‘Multimorbidities’ in RA make impact on treatment efficacy, disease activity

 

While clinicians are accustomed to managing patients with rheumatoid arthritis and comorbidities, RA patients more frequently have “multimorbidities” – the simultaneous presence of two or more chronic conditions.

“For anyone who sees patients, this is the reality of our lives,” said Jeffrey R. Curtis, MD, at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. Some conditions are “bystanders” that don’t impact RA, some are risk factors for RA, and some can be caused by RA treatments, said Dr. Curtis, professor of medicine and William J. Koopman Professor in Rheumatology and Immunology at the University of Alabama at Birmingham. He discussed several comorbid conditions and their interactions with RA.
 

Obesity’s toll on disease activity

It’s long been recognized that obesity along with RA makes things worse for patients, he said: “If you have a patient who is obese, with a BMI [body mass index] over 30-35, they’re less likely clinically to achieve low disease activity or remission.”

There’s a lot of science behind why obesity seems to negatively impact treatment response, he said, but a recent study (Ann Rheum Dis. 2017;76:1743-6) of patients from a golimumab (Simponi) trial that looked at treatment response to the biologic and conducted MRIs found something interesting. The trial, which stratified patients by BMI, found that those with a BMI over 30 kg/m² were about half as likely to achieve remission based on the 28-joint Disease Activity Score (DAS28), a finding compatible with those from other studies. But the MRI findings showed that synovitis scores and inflammation levels among obese patients were really no different from those of nonobese patients, and having a low osteitis score was more common among the obese patients. The authors concluded that “maybe we need more sophisticated tools” to measure the impact of obesity, Dr. Curtis said.

Obesity also affects biomarkers, he said. The multibiomarker disease activity test, marketed as Vectra DA, incorporates several adipokines in its score, but given any level of RA disease, that score is roughly 5 units higher if someone is obese (Sem Arthritis Rheum. 2017 Aug 2. doi: 10.1016/j.semarthrit.2017.07.010). “The company that manufactures the test is working on an adjustment factor to optimize the role of obesity and what those adipokines are doing to better predict x-ray progression to take this influence into account,” he said. “How we measure obesity and how we’re measuring RA are probably very much affected by this issue.”
 

RA and the somatization comorbidity phenotype

A second common co-occurrence is what Dr. Curtis calls a somatization comorbidity phenotype (SCP), defined as RA with several other ailments such as fibromyalgia, depression, anxiety, sleep apnea, or neuropathy. “The troubling thing about this is I could cure this patient’s RA tomorrow, but they actually wouldn’t feel better in their overall health because of other things dragging down their function,” he said, noting patients are more concerned about their fatigue and pain than their swollen joint count or DAS28 score.

Dr. Curtis and his colleagues completed a recent analysis that’s in press in Arthritis Research & Therapy of about 800 RA patients in the United States starting certolizumab pegol (Cimzia) to look for how well patients with this phenotype responded to a tumor necrosis factor (TNF) inhibitor. The percentage of patients with RA plus SCP who achieved American College of Rheumatology (ACR) 20/50/70 scores were all about 10% lower than for patients with RA alone, and about 15% fewer patients achieved remission using a score of less than 2.6 on the DAS28, based on erythrocyte sedimentation rate. There was about a 10% higher withdrawal rate among the RA plus SCP group, compared with those with RA alone, mainly for lack of efficacy, and the RA plus SCP patients had three times the rate of serious infections and twice the rate of nonserious infections of typical RA patients.
 

Impact on choice of therapy

Clinicians have questioned whether multimorbidities should affect the choice of RA therapy, Dr. Curtis said. One of the most vexing scenarios has been in patients with a history of cancer, he noted. There have been five studies worldwide looking at RA therapy in this population. One from Sweden (Ann Rheum Dis. 2015 Dec;74[12]:2137-43), of 240 breast cancer survivors, found no difference in the occurrence or hazard ratio of recurrent breast cancer between those treated with TNF inhibitors versus those who were not. Another study coauthored by Dr. Curtis found similar results (Arthritis Rheumatol. 2016 Dec;68[10]:2403–11).

 

According to the ACR’s 2015 treatment guidelines, “If your RA patient has a previously treated, solid organ malignancy, there’s no restrictions on what you and I should use,” he said. “Basically, treat them like they hadn’t had a history of cancer.” The exception is for patients with previously treated nonmelanoma skin cancer or melanoma, in whom conventional synthetic DMARDs are preferred over biologics or tofacitinib (Xeljanz). In addition, patients with previously treated lymphoproliferative disorders should be given rituximab (Rituxan) – or DMARDs, abatacept (Orencia), or tocilizumab (Actemra) – over TNF inhibitors. “This is good news,” Dr. Curtis said. “It really expands the range of options for patients, now supported by data, who have a history of cancer and bad RA.”

Global Academy for Medical Education and this news organization are owned by the same parent company. Dr. Curtis receives research support or serves as a consultant for Amgen, Bristol-Myers Squibb, Corrona, Lilly, Janssen, Myriad, Pfizer, and Sanofi/Regeneron.

 

While clinicians are accustomed to managing patients with rheumatoid arthritis and comorbidities, RA patients more frequently have “multimorbidities” – the simultaneous presence of two or more chronic conditions.

“For anyone who sees patients, this is the reality of our lives,” said Jeffrey R. Curtis, MD, at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. Some conditions are “bystanders” that don’t impact RA, some are risk factors for RA, and some can be caused by RA treatments, said Dr. Curtis, professor of medicine and William J. Koopman Professor in Rheumatology and Immunology at the University of Alabama at Birmingham. He discussed several comorbid conditions and their interactions with RA.
 

Obesity’s toll on disease activity

It’s long been recognized that obesity along with RA makes things worse for patients, he said: “If you have a patient who is obese, with a BMI [body mass index] over 30-35, they’re less likely clinically to achieve low disease activity or remission.”

There’s a lot of science behind why obesity seems to negatively impact treatment response, he said, but a recent study (Ann Rheum Dis. 2017;76:1743-6) of patients from a golimumab (Simponi) trial that looked at treatment response to the biologic and conducted MRIs found something interesting. The trial, which stratified patients by BMI, found that those with a BMI over 30 kg/m² were about half as likely to achieve remission based on the 28-joint Disease Activity Score (DAS28), a finding compatible with those from other studies. But the MRI findings showed that synovitis scores and inflammation levels among obese patients were really no different from those of nonobese patients, and having a low osteitis score was more common among the obese patients. The authors concluded that “maybe we need more sophisticated tools” to measure the impact of obesity, Dr. Curtis said.

Obesity also affects biomarkers, he said. The multibiomarker disease activity test, marketed as Vectra DA, incorporates several adipokines in its score, but given any level of RA disease, that score is roughly 5 units higher if someone is obese (Sem Arthritis Rheum. 2017 Aug 2. doi: 10.1016/j.semarthrit.2017.07.010). “The company that manufactures the test is working on an adjustment factor to optimize the role of obesity and what those adipokines are doing to better predict x-ray progression to take this influence into account,” he said. “How we measure obesity and how we’re measuring RA are probably very much affected by this issue.”
 

RA and the somatization comorbidity phenotype

A second common co-occurrence is what Dr. Curtis calls a somatization comorbidity phenotype (SCP), defined as RA with several other ailments such as fibromyalgia, depression, anxiety, sleep apnea, or neuropathy. “The troubling thing about this is I could cure this patient’s RA tomorrow, but they actually wouldn’t feel better in their overall health because of other things dragging down their function,” he said, noting patients are more concerned about their fatigue and pain than their swollen joint count or DAS28 score.

Dr. Curtis and his colleagues completed a recent analysis that’s in press in Arthritis Research & Therapy of about 800 RA patients in the United States starting certolizumab pegol (Cimzia) to look for how well patients with this phenotype responded to a tumor necrosis factor (TNF) inhibitor. The percentage of patients with RA plus SCP who achieved American College of Rheumatology (ACR) 20/50/70 scores were all about 10% lower than for patients with RA alone, and about 15% fewer patients achieved remission using a score of less than 2.6 on the DAS28, based on erythrocyte sedimentation rate. There was about a 10% higher withdrawal rate among the RA plus SCP group, compared with those with RA alone, mainly for lack of efficacy, and the RA plus SCP patients had three times the rate of serious infections and twice the rate of nonserious infections of typical RA patients.
 

Impact on choice of therapy

Clinicians have questioned whether multimorbidities should affect the choice of RA therapy, Dr. Curtis said. One of the most vexing scenarios has been in patients with a history of cancer, he noted. There have been five studies worldwide looking at RA therapy in this population. One from Sweden (Ann Rheum Dis. 2015 Dec;74[12]:2137-43), of 240 breast cancer survivors, found no difference in the occurrence or hazard ratio of recurrent breast cancer between those treated with TNF inhibitors versus those who were not. Another study coauthored by Dr. Curtis found similar results (Arthritis Rheumatol. 2016 Dec;68[10]:2403–11).

 

According to the ACR’s 2015 treatment guidelines, “If your RA patient has a previously treated, solid organ malignancy, there’s no restrictions on what you and I should use,” he said. “Basically, treat them like they hadn’t had a history of cancer.” The exception is for patients with previously treated nonmelanoma skin cancer or melanoma, in whom conventional synthetic DMARDs are preferred over biologics or tofacitinib (Xeljanz). In addition, patients with previously treated lymphoproliferative disorders should be given rituximab (Rituxan) – or DMARDs, abatacept (Orencia), or tocilizumab (Actemra) – over TNF inhibitors. “This is good news,” Dr. Curtis said. “It really expands the range of options for patients, now supported by data, who have a history of cancer and bad RA.”

Global Academy for Medical Education and this news organization are owned by the same parent company. Dr. Curtis receives research support or serves as a consultant for Amgen, Bristol-Myers Squibb, Corrona, Lilly, Janssen, Myriad, Pfizer, and Sanofi/Regeneron.

 

While clinicians are accustomed to managing patients with rheumatoid arthritis and comorbidities, RA patients more frequently have “multimorbidities” – the simultaneous presence of two or more chronic conditions.

“For anyone who sees patients, this is the reality of our lives,” said Jeffrey R. Curtis, MD, at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. Some conditions are “bystanders” that don’t impact RA, some are risk factors for RA, and some can be caused by RA treatments, said Dr. Curtis, professor of medicine and William J. Koopman Professor in Rheumatology and Immunology at the University of Alabama at Birmingham. He discussed several comorbid conditions and their interactions with RA.
 

Obesity’s toll on disease activity

It’s long been recognized that obesity along with RA makes things worse for patients, he said: “If you have a patient who is obese, with a BMI [body mass index] over 30-35, they’re less likely clinically to achieve low disease activity or remission.”

There’s a lot of science behind why obesity seems to negatively impact treatment response, he said, but a recent study (Ann Rheum Dis. 2017;76:1743-6) of patients from a golimumab (Simponi) trial that looked at treatment response to the biologic and conducted MRIs found something interesting. The trial, which stratified patients by BMI, found that those with a BMI over 30 kg/m² were about half as likely to achieve remission based on the 28-joint Disease Activity Score (DAS28), a finding compatible with those from other studies. But the MRI findings showed that synovitis scores and inflammation levels among obese patients were really no different from those of nonobese patients, and having a low osteitis score was more common among the obese patients. The authors concluded that “maybe we need more sophisticated tools” to measure the impact of obesity, Dr. Curtis said.

Obesity also affects biomarkers, he said. The multibiomarker disease activity test, marketed as Vectra DA, incorporates several adipokines in its score, but given any level of RA disease, that score is roughly 5 units higher if someone is obese (Sem Arthritis Rheum. 2017 Aug 2. doi: 10.1016/j.semarthrit.2017.07.010). “The company that manufactures the test is working on an adjustment factor to optimize the role of obesity and what those adipokines are doing to better predict x-ray progression to take this influence into account,” he said. “How we measure obesity and how we’re measuring RA are probably very much affected by this issue.”
 

RA and the somatization comorbidity phenotype

A second common co-occurrence is what Dr. Curtis calls a somatization comorbidity phenotype (SCP), defined as RA with several other ailments such as fibromyalgia, depression, anxiety, sleep apnea, or neuropathy. “The troubling thing about this is I could cure this patient’s RA tomorrow, but they actually wouldn’t feel better in their overall health because of other things dragging down their function,” he said, noting patients are more concerned about their fatigue and pain than their swollen joint count or DAS28 score.

Dr. Curtis and his colleagues completed a recent analysis that’s in press in Arthritis Research & Therapy of about 800 RA patients in the United States starting certolizumab pegol (Cimzia) to look for how well patients with this phenotype responded to a tumor necrosis factor (TNF) inhibitor. The percentage of patients with RA plus SCP who achieved American College of Rheumatology (ACR) 20/50/70 scores were all about 10% lower than for patients with RA alone, and about 15% fewer patients achieved remission using a score of less than 2.6 on the DAS28, based on erythrocyte sedimentation rate. There was about a 10% higher withdrawal rate among the RA plus SCP group, compared with those with RA alone, mainly for lack of efficacy, and the RA plus SCP patients had three times the rate of serious infections and twice the rate of nonserious infections of typical RA patients.
 

Impact on choice of therapy

Clinicians have questioned whether multimorbidities should affect the choice of RA therapy, Dr. Curtis said. One of the most vexing scenarios has been in patients with a history of cancer, he noted. There have been five studies worldwide looking at RA therapy in this population. One from Sweden (Ann Rheum Dis. 2015 Dec;74[12]:2137-43), of 240 breast cancer survivors, found no difference in the occurrence or hazard ratio of recurrent breast cancer between those treated with TNF inhibitors versus those who were not. Another study coauthored by Dr. Curtis found similar results (Arthritis Rheumatol. 2016 Dec;68[10]:2403–11).

 

According to the ACR’s 2015 treatment guidelines, “If your RA patient has a previously treated, solid organ malignancy, there’s no restrictions on what you and I should use,” he said. “Basically, treat them like they hadn’t had a history of cancer.” The exception is for patients with previously treated nonmelanoma skin cancer or melanoma, in whom conventional synthetic DMARDs are preferred over biologics or tofacitinib (Xeljanz). In addition, patients with previously treated lymphoproliferative disorders should be given rituximab (Rituxan) – or DMARDs, abatacept (Orencia), or tocilizumab (Actemra) – over TNF inhibitors. “This is good news,” Dr. Curtis said. “It really expands the range of options for patients, now supported by data, who have a history of cancer and bad RA.”

Global Academy for Medical Education and this news organization are owned by the same parent company. Dr. Curtis receives research support or serves as a consultant for Amgen, Bristol-Myers Squibb, Corrona, Lilly, Janssen, Myriad, Pfizer, and Sanofi/Regeneron.