Rheumatoid Arthritis

The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.

Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.

Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.

The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.

Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.

Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.

The VERVE study highlights a crucial topic for rheumatologists treating patients in clinical practice. The traditional thinking is to inform patients never to receive live vaccines when they are using TNF (tumor necrosis factor) inhibitors to treat their autoimmune disease. The VERVE study indicates that in the case of the Zostavax vaccine, patients on this form of biologic therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis can safely receive this preventive measure. This study scratches the surface on an important topic, and other studies need to follow.

Many patients on biologic therapy want to travel. Many times, international travel requires vaccination that is only in the form of a live vaccine – for example, the yellow fever vaccine. It would be useful for us to better understand whether other live vaccines can safely be administered and better inform our patients who want to travel. In addition, many times mothers with young infants are nervous if they are on biologic therapy and their children need to receive a live vaccine. They are concerned that their children will shed the live virus and they will be in jeopardy. This study highlights that this may be more of an antiquated way of thinking. We need more studies of this kind to better understand and advise our patients properly without instilling unwarranted fear.

Dr. Oberstein is a practicing rheumatologist at the University of Miami Health System and is senior medical director of musculoskeletal at Modernizing Medicine in Boca Raton, Fla. She has no relevant disclosures to report.

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

lfranki@mdedge.com

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

lfranki@mdedge.com

The Food and Drug Administration has cleared adalimumab-afzb (Abrilada) as the fifth approved Humira biosimilar and the 25th approved biosimilar drug overall, the agency said in a Nov. 15 announcement.

Olivier Le Moal/Getty Images

According to a press release from Pfizer, approval for Abrilada was based on review of a comprehensive data package demonstrating biosimilarity of the drug to the reference product. This included data from a clinical comparative study, which found no clinically meaningful difference between Abrilada and the reference in terms of efficacy, safety, and immunogenicity in patients with moderate to severe rheumatoid arthritis (RA). In addition to RA, Abrilada is indicated for juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, adult Crohn’s disease, ulcerative colitis, and plaque psoriasis.

Common adverse events in adalimumab clinical trials included infection, injection-site reactions, headache, and rash.

Pfizer said that it “is working to make Abrilada available to U.S. patients as soon as feasible based on the terms of our agreement with AbbVie [the manufacturer of Humira]. Our current plans are to launch in 2023.”

lfranki@mdedge.com

ATLANTA – Elderly-onset and young-onset rheumatoid arthritis patients initiating treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) respond similarly with respect to clinical improvement at 48 weeks and adverse events, data from a large registry in Japan suggest.

Sharon Worcester/MDedge News

The findings have important implications – particularly for elderly-onset rheumatoid arthritis (RA) patients, who tend to present with higher disease activity levels and increased disability, but who nevertheless receive biologics less frequently, compared with young-onset RA patients, according to Sadao Jinno, MD, of the department of rheumatology and clinical immunology, Kobe University Graduate School of Medicine, Osaka, Japan, and colleagues.

The findings were presented in a poster at the annual meeting of the American College of Rheumatology.

Of 7,183 participants in the multicenter observational registry, 989 who initiated bDMARDs and who had a DAS28-erythrocyte sedimentation rate score of at least 3.2 at the time of initiation were included in the current analysis. The proportion of elderly-onset RA patients in the registry was 36.8%, and the proportion of elderly-onset RA patients using bDMARDs was significantly lower than that among young-onset RA patients (18.3% vs. 28.0%; P less than .001), Dr. Jinno and colleagues reported.

However, after adjustment for differences in baseline characteristics between the two age groups, no significant difference was seen in Clinical Disease Activity Index (CDAI) score at 48 weeks (odds ratio, 1.01), Dr. Jinno said during a press conference highlighting the findings.

A trend toward lower remission rates was observed in the early-onset patients (OR, 0.52; P = 1.10). The low-disease activity/remission rate was similar in the groups after adjustment for multiple confounders (OR, 0.86; P = 0.77), he said, adding that drug maintenance rates and adverse event–related discontinuation rates also were similar in the groups (hazard ratio, 0.95; P = 0.78 for drug maintenance; HR, 0.78; P = 0.22 for discontinuation).

Patients were enrolled in the multicenter observational registry between September 2009 and December 2017, and those with onset at age 60 years or older were considered to have elderly-onset RA.

“In my daily practice, I see a lot of patients with elderly-onset RA who are treated with biologics very effectively and safely,” he said. “So we wanted to see if there really is any difference [in outcomes] between the elderly-onset patients and the young-onset patients.”

The findings suggest they can be treated as effectively and safely as younger patients, he said.

In a press release, he further stated that clinicians should “choose wisely which patients with elderly-onset RA are safely treated with biologics given that they are still at risk of developing adverse events, especially infections.”

Conversely, it is important to keep in mind that dysfunction in elderly-onset RA patients may worsen without timely biologic treatment, he noted.

Future investigation will focus on whether elderly-onset RA patients respond differently to “various modes of biologics,” he said.

Dr. Jinno and colleagues reported having no relevant disclosures.

sworcester@mdedge.com

SOURCE: Jinno S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1345.

ATLANTA – Elderly-onset and young-onset rheumatoid arthritis patients initiating treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) respond similarly with respect to clinical improvement at 48 weeks and adverse events, data from a large registry in Japan suggest.

Sharon Worcester/MDedge News

The findings have important implications – particularly for elderly-onset rheumatoid arthritis (RA) patients, who tend to present with higher disease activity levels and increased disability, but who nevertheless receive biologics less frequently, compared with young-onset RA patients, according to Sadao Jinno, MD, of the department of rheumatology and clinical immunology, Kobe University Graduate School of Medicine, Osaka, Japan, and colleagues.

The findings were presented in a poster at the annual meeting of the American College of Rheumatology.

Of 7,183 participants in the multicenter observational registry, 989 who initiated bDMARDs and who had a DAS28-erythrocyte sedimentation rate score of at least 3.2 at the time of initiation were included in the current analysis. The proportion of elderly-onset RA patients in the registry was 36.8%, and the proportion of elderly-onset RA patients using bDMARDs was significantly lower than that among young-onset RA patients (18.3% vs. 28.0%; P less than .001), Dr. Jinno and colleagues reported.

However, after adjustment for differences in baseline characteristics between the two age groups, no significant difference was seen in Clinical Disease Activity Index (CDAI) score at 48 weeks (odds ratio, 1.01), Dr. Jinno said during a press conference highlighting the findings.

A trend toward lower remission rates was observed in the early-onset patients (OR, 0.52; P = 1.10). The low-disease activity/remission rate was similar in the groups after adjustment for multiple confounders (OR, 0.86; P = 0.77), he said, adding that drug maintenance rates and adverse event–related discontinuation rates also were similar in the groups (hazard ratio, 0.95; P = 0.78 for drug maintenance; HR, 0.78; P = 0.22 for discontinuation).

Patients were enrolled in the multicenter observational registry between September 2009 and December 2017, and those with onset at age 60 years or older were considered to have elderly-onset RA.

“In my daily practice, I see a lot of patients with elderly-onset RA who are treated with biologics very effectively and safely,” he said. “So we wanted to see if there really is any difference [in outcomes] between the elderly-onset patients and the young-onset patients.”

The findings suggest they can be treated as effectively and safely as younger patients, he said.

In a press release, he further stated that clinicians should “choose wisely which patients with elderly-onset RA are safely treated with biologics given that they are still at risk of developing adverse events, especially infections.”

Conversely, it is important to keep in mind that dysfunction in elderly-onset RA patients may worsen without timely biologic treatment, he noted.

Future investigation will focus on whether elderly-onset RA patients respond differently to “various modes of biologics,” he said.

Dr. Jinno and colleagues reported having no relevant disclosures.

sworcester@mdedge.com

SOURCE: Jinno S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1345.

ATLANTA – Elderly-onset and young-onset rheumatoid arthritis patients initiating treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) respond similarly with respect to clinical improvement at 48 weeks and adverse events, data from a large registry in Japan suggest.

Sharon Worcester/MDedge News

The findings have important implications – particularly for elderly-onset rheumatoid arthritis (RA) patients, who tend to present with higher disease activity levels and increased disability, but who nevertheless receive biologics less frequently, compared with young-onset RA patients, according to Sadao Jinno, MD, of the department of rheumatology and clinical immunology, Kobe University Graduate School of Medicine, Osaka, Japan, and colleagues.

The findings were presented in a poster at the annual meeting of the American College of Rheumatology.

Of 7,183 participants in the multicenter observational registry, 989 who initiated bDMARDs and who had a DAS28-erythrocyte sedimentation rate score of at least 3.2 at the time of initiation were included in the current analysis. The proportion of elderly-onset RA patients in the registry was 36.8%, and the proportion of elderly-onset RA patients using bDMARDs was significantly lower than that among young-onset RA patients (18.3% vs. 28.0%; P less than .001), Dr. Jinno and colleagues reported.

However, after adjustment for differences in baseline characteristics between the two age groups, no significant difference was seen in Clinical Disease Activity Index (CDAI) score at 48 weeks (odds ratio, 1.01), Dr. Jinno said during a press conference highlighting the findings.

A trend toward lower remission rates was observed in the early-onset patients (OR, 0.52; P = 1.10). The low-disease activity/remission rate was similar in the groups after adjustment for multiple confounders (OR, 0.86; P = 0.77), he said, adding that drug maintenance rates and adverse event–related discontinuation rates also were similar in the groups (hazard ratio, 0.95; P = 0.78 for drug maintenance; HR, 0.78; P = 0.22 for discontinuation).

Patients were enrolled in the multicenter observational registry between September 2009 and December 2017, and those with onset at age 60 years or older were considered to have elderly-onset RA.

“In my daily practice, I see a lot of patients with elderly-onset RA who are treated with biologics very effectively and safely,” he said. “So we wanted to see if there really is any difference [in outcomes] between the elderly-onset patients and the young-onset patients.”

The findings suggest they can be treated as effectively and safely as younger patients, he said.

In a press release, he further stated that clinicians should “choose wisely which patients with elderly-onset RA are safely treated with biologics given that they are still at risk of developing adverse events, especially infections.”

Conversely, it is important to keep in mind that dysfunction in elderly-onset RA patients may worsen without timely biologic treatment, he noted.

Future investigation will focus on whether elderly-onset RA patients respond differently to “various modes of biologics,” he said.

Dr. Jinno and colleagues reported having no relevant disclosures.

sworcester@mdedge.com

SOURCE: Jinno S et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 1345.

ATLANTA – Opportunities to escalate or deescalate medications for patients with rheumatoid arthritis via an electronic health record at the point of care led rheumatologists at the Geisinger Medical Center in Danville, Pa., to increase the number of such decisions in their practice.

Jeff Craven/MDedge News

“Opportunities for escalation and de-escalation of therapy are common, even in a well-managed RA population,” Eric D. Newman, MD, director of the department of rheumatology at Geisinger, said in a presentation at the annual meeting of the American College of Rheumatology. “In our hands, over a third of the time, there was an opportunity to change therapy.”

Dr. Newman and colleagues developed a new treat-to-target tab for their (Patient Centric Electronic Redesign) PACER project, an EHR-adjacent system that captures patient and provider data and presents the information in different views, based on desired action items. The target in the study was low disease activity or remission, which was assessed using Clinical Disease Activity Index (CDAI) scores.

The treat-to-target tab offered three options to rheumatologists in real time when meeting with a patient: an escalation opportunity, which was defined as the patient’s two most recent CDAI scores showing moderate to high disease activity; and a deescalation opportunity, defined as a look-back up to 1 year during which at least two CDAI measures were within low to-moderate disease range. There was also a third “leave-alone” option to neither escalate nor deescalate therapy, but the rheumatologist was prompted to explain why if that option is selected, Dr. Newman noted.

In the first phase of releasing the treat-to-target tab, there was low adoption among the 17 rheumatologists at Geisinger: 82% of rheumatologists did not use the tab for escalation therapy, and 64% did not use the tab for deescalation therapy.

That prompted Dr. Newman and colleagues to develop a new version of the treat-to-target tab for phase 2 of the program. “Once they complete their CDAI, if there’s an opportunity, there would be a bright orange button that would glow right in front of them,” Dr. Newman said. “It was really hard to miss, and all they would have to do is click it and it would bring them right to the treat-to-target tab.”

To increase rheumatologists’ use of the new treat-to-target tab, the amount of time spent using the tab and making decisions is presented to them, he said. “It’s actually now part of our quality measure bundle, so every month, they get a leaderboard to see how they compare with their partners,” he noted. “It’s a great way to drive down variability and get everybody approaching the same sort of mean.”

Overall, between July 2018 and May 2019, there were 1,428 treat-to-target opportunities, consisting of 34.2% of RA office visits. Of these, 11.3% were escalation opportunities and 22.9% were deescalation opportunities, Dr. Newman said.

Between phase 1 and phase 2, the rheumatologists’ nonuse of the treat-to-target tab decreased from 82% to 36% for escalation opportunities, and decisions to escalate therapy increased from 10% to 46%. Similarly, nonuse of the treat-to-target tab for deescalation therapy decreased from 64% to 34%, and decisions to deescalate therapy increased from 5% to 17%.

In 49% of escalation opportunities and 80% of deescalation opportunities in phase 2 of the program, rheumatologists made the decision to leave the patient alone. The reasons for not escalating therapy for a patient included an inaccurate CDAI (34%), patient decision (15%), risks outweighing the benefits (15%), and other (37%). “This is interesting, because if you take 49% times 34%, that means that only 17% of the time they felt it didn’t represent what was going on in our department, which is not what we heard from them verbally before this project,” he said. For deescalation opportunities in which the rheumatologist left the patient alone, the most common reasons were hard-to-control disease (46%), patient preference (29%), and poor prognostic factors (25%).

“Keep in mind, some of these patients may have actually already been deescalated prior to this,” Dr. Newman noted. “We’ve actually done some previous work 3 years ago – we provided a visual signal to our physicians that there was a deescalation opportunity, so we may have already accounted for that portion of the population to some extent.”

Dr. Newman said a future goal of the treat-to-target system is to developed more specific treat-to-target strategies to improve the “signal-to-noise” ratio in the system. “Now [that] it’s fully embedded into our routine RA care delivery across our system, our next steps are going to be to use this tool to proactively drive value-concordant decision making and monitor the effect this has on both disease control as well as cost of care,” he said.

Dr. Newman reported no relevant financial disclosures.
 

SOURCE: Newman ED et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1862.

ATLANTA – Opportunities to escalate or deescalate medications for patients with rheumatoid arthritis via an electronic health record at the point of care led rheumatologists at the Geisinger Medical Center in Danville, Pa., to increase the number of such decisions in their practice.

Jeff Craven/MDedge News

“Opportunities for escalation and de-escalation of therapy are common, even in a well-managed RA population,” Eric D. Newman, MD, director of the department of rheumatology at Geisinger, said in a presentation at the annual meeting of the American College of Rheumatology. “In our hands, over a third of the time, there was an opportunity to change therapy.”

Dr. Newman and colleagues developed a new treat-to-target tab for their (Patient Centric Electronic Redesign) PACER project, an EHR-adjacent system that captures patient and provider data and presents the information in different views, based on desired action items. The target in the study was low disease activity or remission, which was assessed using Clinical Disease Activity Index (CDAI) scores.

The treat-to-target tab offered three options to rheumatologists in real time when meeting with a patient: an escalation opportunity, which was defined as the patient’s two most recent CDAI scores showing moderate to high disease activity; and a deescalation opportunity, defined as a look-back up to 1 year during which at least two CDAI measures were within low to-moderate disease range. There was also a third “leave-alone” option to neither escalate nor deescalate therapy, but the rheumatologist was prompted to explain why if that option is selected, Dr. Newman noted.

In the first phase of releasing the treat-to-target tab, there was low adoption among the 17 rheumatologists at Geisinger: 82% of rheumatologists did not use the tab for escalation therapy, and 64% did not use the tab for deescalation therapy.

That prompted Dr. Newman and colleagues to develop a new version of the treat-to-target tab for phase 2 of the program. “Once they complete their CDAI, if there’s an opportunity, there would be a bright orange button that would glow right in front of them,” Dr. Newman said. “It was really hard to miss, and all they would have to do is click it and it would bring them right to the treat-to-target tab.”

To increase rheumatologists’ use of the new treat-to-target tab, the amount of time spent using the tab and making decisions is presented to them, he said. “It’s actually now part of our quality measure bundle, so every month, they get a leaderboard to see how they compare with their partners,” he noted. “It’s a great way to drive down variability and get everybody approaching the same sort of mean.”

Overall, between July 2018 and May 2019, there were 1,428 treat-to-target opportunities, consisting of 34.2% of RA office visits. Of these, 11.3% were escalation opportunities and 22.9% were deescalation opportunities, Dr. Newman said.

Between phase 1 and phase 2, the rheumatologists’ nonuse of the treat-to-target tab decreased from 82% to 36% for escalation opportunities, and decisions to escalate therapy increased from 10% to 46%. Similarly, nonuse of the treat-to-target tab for deescalation therapy decreased from 64% to 34%, and decisions to deescalate therapy increased from 5% to 17%.

In 49% of escalation opportunities and 80% of deescalation opportunities in phase 2 of the program, rheumatologists made the decision to leave the patient alone. The reasons for not escalating therapy for a patient included an inaccurate CDAI (34%), patient decision (15%), risks outweighing the benefits (15%), and other (37%). “This is interesting, because if you take 49% times 34%, that means that only 17% of the time they felt it didn’t represent what was going on in our department, which is not what we heard from them verbally before this project,” he said. For deescalation opportunities in which the rheumatologist left the patient alone, the most common reasons were hard-to-control disease (46%), patient preference (29%), and poor prognostic factors (25%).

“Keep in mind, some of these patients may have actually already been deescalated prior to this,” Dr. Newman noted. “We’ve actually done some previous work 3 years ago – we provided a visual signal to our physicians that there was a deescalation opportunity, so we may have already accounted for that portion of the population to some extent.”

Dr. Newman said a future goal of the treat-to-target system is to developed more specific treat-to-target strategies to improve the “signal-to-noise” ratio in the system. “Now [that] it’s fully embedded into our routine RA care delivery across our system, our next steps are going to be to use this tool to proactively drive value-concordant decision making and monitor the effect this has on both disease control as well as cost of care,” he said.

Dr. Newman reported no relevant financial disclosures.
 

SOURCE: Newman ED et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1862.

ATLANTA – Opportunities to escalate or deescalate medications for patients with rheumatoid arthritis via an electronic health record at the point of care led rheumatologists at the Geisinger Medical Center in Danville, Pa., to increase the number of such decisions in their practice.

Jeff Craven/MDedge News

“Opportunities for escalation and de-escalation of therapy are common, even in a well-managed RA population,” Eric D. Newman, MD, director of the department of rheumatology at Geisinger, said in a presentation at the annual meeting of the American College of Rheumatology. “In our hands, over a third of the time, there was an opportunity to change therapy.”

Dr. Newman and colleagues developed a new treat-to-target tab for their (Patient Centric Electronic Redesign) PACER project, an EHR-adjacent system that captures patient and provider data and presents the information in different views, based on desired action items. The target in the study was low disease activity or remission, which was assessed using Clinical Disease Activity Index (CDAI) scores.

The treat-to-target tab offered three options to rheumatologists in real time when meeting with a patient: an escalation opportunity, which was defined as the patient’s two most recent CDAI scores showing moderate to high disease activity; and a deescalation opportunity, defined as a look-back up to 1 year during which at least two CDAI measures were within low to-moderate disease range. There was also a third “leave-alone” option to neither escalate nor deescalate therapy, but the rheumatologist was prompted to explain why if that option is selected, Dr. Newman noted.

In the first phase of releasing the treat-to-target tab, there was low adoption among the 17 rheumatologists at Geisinger: 82% of rheumatologists did not use the tab for escalation therapy, and 64% did not use the tab for deescalation therapy.

That prompted Dr. Newman and colleagues to develop a new version of the treat-to-target tab for phase 2 of the program. “Once they complete their CDAI, if there’s an opportunity, there would be a bright orange button that would glow right in front of them,” Dr. Newman said. “It was really hard to miss, and all they would have to do is click it and it would bring them right to the treat-to-target tab.”

To increase rheumatologists’ use of the new treat-to-target tab, the amount of time spent using the tab and making decisions is presented to them, he said. “It’s actually now part of our quality measure bundle, so every month, they get a leaderboard to see how they compare with their partners,” he noted. “It’s a great way to drive down variability and get everybody approaching the same sort of mean.”

Overall, between July 2018 and May 2019, there were 1,428 treat-to-target opportunities, consisting of 34.2% of RA office visits. Of these, 11.3% were escalation opportunities and 22.9% were deescalation opportunities, Dr. Newman said.

Between phase 1 and phase 2, the rheumatologists’ nonuse of the treat-to-target tab decreased from 82% to 36% for escalation opportunities, and decisions to escalate therapy increased from 10% to 46%. Similarly, nonuse of the treat-to-target tab for deescalation therapy decreased from 64% to 34%, and decisions to deescalate therapy increased from 5% to 17%.

In 49% of escalation opportunities and 80% of deescalation opportunities in phase 2 of the program, rheumatologists made the decision to leave the patient alone. The reasons for not escalating therapy for a patient included an inaccurate CDAI (34%), patient decision (15%), risks outweighing the benefits (15%), and other (37%). “This is interesting, because if you take 49% times 34%, that means that only 17% of the time they felt it didn’t represent what was going on in our department, which is not what we heard from them verbally before this project,” he said. For deescalation opportunities in which the rheumatologist left the patient alone, the most common reasons were hard-to-control disease (46%), patient preference (29%), and poor prognostic factors (25%).

“Keep in mind, some of these patients may have actually already been deescalated prior to this,” Dr. Newman noted. “We’ve actually done some previous work 3 years ago – we provided a visual signal to our physicians that there was a deescalation opportunity, so we may have already accounted for that portion of the population to some extent.”

Dr. Newman said a future goal of the treat-to-target system is to developed more specific treat-to-target strategies to improve the “signal-to-noise” ratio in the system. “Now [that] it’s fully embedded into our routine RA care delivery across our system, our next steps are going to be to use this tool to proactively drive value-concordant decision making and monitor the effect this has on both disease control as well as cost of care,” he said.

Dr. Newman reported no relevant financial disclosures.
 

SOURCE: Newman ED et al. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1862.

ATLANTA – Tocilizumab proved more effective than rituximab in B-cell-poor but not in B-cell-rich patients with RA who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibition in the randomized, open-label, 48-week, phase 4 R4-RA trial.

Sharon Worcester/MDedge News

If validated, the findings of the trial – the first randomized, controlled, biopsy-driven trial in RA – could have “massive implications” for treatment selection and improved outcomes, Constantino Pitzalis, MD, reported during a press conference at the annual meeting of the American College of Rheumatology.

Of 164 RA patients who were failing or intolerant to conventional synthetic (cs) DMARD therapy and at least one tumor necrosis factor inhibitor (TNFi), 83 were randomized to receive rituximab and 81 received tocilizumab. Of those patients, 49.1% were considered B-cell poor (BCP) based on synovial tissue biopsies obtained at trial entry.

The BCP patients treated with tocilizumab were numerically more likely than those treated with rituximab to achieve the coprimary endpoint of Clinical Disease Activity Index (CDAI) improvement of at least 50% from baseline at 16 weeks (56.1% vs. 44.7%), and they were significantly more likely – twice as likely, in fact – to achieve the coprimary endpoint of CDAI improvement of at least 50% from baseline at 16 weeks as well as CDAI score less than 10, indicating a major treatment response (46.3% vs. 23.7%), said Dr. Pitzalis, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London.

BCP patients receiving tocilizumab also were significantly more likely to achieve a number of secondary endpoints, he noted.

In the B-cell-rich (BCR) population, no significant differences were seen in the majority of endpoints with tocilizumab versus rituximab, he said.

Study participants had a mean age of 55-56 years and were intolerant of or refractory to csDMARDs and at least one TNFi. They were recruited from 19 centers in Europe, were randomized and treated with standard doses of rituximab or tocilizumab, and were stratified based on histologic classification (BCP vs. BCR). Baseline characteristics were comparable among the treatment groups, Dr. Pitzalis said.

Adverse events occurred in 62 and 68 patients in the rituximab and tocilizumab groups, respectively, and serious adverse events occurred in 8 and 12 patients, respectively, thus 40% of all serious adverse events occurred in the rituximab group and 60% in the tocilizumab group. Infections and serious infections each occurred in three patients in each group, and two patients in each group discontinued treatment because of adverse events.

B cells are pivotal to RA pathogenesis, as demonstrated by the efficacy of the B-cell-depleting agent, rituximab. However, rituximab, which is licensed for use following failure of csDMARDs and TNFi therapy, is only effective for achieving a 50% improvement in ACR response criteria at 6 months in about 30% of such patients, Dr. Pitzalis noted. In a recent early RA cohort, he and his colleagues found synovial heterogeneity, with more than half of patients showing low or no synovial B-cell infiltration.

“So why would you give them rituximab?” he asked, explaining the rationale for the R4-RA trial: The hypothesis was that alternative biologic agents targeting alternative pathways may be more effective in BCP patients.

“The results showed quite clearly that rituximab was inferior to tocilizumab in this patient group,” he said. “We demonstrated that tocilizumab is more effective than rituximab in achieving low disease activity in patients who had, on synovial biopsy, low levels of B-cell infiltration.

“The study really highlights the importance of integrating molecular pathology into the clinical algorithms, because making the diagnosis is not sufficient. We really need to know what the pathology of the patient is so we can give the right drug to the right patients.”

Donald Thomas, MD, a rheumatologist in private practice in Silver Spring, Md., called the study “fascinating,” and noted during a question-and-answer period during the press conference that, during his lifetime, he “has probably wasted tens of thousands to hundreds of thousands of dollars,” using the trial-and-error approach to treatment.

“We can only treat by trial and error ... so being able to pinpoint therapy is just phenomenal,” he added, further noting in an interview after the press conference that finding the right treatment can be “such a struggle.”

“I literally have patients who have gone through 10 medicines and wasted thousands of dollars,” he said.

In response to a question from Dr. Thomas about the potential for rheumatologists to do their own synovial biopsies to help guide treatment in the event the findings are validated, Dr. Pitzalis said that is both feasible and an important goal.

“All the biopsies [in the study] were carried out by rheumatologists,” he noted. “We have trained over 150 rheumatologists worldwide, including at 15 centers in the United States. ... We want to empower the rheumatologists to do it.”

He added that “this is early data ... and will require validation in larger trials,” but said the point is that “we can’t continue to just give these drugs and see if the patient responds.”

R4-RA is funded by the National Institute of Health Research Efficacy and Mechanism Evaluation program. Dr. Pitzalis and some of the other study authors reported financial relationships with Roche/Genentech, which markets tocilizumab and rituximab, and other pharmaceutical companies.

sworcester@mdedge.com

SOURCE: Pitzalis C et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2911.

ATLANTA – Tocilizumab proved more effective than rituximab in B-cell-poor but not in B-cell-rich patients with RA who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibition in the randomized, open-label, 48-week, phase 4 R4-RA trial.

Sharon Worcester/MDedge News

If validated, the findings of the trial – the first randomized, controlled, biopsy-driven trial in RA – could have “massive implications” for treatment selection and improved outcomes, Constantino Pitzalis, MD, reported during a press conference at the annual meeting of the American College of Rheumatology.

Of 164 RA patients who were failing or intolerant to conventional synthetic (cs) DMARD therapy and at least one tumor necrosis factor inhibitor (TNFi), 83 were randomized to receive rituximab and 81 received tocilizumab. Of those patients, 49.1% were considered B-cell poor (BCP) based on synovial tissue biopsies obtained at trial entry.

The BCP patients treated with tocilizumab were numerically more likely than those treated with rituximab to achieve the coprimary endpoint of Clinical Disease Activity Index (CDAI) improvement of at least 50% from baseline at 16 weeks (56.1% vs. 44.7%), and they were significantly more likely – twice as likely, in fact – to achieve the coprimary endpoint of CDAI improvement of at least 50% from baseline at 16 weeks as well as CDAI score less than 10, indicating a major treatment response (46.3% vs. 23.7%), said Dr. Pitzalis, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London.

BCP patients receiving tocilizumab also were significantly more likely to achieve a number of secondary endpoints, he noted.

In the B-cell-rich (BCR) population, no significant differences were seen in the majority of endpoints with tocilizumab versus rituximab, he said.

Study participants had a mean age of 55-56 years and were intolerant of or refractory to csDMARDs and at least one TNFi. They were recruited from 19 centers in Europe, were randomized and treated with standard doses of rituximab or tocilizumab, and were stratified based on histologic classification (BCP vs. BCR). Baseline characteristics were comparable among the treatment groups, Dr. Pitzalis said.

Adverse events occurred in 62 and 68 patients in the rituximab and tocilizumab groups, respectively, and serious adverse events occurred in 8 and 12 patients, respectively, thus 40% of all serious adverse events occurred in the rituximab group and 60% in the tocilizumab group. Infections and serious infections each occurred in three patients in each group, and two patients in each group discontinued treatment because of adverse events.

B cells are pivotal to RA pathogenesis, as demonstrated by the efficacy of the B-cell-depleting agent, rituximab. However, rituximab, which is licensed for use following failure of csDMARDs and TNFi therapy, is only effective for achieving a 50% improvement in ACR response criteria at 6 months in about 30% of such patients, Dr. Pitzalis noted. In a recent early RA cohort, he and his colleagues found synovial heterogeneity, with more than half of patients showing low or no synovial B-cell infiltration.

“So why would you give them rituximab?” he asked, explaining the rationale for the R4-RA trial: The hypothesis was that alternative biologic agents targeting alternative pathways may be more effective in BCP patients.

“The results showed quite clearly that rituximab was inferior to tocilizumab in this patient group,” he said. “We demonstrated that tocilizumab is more effective than rituximab in achieving low disease activity in patients who had, on synovial biopsy, low levels of B-cell infiltration.

“The study really highlights the importance of integrating molecular pathology into the clinical algorithms, because making the diagnosis is not sufficient. We really need to know what the pathology of the patient is so we can give the right drug to the right patients.”

Donald Thomas, MD, a rheumatologist in private practice in Silver Spring, Md., called the study “fascinating,” and noted during a question-and-answer period during the press conference that, during his lifetime, he “has probably wasted tens of thousands to hundreds of thousands of dollars,” using the trial-and-error approach to treatment.

“We can only treat by trial and error ... so being able to pinpoint therapy is just phenomenal,” he added, further noting in an interview after the press conference that finding the right treatment can be “such a struggle.”

“I literally have patients who have gone through 10 medicines and wasted thousands of dollars,” he said.

In response to a question from Dr. Thomas about the potential for rheumatologists to do their own synovial biopsies to help guide treatment in the event the findings are validated, Dr. Pitzalis said that is both feasible and an important goal.

“All the biopsies [in the study] were carried out by rheumatologists,” he noted. “We have trained over 150 rheumatologists worldwide, including at 15 centers in the United States. ... We want to empower the rheumatologists to do it.”

He added that “this is early data ... and will require validation in larger trials,” but said the point is that “we can’t continue to just give these drugs and see if the patient responds.”

R4-RA is funded by the National Institute of Health Research Efficacy and Mechanism Evaluation program. Dr. Pitzalis and some of the other study authors reported financial relationships with Roche/Genentech, which markets tocilizumab and rituximab, and other pharmaceutical companies.

sworcester@mdedge.com

SOURCE: Pitzalis C et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2911.

ATLANTA – Tocilizumab proved more effective than rituximab in B-cell-poor but not in B-cell-rich patients with RA who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibition in the randomized, open-label, 48-week, phase 4 R4-RA trial.

Sharon Worcester/MDedge News

If validated, the findings of the trial – the first randomized, controlled, biopsy-driven trial in RA – could have “massive implications” for treatment selection and improved outcomes, Constantino Pitzalis, MD, reported during a press conference at the annual meeting of the American College of Rheumatology.

Of 164 RA patients who were failing or intolerant to conventional synthetic (cs) DMARD therapy and at least one tumor necrosis factor inhibitor (TNFi), 83 were randomized to receive rituximab and 81 received tocilizumab. Of those patients, 49.1% were considered B-cell poor (BCP) based on synovial tissue biopsies obtained at trial entry.

The BCP patients treated with tocilizumab were numerically more likely than those treated with rituximab to achieve the coprimary endpoint of Clinical Disease Activity Index (CDAI) improvement of at least 50% from baseline at 16 weeks (56.1% vs. 44.7%), and they were significantly more likely – twice as likely, in fact – to achieve the coprimary endpoint of CDAI improvement of at least 50% from baseline at 16 weeks as well as CDAI score less than 10, indicating a major treatment response (46.3% vs. 23.7%), said Dr. Pitzalis, head of the Centre for Experimental Medicine & Rheumatology at Queen Mary University of London.

BCP patients receiving tocilizumab also were significantly more likely to achieve a number of secondary endpoints, he noted.

In the B-cell-rich (BCR) population, no significant differences were seen in the majority of endpoints with tocilizumab versus rituximab, he said.

Study participants had a mean age of 55-56 years and were intolerant of or refractory to csDMARDs and at least one TNFi. They were recruited from 19 centers in Europe, were randomized and treated with standard doses of rituximab or tocilizumab, and were stratified based on histologic classification (BCP vs. BCR). Baseline characteristics were comparable among the treatment groups, Dr. Pitzalis said.

Adverse events occurred in 62 and 68 patients in the rituximab and tocilizumab groups, respectively, and serious adverse events occurred in 8 and 12 patients, respectively, thus 40% of all serious adverse events occurred in the rituximab group and 60% in the tocilizumab group. Infections and serious infections each occurred in three patients in each group, and two patients in each group discontinued treatment because of adverse events.

B cells are pivotal to RA pathogenesis, as demonstrated by the efficacy of the B-cell-depleting agent, rituximab. However, rituximab, which is licensed for use following failure of csDMARDs and TNFi therapy, is only effective for achieving a 50% improvement in ACR response criteria at 6 months in about 30% of such patients, Dr. Pitzalis noted. In a recent early RA cohort, he and his colleagues found synovial heterogeneity, with more than half of patients showing low or no synovial B-cell infiltration.

“So why would you give them rituximab?” he asked, explaining the rationale for the R4-RA trial: The hypothesis was that alternative biologic agents targeting alternative pathways may be more effective in BCP patients.

“The results showed quite clearly that rituximab was inferior to tocilizumab in this patient group,” he said. “We demonstrated that tocilizumab is more effective than rituximab in achieving low disease activity in patients who had, on synovial biopsy, low levels of B-cell infiltration.

“The study really highlights the importance of integrating molecular pathology into the clinical algorithms, because making the diagnosis is not sufficient. We really need to know what the pathology of the patient is so we can give the right drug to the right patients.”

Donald Thomas, MD, a rheumatologist in private practice in Silver Spring, Md., called the study “fascinating,” and noted during a question-and-answer period during the press conference that, during his lifetime, he “has probably wasted tens of thousands to hundreds of thousands of dollars,” using the trial-and-error approach to treatment.

“We can only treat by trial and error ... so being able to pinpoint therapy is just phenomenal,” he added, further noting in an interview after the press conference that finding the right treatment can be “such a struggle.”

“I literally have patients who have gone through 10 medicines and wasted thousands of dollars,” he said.

In response to a question from Dr. Thomas about the potential for rheumatologists to do their own synovial biopsies to help guide treatment in the event the findings are validated, Dr. Pitzalis said that is both feasible and an important goal.

“All the biopsies [in the study] were carried out by rheumatologists,” he noted. “We have trained over 150 rheumatologists worldwide, including at 15 centers in the United States. ... We want to empower the rheumatologists to do it.”

He added that “this is early data ... and will require validation in larger trials,” but said the point is that “we can’t continue to just give these drugs and see if the patient responds.”

R4-RA is funded by the National Institute of Health Research Efficacy and Mechanism Evaluation program. Dr. Pitzalis and some of the other study authors reported financial relationships with Roche/Genentech, which markets tocilizumab and rituximab, and other pharmaceutical companies.

sworcester@mdedge.com

SOURCE: Pitzalis C et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 2911.

ATLANTA – Concomitant use of even low-dose steroids increases the risk of serious infections with antirheumatic drugs, according to a review of 170,357 Medicare patients by investigators at the University of Pennsylvania, Philadelphia.

Infections are a well-known side effect of high-dose glucocorticoids, but there’s been debate about prednisone doses in the 5-10 mg/day range. Guidelines generally advise tapering RA patients off steroids after they start a biologic or methotrexate, but that doesn’t always happen because there’s a common perception that low-dose steroids are safe, said lead investigator Michael George, MD, assistant professor of medicine and epidemiology at the university.

“Many people continue low-dose steroids over the long term, but even low dose seems to be associated with infection. It’s a small risk, but it should be something you are aware of; for some patients, it might be quite important,” he said in an interview at the annual meeting of the American College of Rheumatology.

The team wanted to mimic real-world practice, so they compared infection incidence between the 53% of patients who were not on low-dose steroids with the 47% who were after at least 6 months of disease-modifying antirheumatic drug (DMARD) therapy. About 56% of patients were on methotrexate, with the rest on biologics or a targeted synthetic DMARD (tsDMARD). Average follow up was an additional 6 months, but some people were followed for several years; prednisone 5 mg/day or less was the most common dose.

There were 20,630 serious infections requiring hospitalization, most often urinary tract infection, pneumonia, bacteremia/septicemia, and skin or soft-tissue infections. The crude incidence was 11 per 100 person-years.

After propensity-score weighting to balance out about 50 potential confounders, the predicted 1-year incidence of infection was 9.3% among patients not on steroids. Among those on up to 5 mg/day of prednisone, it was 12.5%; among those on 5-10 mg/day, 17.2%; and among those on more than 10 mg/day, 23.9%.

Glucocorticoids were associated with a 37% increased rate of serious infections, even with doses at or below 5mg/day. The effect “was really similar” whether people were on a biologic, tsDMARD, or methotrexate, which was “surprising,” Dr. George said.

“When I see a patient now who is on long-term, low-dose prednisone, I don’t just say ‘okay, that’s probably safe.’ I think really hard about how much benefit they’re getting. For some people, that means I try to get them off it,” he said. For those who flare otherwise, “I might continue them on it, but recognize there is likely some risk.”

The magnitude of the infection risk was similar to that reported with tumor necrosis factors inhibitors, which might reassure patients who are reluctant to switch to a tumor necrosis factor inhibitor.

“Now I can say you’ve been taking 10 mg prednisone a day, and that’s probably at least as risky,” Dr. George said.

Frequency of office visits, hospitalizations, and ED visits, as well as prior infections, comorbidities, nursing-home admissions, and use of durable medical equipment were among the potential confounders controlled for in the analysis. They stood in for direct markers of RA severity, which weren’t available in the data. “We spent a lot of time trying to make sure our groups were as similar as possible in every way except prednisone use,” he said.

Patients were in their late 60s on average, 71% white, and 81% were women. People with other autoimmune rheumatic diseases, cancer, or HIV were excluded. Dr. George said the next step is to run the same analysis in a younger cohort.

The work was funded by the National Institutes of Health. Dr. George disclosed relationships with AbbVie and Bristol-Myers Squibb.

aotto@mdedge.com

SOURCE: George M et al. ACR 2019, Abstract 848

ATLANTA – Concomitant use of even low-dose steroids increases the risk of serious infections with antirheumatic drugs, according to a review of 170,357 Medicare patients by investigators at the University of Pennsylvania, Philadelphia.

Infections are a well-known side effect of high-dose glucocorticoids, but there’s been debate about prednisone doses in the 5-10 mg/day range. Guidelines generally advise tapering RA patients off steroids after they start a biologic or methotrexate, but that doesn’t always happen because there’s a common perception that low-dose steroids are safe, said lead investigator Michael George, MD, assistant professor of medicine and epidemiology at the university.

“Many people continue low-dose steroids over the long term, but even low dose seems to be associated with infection. It’s a small risk, but it should be something you are aware of; for some patients, it might be quite important,” he said in an interview at the annual meeting of the American College of Rheumatology.

The team wanted to mimic real-world practice, so they compared infection incidence between the 53% of patients who were not on low-dose steroids with the 47% who were after at least 6 months of disease-modifying antirheumatic drug (DMARD) therapy. About 56% of patients were on methotrexate, with the rest on biologics or a targeted synthetic DMARD (tsDMARD). Average follow up was an additional 6 months, but some people were followed for several years; prednisone 5 mg/day or less was the most common dose.

There were 20,630 serious infections requiring hospitalization, most often urinary tract infection, pneumonia, bacteremia/septicemia, and skin or soft-tissue infections. The crude incidence was 11 per 100 person-years.

After propensity-score weighting to balance out about 50 potential confounders, the predicted 1-year incidence of infection was 9.3% among patients not on steroids. Among those on up to 5 mg/day of prednisone, it was 12.5%; among those on 5-10 mg/day, 17.2%; and among those on more than 10 mg/day, 23.9%.

Glucocorticoids were associated with a 37% increased rate of serious infections, even with doses at or below 5mg/day. The effect “was really similar” whether people were on a biologic, tsDMARD, or methotrexate, which was “surprising,” Dr. George said.

“When I see a patient now who is on long-term, low-dose prednisone, I don’t just say ‘okay, that’s probably safe.’ I think really hard about how much benefit they’re getting. For some people, that means I try to get them off it,” he said. For those who flare otherwise, “I might continue them on it, but recognize there is likely some risk.”

The magnitude of the infection risk was similar to that reported with tumor necrosis factors inhibitors, which might reassure patients who are reluctant to switch to a tumor necrosis factor inhibitor.

“Now I can say you’ve been taking 10 mg prednisone a day, and that’s probably at least as risky,” Dr. George said.

Frequency of office visits, hospitalizations, and ED visits, as well as prior infections, comorbidities, nursing-home admissions, and use of durable medical equipment were among the potential confounders controlled for in the analysis. They stood in for direct markers of RA severity, which weren’t available in the data. “We spent a lot of time trying to make sure our groups were as similar as possible in every way except prednisone use,” he said.

Patients were in their late 60s on average, 71% white, and 81% were women. People with other autoimmune rheumatic diseases, cancer, or HIV were excluded. Dr. George said the next step is to run the same analysis in a younger cohort.

The work was funded by the National Institutes of Health. Dr. George disclosed relationships with AbbVie and Bristol-Myers Squibb.

aotto@mdedge.com

SOURCE: George M et al. ACR 2019, Abstract 848

ATLANTA – Concomitant use of even low-dose steroids increases the risk of serious infections with antirheumatic drugs, according to a review of 170,357 Medicare patients by investigators at the University of Pennsylvania, Philadelphia.

Infections are a well-known side effect of high-dose glucocorticoids, but there’s been debate about prednisone doses in the 5-10 mg/day range. Guidelines generally advise tapering RA patients off steroids after they start a biologic or methotrexate, but that doesn’t always happen because there’s a common perception that low-dose steroids are safe, said lead investigator Michael George, MD, assistant professor of medicine and epidemiology at the university.

“Many people continue low-dose steroids over the long term, but even low dose seems to be associated with infection. It’s a small risk, but it should be something you are aware of; for some patients, it might be quite important,” he said in an interview at the annual meeting of the American College of Rheumatology.

The team wanted to mimic real-world practice, so they compared infection incidence between the 53% of patients who were not on low-dose steroids with the 47% who were after at least 6 months of disease-modifying antirheumatic drug (DMARD) therapy. About 56% of patients were on methotrexate, with the rest on biologics or a targeted synthetic DMARD (tsDMARD). Average follow up was an additional 6 months, but some people were followed for several years; prednisone 5 mg/day or less was the most common dose.

There were 20,630 serious infections requiring hospitalization, most often urinary tract infection, pneumonia, bacteremia/septicemia, and skin or soft-tissue infections. The crude incidence was 11 per 100 person-years.

After propensity-score weighting to balance out about 50 potential confounders, the predicted 1-year incidence of infection was 9.3% among patients not on steroids. Among those on up to 5 mg/day of prednisone, it was 12.5%; among those on 5-10 mg/day, 17.2%; and among those on more than 10 mg/day, 23.9%.

Glucocorticoids were associated with a 37% increased rate of serious infections, even with doses at or below 5mg/day. The effect “was really similar” whether people were on a biologic, tsDMARD, or methotrexate, which was “surprising,” Dr. George said.

“When I see a patient now who is on long-term, low-dose prednisone, I don’t just say ‘okay, that’s probably safe.’ I think really hard about how much benefit they’re getting. For some people, that means I try to get them off it,” he said. For those who flare otherwise, “I might continue them on it, but recognize there is likely some risk.”

The magnitude of the infection risk was similar to that reported with tumor necrosis factors inhibitors, which might reassure patients who are reluctant to switch to a tumor necrosis factor inhibitor.

“Now I can say you’ve been taking 10 mg prednisone a day, and that’s probably at least as risky,” Dr. George said.

Frequency of office visits, hospitalizations, and ED visits, as well as prior infections, comorbidities, nursing-home admissions, and use of durable medical equipment were among the potential confounders controlled for in the analysis. They stood in for direct markers of RA severity, which weren’t available in the data. “We spent a lot of time trying to make sure our groups were as similar as possible in every way except prednisone use,” he said.

Patients were in their late 60s on average, 71% white, and 81% were women. People with other autoimmune rheumatic diseases, cancer, or HIV were excluded. Dr. George said the next step is to run the same analysis in a younger cohort.

The work was funded by the National Institutes of Health. Dr. George disclosed relationships with AbbVie and Bristol-Myers Squibb.

aotto@mdedge.com

SOURCE: George M et al. ACR 2019, Abstract 848

ATLANTA – A group of patients using a tumor necrosis factor inhibitor safely received the live-attenuated varicella vaccine Zostavax without any cases of herpes zoster in the first 6 weeks after vaccination in the blinded, randomized, placebo-controlled Varicella Zoster Vaccine (VERVE) trial .

According to guidelines from the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, there is a theoretical concern that patients using a tumor necrosis factor inhibitor (TNFi) and other biologic therapies who receive a live-attenuated version of the varicella vaccine (Zostavax) could become infected with varicella from the vaccine. Patients with RA and psoriatic arthritis as well as other autoimmune and inflammatory conditions who are likely to receive TNFi therapy are also at risk for herpes zoster reactivation, Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology of the University of Alabama at Birmingham, said in his presentation at the annual meeting of the American College of Rheumatology. There also exists a risk for patients receiving low-dose glucocorticoids.

“The challenge, of course, is there’s not a great definition and there certainly is not a well-standardized assay for how immunocompromised someone is, and so that led to the uncertainty in this patient population for this and other live-virus vaccines,” Dr. Curtis said.

Dr. Curtis and colleagues enrolled 627 participants from 33 centers into the VERVE trial. Participants were aged at least 50 years, were taking a TNFi, and had not previously received Zostavax.

Patients in both groups had a mean age of about 63 years and about two-thirds were women. The most common indications for TNFi use in the Zostavax group and the placebo group were RA (59.2% vs. 56.0%, respectively), psoriatic arthritis (24.3% vs. 23.9%), and ankylosing spondylitis (7.2% vs. 8.5%), while the anti-TNF agents used were adalimumab (38.1% vs. 27.4%), infliximab (28.4% vs. 34.2%), etanercept (19.0% vs. 23.5%), golimumab (10.0% vs. 8.1%), and certolizumab pegol (4.5% vs. 6.8%). In addition, some patients in the Zostavax and placebo groups were also taking concomitant therapies with TNFi, such as oral glucocorticoids (9.7% vs. 11.4%).

The researchers randomized participants to receive Zostavax or placebo (saline) and then followed them for 6 weeks, and looked for signs of wild-type or vaccine-strain varicella infection. If participants were suspected to have varicella, they were assessed clinically, underwent polymerase chain reaction testing, and rashes were photographed. At baseline and at 6 weeks, the researchers collected serum and peripheral blood mononuclear cells to determine patient immunity to varicella. After 6 months, participants were unmasked to the treatment arm of the study.

Dr. Curtis and colleagues found no confirmed varicella infection cases at 6 weeks. “To the extent that 0 cases out of 317 vaccinated people is reassuring, there were no cases, so that was exceedingly heartening as a result,” he said.

Out of 20 serious adverse events total in the groups, 15 events occurred before 6 months, including 8 suspected varicella cases in the Zostavax group and 7 in the placebo group. However, there were no positive cases of varicella – either wild type or vaccine type – after polymerase chain reaction tests. Overall, there were 268 adverse events in 195 participants, with 73 events (27.2%) consisting of injection-site reactions. The researchers also found no difference in the rate of disease flares, and found no differences in adverse reactions between groups, apart from a higher rate of injection-site reactions in the varicella group (19.4% vs. 4.2%).

With regard to immunogenicity, the humoral immune response was measured through IgG, which showed an immune response in the varicella group at 6 weeks (geometric mean fold ratio, 1.33; 95% confidence interval, 1.18-1.51), compared with the placebo group (GMFR, 1.02; 95% CI, 0.91-1.14); cell-mediated immune response was measured by interferon-gamma, which also showed an immune response in the live-vaccine group (GMFR, 1.49; 95% CI, 1.14-1.94), compared with participants who received placebo (GMFR, 1.14; 95% CI, 0.87-1.48). In preliminary 1-year data, IgG immune response was elevated in the varicella group (GMFR, 1.46; 95% CI, 1.08-1.99), but there was no elevated immune response for interferon-gamma (GMFR, 0.78; 95% CI, 0.49-1.25).

“I think the trial is encouraging not only for its result with the live zoster vaccine and TNF-treated patients, but also challenge the notion that, if you need to, a live-virus vaccine may in fact be able to be safely given to people with autoimmune and inflammatory diseases, even those treated with biologics like tumor necrosis factor inhibitors,” Dr. Curtis said.

As patients in VERVE consented to long-term follow-up in health plan claims and EHR data, it will be possible to follow these patients in the future to assess herpes zoster reactivation. Dr. Curtis also noted that a new trial involving the recombinant, adjuvanted zoster vaccine (Shingrix) is currently in development and should begin next year.

The VERVE trial was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Curtis reported serving as a current member of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices Herpes Zoster Work Group. He and some of the other authors reported financial relationships with many pharmaceutical companies.

SOURCE: Curtis J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 824.

ATLANTA – A group of patients using a tumor necrosis factor inhibitor safely received the live-attenuated varicella vaccine Zostavax without any cases of herpes zoster in the first 6 weeks after vaccination in the blinded, randomized, placebo-controlled Varicella Zoster Vaccine (VERVE) trial .

According to guidelines from the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, there is a theoretical concern that patients using a tumor necrosis factor inhibitor (TNFi) and other biologic therapies who receive a live-attenuated version of the varicella vaccine (Zostavax) could become infected with varicella from the vaccine. Patients with RA and psoriatic arthritis as well as other autoimmune and inflammatory conditions who are likely to receive TNFi therapy are also at risk for herpes zoster reactivation, Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology of the University of Alabama at Birmingham, said in his presentation at the annual meeting of the American College of Rheumatology. There also exists a risk for patients receiving low-dose glucocorticoids.

“The challenge, of course, is there’s not a great definition and there certainly is not a well-standardized assay for how immunocompromised someone is, and so that led to the uncertainty in this patient population for this and other live-virus vaccines,” Dr. Curtis said.

Dr. Curtis and colleagues enrolled 627 participants from 33 centers into the VERVE trial. Participants were aged at least 50 years, were taking a TNFi, and had not previously received Zostavax.

Patients in both groups had a mean age of about 63 years and about two-thirds were women. The most common indications for TNFi use in the Zostavax group and the placebo group were RA (59.2% vs. 56.0%, respectively), psoriatic arthritis (24.3% vs. 23.9%), and ankylosing spondylitis (7.2% vs. 8.5%), while the anti-TNF agents used were adalimumab (38.1% vs. 27.4%), infliximab (28.4% vs. 34.2%), etanercept (19.0% vs. 23.5%), golimumab (10.0% vs. 8.1%), and certolizumab pegol (4.5% vs. 6.8%). In addition, some patients in the Zostavax and placebo groups were also taking concomitant therapies with TNFi, such as oral glucocorticoids (9.7% vs. 11.4%).

The researchers randomized participants to receive Zostavax or placebo (saline) and then followed them for 6 weeks, and looked for signs of wild-type or vaccine-strain varicella infection. If participants were suspected to have varicella, they were assessed clinically, underwent polymerase chain reaction testing, and rashes were photographed. At baseline and at 6 weeks, the researchers collected serum and peripheral blood mononuclear cells to determine patient immunity to varicella. After 6 months, participants were unmasked to the treatment arm of the study.

Dr. Curtis and colleagues found no confirmed varicella infection cases at 6 weeks. “To the extent that 0 cases out of 317 vaccinated people is reassuring, there were no cases, so that was exceedingly heartening as a result,” he said.

Out of 20 serious adverse events total in the groups, 15 events occurred before 6 months, including 8 suspected varicella cases in the Zostavax group and 7 in the placebo group. However, there were no positive cases of varicella – either wild type or vaccine type – after polymerase chain reaction tests. Overall, there were 268 adverse events in 195 participants, with 73 events (27.2%) consisting of injection-site reactions. The researchers also found no difference in the rate of disease flares, and found no differences in adverse reactions between groups, apart from a higher rate of injection-site reactions in the varicella group (19.4% vs. 4.2%).

With regard to immunogenicity, the humoral immune response was measured through IgG, which showed an immune response in the varicella group at 6 weeks (geometric mean fold ratio, 1.33; 95% confidence interval, 1.18-1.51), compared with the placebo group (GMFR, 1.02; 95% CI, 0.91-1.14); cell-mediated immune response was measured by interferon-gamma, which also showed an immune response in the live-vaccine group (GMFR, 1.49; 95% CI, 1.14-1.94), compared with participants who received placebo (GMFR, 1.14; 95% CI, 0.87-1.48). In preliminary 1-year data, IgG immune response was elevated in the varicella group (GMFR, 1.46; 95% CI, 1.08-1.99), but there was no elevated immune response for interferon-gamma (GMFR, 0.78; 95% CI, 0.49-1.25).

“I think the trial is encouraging not only for its result with the live zoster vaccine and TNF-treated patients, but also challenge the notion that, if you need to, a live-virus vaccine may in fact be able to be safely given to people with autoimmune and inflammatory diseases, even those treated with biologics like tumor necrosis factor inhibitors,” Dr. Curtis said.

As patients in VERVE consented to long-term follow-up in health plan claims and EHR data, it will be possible to follow these patients in the future to assess herpes zoster reactivation. Dr. Curtis also noted that a new trial involving the recombinant, adjuvanted zoster vaccine (Shingrix) is currently in development and should begin next year.

The VERVE trial was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Curtis reported serving as a current member of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices Herpes Zoster Work Group. He and some of the other authors reported financial relationships with many pharmaceutical companies.

SOURCE: Curtis J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 824.

ATLANTA – A group of patients using a tumor necrosis factor inhibitor safely received the live-attenuated varicella vaccine Zostavax without any cases of herpes zoster in the first 6 weeks after vaccination in the blinded, randomized, placebo-controlled Varicella Zoster Vaccine (VERVE) trial .

According to guidelines from the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, there is a theoretical concern that patients using a tumor necrosis factor inhibitor (TNFi) and other biologic therapies who receive a live-attenuated version of the varicella vaccine (Zostavax) could become infected with varicella from the vaccine. Patients with RA and psoriatic arthritis as well as other autoimmune and inflammatory conditions who are likely to receive TNFi therapy are also at risk for herpes zoster reactivation, Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology of the University of Alabama at Birmingham, said in his presentation at the annual meeting of the American College of Rheumatology. There also exists a risk for patients receiving low-dose glucocorticoids.

“The challenge, of course, is there’s not a great definition and there certainly is not a well-standardized assay for how immunocompromised someone is, and so that led to the uncertainty in this patient population for this and other live-virus vaccines,” Dr. Curtis said.

Dr. Curtis and colleagues enrolled 627 participants from 33 centers into the VERVE trial. Participants were aged at least 50 years, were taking a TNFi, and had not previously received Zostavax.

Patients in both groups had a mean age of about 63 years and about two-thirds were women. The most common indications for TNFi use in the Zostavax group and the placebo group were RA (59.2% vs. 56.0%, respectively), psoriatic arthritis (24.3% vs. 23.9%), and ankylosing spondylitis (7.2% vs. 8.5%), while the anti-TNF agents used were adalimumab (38.1% vs. 27.4%), infliximab (28.4% vs. 34.2%), etanercept (19.0% vs. 23.5%), golimumab (10.0% vs. 8.1%), and certolizumab pegol (4.5% vs. 6.8%). In addition, some patients in the Zostavax and placebo groups were also taking concomitant therapies with TNFi, such as oral glucocorticoids (9.7% vs. 11.4%).

The researchers randomized participants to receive Zostavax or placebo (saline) and then followed them for 6 weeks, and looked for signs of wild-type or vaccine-strain varicella infection. If participants were suspected to have varicella, they were assessed clinically, underwent polymerase chain reaction testing, and rashes were photographed. At baseline and at 6 weeks, the researchers collected serum and peripheral blood mononuclear cells to determine patient immunity to varicella. After 6 months, participants were unmasked to the treatment arm of the study.

Dr. Curtis and colleagues found no confirmed varicella infection cases at 6 weeks. “To the extent that 0 cases out of 317 vaccinated people is reassuring, there were no cases, so that was exceedingly heartening as a result,” he said.

Out of 20 serious adverse events total in the groups, 15 events occurred before 6 months, including 8 suspected varicella cases in the Zostavax group and 7 in the placebo group. However, there were no positive cases of varicella – either wild type or vaccine type – after polymerase chain reaction tests. Overall, there were 268 adverse events in 195 participants, with 73 events (27.2%) consisting of injection-site reactions. The researchers also found no difference in the rate of disease flares, and found no differences in adverse reactions between groups, apart from a higher rate of injection-site reactions in the varicella group (19.4% vs. 4.2%).

With regard to immunogenicity, the humoral immune response was measured through IgG, which showed an immune response in the varicella group at 6 weeks (geometric mean fold ratio, 1.33; 95% confidence interval, 1.18-1.51), compared with the placebo group (GMFR, 1.02; 95% CI, 0.91-1.14); cell-mediated immune response was measured by interferon-gamma, which also showed an immune response in the live-vaccine group (GMFR, 1.49; 95% CI, 1.14-1.94), compared with participants who received placebo (GMFR, 1.14; 95% CI, 0.87-1.48). In preliminary 1-year data, IgG immune response was elevated in the varicella group (GMFR, 1.46; 95% CI, 1.08-1.99), but there was no elevated immune response for interferon-gamma (GMFR, 0.78; 95% CI, 0.49-1.25).

“I think the trial is encouraging not only for its result with the live zoster vaccine and TNF-treated patients, but also challenge the notion that, if you need to, a live-virus vaccine may in fact be able to be safely given to people with autoimmune and inflammatory diseases, even those treated with biologics like tumor necrosis factor inhibitors,” Dr. Curtis said.

As patients in VERVE consented to long-term follow-up in health plan claims and EHR data, it will be possible to follow these patients in the future to assess herpes zoster reactivation. Dr. Curtis also noted that a new trial involving the recombinant, adjuvanted zoster vaccine (Shingrix) is currently in development and should begin next year.

The VERVE trial was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Curtis reported serving as a current member of the Center for Disease Control and Prevention’s Advisory Committee on Immunization Practices Herpes Zoster Work Group. He and some of the other authors reported financial relationships with many pharmaceutical companies.

SOURCE: Curtis J et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract 824.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Zffoto/Thinkstock

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

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

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

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

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

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

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

Zffoto/Thinkstock

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

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

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

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

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

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

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

Zffoto/Thinkstock

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

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

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

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

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

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

LAS VEGAS – Rheumatoid arthritis that is difficult to treat may occur in about 10% of patients with the disease. The definition of difficult-to-treat rheumatoid arthritis varies among experts, however, and the reasons for refractoriness are often unknown, said Iain McInnes, MD, PhD, professor of experimental medicine and director of the Institute of Infection, Immunity and Inflammation at the University of Glasgow and current president of the European League Against Rheumatism.

There may be an intrinsic refractory disease state, where the disease will manifest despite the use of any existing medications. Patients may have pharmacokinetic refractory disease, which could result from antidrug antibodies. There may be false positives. “It could well be that the patient is sore, but it is not because of the active inflammation,” he said. “It is because of biomechanical disease or pain sensitization. Or it could be that there is osteoarthritis.”

In the end, managing patients with difficult-to-treat rheumatoid arthritis may come down to setting reasonable expectations and addressing practical concerns, such as medication adherence, comorbidities, and adverse drug reactions – “the realpolitik of rheumatological care,” Dr. McInnes said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
 

Defining difficult to treat

In a recently published study, Dr. McInnes and colleagues surveyed rheumatologists about what characterizes difficult-to-treat rheumatoid arthritis (Ann Rheum Dis. 2018 Dec;77[12]:1705-9).

“There was remarkable variation,” Dr. McInnes said. “Should fatigue be involved? Do the types of drugs that you have failed matter? Should a patient’s need for glucocorticoids be part of the definition? ... We did not really find much of a consensus.”

The presence of cardiovascular disease, extra-articular manifestations, infection, malignancy, diabetes mellitus, and other factors add to the challenge. “These are all very familiar problems that you face in your routine practice, whether you are in rheumatology care primarily or whether you are in family practice,” he said.

Although it is difficult to determine how many patients have refractory rheumatoid arthritis, “the rule of thumb is about 10%,” Dr. McInnes said. Using data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis, researchers estimated that approximately 6% of patients would be refractory to a biologic drug, defined as patients who move on to a third class of biologic therapy (Ann Rheum Dis. 2018 Oct;77[10]:1405-12).

The same study found that, in recent years, patients have cycled through drugs more quickly than they had in the past. Many patients prove difficult to treat within 4 or 5 years, “which is pretty terrifying with a disease whose median age of onset is early 50s, but whose clinics are full of people in their teens, 20s, and 30s,” Dr. McInnes said.

Approaches to treatment

New medications, therapeutic targets, and treatment approaches eventually may help treat or prevent refractory disease. In the meantime, it may be beneficial to “go back to the beginning” when caring for patients with difficult-to-treat rheumatoid arthritis, Dr. McInnes said. “Make absolutely certain that we understand what is going on in that patient. Even just the opportunity to go through the disease course is reassuring for our patients. If nothing else, it tells them that we are listening, paying attention, and we are taking it seriously.”

Physicians may need to recognize the presence of antidrug antibodies. In addition, medication adherence may be a problem. About one-third of patients who are prescribed methotrexate do not take the medication, which may be a difficult topic for them to discuss, he said.

“Detect that inflammation which is there and treat it,” Dr. McInnes said. “And detect that which is not of an inflammatory origin and manage it on its own merits.”

Dr. McInnes is a consultant for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galvani, GlaxoSmithKline, Leo Pharma, Novartis, Pfizer, and UCB. He has received grant or research support from AstraZeneca, Bristol-Myers Squibb, Compugen, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.

jremaly@mdedge.com

LAS VEGAS – Rheumatoid arthritis that is difficult to treat may occur in about 10% of patients with the disease. The definition of difficult-to-treat rheumatoid arthritis varies among experts, however, and the reasons for refractoriness are often unknown, said Iain McInnes, MD, PhD, professor of experimental medicine and director of the Institute of Infection, Immunity and Inflammation at the University of Glasgow and current president of the European League Against Rheumatism.

There may be an intrinsic refractory disease state, where the disease will manifest despite the use of any existing medications. Patients may have pharmacokinetic refractory disease, which could result from antidrug antibodies. There may be false positives. “It could well be that the patient is sore, but it is not because of the active inflammation,” he said. “It is because of biomechanical disease or pain sensitization. Or it could be that there is osteoarthritis.”

In the end, managing patients with difficult-to-treat rheumatoid arthritis may come down to setting reasonable expectations and addressing practical concerns, such as medication adherence, comorbidities, and adverse drug reactions – “the realpolitik of rheumatological care,” Dr. McInnes said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
 

Defining difficult to treat

In a recently published study, Dr. McInnes and colleagues surveyed rheumatologists about what characterizes difficult-to-treat rheumatoid arthritis (Ann Rheum Dis. 2018 Dec;77[12]:1705-9).

“There was remarkable variation,” Dr. McInnes said. “Should fatigue be involved? Do the types of drugs that you have failed matter? Should a patient’s need for glucocorticoids be part of the definition? ... We did not really find much of a consensus.”

The presence of cardiovascular disease, extra-articular manifestations, infection, malignancy, diabetes mellitus, and other factors add to the challenge. “These are all very familiar problems that you face in your routine practice, whether you are in rheumatology care primarily or whether you are in family practice,” he said.

Although it is difficult to determine how many patients have refractory rheumatoid arthritis, “the rule of thumb is about 10%,” Dr. McInnes said. Using data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis, researchers estimated that approximately 6% of patients would be refractory to a biologic drug, defined as patients who move on to a third class of biologic therapy (Ann Rheum Dis. 2018 Oct;77[10]:1405-12).

The same study found that, in recent years, patients have cycled through drugs more quickly than they had in the past. Many patients prove difficult to treat within 4 or 5 years, “which is pretty terrifying with a disease whose median age of onset is early 50s, but whose clinics are full of people in their teens, 20s, and 30s,” Dr. McInnes said.

Approaches to treatment

New medications, therapeutic targets, and treatment approaches eventually may help treat or prevent refractory disease. In the meantime, it may be beneficial to “go back to the beginning” when caring for patients with difficult-to-treat rheumatoid arthritis, Dr. McInnes said. “Make absolutely certain that we understand what is going on in that patient. Even just the opportunity to go through the disease course is reassuring for our patients. If nothing else, it tells them that we are listening, paying attention, and we are taking it seriously.”

Physicians may need to recognize the presence of antidrug antibodies. In addition, medication adherence may be a problem. About one-third of patients who are prescribed methotrexate do not take the medication, which may be a difficult topic for them to discuss, he said.

“Detect that inflammation which is there and treat it,” Dr. McInnes said. “And detect that which is not of an inflammatory origin and manage it on its own merits.”

Dr. McInnes is a consultant for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galvani, GlaxoSmithKline, Leo Pharma, Novartis, Pfizer, and UCB. He has received grant or research support from AstraZeneca, Bristol-Myers Squibb, Compugen, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.

jremaly@mdedge.com

LAS VEGAS – Rheumatoid arthritis that is difficult to treat may occur in about 10% of patients with the disease. The definition of difficult-to-treat rheumatoid arthritis varies among experts, however, and the reasons for refractoriness are often unknown, said Iain McInnes, MD, PhD, professor of experimental medicine and director of the Institute of Infection, Immunity and Inflammation at the University of Glasgow and current president of the European League Against Rheumatism.

There may be an intrinsic refractory disease state, where the disease will manifest despite the use of any existing medications. Patients may have pharmacokinetic refractory disease, which could result from antidrug antibodies. There may be false positives. “It could well be that the patient is sore, but it is not because of the active inflammation,” he said. “It is because of biomechanical disease or pain sensitization. Or it could be that there is osteoarthritis.”

In the end, managing patients with difficult-to-treat rheumatoid arthritis may come down to setting reasonable expectations and addressing practical concerns, such as medication adherence, comorbidities, and adverse drug reactions – “the realpolitik of rheumatological care,” Dr. McInnes said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.
 

Defining difficult to treat

In a recently published study, Dr. McInnes and colleagues surveyed rheumatologists about what characterizes difficult-to-treat rheumatoid arthritis (Ann Rheum Dis. 2018 Dec;77[12]:1705-9).

“There was remarkable variation,” Dr. McInnes said. “Should fatigue be involved? Do the types of drugs that you have failed matter? Should a patient’s need for glucocorticoids be part of the definition? ... We did not really find much of a consensus.”

The presence of cardiovascular disease, extra-articular manifestations, infection, malignancy, diabetes mellitus, and other factors add to the challenge. “These are all very familiar problems that you face in your routine practice, whether you are in rheumatology care primarily or whether you are in family practice,” he said.

Although it is difficult to determine how many patients have refractory rheumatoid arthritis, “the rule of thumb is about 10%,” Dr. McInnes said. Using data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis, researchers estimated that approximately 6% of patients would be refractory to a biologic drug, defined as patients who move on to a third class of biologic therapy (Ann Rheum Dis. 2018 Oct;77[10]:1405-12).

The same study found that, in recent years, patients have cycled through drugs more quickly than they had in the past. Many patients prove difficult to treat within 4 or 5 years, “which is pretty terrifying with a disease whose median age of onset is early 50s, but whose clinics are full of people in their teens, 20s, and 30s,” Dr. McInnes said.

Approaches to treatment

New medications, therapeutic targets, and treatment approaches eventually may help treat or prevent refractory disease. In the meantime, it may be beneficial to “go back to the beginning” when caring for patients with difficult-to-treat rheumatoid arthritis, Dr. McInnes said. “Make absolutely certain that we understand what is going on in that patient. Even just the opportunity to go through the disease course is reassuring for our patients. If nothing else, it tells them that we are listening, paying attention, and we are taking it seriously.”

Physicians may need to recognize the presence of antidrug antibodies. In addition, medication adherence may be a problem. About one-third of patients who are prescribed methotrexate do not take the medication, which may be a difficult topic for them to discuss, he said.

“Detect that inflammation which is there and treat it,” Dr. McInnes said. “And detect that which is not of an inflammatory origin and manage it on its own merits.”

Dr. McInnes is a consultant for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galvani, GlaxoSmithKline, Leo Pharma, Novartis, Pfizer, and UCB. He has received grant or research support from AstraZeneca, Bristol-Myers Squibb, Compugen, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.

jremaly@mdedge.com