: 381 RA patients with moderately to severely active RA at baseline who were randomized to 52 weeks of double-blind baricitinib at 4 mg once daily in the previously reported phase 3 RA-BEAM trial (N Engl J Med. 2017 Feb 16;376[7]:652-62), after which they immediately enrolled in RA-BEYOND and were switched to 48 weeks of open-label, unblinded baricitinib; and 238 RA patients who were randomized to double-blind subcutaneous adalimumab (Humira) at 40 mg every 2 weeks in RA-BEAM before being switched to unblinded baricitinib in RA-BEYOND. All participants were on background oral methotrexate throughout.

Here’s the finding that captured Dr. Weinblatt’s attention: At the time of the switch, 28.2% of patients who’d been on blinded baricitinib for 52 weeks were nonresponders to the drug, meaning that after a full year of treatment they had a Clinical Disease Activity Index (CDAI) score greater than 10. Yet after a mere additional 4 weeks on the same drug in RA-BEYOND – this time unblinded as to their treatment – 23.4% of this group were transformed into responders, with low disease activity as defined by a CDAI of 10 or less. This finding speaks eloquently as to the power of the placebo effect. It’s a real issue for clinical trialists, the rheumatologist observed.

In the adalimumab-to-baricitinib group, 31.1% of patients were nonresponders to 52 weeks of blinded adalimumab. Four weeks after switching to open-label baricitinib, 29.7% of this group had a CDAI of 10 or less.

At week 48 of open-label baricitinib in RA-BEYOND, 54.2% of nonresponders to the 52 weeks of blinded baricitinib had become responders, as did 50% of nonresponders to a year of blinded adalimumab.

Taking a step back to describe the primary outcomes in RA-BEYOND, Dr. Weinblatt noted that at enrollment in RA-BEYOND, after 52 weeks on double-blind baricitinib, 71.8% of patients had a CDAI of 10 or less and 27% were in remission as defined by a CDAI of 2.8 or less. Subsequently, after 48 weeks on unblinded baricitinib, these rates climbed to 78.2% and 31.6%, respectively.

Similarly, in the adalimumab-to-baricitinib study arm, the low disease activity and remission rates at enrollment in RA-BEYOND were 68.9% and 24.4%, improving to 73.5% and 28.2% after 48 weeks on open-label baricitinib.

Scores on the SDAI (Simplified Disease Activity Index) and DAS28-ESR (Disease Activity Score based on 28 joints with erythrocyte sedimentation rate) followed suit in both groups.

During the 48 weeks of open-label baricitinib in RA-BEYOND, the incidence of herpes zoster was roughly 2.2% in both study arms, and the rate of adverse events leading to permanent drug discontinuation was 2.7%. During RA-BEYOND, serious infections occurred in 3.8% of the baricitinib-to-baricitinib group and 2.2% of the adalimumab-to-baricitinib group.

Dr. Weinblatt drew attention to the fact that the dose of baricitinib employed in RA-BEAM and RA-BEYOND was 4 mg/day, whereas the dose approved by the Food and Drug Administration is 2 mg/day.

The RA-BEAM and RA-BEYOND trials were sponsored by Eli Lilly. Dr. Weinblatt reported serving as a paid consultant to that pharmaceutical company and more than a dozen others.

[email protected]

SOURCE: Weinblatt ME et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 886.

CHICAGO – After 52 weeks of blinded adalimumab, a switch to 48 weeks of unblinded baricitinib without an adalimumab washout period resulted in an uptick in rheumatoid arthritis control with no flares and no increase in serious adverse events in the phase 3 RA-BEYOND baricitinib long-term extension study, Michael E. Weinblatt, MD, reported at the annual meeting of the American College of Rheumatology. 

That’s information of practical clinical utility now that baricitinib, an oral inhibitor of Janus kinase subtypes 1 and 2, is approved as Olumiant for the treatment of moderate to severely active rheumatoid arthritis (RA). Perhaps even more interesting, however, is the way RA-BEYOND shined a spotlight on the high placebo response rate endemic to RA clinical trials, according to Dr. Weinblatt, professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital, Boston.

He presented an analysis of two patient groups: 381 RA patients with moderately to severely active RA at baseline who were randomized to 52 weeks of double-blind baricitinib at 4 mg once daily in the previously reported phase 3 RA-BEAM trial (N Engl J Med. 2017 Feb 16;376[7]:652-62), after which they immediately enrolled in RA-BEYOND and were switched to 48 weeks of open-label, unblinded baricitinib; and 238 RA patients who were randomized to double-blind subcutaneous adalimumab (Humira) at 40 mg every 2 weeks in RA-BEAM before being switched to unblinded baricitinib in RA-BEYOND. All participants were on background oral methotrexate throughout.

Here’s the finding that captured Dr. Weinblatt’s attention: At the time of the switch, 28.2% of patients who’d been on blinded baricitinib for 52 weeks were nonresponders to the drug, meaning that after a full year of treatment they had a Clinical Disease Activity Index (CDAI) score greater than 10. Yet after a mere additional 4 weeks on the same drug in RA-BEYOND – this time unblinded as to their treatment – 23.4% of this group were transformed into responders, with low disease activity as defined by a CDAI of 10 or less. This finding speaks eloquently as to the power of the placebo effect. It’s a real issue for clinical trialists, the rheumatologist observed.

In the adalimumab-to-baricitinib group, 31.1% of patients were nonresponders to 52 weeks of blinded adalimumab. Four weeks after switching to open-label baricitinib, 29.7% of this group had a CDAI of 10 or less.

At week 48 of open-label baricitinib in RA-BEYOND, 54.2% of nonresponders to the 52 weeks of blinded baricitinib had become responders, as did 50% of nonresponders to a year of blinded adalimumab.

Taking a step back to describe the primary outcomes in RA-BEYOND, Dr. Weinblatt noted that at enrollment in RA-BEYOND, after 52 weeks on double-blind baricitinib, 71.8% of patients had a CDAI of 10 or less and 27% were in remission as defined by a CDAI of 2.8 or less. Subsequently, after 48 weeks on unblinded baricitinib, these rates climbed to 78.2% and 31.6%, respectively.

Similarly, in the adalimumab-to-baricitinib study arm, the low disease activity and remission rates at enrollment in RA-BEYOND were 68.9% and 24.4%, improving to 73.5% and 28.2% after 48 weeks on open-label baricitinib.

Scores on the SDAI (Simplified Disease Activity Index) and DAS28-ESR (Disease Activity Score based on 28 joints with erythrocyte sedimentation rate) followed suit in both groups.

During the 48 weeks of open-label baricitinib in RA-BEYOND, the incidence of herpes zoster was roughly 2.2% in both study arms, and the rate of adverse events leading to permanent drug discontinuation was 2.7%. During RA-BEYOND, serious infections occurred in 3.8% of the baricitinib-to-baricitinib group and 2.2% of the adalimumab-to-baricitinib group.

Dr. Weinblatt drew attention to the fact that the dose of baricitinib employed in RA-BEAM and RA-BEYOND was 4 mg/day, whereas the dose approved by the Food and Drug Administration is 2 mg/day.

The RA-BEAM and RA-BEYOND trials were sponsored by Eli Lilly. Dr. Weinblatt reported serving as a paid consultant to that pharmaceutical company and more than a dozen others.

[email protected]

SOURCE: Weinblatt ME et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 886.

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

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

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

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

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

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


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

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

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

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

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

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

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

Dr. Nihtyanova reported having no disclosures.

[email protected]

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

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

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

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

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

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

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


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

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

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

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

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

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

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

Dr. Nihtyanova reported having no disclosures.

[email protected]

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

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

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

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

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

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

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


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

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

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

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

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

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

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

Dr. Nihtyanova reported having no disclosures.

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Tsuji reported having no disclosures.

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Tsuji reported having no disclosures.

[email protected]

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

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

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

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

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

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

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

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

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

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

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

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

Dr. Tsuji reported having no disclosures.

[email protected]

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