TBD Meeting (5439-21)

Older age, higher subjective disease activity, and exercising for more than 120 minutes per week were three factors linked to patients with ankylosing spondylitis (AS) who switched from their original tumor necrosis factor inhibitor (TNFi) treatment within 2 years in a U.S.-based study.

Data from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) also found that higher levels of inflammation, but not radiographic disease, were linked to patients changing from one TNFi to another, or to an interleukin (IL)-17 inhibitor or Janus kinase (JAK) inhibitor.

“Different factors were associated in AS patients who switch from their initial TNF inhibitor to another TNF inhibitor, IL-17 inhibitor, or JAK inhibitor within 2 years versus after 2 years of treatment,” John D. Reveille, MD, professor and vice chair of rheumatology and clinical immunogenetics with McGovern Medical School at UTHealth Houston, said at the 12th International Congress on Spondyloarthritides.

“We’re currently looking at different approaches to analyzing these data. And, certainly, this needs need to be looked at in other cohorts,” Dr. Reveille said.

PSOAS is a prospective observational cohort study that has been looking at predictors of AS severity for almost 20 years. Started in 2002, the study has routinely collected a whole host of data on various demographic and disease-related factors.

The reasoning behind the current analysis of PSOAS data was that a relatively recent study based on a commercial claims database had found that many patients with AS do not remain on their initial TNFi 2 years after initiation. So, Dr. Reveille and associates decided to look at the factors that could be influencing whether patients who started a TNFi would remain on their original drug in the PSOAS cohort.

In all, 533 patients from the PSOAS cohort who had at least 2 years of follow-up were included in the analysis. The majority (n = 496) were treated with a TNFi, 34 had received an IL-17 inhibitor, and 3 had received a JAK inhibitor.

Of the 496 patients treated with a TNFi, almost 70% (n = 344) persisted with this treatment for the duration of the study. Of those that switched to another TNFi or IL-17 or JAK inhibitor treatment, 20% (n = 101) did so within 2 years and the remaining 10% (n = 51) after 2 years.

Multinominal logistic regression modeling revealed a number of different factors that were associated with switching within 2 years versus switching after 2 years.

Compared to patients who persisted with treatment throughout the study period, patients who switched from their original TNFi within 2 years were more likely to be older (odds ratio [OR], 2.0 for ≥ 40 vs. < 40 years; P = .002), have a higher Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) score at baseline (OR, 1.73 for ≥ 4 vs. < 4; P = .03), higher C-reactive protein levels (OR, 1.94 for ≥ 0.8 mg/dL vs. < 0.8 mg/dL, P = .004), and greater weekly duration of exercise (OR, 1.95 for ≥ 120 minutes per week vs. < 120; P <.001).

Switchers also were less likely to have severe radiographic disease at baseline, as determined by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, OR, 0.63; P = .03), and less likely to be current smokers (OR, 0.69; P < .001).

Factors associated with switching after 2 years versus persisting with treatment were higher baseline BASDAI (OR, 2.31; P = .01), exercising more than 120 minutes per week (OR, 1.66; P = .03), and having more comorbidities (OR, 1.63 for ≥ 2 vs. < 2, P = .04).

However, patients who switched after 2 years were less likely to be depressed (OR, 0.35; P = .002) or to have a longer baseline disease duration (OR, 0.27 for ≥ 20 years vs. < 20 years P < .001).

The association observed between switching within 2 years and lower likelihood of currently smoking was a “little bit puzzling,” one delegate said after Dr. Reveille’s presentation. “The opposite has been shown in the literature, and current smokers seem to be refractory to TNF inhibitor therapy,” the delegate observed.

“I was confounded when I saw the data,” Dr. Reveille acknowledged. Because this was an observational study, this finding needs more investigation, he agreed. “Interestingly, we have seen this negative association with some other parameters, too,” he added.

The HLA-B27 carrier and radiographic status were carefully checked, so there should not be a problem with the diagnosis, Dr. Reveille reassured. Further analyses of the findings are now warranted.

Funding for the study was provided by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Additional funding was received from the Spondyloarthritis Association of America and Eli Lilly.

Dr. Reveille made no personal disclosures; a coauthor of the abstract was an employee of Eli Lilly.

Older age, higher subjective disease activity, and exercising for more than 120 minutes per week were three factors linked to patients with ankylosing spondylitis (AS) who switched from their original tumor necrosis factor inhibitor (TNFi) treatment within 2 years in a U.S.-based study.

Data from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) also found that higher levels of inflammation, but not radiographic disease, were linked to patients changing from one TNFi to another, or to an interleukin (IL)-17 inhibitor or Janus kinase (JAK) inhibitor.

“Different factors were associated in AS patients who switch from their initial TNF inhibitor to another TNF inhibitor, IL-17 inhibitor, or JAK inhibitor within 2 years versus after 2 years of treatment,” John D. Reveille, MD, professor and vice chair of rheumatology and clinical immunogenetics with McGovern Medical School at UTHealth Houston, said at the 12th International Congress on Spondyloarthritides.

“We’re currently looking at different approaches to analyzing these data. And, certainly, this needs need to be looked at in other cohorts,” Dr. Reveille said.

PSOAS is a prospective observational cohort study that has been looking at predictors of AS severity for almost 20 years. Started in 2002, the study has routinely collected a whole host of data on various demographic and disease-related factors.

The reasoning behind the current analysis of PSOAS data was that a relatively recent study based on a commercial claims database had found that many patients with AS do not remain on their initial TNFi 2 years after initiation. So, Dr. Reveille and associates decided to look at the factors that could be influencing whether patients who started a TNFi would remain on their original drug in the PSOAS cohort.

In all, 533 patients from the PSOAS cohort who had at least 2 years of follow-up were included in the analysis. The majority (n = 496) were treated with a TNFi, 34 had received an IL-17 inhibitor, and 3 had received a JAK inhibitor.

Of the 496 patients treated with a TNFi, almost 70% (n = 344) persisted with this treatment for the duration of the study. Of those that switched to another TNFi or IL-17 or JAK inhibitor treatment, 20% (n = 101) did so within 2 years and the remaining 10% (n = 51) after 2 years.

Multinominal logistic regression modeling revealed a number of different factors that were associated with switching within 2 years versus switching after 2 years.

Compared to patients who persisted with treatment throughout the study period, patients who switched from their original TNFi within 2 years were more likely to be older (odds ratio [OR], 2.0 for ≥ 40 vs. < 40 years; P = .002), have a higher Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) score at baseline (OR, 1.73 for ≥ 4 vs. < 4; P = .03), higher C-reactive protein levels (OR, 1.94 for ≥ 0.8 mg/dL vs. < 0.8 mg/dL, P = .004), and greater weekly duration of exercise (OR, 1.95 for ≥ 120 minutes per week vs. < 120; P <.001).

Switchers also were less likely to have severe radiographic disease at baseline, as determined by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, OR, 0.63; P = .03), and less likely to be current smokers (OR, 0.69; P < .001).

Factors associated with switching after 2 years versus persisting with treatment were higher baseline BASDAI (OR, 2.31; P = .01), exercising more than 120 minutes per week (OR, 1.66; P = .03), and having more comorbidities (OR, 1.63 for ≥ 2 vs. < 2, P = .04).

However, patients who switched after 2 years were less likely to be depressed (OR, 0.35; P = .002) or to have a longer baseline disease duration (OR, 0.27 for ≥ 20 years vs. < 20 years P < .001).

The association observed between switching within 2 years and lower likelihood of currently smoking was a “little bit puzzling,” one delegate said after Dr. Reveille’s presentation. “The opposite has been shown in the literature, and current smokers seem to be refractory to TNF inhibitor therapy,” the delegate observed.

“I was confounded when I saw the data,” Dr. Reveille acknowledged. Because this was an observational study, this finding needs more investigation, he agreed. “Interestingly, we have seen this negative association with some other parameters, too,” he added.

The HLA-B27 carrier and radiographic status were carefully checked, so there should not be a problem with the diagnosis, Dr. Reveille reassured. Further analyses of the findings are now warranted.

Funding for the study was provided by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Additional funding was received from the Spondyloarthritis Association of America and Eli Lilly.

Dr. Reveille made no personal disclosures; a coauthor of the abstract was an employee of Eli Lilly.

Older age, higher subjective disease activity, and exercising for more than 120 minutes per week were three factors linked to patients with ankylosing spondylitis (AS) who switched from their original tumor necrosis factor inhibitor (TNFi) treatment within 2 years in a U.S.-based study.

Data from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) also found that higher levels of inflammation, but not radiographic disease, were linked to patients changing from one TNFi to another, or to an interleukin (IL)-17 inhibitor or Janus kinase (JAK) inhibitor.

“Different factors were associated in AS patients who switch from their initial TNF inhibitor to another TNF inhibitor, IL-17 inhibitor, or JAK inhibitor within 2 years versus after 2 years of treatment,” John D. Reveille, MD, professor and vice chair of rheumatology and clinical immunogenetics with McGovern Medical School at UTHealth Houston, said at the 12th International Congress on Spondyloarthritides.

“We’re currently looking at different approaches to analyzing these data. And, certainly, this needs need to be looked at in other cohorts,” Dr. Reveille said.

PSOAS is a prospective observational cohort study that has been looking at predictors of AS severity for almost 20 years. Started in 2002, the study has routinely collected a whole host of data on various demographic and disease-related factors.

The reasoning behind the current analysis of PSOAS data was that a relatively recent study based on a commercial claims database had found that many patients with AS do not remain on their initial TNFi 2 years after initiation. So, Dr. Reveille and associates decided to look at the factors that could be influencing whether patients who started a TNFi would remain on their original drug in the PSOAS cohort.

In all, 533 patients from the PSOAS cohort who had at least 2 years of follow-up were included in the analysis. The majority (n = 496) were treated with a TNFi, 34 had received an IL-17 inhibitor, and 3 had received a JAK inhibitor.

Of the 496 patients treated with a TNFi, almost 70% (n = 344) persisted with this treatment for the duration of the study. Of those that switched to another TNFi or IL-17 or JAK inhibitor treatment, 20% (n = 101) did so within 2 years and the remaining 10% (n = 51) after 2 years.

Multinominal logistic regression modeling revealed a number of different factors that were associated with switching within 2 years versus switching after 2 years.

Compared to patients who persisted with treatment throughout the study period, patients who switched from their original TNFi within 2 years were more likely to be older (odds ratio [OR], 2.0 for ≥ 40 vs. < 40 years; P = .002), have a higher Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) score at baseline (OR, 1.73 for ≥ 4 vs. < 4; P = .03), higher C-reactive protein levels (OR, 1.94 for ≥ 0.8 mg/dL vs. < 0.8 mg/dL, P = .004), and greater weekly duration of exercise (OR, 1.95 for ≥ 120 minutes per week vs. < 120; P <.001).

Switchers also were less likely to have severe radiographic disease at baseline, as determined by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, OR, 0.63; P = .03), and less likely to be current smokers (OR, 0.69; P < .001).

Factors associated with switching after 2 years versus persisting with treatment were higher baseline BASDAI (OR, 2.31; P = .01), exercising more than 120 minutes per week (OR, 1.66; P = .03), and having more comorbidities (OR, 1.63 for ≥ 2 vs. < 2, P = .04).

However, patients who switched after 2 years were less likely to be depressed (OR, 0.35; P = .002) or to have a longer baseline disease duration (OR, 0.27 for ≥ 20 years vs. < 20 years P < .001).

The association observed between switching within 2 years and lower likelihood of currently smoking was a “little bit puzzling,” one delegate said after Dr. Reveille’s presentation. “The opposite has been shown in the literature, and current smokers seem to be refractory to TNF inhibitor therapy,” the delegate observed.

“I was confounded when I saw the data,” Dr. Reveille acknowledged. Because this was an observational study, this finding needs more investigation, he agreed. “Interestingly, we have seen this negative association with some other parameters, too,” he added.

The HLA-B27 carrier and radiographic status were carefully checked, so there should not be a problem with the diagnosis, Dr. Reveille reassured. Further analyses of the findings are now warranted.

Funding for the study was provided by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Additional funding was received from the Spondyloarthritis Association of America and Eli Lilly.

Dr. Reveille made no personal disclosures; a coauthor of the abstract was an employee of Eli Lilly.

How best to define axial spondyloarthritis (axSpA) flares in practice remains the subject of some debate as evidenced by the discussion that followed an abstract presentation at the 12th International Congress on Spondyloarthritides.

It’s an important topic, said Maxime Breban, MD, PhD, of Ambroise Paré Hospital in Paris, as flares can adversely affect patient outcomes. The absence of flares may also a useful measure of how well a patient is responding to treatment in clinical trials and whether a treatment can be tapered.

“There have been many ways to define flares in the past and there is no consensus,” he observed.

Although the Assessment of Spondyloarthritis International Society (ASAS) devised 12 preliminary definitions of flare in 2016, “these were not that good when we moved to patients,” Dr. Breban suggested.

The ASAS definitions were based on patient vignettes, he explained, and used a combination of variables from the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a visual analog scale (VAS) of pain, and the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP).

The study that Dr. Breban presented looked at the performance of the ASAS preliminary definitions of axSpA flares in a real-life patient population, as well as prospectively determining how variations in BASDAI and VAS pain were associated with patient-perceived flares of disease.

A total of 99 patients took part in the study, recruited through a secure e-health platform called SPONDY+. Once a week, patients completed the BASDAI questionnaire and the pain VAS, and stated whether their disease had flared in the past week.

Receiver operating characteristic (ROC) curves were calculated to see how well the BASDAI and pain VAS identified patients who were experiencing a flare or had a recently resolved flare of axSpA.

Dr. Breban reported that variation in the BASDAI “appears a suitable variable to monitor the occurrence and resolution of patient-reported flare in axial spondylarthritis.”

In predicting a flare, the area under the curve (AUC) was significantly higher for the change in BASDAI than for the change in pain VAS, at a respective 0.81 and 0.77 (P = .01). However, both variables were similarly accurate in predicting the resolution of a flare, with respective AUCs of 0.78 and 0.80 (P = .3).

A 0.22-point increase in BASDAI was reported to be the best balance between sensitivity (70%) and specificity (79%) for a flare. However, this is “outside of what is possible within a test–retest situation,” Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, said during discussion.

Dr. van der Heijde told Dr. Breban: “I understand that that comes out of your data, that that’s the best combination for sensitivity and specificity, but the next step is to decide if that makes sense.”

The ROC curves that Dr. Breban presented showed the range of sensitivities and specificities that could be achieved. If the specificity was increased to be 90% or higher, the specificity fell to 55%, with the change in BASDAI being an increase of 0.8 points. Conversely, bringing the sensitivity above 90% meant the specificity dropped to 39% and the change in BASDAI was a decrease of 0.1 point.

“So that means you can choose whatever you want as a cutoff,” Dr. Breban said. It depends on what you are aiming to do. “If you want to identify a flare, you can increase sensitivity, or specificity, according to what your purpose is,” he suggested.

“The next step, of course, is what to choose as a flare. Then it depends on how you want to use a flare if you want to use a flare to change the treatment,” agreed Dr. van der Heijde. “That was why, in the ASAS group, it was decided to have a high specificity so that you are not changing treatment all the time.”

In the data that Dr. Breban presented, the ASAS preliminary definitions were highly specific but lacked sensitivity. None of the ASAS definitions yielded sensitivity values higher than 37%, whereas specificity was higher than 95% for all of them.

The study’s design did not allow researchers to test the ASDAS-CRP as a definition of flare in its real-world patient sample. Thus, it is looking only at the patient’s perspective on flare, and there is a “huge discrepancy” between patient and physician-reported disease activity, Dr. van der Heijde noted. “So, I think before using your data to really choose the flare definition, I think we need to take it all into account.”

Maxime Dougados, MD, PhD, of Cochin Hospital in Paris, who has been “deeply involved in the elaboration of the definition of flare” added his thoughts: “Flare means for me, not a status, but a change,” he observed.

But if the aim of treating people with axSpA is to achieve a good or acceptable state of health, he questioned whether work should be continued to define the concept of a flare.

The definition of a flare was conceived for use in clinical trials mainly, Dr. van der Heijde noted. It helped to assess how changes in treatment might affect the outcomes of patients. In clinical practice, especially now with treat-to-target gaining more and more traction in axSpA, she agreed that perhaps the goal should be to focus more on the health status of patients.

Dr. Breban acknowledged that the SPONDY+ platform has been developed by bepatient with support from Merck Sharp & Dohme. No other disclosures were made.

How best to define axial spondyloarthritis (axSpA) flares in practice remains the subject of some debate as evidenced by the discussion that followed an abstract presentation at the 12th International Congress on Spondyloarthritides.

It’s an important topic, said Maxime Breban, MD, PhD, of Ambroise Paré Hospital in Paris, as flares can adversely affect patient outcomes. The absence of flares may also a useful measure of how well a patient is responding to treatment in clinical trials and whether a treatment can be tapered.

“There have been many ways to define flares in the past and there is no consensus,” he observed.

Although the Assessment of Spondyloarthritis International Society (ASAS) devised 12 preliminary definitions of flare in 2016, “these were not that good when we moved to patients,” Dr. Breban suggested.

The ASAS definitions were based on patient vignettes, he explained, and used a combination of variables from the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a visual analog scale (VAS) of pain, and the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP).

The study that Dr. Breban presented looked at the performance of the ASAS preliminary definitions of axSpA flares in a real-life patient population, as well as prospectively determining how variations in BASDAI and VAS pain were associated with patient-perceived flares of disease.

A total of 99 patients took part in the study, recruited through a secure e-health platform called SPONDY+. Once a week, patients completed the BASDAI questionnaire and the pain VAS, and stated whether their disease had flared in the past week.

Receiver operating characteristic (ROC) curves were calculated to see how well the BASDAI and pain VAS identified patients who were experiencing a flare or had a recently resolved flare of axSpA.

Dr. Breban reported that variation in the BASDAI “appears a suitable variable to monitor the occurrence and resolution of patient-reported flare in axial spondylarthritis.”

In predicting a flare, the area under the curve (AUC) was significantly higher for the change in BASDAI than for the change in pain VAS, at a respective 0.81 and 0.77 (P = .01). However, both variables were similarly accurate in predicting the resolution of a flare, with respective AUCs of 0.78 and 0.80 (P = .3).

A 0.22-point increase in BASDAI was reported to be the best balance between sensitivity (70%) and specificity (79%) for a flare. However, this is “outside of what is possible within a test–retest situation,” Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, said during discussion.

Dr. van der Heijde told Dr. Breban: “I understand that that comes out of your data, that that’s the best combination for sensitivity and specificity, but the next step is to decide if that makes sense.”

The ROC curves that Dr. Breban presented showed the range of sensitivities and specificities that could be achieved. If the specificity was increased to be 90% or higher, the specificity fell to 55%, with the change in BASDAI being an increase of 0.8 points. Conversely, bringing the sensitivity above 90% meant the specificity dropped to 39% and the change in BASDAI was a decrease of 0.1 point.

“So that means you can choose whatever you want as a cutoff,” Dr. Breban said. It depends on what you are aiming to do. “If you want to identify a flare, you can increase sensitivity, or specificity, according to what your purpose is,” he suggested.

“The next step, of course, is what to choose as a flare. Then it depends on how you want to use a flare if you want to use a flare to change the treatment,” agreed Dr. van der Heijde. “That was why, in the ASAS group, it was decided to have a high specificity so that you are not changing treatment all the time.”

In the data that Dr. Breban presented, the ASAS preliminary definitions were highly specific but lacked sensitivity. None of the ASAS definitions yielded sensitivity values higher than 37%, whereas specificity was higher than 95% for all of them.

The study’s design did not allow researchers to test the ASDAS-CRP as a definition of flare in its real-world patient sample. Thus, it is looking only at the patient’s perspective on flare, and there is a “huge discrepancy” between patient and physician-reported disease activity, Dr. van der Heijde noted. “So, I think before using your data to really choose the flare definition, I think we need to take it all into account.”

Maxime Dougados, MD, PhD, of Cochin Hospital in Paris, who has been “deeply involved in the elaboration of the definition of flare” added his thoughts: “Flare means for me, not a status, but a change,” he observed.

But if the aim of treating people with axSpA is to achieve a good or acceptable state of health, he questioned whether work should be continued to define the concept of a flare.

The definition of a flare was conceived for use in clinical trials mainly, Dr. van der Heijde noted. It helped to assess how changes in treatment might affect the outcomes of patients. In clinical practice, especially now with treat-to-target gaining more and more traction in axSpA, she agreed that perhaps the goal should be to focus more on the health status of patients.

Dr. Breban acknowledged that the SPONDY+ platform has been developed by bepatient with support from Merck Sharp & Dohme. No other disclosures were made.

How best to define axial spondyloarthritis (axSpA) flares in practice remains the subject of some debate as evidenced by the discussion that followed an abstract presentation at the 12th International Congress on Spondyloarthritides.

It’s an important topic, said Maxime Breban, MD, PhD, of Ambroise Paré Hospital in Paris, as flares can adversely affect patient outcomes. The absence of flares may also a useful measure of how well a patient is responding to treatment in clinical trials and whether a treatment can be tapered.

“There have been many ways to define flares in the past and there is no consensus,” he observed.

Although the Assessment of Spondyloarthritis International Society (ASAS) devised 12 preliminary definitions of flare in 2016, “these were not that good when we moved to patients,” Dr. Breban suggested.

The ASAS definitions were based on patient vignettes, he explained, and used a combination of variables from the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a visual analog scale (VAS) of pain, and the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP).

The study that Dr. Breban presented looked at the performance of the ASAS preliminary definitions of axSpA flares in a real-life patient population, as well as prospectively determining how variations in BASDAI and VAS pain were associated with patient-perceived flares of disease.

A total of 99 patients took part in the study, recruited through a secure e-health platform called SPONDY+. Once a week, patients completed the BASDAI questionnaire and the pain VAS, and stated whether their disease had flared in the past week.

Receiver operating characteristic (ROC) curves were calculated to see how well the BASDAI and pain VAS identified patients who were experiencing a flare or had a recently resolved flare of axSpA.

Dr. Breban reported that variation in the BASDAI “appears a suitable variable to monitor the occurrence and resolution of patient-reported flare in axial spondylarthritis.”

In predicting a flare, the area under the curve (AUC) was significantly higher for the change in BASDAI than for the change in pain VAS, at a respective 0.81 and 0.77 (P = .01). However, both variables were similarly accurate in predicting the resolution of a flare, with respective AUCs of 0.78 and 0.80 (P = .3).

A 0.22-point increase in BASDAI was reported to be the best balance between sensitivity (70%) and specificity (79%) for a flare. However, this is “outside of what is possible within a test–retest situation,” Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, said during discussion.

Dr. van der Heijde told Dr. Breban: “I understand that that comes out of your data, that that’s the best combination for sensitivity and specificity, but the next step is to decide if that makes sense.”

The ROC curves that Dr. Breban presented showed the range of sensitivities and specificities that could be achieved. If the specificity was increased to be 90% or higher, the specificity fell to 55%, with the change in BASDAI being an increase of 0.8 points. Conversely, bringing the sensitivity above 90% meant the specificity dropped to 39% and the change in BASDAI was a decrease of 0.1 point.

“So that means you can choose whatever you want as a cutoff,” Dr. Breban said. It depends on what you are aiming to do. “If you want to identify a flare, you can increase sensitivity, or specificity, according to what your purpose is,” he suggested.

“The next step, of course, is what to choose as a flare. Then it depends on how you want to use a flare if you want to use a flare to change the treatment,” agreed Dr. van der Heijde. “That was why, in the ASAS group, it was decided to have a high specificity so that you are not changing treatment all the time.”

In the data that Dr. Breban presented, the ASAS preliminary definitions were highly specific but lacked sensitivity. None of the ASAS definitions yielded sensitivity values higher than 37%, whereas specificity was higher than 95% for all of them.

The study’s design did not allow researchers to test the ASDAS-CRP as a definition of flare in its real-world patient sample. Thus, it is looking only at the patient’s perspective on flare, and there is a “huge discrepancy” between patient and physician-reported disease activity, Dr. van der Heijde noted. “So, I think before using your data to really choose the flare definition, I think we need to take it all into account.”

Maxime Dougados, MD, PhD, of Cochin Hospital in Paris, who has been “deeply involved in the elaboration of the definition of flare” added his thoughts: “Flare means for me, not a status, but a change,” he observed.

But if the aim of treating people with axSpA is to achieve a good or acceptable state of health, he questioned whether work should be continued to define the concept of a flare.

The definition of a flare was conceived for use in clinical trials mainly, Dr. van der Heijde noted. It helped to assess how changes in treatment might affect the outcomes of patients. In clinical practice, especially now with treat-to-target gaining more and more traction in axSpA, she agreed that perhaps the goal should be to focus more on the health status of patients.

Dr. Breban acknowledged that the SPONDY+ platform has been developed by bepatient with support from Merck Sharp & Dohme. No other disclosures were made.

Interleukin (IL)–23 inhibition may still have a role to play in the treatment of patients with axial spondyloarthritis (SpA), suggests research presented at the 12th International Congress on Spondyloarthritides.

There is a strong rationale for using IL-23 inhibitors in patients with axial SpA, and the IL-23/IL-17 axis has been proposed as a critical player in the pathophysiology of the disease. But around 2018 it became clear from randomized, controlled trials that IL-23 inhibition was ineffective at improving key clinical outcomes, at least in patients with axial disease.

Although the overall results of a systematic review and meta-analysis that was presented at the meeting corroborated the negative results seen with IL-23–inhibiting agents in clinical trials, there were some data showing benefits of the IL-23 inhibitor risankizumab on secondary outcomes in one trial.

To look at the available evidence, Louise Vanhoutte, a 2nd-year internal medicine student at University Hospitals Leuven (Belgium) worked under the guidance of Rik Lories, MD, PhD, head of the division of rheumatology at University Hospitals Leuven. Together they searched known databases for randomized, controlled trials investigating the use of IL-23 and IL-17 inhibitors for the treatment of adults with axial SpA or psoriatic arthritis. Studies could be either phase 2 or phase 3, but had to have included a placebo and used the ASAS40 (40% Improvement in Assessment of SpondyloArthritis International Society Response criteria), ASAS20, Bath Ankylosing Spondylitis Disease Activity Index, or SPARCC (Spondyloarthritis Research Consortium of Canada) index score to assess outcomes.

The systematic review whittled the number of clinical trials in the meta-analysis to 12, which concerned the use of ustekinumab, an IL-12/23 inhibitor, and risankizumab, along with two IL-17 inhibitors, ixekizumab and secukinumab. Data for the IL-23 inhibitors guselkumab and tildrakizumab were not available.

“To no surprise, Forest plots showed that there was a lack of efficacy for IL-23 agents in the treatment of axial spondyloarthritis and a superior efficacy for IL-17 inhibitors in the treatment of axial spondyloarthritis,” Ms. Vanhoutte reported.

The respective odds ratios for IL-23 and IL-17 inhibitors in getting patients to meet ASAS40 response criteria in comparison to baseline were 1.51 (95% confidence interval, 0.98-2.31) and 2.54 (95% CI, 2.02-3.19).

“Does this mean it is a dead-end street for all IL-23 inhibition?” she asked. Not necessarily. In the meta-analysis, not only did risankizumab lower the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) by a mean difference (MD) of –0.30 (95% CI, –0.41 to –0.19) from baseline values, but it also led to statistically significant reductions in SPARCC index score for the spine (MD, –3.10; 95% CI, –4.50 to –1.70) and high-sensitivity CRP (MD, –2.10; 95% CI, –2.56 to –1.64). The risankizumab findings might suggest there are potential disease-modifying properties for specifically targeting IL-23p19. There could also be a window of opportunity to use IL-23 inhibitors earlier.

“These are only results from one randomized, controlled trial in a small sample size where outcomes were reported as medians and interquartile ranges, so they had to be converted to means and standard deviations to have an odds ratio in the end,” she explained.

“Also, these were results from a radiographic axial spondyloarthritis population and not a nonradiographic axial spondyloarthritis population,” she added.

While that might limit the interpretation of the findings, “what we see here is both reduction in inflammation and reduction in structural disease progression as [measured] by SPARCC,” Ms. Vanhoutte said.

“Since IL-23 is an upstream molecule from IL-17 it’s probable that IL-23 is present in the prephase of the disease, in a prephase inflammation state,” she hypothesized. “This is especially interesting because there are very few randomized, controlled trials that examine therapeutic agents in nonradiographic axial spondyloarthritis,” she observed. Looking at IL-23 in radiographic, or established, disease therefore may not be as useful.

“I’m thinking you’re making actually a very important point for us,” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center.

“We are discussing whether or not IL-23 is important in inhibiting the disease activity of patients with axial spondyloarthritis, and we are surprised that it is not shown in RCTs.

“Why is it completely ineffective in axial spondyloarthritis? You show us that that is probably not the case,” Dr. Landewé suggested.

“What you make very clear here is that indeed there is some efficacy, and from a pathophysiological way of thinking it might be slightly different as compared with what most clinicians nowadays think.”

The study had no specific funding, and no disclosures were reported.

Interleukin (IL)–23 inhibition may still have a role to play in the treatment of patients with axial spondyloarthritis (SpA), suggests research presented at the 12th International Congress on Spondyloarthritides.

There is a strong rationale for using IL-23 inhibitors in patients with axial SpA, and the IL-23/IL-17 axis has been proposed as a critical player in the pathophysiology of the disease. But around 2018 it became clear from randomized, controlled trials that IL-23 inhibition was ineffective at improving key clinical outcomes, at least in patients with axial disease.

Although the overall results of a systematic review and meta-analysis that was presented at the meeting corroborated the negative results seen with IL-23–inhibiting agents in clinical trials, there were some data showing benefits of the IL-23 inhibitor risankizumab on secondary outcomes in one trial.

To look at the available evidence, Louise Vanhoutte, a 2nd-year internal medicine student at University Hospitals Leuven (Belgium) worked under the guidance of Rik Lories, MD, PhD, head of the division of rheumatology at University Hospitals Leuven. Together they searched known databases for randomized, controlled trials investigating the use of IL-23 and IL-17 inhibitors for the treatment of adults with axial SpA or psoriatic arthritis. Studies could be either phase 2 or phase 3, but had to have included a placebo and used the ASAS40 (40% Improvement in Assessment of SpondyloArthritis International Society Response criteria), ASAS20, Bath Ankylosing Spondylitis Disease Activity Index, or SPARCC (Spondyloarthritis Research Consortium of Canada) index score to assess outcomes.

The systematic review whittled the number of clinical trials in the meta-analysis to 12, which concerned the use of ustekinumab, an IL-12/23 inhibitor, and risankizumab, along with two IL-17 inhibitors, ixekizumab and secukinumab. Data for the IL-23 inhibitors guselkumab and tildrakizumab were not available.

“To no surprise, Forest plots showed that there was a lack of efficacy for IL-23 agents in the treatment of axial spondyloarthritis and a superior efficacy for IL-17 inhibitors in the treatment of axial spondyloarthritis,” Ms. Vanhoutte reported.

The respective odds ratios for IL-23 and IL-17 inhibitors in getting patients to meet ASAS40 response criteria in comparison to baseline were 1.51 (95% confidence interval, 0.98-2.31) and 2.54 (95% CI, 2.02-3.19).

“Does this mean it is a dead-end street for all IL-23 inhibition?” she asked. Not necessarily. In the meta-analysis, not only did risankizumab lower the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) by a mean difference (MD) of –0.30 (95% CI, –0.41 to –0.19) from baseline values, but it also led to statistically significant reductions in SPARCC index score for the spine (MD, –3.10; 95% CI, –4.50 to –1.70) and high-sensitivity CRP (MD, –2.10; 95% CI, –2.56 to –1.64). The risankizumab findings might suggest there are potential disease-modifying properties for specifically targeting IL-23p19. There could also be a window of opportunity to use IL-23 inhibitors earlier.

“These are only results from one randomized, controlled trial in a small sample size where outcomes were reported as medians and interquartile ranges, so they had to be converted to means and standard deviations to have an odds ratio in the end,” she explained.

“Also, these were results from a radiographic axial spondyloarthritis population and not a nonradiographic axial spondyloarthritis population,” she added.

While that might limit the interpretation of the findings, “what we see here is both reduction in inflammation and reduction in structural disease progression as [measured] by SPARCC,” Ms. Vanhoutte said.

“Since IL-23 is an upstream molecule from IL-17 it’s probable that IL-23 is present in the prephase of the disease, in a prephase inflammation state,” she hypothesized. “This is especially interesting because there are very few randomized, controlled trials that examine therapeutic agents in nonradiographic axial spondyloarthritis,” she observed. Looking at IL-23 in radiographic, or established, disease therefore may not be as useful.

“I’m thinking you’re making actually a very important point for us,” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center.

“We are discussing whether or not IL-23 is important in inhibiting the disease activity of patients with axial spondyloarthritis, and we are surprised that it is not shown in RCTs.

“Why is it completely ineffective in axial spondyloarthritis? You show us that that is probably not the case,” Dr. Landewé suggested.

“What you make very clear here is that indeed there is some efficacy, and from a pathophysiological way of thinking it might be slightly different as compared with what most clinicians nowadays think.”

The study had no specific funding, and no disclosures were reported.

Interleukin (IL)–23 inhibition may still have a role to play in the treatment of patients with axial spondyloarthritis (SpA), suggests research presented at the 12th International Congress on Spondyloarthritides.

There is a strong rationale for using IL-23 inhibitors in patients with axial SpA, and the IL-23/IL-17 axis has been proposed as a critical player in the pathophysiology of the disease. But around 2018 it became clear from randomized, controlled trials that IL-23 inhibition was ineffective at improving key clinical outcomes, at least in patients with axial disease.

Although the overall results of a systematic review and meta-analysis that was presented at the meeting corroborated the negative results seen with IL-23–inhibiting agents in clinical trials, there were some data showing benefits of the IL-23 inhibitor risankizumab on secondary outcomes in one trial.

To look at the available evidence, Louise Vanhoutte, a 2nd-year internal medicine student at University Hospitals Leuven (Belgium) worked under the guidance of Rik Lories, MD, PhD, head of the division of rheumatology at University Hospitals Leuven. Together they searched known databases for randomized, controlled trials investigating the use of IL-23 and IL-17 inhibitors for the treatment of adults with axial SpA or psoriatic arthritis. Studies could be either phase 2 or phase 3, but had to have included a placebo and used the ASAS40 (40% Improvement in Assessment of SpondyloArthritis International Society Response criteria), ASAS20, Bath Ankylosing Spondylitis Disease Activity Index, or SPARCC (Spondyloarthritis Research Consortium of Canada) index score to assess outcomes.

The systematic review whittled the number of clinical trials in the meta-analysis to 12, which concerned the use of ustekinumab, an IL-12/23 inhibitor, and risankizumab, along with two IL-17 inhibitors, ixekizumab and secukinumab. Data for the IL-23 inhibitors guselkumab and tildrakizumab were not available.

“To no surprise, Forest plots showed that there was a lack of efficacy for IL-23 agents in the treatment of axial spondyloarthritis and a superior efficacy for IL-17 inhibitors in the treatment of axial spondyloarthritis,” Ms. Vanhoutte reported.

The respective odds ratios for IL-23 and IL-17 inhibitors in getting patients to meet ASAS40 response criteria in comparison to baseline were 1.51 (95% confidence interval, 0.98-2.31) and 2.54 (95% CI, 2.02-3.19).

“Does this mean it is a dead-end street for all IL-23 inhibition?” she asked. Not necessarily. In the meta-analysis, not only did risankizumab lower the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) by a mean difference (MD) of –0.30 (95% CI, –0.41 to –0.19) from baseline values, but it also led to statistically significant reductions in SPARCC index score for the spine (MD, –3.10; 95% CI, –4.50 to –1.70) and high-sensitivity CRP (MD, –2.10; 95% CI, –2.56 to –1.64). The risankizumab findings might suggest there are potential disease-modifying properties for specifically targeting IL-23p19. There could also be a window of opportunity to use IL-23 inhibitors earlier.

“These are only results from one randomized, controlled trial in a small sample size where outcomes were reported as medians and interquartile ranges, so they had to be converted to means and standard deviations to have an odds ratio in the end,” she explained.

“Also, these were results from a radiographic axial spondyloarthritis population and not a nonradiographic axial spondyloarthritis population,” she added.

While that might limit the interpretation of the findings, “what we see here is both reduction in inflammation and reduction in structural disease progression as [measured] by SPARCC,” Ms. Vanhoutte said.

“Since IL-23 is an upstream molecule from IL-17 it’s probable that IL-23 is present in the prephase of the disease, in a prephase inflammation state,” she hypothesized. “This is especially interesting because there are very few randomized, controlled trials that examine therapeutic agents in nonradiographic axial spondyloarthritis,” she observed. Looking at IL-23 in radiographic, or established, disease therefore may not be as useful.

“I’m thinking you’re making actually a very important point for us,” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center.

“We are discussing whether or not IL-23 is important in inhibiting the disease activity of patients with axial spondyloarthritis, and we are surprised that it is not shown in RCTs.

“Why is it completely ineffective in axial spondyloarthritis? You show us that that is probably not the case,” Dr. Landewé suggested.

“What you make very clear here is that indeed there is some efficacy, and from a pathophysiological way of thinking it might be slightly different as compared with what most clinicians nowadays think.”

The study had no specific funding, and no disclosures were reported.

Better retention and remission rates with tumor necrosis factor inhibitors (TNFi) have been observed in patients with spondyloarthritis (SpA) who were also treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) rather than monotherapy.

Data from the EuroSpA Research Collaboration have shown that 82% of patients who received TNFi and csDMARD cotherapy were still taking their TNFi at 1 year versus 79% of those who were taking the biologic alone (P < .001).

Combination therapy led to remission in 21.8%, compared with TNFi monotherapy at 19.5% (P < .0001), with rates of remission according to Ankylosing Spondylitis Disease Activity Score <1.3 (23.7% vs. 21.8%, P = .011) and Bath Ankylosing Spondylitis Disease Activity Index <2 (5.9% vs. 7.7%, P < .0001) also favoring the cotherapy group.

“We did see a considerable heterogeneity across the countries in this study, both in the use of csDMARD therapy and in the TNF [inhibitor] retention,” Michael J. Nissen, MBBS, FRACP, MD, a rheumatologist at the University of Geneva, said in an oral abstract presentation at the 12th International Congress on Spondyloarthritides.

“Overall, the 1-year TNFi retention was better with cotherapy, particularly in countries in the Scandinavian region and Switzerland,” Dr. Nissen observed.

“The csDMARD cotherapy significantly improved remission; we could perhaps argue whether these small differences are clinically meaningful, but they were highly significant in the study.”
 

Why look at csDMARD and TNFi cotherapy?

European guidelines suggest that csDMARDs are not that useful for treating people with SpA, stating that they should not be used in axial disease and used only as monotherapy in those with peripheral disease.

“Nevertheless, these medications are often used, which begs us to ask the question why is that the case?” Dr. Nissen said.

As previous work by Dr. Nissen and others had suggested that there might be a benefit of combining a csDMARD and a TNFi, the aim was to build upon this and see if looking at a very large patient population might be able to provide some clear answers.

The analysis included data from 13 European registries and more than 24,000 patients who had started their first TNFi between 2006 and 2017. The mean age of the study population was 42.5 years, and 58% were male, with an average disease duration of 5.9 years. Nearly one-third of patients were receiving comedication with a csDMARD, although this ranged from 13.5% to 71.2% depending on the country.

The most frequently used TNFi were adalimumab (31% of patients overall), etanercept (24%), and infliximab (25%), and the most-used csDMARDs were methotrexate (56%) and sulfasalazine (45%).

The effectiveness of treatment in achieving clinical remission was examined according to the TNFi used and for the use of csDMARDs.

“We found that sulfasalazine and methotrexate were similarly effective in terms of improving outcomes in addition to a TNF inhibitor,” Dr. Nissen said. For example, the adjusted odds ratios for using sulfasalazine or methotrexate with infliximab were a respective 1.32 and 1.37, and the aORs for uses these specific csDMARDs with etanercept were 1.38 and 1.35.

The researchers reported finding significantly higher aORs if both sulfasalazine and methotrexate were used with a TNFi (1.67 for any TNFi, 1.95 for infliximab, 1.45 foretanercept, and 1.85 for adalimumab).

This perhaps suggests “there’s some role for combining csDMARDs to have an even greater effect,” Dr. Nissen put forward.
 

A ‘very provocative conclusion’

That’s “a very provocative conclusion” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center who chaired the sessions. “You can see it by the [number] of people that want to ask questions.”

Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, commented these data were “timely as we are updating the ASAS/EULAR [Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology] recommendations at the moment.” She queried, however, if the differences were clinically significant.

“I think if you have a database of 24,000 patients, highly, statistically significant doesn’t tell me a lot. So, I want to look at the clinical meaning of the differences. So, if you have a 2% difference in retention rate, is that worth prescribing comedication?” Dr. van der Heijde said.

“I think you’re absolutely right,” Dr. Nissen responded. “We’re obviously going to find highly significant differences with such a big patient group.” While the small statistical differences seen may not look very clinically relevant at face value, they could provide some guidance for clinical decision making.

“It may alter our approach if that patient is already on a csDMARD and has peripheral disease; perhaps there’s tendency to then to keep that csDMARD rather than then stopping it and switching to a biologic agent,” Dr. Nissen argued. It’s a topic that has been debated for some time, he added, and further study is needed, but “I think it helps give a little bit more clarity to the idea.”

Another point of discussion was the proportion of patients who had “pure axial disease.” More patients in the comedication group had peripheral disease, Dr. van der Heijde pointed out, “that’s also where we expect to see the differences.”

Further research is needed, but there doesn’t seem to be any impact in terms of the effect on retention, Dr. Nissen said, “but it’s a little bit harder to interpret for efficacy.”

Confounding by indication was another issued raised, which “is very difficult to control for in this type of study,” Dr. Nissen said.

“The hope is that you have a big enough population” so this doesn’t matter, but as is the nature there were lots of missing data that would have been useful to have and adjust for, such as psoriasis and smoking status. There was also no adjustment for the number of patient visits, as it’s very different from registry to registry.

Dr. Nissen disclosed grant/research support from AbbVie and Novartis. He also acknowledged acting as a consultant or speaker for AbbVie, Celgene, Janssen, Eli Lilly, Novartis, and Pfizer.

Better retention and remission rates with tumor necrosis factor inhibitors (TNFi) have been observed in patients with spondyloarthritis (SpA) who were also treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) rather than monotherapy.

Data from the EuroSpA Research Collaboration have shown that 82% of patients who received TNFi and csDMARD cotherapy were still taking their TNFi at 1 year versus 79% of those who were taking the biologic alone (P < .001).

Combination therapy led to remission in 21.8%, compared with TNFi monotherapy at 19.5% (P < .0001), with rates of remission according to Ankylosing Spondylitis Disease Activity Score <1.3 (23.7% vs. 21.8%, P = .011) and Bath Ankylosing Spondylitis Disease Activity Index <2 (5.9% vs. 7.7%, P < .0001) also favoring the cotherapy group.

“We did see a considerable heterogeneity across the countries in this study, both in the use of csDMARD therapy and in the TNF [inhibitor] retention,” Michael J. Nissen, MBBS, FRACP, MD, a rheumatologist at the University of Geneva, said in an oral abstract presentation at the 12th International Congress on Spondyloarthritides.

“Overall, the 1-year TNFi retention was better with cotherapy, particularly in countries in the Scandinavian region and Switzerland,” Dr. Nissen observed.

“The csDMARD cotherapy significantly improved remission; we could perhaps argue whether these small differences are clinically meaningful, but they were highly significant in the study.”
 

Why look at csDMARD and TNFi cotherapy?

European guidelines suggest that csDMARDs are not that useful for treating people with SpA, stating that they should not be used in axial disease and used only as monotherapy in those with peripheral disease.

“Nevertheless, these medications are often used, which begs us to ask the question why is that the case?” Dr. Nissen said.

As previous work by Dr. Nissen and others had suggested that there might be a benefit of combining a csDMARD and a TNFi, the aim was to build upon this and see if looking at a very large patient population might be able to provide some clear answers.

The analysis included data from 13 European registries and more than 24,000 patients who had started their first TNFi between 2006 and 2017. The mean age of the study population was 42.5 years, and 58% were male, with an average disease duration of 5.9 years. Nearly one-third of patients were receiving comedication with a csDMARD, although this ranged from 13.5% to 71.2% depending on the country.

The most frequently used TNFi were adalimumab (31% of patients overall), etanercept (24%), and infliximab (25%), and the most-used csDMARDs were methotrexate (56%) and sulfasalazine (45%).

The effectiveness of treatment in achieving clinical remission was examined according to the TNFi used and for the use of csDMARDs.

“We found that sulfasalazine and methotrexate were similarly effective in terms of improving outcomes in addition to a TNF inhibitor,” Dr. Nissen said. For example, the adjusted odds ratios for using sulfasalazine or methotrexate with infliximab were a respective 1.32 and 1.37, and the aORs for uses these specific csDMARDs with etanercept were 1.38 and 1.35.

The researchers reported finding significantly higher aORs if both sulfasalazine and methotrexate were used with a TNFi (1.67 for any TNFi, 1.95 for infliximab, 1.45 foretanercept, and 1.85 for adalimumab).

This perhaps suggests “there’s some role for combining csDMARDs to have an even greater effect,” Dr. Nissen put forward.
 

A ‘very provocative conclusion’

That’s “a very provocative conclusion” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center who chaired the sessions. “You can see it by the [number] of people that want to ask questions.”

Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, commented these data were “timely as we are updating the ASAS/EULAR [Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology] recommendations at the moment.” She queried, however, if the differences were clinically significant.

“I think if you have a database of 24,000 patients, highly, statistically significant doesn’t tell me a lot. So, I want to look at the clinical meaning of the differences. So, if you have a 2% difference in retention rate, is that worth prescribing comedication?” Dr. van der Heijde said.

“I think you’re absolutely right,” Dr. Nissen responded. “We’re obviously going to find highly significant differences with such a big patient group.” While the small statistical differences seen may not look very clinically relevant at face value, they could provide some guidance for clinical decision making.

“It may alter our approach if that patient is already on a csDMARD and has peripheral disease; perhaps there’s tendency to then to keep that csDMARD rather than then stopping it and switching to a biologic agent,” Dr. Nissen argued. It’s a topic that has been debated for some time, he added, and further study is needed, but “I think it helps give a little bit more clarity to the idea.”

Another point of discussion was the proportion of patients who had “pure axial disease.” More patients in the comedication group had peripheral disease, Dr. van der Heijde pointed out, “that’s also where we expect to see the differences.”

Further research is needed, but there doesn’t seem to be any impact in terms of the effect on retention, Dr. Nissen said, “but it’s a little bit harder to interpret for efficacy.”

Confounding by indication was another issued raised, which “is very difficult to control for in this type of study,” Dr. Nissen said.

“The hope is that you have a big enough population” so this doesn’t matter, but as is the nature there were lots of missing data that would have been useful to have and adjust for, such as psoriasis and smoking status. There was also no adjustment for the number of patient visits, as it’s very different from registry to registry.

Dr. Nissen disclosed grant/research support from AbbVie and Novartis. He also acknowledged acting as a consultant or speaker for AbbVie, Celgene, Janssen, Eli Lilly, Novartis, and Pfizer.

Better retention and remission rates with tumor necrosis factor inhibitors (TNFi) have been observed in patients with spondyloarthritis (SpA) who were also treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) rather than monotherapy.

Data from the EuroSpA Research Collaboration have shown that 82% of patients who received TNFi and csDMARD cotherapy were still taking their TNFi at 1 year versus 79% of those who were taking the biologic alone (P < .001).

Combination therapy led to remission in 21.8%, compared with TNFi monotherapy at 19.5% (P < .0001), with rates of remission according to Ankylosing Spondylitis Disease Activity Score <1.3 (23.7% vs. 21.8%, P = .011) and Bath Ankylosing Spondylitis Disease Activity Index <2 (5.9% vs. 7.7%, P < .0001) also favoring the cotherapy group.

“We did see a considerable heterogeneity across the countries in this study, both in the use of csDMARD therapy and in the TNF [inhibitor] retention,” Michael J. Nissen, MBBS, FRACP, MD, a rheumatologist at the University of Geneva, said in an oral abstract presentation at the 12th International Congress on Spondyloarthritides.

“Overall, the 1-year TNFi retention was better with cotherapy, particularly in countries in the Scandinavian region and Switzerland,” Dr. Nissen observed.

“The csDMARD cotherapy significantly improved remission; we could perhaps argue whether these small differences are clinically meaningful, but they were highly significant in the study.”
 

Why look at csDMARD and TNFi cotherapy?

European guidelines suggest that csDMARDs are not that useful for treating people with SpA, stating that they should not be used in axial disease and used only as monotherapy in those with peripheral disease.

“Nevertheless, these medications are often used, which begs us to ask the question why is that the case?” Dr. Nissen said.

As previous work by Dr. Nissen and others had suggested that there might be a benefit of combining a csDMARD and a TNFi, the aim was to build upon this and see if looking at a very large patient population might be able to provide some clear answers.

The analysis included data from 13 European registries and more than 24,000 patients who had started their first TNFi between 2006 and 2017. The mean age of the study population was 42.5 years, and 58% were male, with an average disease duration of 5.9 years. Nearly one-third of patients were receiving comedication with a csDMARD, although this ranged from 13.5% to 71.2% depending on the country.

The most frequently used TNFi were adalimumab (31% of patients overall), etanercept (24%), and infliximab (25%), and the most-used csDMARDs were methotrexate (56%) and sulfasalazine (45%).

The effectiveness of treatment in achieving clinical remission was examined according to the TNFi used and for the use of csDMARDs.

“We found that sulfasalazine and methotrexate were similarly effective in terms of improving outcomes in addition to a TNF inhibitor,” Dr. Nissen said. For example, the adjusted odds ratios for using sulfasalazine or methotrexate with infliximab were a respective 1.32 and 1.37, and the aORs for uses these specific csDMARDs with etanercept were 1.38 and 1.35.

The researchers reported finding significantly higher aORs if both sulfasalazine and methotrexate were used with a TNFi (1.67 for any TNFi, 1.95 for infliximab, 1.45 foretanercept, and 1.85 for adalimumab).

This perhaps suggests “there’s some role for combining csDMARDs to have an even greater effect,” Dr. Nissen put forward.
 

A ‘very provocative conclusion’

That’s “a very provocative conclusion” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center who chaired the sessions. “You can see it by the [number] of people that want to ask questions.”

Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, commented these data were “timely as we are updating the ASAS/EULAR [Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology] recommendations at the moment.” She queried, however, if the differences were clinically significant.

“I think if you have a database of 24,000 patients, highly, statistically significant doesn’t tell me a lot. So, I want to look at the clinical meaning of the differences. So, if you have a 2% difference in retention rate, is that worth prescribing comedication?” Dr. van der Heijde said.

“I think you’re absolutely right,” Dr. Nissen responded. “We’re obviously going to find highly significant differences with such a big patient group.” While the small statistical differences seen may not look very clinically relevant at face value, they could provide some guidance for clinical decision making.

“It may alter our approach if that patient is already on a csDMARD and has peripheral disease; perhaps there’s tendency to then to keep that csDMARD rather than then stopping it and switching to a biologic agent,” Dr. Nissen argued. It’s a topic that has been debated for some time, he added, and further study is needed, but “I think it helps give a little bit more clarity to the idea.”

Another point of discussion was the proportion of patients who had “pure axial disease.” More patients in the comedication group had peripheral disease, Dr. van der Heijde pointed out, “that’s also where we expect to see the differences.”

Further research is needed, but there doesn’t seem to be any impact in terms of the effect on retention, Dr. Nissen said, “but it’s a little bit harder to interpret for efficacy.”

Confounding by indication was another issued raised, which “is very difficult to control for in this type of study,” Dr. Nissen said.

“The hope is that you have a big enough population” so this doesn’t matter, but as is the nature there were lots of missing data that would have been useful to have and adjust for, such as psoriasis and smoking status. There was also no adjustment for the number of patient visits, as it’s very different from registry to registry.

Dr. Nissen disclosed grant/research support from AbbVie and Novartis. He also acknowledged acting as a consultant or speaker for AbbVie, Celgene, Janssen, Eli Lilly, Novartis, and Pfizer.