Spondyloarthropathies

Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.

Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.

Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.

Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.

To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).

After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.

After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.

Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.

A similar pattern emerged when looking at improvement in EIM.

At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).

At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).

Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.

Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”

Limitations of the study include its retrospective design and small cohort size.

Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.

Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.

Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.

Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.

The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.

A version of this article first appeared on Medscape.com.

Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.

Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.

Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.

Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.

To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).

After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.

After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.

Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.

A similar pattern emerged when looking at improvement in EIM.

At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).

At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).

Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.

Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”

Limitations of the study include its retrospective design and small cohort size.

Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.

Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.

Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.

Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.

The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.

A version of this article first appeared on Medscape.com.

Vedolizumab (Entyvio) and ustekinumab (Stelara) appear to be equally effective for extraintestinal manifestation (EIM) of inflammatory bowel disease (IBD), according to results of a retrospective study published online in Digestive and Liver Disease.

Between 25% and 40% of patients with IBD experience EIM, which reduces quality of life, according to the Crohn’s & Colitis Foundation. EIM commonly involves the joints, skin, bones, eyes, kidney, and liver. Anemia is another extraintestinal complication.

Until now, it’s been unclear whether vedolizumab and ustekinumab are equally effective for treating EIM.

Vedolizumab specifically targets the gastrointestinal tract, a potential disadvantage in reducing EIM, while ustekinumab is thought to have a systemic effect, a potential treatment advantage, Moran Livne-Margolin, MD, and colleagues, Chaim Sheba Medical Center, Ramat Gan, Israel, point out.

To investigate, they included 111 adults with IBD who were treated at the medical center between 2015 and 2021 – 53 with vedolizumab and 58 with ustekinumab. Before starting treatment, all of them had active EIM, most commonly arthralgia (84%).

After 6 weeks of treatment, 66% of patients in both groups had a clinical response to their intestinal disease.

After 14 and 26 weeks of treatment, clinical response rates were 59% and 50%, respectively, with vedolizumab, and 48% and 41%, respectively, with ustekinumab.

Over 52 weeks, both biologics were equally effective against the intestinal disease, with clinical response rates of 42% with vedolizumab and 44% with ustekinumab.

A similar pattern emerged when looking at improvement in EIM.

At week 6, 44% of patients taking vedolizumab and 35% taking ustekinumab had improvement in EIM, with no significant difference between the two biologics (P = .4).

At week 14, rates of improvement in EIM were 43% for vedolizumab and 33% for ustekinumab (P = .39); at 26 weeks, rates were 39% and 33%, respectively (P = .6); and at 52 weeks, rates were 34% and 36% (P = .9).

Researchers also found a significant positive correlation between improvement of the intestinal disease and clinical improvement of EIM at each time point.

Ustekinumab is usually preferred in patients with EIM, Dr. Livne-Margolin and colleagues note. But their findings “may raise some questions whether ustekinumab is, in fact, a better choice in those specific patients.”

Limitations of the study include its retrospective design and small cohort size.

Additionally, vedolizumab is given intravenously in the clinic and mandates patients to have a routine checkup every 1-2 months, whereas ustekinumab can be given at home. As a result, data were missing on some of the patients treated with ustekinumab during the follow-up.

Another limitation is that most of the patients had articular complaints with a small presentation of other EIM.

Also, most of the patients had Crohn’s disease, with only one patient with ulcerative colitis in the ustekinumab group, compared with 12 in the vedolizumab group.

Finally, patients treated with ustekinumab had more experience with anti-TNF treatment, compared with the vedolizumab group, which might have influenced the results with a negative bias toward ustekinumab.

The study had no specific funding. Three authors have disclosed relationships with Janssen, which makes ustekinumab.

A version of this article first appeared on Medscape.com.

The United States Food and Drug Administration has approved the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) for adults with nonradiographic axial spondyloarthritis (nr-axSpA) who have objective signs of inflammation and who have had an inadequate response to or are intolerant of one or more tumor necrosis factor (TNF) inhibitors, according to an announcement from the manufacturer, AbbVie.

The indication is the sixth in the United States for the JAK inhibitor. Upadacitinib 15 mg once daily is already approved in the United States for adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis (PsA), and active ankylosing spondylitis (AS). All these indications are for patients who have had an inadequate response to or are intolerant of one or more TNF inhibitors.

Upadacitinib is now the only JAK inhibitor that has been approved for both nr-axSpA and AS.

“Many patients living with nr-axSpA continue to experience symptoms and are unable to control disease with current treatments. In the SELECT-AXIS 2 trials, Rinvoq demonstrated efficacy in both nr-axSpA and AS with safety that was consistent across indications,” Atul Deodhar, MD, lead investigator of the trial, said in the announcement. “Today’s FDA approval offers an important new therapeutic option for patients and their caregivers to help take control of their symptoms and disease.”

Upadacitinib is also approved at a dose of 15 mg once daily for adults and children 12 years of age and older who weigh at least 40 kg and who have refractory, moderate to severe atopic dermatitis that is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

It is approved as well at 45 mg once daily for 8 weeks as an induction therapy for adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to or are intolerant of one or more TNF blockers. Following induction therapy for patients with ulcerative colitis, the recommended dose for maintenance treatment is 15 mg once daily, but a dose of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease.

The FDA’s decision is supported by data from the phase 3 SELECT-AXIS 2 clinical trial, which assessed the efficacy, safety, and tolerability of upadacitinib in adults with active nr-axSpA.

Nearly half of patients treated with upadacitinib had achieved 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40), the primary endpoint, at week 14, compared with placebo (44.9% vs. 22.3%). These responses were observed as early as 2 weeks after initiation of therapy. The safety profile was consistent with what’s known in patients with RA, PsA, and AS.

Upadacitinib can lower the ability to fight infections. Serious infections, some fatal, have occurred, including tuberculosis and infections caused by bacteria, fungi, or viruses. It is associated with an increased risk of death and major cardiovascular events in people aged 50 and older who have at least one heart disease risk factor, and it is associated with an increased risk of some cancers, including lymphoma and skin cancers.

A version of this article first appeared on Medscape.com.

The United States Food and Drug Administration has approved the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) for adults with nonradiographic axial spondyloarthritis (nr-axSpA) who have objective signs of inflammation and who have had an inadequate response to or are intolerant of one or more tumor necrosis factor (TNF) inhibitors, according to an announcement from the manufacturer, AbbVie.

The indication is the sixth in the United States for the JAK inhibitor. Upadacitinib 15 mg once daily is already approved in the United States for adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis (PsA), and active ankylosing spondylitis (AS). All these indications are for patients who have had an inadequate response to or are intolerant of one or more TNF inhibitors.

Upadacitinib is now the only JAK inhibitor that has been approved for both nr-axSpA and AS.

“Many patients living with nr-axSpA continue to experience symptoms and are unable to control disease with current treatments. In the SELECT-AXIS 2 trials, Rinvoq demonstrated efficacy in both nr-axSpA and AS with safety that was consistent across indications,” Atul Deodhar, MD, lead investigator of the trial, said in the announcement. “Today’s FDA approval offers an important new therapeutic option for patients and their caregivers to help take control of their symptoms and disease.”

Upadacitinib is also approved at a dose of 15 mg once daily for adults and children 12 years of age and older who weigh at least 40 kg and who have refractory, moderate to severe atopic dermatitis that is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

It is approved as well at 45 mg once daily for 8 weeks as an induction therapy for adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to or are intolerant of one or more TNF blockers. Following induction therapy for patients with ulcerative colitis, the recommended dose for maintenance treatment is 15 mg once daily, but a dose of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease.

The FDA’s decision is supported by data from the phase 3 SELECT-AXIS 2 clinical trial, which assessed the efficacy, safety, and tolerability of upadacitinib in adults with active nr-axSpA.

Nearly half of patients treated with upadacitinib had achieved 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40), the primary endpoint, at week 14, compared with placebo (44.9% vs. 22.3%). These responses were observed as early as 2 weeks after initiation of therapy. The safety profile was consistent with what’s known in patients with RA, PsA, and AS.

Upadacitinib can lower the ability to fight infections. Serious infections, some fatal, have occurred, including tuberculosis and infections caused by bacteria, fungi, or viruses. It is associated with an increased risk of death and major cardiovascular events in people aged 50 and older who have at least one heart disease risk factor, and it is associated with an increased risk of some cancers, including lymphoma and skin cancers.

A version of this article first appeared on Medscape.com.

The United States Food and Drug Administration has approved the Janus kinase (JAK) inhibitor upadacitinib (Rinvoq) for adults with nonradiographic axial spondyloarthritis (nr-axSpA) who have objective signs of inflammation and who have had an inadequate response to or are intolerant of one or more tumor necrosis factor (TNF) inhibitors, according to an announcement from the manufacturer, AbbVie.

The indication is the sixth in the United States for the JAK inhibitor. Upadacitinib 15 mg once daily is already approved in the United States for adults with moderately to severely active rheumatoid arthritis, active psoriatic arthritis (PsA), and active ankylosing spondylitis (AS). All these indications are for patients who have had an inadequate response to or are intolerant of one or more TNF inhibitors.

Upadacitinib is now the only JAK inhibitor that has been approved for both nr-axSpA and AS.

“Many patients living with nr-axSpA continue to experience symptoms and are unable to control disease with current treatments. In the SELECT-AXIS 2 trials, Rinvoq demonstrated efficacy in both nr-axSpA and AS with safety that was consistent across indications,” Atul Deodhar, MD, lead investigator of the trial, said in the announcement. “Today’s FDA approval offers an important new therapeutic option for patients and their caregivers to help take control of their symptoms and disease.”

Upadacitinib is also approved at a dose of 15 mg once daily for adults and children 12 years of age and older who weigh at least 40 kg and who have refractory, moderate to severe atopic dermatitis that is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

It is approved as well at 45 mg once daily for 8 weeks as an induction therapy for adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to or are intolerant of one or more TNF blockers. Following induction therapy for patients with ulcerative colitis, the recommended dose for maintenance treatment is 15 mg once daily, but a dose of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease.

The FDA’s decision is supported by data from the phase 3 SELECT-AXIS 2 clinical trial, which assessed the efficacy, safety, and tolerability of upadacitinib in adults with active nr-axSpA.

Nearly half of patients treated with upadacitinib had achieved 40% improvement in Assessment of Spondyloarthritis International Society response criteria (ASAS 40), the primary endpoint, at week 14, compared with placebo (44.9% vs. 22.3%). These responses were observed as early as 2 weeks after initiation of therapy. The safety profile was consistent with what’s known in patients with RA, PsA, and AS.

Upadacitinib can lower the ability to fight infections. Serious infections, some fatal, have occurred, including tuberculosis and infections caused by bacteria, fungi, or viruses. It is associated with an increased risk of death and major cardiovascular events in people aged 50 and older who have at least one heart disease risk factor, and it is associated with an increased risk of some cancers, including lymphoma and skin cancers.

A version of this article first appeared on Medscape.com.

Syndesmophytes are not present in a subgroup of patients with ankylosing spondylitis (AS) and sacroiliac (SI) joint fusion who have had the disease for 20 years or longer, according to findings from a nested case-control study.

Syndesmophytes did not occur in only 23 (7%) of 354 patients, and these patients without spinal-fusing bone growths were less likely to be female but very likely to be HLA-B27 positive, Lauren K. Ridley, MD, a rheumatologist at the University of Texas Health Science Center at Houston, and colleagues reported in The Journal of Rheumatology.

“Women appear to have a different phenotype in AS; we found that they are less likely to form syndesmophytes despite fused SI joints with at least 20 years of disease duration. We do not understand the reasons behind these differences among the possibilities of genetic, hormonal, and bio-mechanical factors,” the authors wrote.

AS is a heterogenous disease that affects different people in various ways, Dr. Ridley noted. “Prior research has shown that and hasn’t really elucidated how different people manifest their disease. Previous research has shown that women tend to have more nonradiographic spondylitis,” Dr. Ridley said in an interview.

“This is still a very heterogenous disease. We don’t fully understand it, and we don’t know why some patients present with SI joint disease [and] no syndesmophytes, or some patients have the opposite. Truly, we do need to do more studies to find out why some patients behave differently and if there are ways we can try to alter that,” Dr. Ridley continued.

The researchers evaluated 354 patients from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS). Of these patients, 23 did not have syndesmophytes. Patients were selected if they had fused SI joints (bilateral grade 4 sacroiliac joint disease) and had a disease course lasting 20 years or more. The researchers identified risk factors for syndesmophytes using classification and regression trees (CART) analysis and then reassessed their validity with univariable logistic regression models.

All 23 patients who had no syndesmophytes were HLA-B27 positive, and all patients older than 45 years at symptom onset had syndesmophytes.

The results also highlighted age of disease onset as an important predictor of syndesmophytes in males. Syndesmophytes were less likely to be reported in males with a disease onset at 16 years or younger.

The presence of syndesmophytes was linked with an age older than 16 years at symptom onset (OR, 2.72; 95% confidence interval, 1.15-6.45), and syndesmophytes were less likely to occur among HLA-B27 positive individuals (P = .03).

Females were less likely than males to have syndesmophytes, as verified by univariable analysis (odds ratio, 0.17; 95% confidence interval, 0.07-0.41).

“There is likely a complex interplay of factors leading to differences in radiographic damage between the sacroiliac joints and the spine in AS, and it is interesting to consider if HLA-B27 may have more effect on sacroiliac joint damage than spinal damage,” the authors noted.

Some limitations of the study include the researchers’ choice to compare a subtype with overt spinal involvement and a subtype with limited spinal involvement when other criteria could have been used to separate cases, and their use of the modified Stoke Ankylosing Spondylitis Scoring System (mSaSSS) to examine radiographic changes over time, as the mSaSSS does not take into account radiographic variation in the zygaphophyseal joints and thoracic spine (and were not part of the dataset). Another limitation was the relatively small cohort size, the researchers noted.

“This was a small study, and further studies are needed to elucidate why AS disease may behave differently in this and other subgroups,” Dr. Ridley and colleagues concluded.
 

Expert commentary

Researchers agree that spinal structural damage is a predictor of further damage in patients with radiographic AS, Marina Magrey, MD, the Roland W. Moskowitz Professor in Rheumatic Diseases at Case Western Reserve University, Cleveland, said in an interview. She pointed out that previous literature has shown that longer disease durations make it more likely that patients will have syndesmophytes.

Previous research has also shown that there was an association between structural damage in the SI joints and the function and mobility of the spine. This observation was independent of the disease activity and prior structural damage in the spine, Dr. Magrey noted.

“This is a very complex disease with very diverse manifestations. Traditionally, it was thought to be a disease of men, but now we believe it is equally common between men and women. The burden is equal between men and women, and they need to be treated equally. Both of them need to be treated early on to prevent this radiographic damage,” she said.

Looking ahead, there need to be more translational studies looking for answers as to why there are phenotypic differences between men and women, as well as why men have spinal fusion more often than women. Bed-to-the-bench studies are warranted to get more answers, she said.

The study was supported by an NIH Centers for Translational Science Award grant. The researchers declared having no conflicts of interest related to the study. One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural Research Program, and another by the Spondyloarthritis Association of America and the University of Texas Health Center for Clinical and Translational Sciences KL2 program. Another author is an adviser for AbbVie, Eli Lilly, Gilead, Janssen, MoonLake, Novartis, Pfizer, and UCB, and has grant support from Novartis, Pfizer, and UCB.

Dr. Magrey disclosed being a consultant for Novartis, UCB, Pfizer, AbbVie, Janssen, Bristol-Myers Squibb, and Eli Lilly.

Syndesmophytes are not present in a subgroup of patients with ankylosing spondylitis (AS) and sacroiliac (SI) joint fusion who have had the disease for 20 years or longer, according to findings from a nested case-control study.

Syndesmophytes did not occur in only 23 (7%) of 354 patients, and these patients without spinal-fusing bone growths were less likely to be female but very likely to be HLA-B27 positive, Lauren K. Ridley, MD, a rheumatologist at the University of Texas Health Science Center at Houston, and colleagues reported in The Journal of Rheumatology.

“Women appear to have a different phenotype in AS; we found that they are less likely to form syndesmophytes despite fused SI joints with at least 20 years of disease duration. We do not understand the reasons behind these differences among the possibilities of genetic, hormonal, and bio-mechanical factors,” the authors wrote.

AS is a heterogenous disease that affects different people in various ways, Dr. Ridley noted. “Prior research has shown that and hasn’t really elucidated how different people manifest their disease. Previous research has shown that women tend to have more nonradiographic spondylitis,” Dr. Ridley said in an interview.

“This is still a very heterogenous disease. We don’t fully understand it, and we don’t know why some patients present with SI joint disease [and] no syndesmophytes, or some patients have the opposite. Truly, we do need to do more studies to find out why some patients behave differently and if there are ways we can try to alter that,” Dr. Ridley continued.

The researchers evaluated 354 patients from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS). Of these patients, 23 did not have syndesmophytes. Patients were selected if they had fused SI joints (bilateral grade 4 sacroiliac joint disease) and had a disease course lasting 20 years or more. The researchers identified risk factors for syndesmophytes using classification and regression trees (CART) analysis and then reassessed their validity with univariable logistic regression models.

All 23 patients who had no syndesmophytes were HLA-B27 positive, and all patients older than 45 years at symptom onset had syndesmophytes.

The results also highlighted age of disease onset as an important predictor of syndesmophytes in males. Syndesmophytes were less likely to be reported in males with a disease onset at 16 years or younger.

The presence of syndesmophytes was linked with an age older than 16 years at symptom onset (OR, 2.72; 95% confidence interval, 1.15-6.45), and syndesmophytes were less likely to occur among HLA-B27 positive individuals (P = .03).

Females were less likely than males to have syndesmophytes, as verified by univariable analysis (odds ratio, 0.17; 95% confidence interval, 0.07-0.41).

“There is likely a complex interplay of factors leading to differences in radiographic damage between the sacroiliac joints and the spine in AS, and it is interesting to consider if HLA-B27 may have more effect on sacroiliac joint damage than spinal damage,” the authors noted.

Some limitations of the study include the researchers’ choice to compare a subtype with overt spinal involvement and a subtype with limited spinal involvement when other criteria could have been used to separate cases, and their use of the modified Stoke Ankylosing Spondylitis Scoring System (mSaSSS) to examine radiographic changes over time, as the mSaSSS does not take into account radiographic variation in the zygaphophyseal joints and thoracic spine (and were not part of the dataset). Another limitation was the relatively small cohort size, the researchers noted.

“This was a small study, and further studies are needed to elucidate why AS disease may behave differently in this and other subgroups,” Dr. Ridley and colleagues concluded.
 

Expert commentary

Researchers agree that spinal structural damage is a predictor of further damage in patients with radiographic AS, Marina Magrey, MD, the Roland W. Moskowitz Professor in Rheumatic Diseases at Case Western Reserve University, Cleveland, said in an interview. She pointed out that previous literature has shown that longer disease durations make it more likely that patients will have syndesmophytes.

Previous research has also shown that there was an association between structural damage in the SI joints and the function and mobility of the spine. This observation was independent of the disease activity and prior structural damage in the spine, Dr. Magrey noted.

“This is a very complex disease with very diverse manifestations. Traditionally, it was thought to be a disease of men, but now we believe it is equally common between men and women. The burden is equal between men and women, and they need to be treated equally. Both of them need to be treated early on to prevent this radiographic damage,” she said.

Looking ahead, there need to be more translational studies looking for answers as to why there are phenotypic differences between men and women, as well as why men have spinal fusion more often than women. Bed-to-the-bench studies are warranted to get more answers, she said.

The study was supported by an NIH Centers for Translational Science Award grant. The researchers declared having no conflicts of interest related to the study. One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural Research Program, and another by the Spondyloarthritis Association of America and the University of Texas Health Center for Clinical and Translational Sciences KL2 program. Another author is an adviser for AbbVie, Eli Lilly, Gilead, Janssen, MoonLake, Novartis, Pfizer, and UCB, and has grant support from Novartis, Pfizer, and UCB.

Dr. Magrey disclosed being a consultant for Novartis, UCB, Pfizer, AbbVie, Janssen, Bristol-Myers Squibb, and Eli Lilly.

Syndesmophytes are not present in a subgroup of patients with ankylosing spondylitis (AS) and sacroiliac (SI) joint fusion who have had the disease for 20 years or longer, according to findings from a nested case-control study.

Syndesmophytes did not occur in only 23 (7%) of 354 patients, and these patients without spinal-fusing bone growths were less likely to be female but very likely to be HLA-B27 positive, Lauren K. Ridley, MD, a rheumatologist at the University of Texas Health Science Center at Houston, and colleagues reported in The Journal of Rheumatology.

“Women appear to have a different phenotype in AS; we found that they are less likely to form syndesmophytes despite fused SI joints with at least 20 years of disease duration. We do not understand the reasons behind these differences among the possibilities of genetic, hormonal, and bio-mechanical factors,” the authors wrote.

AS is a heterogenous disease that affects different people in various ways, Dr. Ridley noted. “Prior research has shown that and hasn’t really elucidated how different people manifest their disease. Previous research has shown that women tend to have more nonradiographic spondylitis,” Dr. Ridley said in an interview.

“This is still a very heterogenous disease. We don’t fully understand it, and we don’t know why some patients present with SI joint disease [and] no syndesmophytes, or some patients have the opposite. Truly, we do need to do more studies to find out why some patients behave differently and if there are ways we can try to alter that,” Dr. Ridley continued.

The researchers evaluated 354 patients from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS). Of these patients, 23 did not have syndesmophytes. Patients were selected if they had fused SI joints (bilateral grade 4 sacroiliac joint disease) and had a disease course lasting 20 years or more. The researchers identified risk factors for syndesmophytes using classification and regression trees (CART) analysis and then reassessed their validity with univariable logistic regression models.

All 23 patients who had no syndesmophytes were HLA-B27 positive, and all patients older than 45 years at symptom onset had syndesmophytes.

The results also highlighted age of disease onset as an important predictor of syndesmophytes in males. Syndesmophytes were less likely to be reported in males with a disease onset at 16 years or younger.

The presence of syndesmophytes was linked with an age older than 16 years at symptom onset (OR, 2.72; 95% confidence interval, 1.15-6.45), and syndesmophytes were less likely to occur among HLA-B27 positive individuals (P = .03).

Females were less likely than males to have syndesmophytes, as verified by univariable analysis (odds ratio, 0.17; 95% confidence interval, 0.07-0.41).

“There is likely a complex interplay of factors leading to differences in radiographic damage between the sacroiliac joints and the spine in AS, and it is interesting to consider if HLA-B27 may have more effect on sacroiliac joint damage than spinal damage,” the authors noted.

Some limitations of the study include the researchers’ choice to compare a subtype with overt spinal involvement and a subtype with limited spinal involvement when other criteria could have been used to separate cases, and their use of the modified Stoke Ankylosing Spondylitis Scoring System (mSaSSS) to examine radiographic changes over time, as the mSaSSS does not take into account radiographic variation in the zygaphophyseal joints and thoracic spine (and were not part of the dataset). Another limitation was the relatively small cohort size, the researchers noted.

“This was a small study, and further studies are needed to elucidate why AS disease may behave differently in this and other subgroups,” Dr. Ridley and colleagues concluded.
 

Expert commentary

Researchers agree that spinal structural damage is a predictor of further damage in patients with radiographic AS, Marina Magrey, MD, the Roland W. Moskowitz Professor in Rheumatic Diseases at Case Western Reserve University, Cleveland, said in an interview. She pointed out that previous literature has shown that longer disease durations make it more likely that patients will have syndesmophytes.

Previous research has also shown that there was an association between structural damage in the SI joints and the function and mobility of the spine. This observation was independent of the disease activity and prior structural damage in the spine, Dr. Magrey noted.

“This is a very complex disease with very diverse manifestations. Traditionally, it was thought to be a disease of men, but now we believe it is equally common between men and women. The burden is equal between men and women, and they need to be treated equally. Both of them need to be treated early on to prevent this radiographic damage,” she said.

Looking ahead, there need to be more translational studies looking for answers as to why there are phenotypic differences between men and women, as well as why men have spinal fusion more often than women. Bed-to-the-bench studies are warranted to get more answers, she said.

The study was supported by an NIH Centers for Translational Science Award grant. The researchers declared having no conflicts of interest related to the study. One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural Research Program, and another by the Spondyloarthritis Association of America and the University of Texas Health Center for Clinical and Translational Sciences KL2 program. Another author is an adviser for AbbVie, Eli Lilly, Gilead, Janssen, MoonLake, Novartis, Pfizer, and UCB, and has grant support from Novartis, Pfizer, and UCB.

Dr. Magrey disclosed being a consultant for Novartis, UCB, Pfizer, AbbVie, Janssen, Bristol-Myers Squibb, and Eli Lilly.

People with immune-mediated inflammatory diseases who are taking immunosuppressants don’t mount as strong of an immune defense against the Omicron variant as they did against the original SARS-CoV-2 wild-type virus, according to two studies published in Annals of the Rheumatic Diseases. One of the studies further showed that vaccinated individuals taking immunosuppressants have poorer cross-neutralizing responses to Omicron than do healthy vaccinated individuals, even after three doses of the COVID-19 mRNA vaccines.

filadendron/E+/Getty Images

“We carefully suggest that if Omicron-specific vaccination can be administered, it may be an effective way to reduce the risk of breakthrough infections in patients with autoimmune rheumatic disease,” Sang Tae Choi, MD, PhD, of the University College of Medicine, Seoul, Korea, and one of the authors of the study on cross-neutralizing protection, told this news organization. “However, further research is needed on Omicron-specific vaccine effectiveness in patients with immune dysfunctions. We believe that these study results can be of great benefit in determining the strategy of vaccination in the future.”

The earlier study, published in July, examined the ability of COVID-19 vaccines to induce cross-reactive antibody responses against Omicron infections in patients with autoimmune rheumatic diseases (ARDs). The observational study involved 149 patients with ARDs and 94 health care workers as controls, all of whom provided blood samples a median 15 weeks after their second COVID vaccine dose or a median 8 weeks after their third dose. A little more than two-thirds of the patients (68.5%) had received a third mRNA vaccine dose. None of the participants previously had COVID-19.

The researchers compared the rate of breakthrough infections with the Omicron variant to the neutralizing responses in patients’ blood, specifically the cross-neutralizing antibody responses because the original mRNA vaccines targeted a different variant than Omicron. Breakthrough infections were assessed by survey questions.

“Our findings suggested that neither primary series vaccinations nor booster doses are sufficient to induce Omicron-neutralizing responses above the threshold in patients with ARDs, although responses were noticeably increased following the third dose of an mRNA vaccine,” write Woo-Joong Kim, of the Chung-Ang University College of Medicine, Seoul, Korea, and his colleagues. “This impairment of cross-neutralization responses across most of our patients contrasts starkly with a potent elicitation of the Omicron-neutralizing responses after the third vaccination in healthy recipients.”

The average neutralizing responses against the original SARS-CoV-2 strain were similar in both groups: 76% in patients with ARDs and 72% in health care workers after the second dose. The mean response after a third dose was 97% in health care workers and 88% in patients.

The average cross-neutralizing response against the Omicron variant was far lower, particularly in those with rheumatic disease: only 11.5%, which rose to 27% after the third dose. Only 39% of the patient sera showed neutralization of Omicron, even after the third dose. Meanwhile, the mean cross-neutralizing response in health care workers was 18% after the second dose and 50% after the third.

When the researchers compared seropositivity rates against the original virus to neutralizing responses against Omicron, the association between these was stronger in health care workers than in those with ARDs. In fact, among patients with ARDs who seroconverted, only 41% showed any response against Omicron. Among all the patients, most of those who didn’t respond to Omicron (93.5%) had initially seroconverted.

The researchers also looked at the ability to neutralize Omicron on the basis of disease in those who received three doses of the vaccine. About half of those with lupus (52%) showed any neutralization against Omicron, compared with 25% of those with rheumatoid arthritis, 37.5% of those with ankylosing spondylitis, 33% of those with Behçet snydrome, and all of those with adult-onset Still’s disease.

The rate of breakthrough infections was lower in patients (19%) than in health care workers (33%). A similar pattern was seen in the more recent study published Sept. 5. Researchers used data from a prospective cohort study in the Netherlands to examine incidence and severity of Omicron breakthrough infections in patients with immune-mediated inflammatory diseases. The researchers compared infection rates and severity among 1,593 vaccinated patients with inflammatory disease who were taking immunosuppressants and 579 vaccinated controls (418 patients with inflammatory disease not on immunosuppressants and 161 healthy controls).

One in five patients with inflammatory disease (21%) were taking immunosuppressants that substantially impair antibodies, such as anti-CD20 therapy, S1P modulators, or mycophenolate mofetil combination therapy, and 48% of these patients seroconverted after primary vaccination, compared with 96% of patients taking other immunosuppressants and 98% of controls.

Breakthrough infection rates were similar between the control group (31%) and those taking immunosuppressants (30%). Only three participants had severe disease requiring hospitalization: one control and two patients taking immunosuppressants.

“In both studies, the controls had similar or higher rates of breakthrough infections, compared with the immunosuppressed,” noted Alfred Kim, MD, an assistant professor of medicine at Washington University, St Louis, but he added, “one has to consider differences in mitigation strategies, such as masking, that may explain these findings.” That is, patients taking immunosuppressants may be taking fewer risks in the community or have fewer potential exposures, especially in the Korean study, wherein the controls were health care workers.

A greater disparity in infections occurred when considering seroconversion rates. Breakthrough incidence was 38% among those taking immunosuppressants who did not seroconvert, compared with 29% among those who did. A similar trend was seen in breakthrough incidence between those taking strongly antibody-impairing immunosuppressants (36% breakthrough rate) and those taking other immunosuppressants (28%).

A version of this article first appeared on Medscape.com.

People with immune-mediated inflammatory diseases who are taking immunosuppressants don’t mount as strong of an immune defense against the Omicron variant as they did against the original SARS-CoV-2 wild-type virus, according to two studies published in Annals of the Rheumatic Diseases. One of the studies further showed that vaccinated individuals taking immunosuppressants have poorer cross-neutralizing responses to Omicron than do healthy vaccinated individuals, even after three doses of the COVID-19 mRNA vaccines.

filadendron/E+/Getty Images

“We carefully suggest that if Omicron-specific vaccination can be administered, it may be an effective way to reduce the risk of breakthrough infections in patients with autoimmune rheumatic disease,” Sang Tae Choi, MD, PhD, of the University College of Medicine, Seoul, Korea, and one of the authors of the study on cross-neutralizing protection, told this news organization. “However, further research is needed on Omicron-specific vaccine effectiveness in patients with immune dysfunctions. We believe that these study results can be of great benefit in determining the strategy of vaccination in the future.”

The earlier study, published in July, examined the ability of COVID-19 vaccines to induce cross-reactive antibody responses against Omicron infections in patients with autoimmune rheumatic diseases (ARDs). The observational study involved 149 patients with ARDs and 94 health care workers as controls, all of whom provided blood samples a median 15 weeks after their second COVID vaccine dose or a median 8 weeks after their third dose. A little more than two-thirds of the patients (68.5%) had received a third mRNA vaccine dose. None of the participants previously had COVID-19.

The researchers compared the rate of breakthrough infections with the Omicron variant to the neutralizing responses in patients’ blood, specifically the cross-neutralizing antibody responses because the original mRNA vaccines targeted a different variant than Omicron. Breakthrough infections were assessed by survey questions.

“Our findings suggested that neither primary series vaccinations nor booster doses are sufficient to induce Omicron-neutralizing responses above the threshold in patients with ARDs, although responses were noticeably increased following the third dose of an mRNA vaccine,” write Woo-Joong Kim, of the Chung-Ang University College of Medicine, Seoul, Korea, and his colleagues. “This impairment of cross-neutralization responses across most of our patients contrasts starkly with a potent elicitation of the Omicron-neutralizing responses after the third vaccination in healthy recipients.”

The average neutralizing responses against the original SARS-CoV-2 strain were similar in both groups: 76% in patients with ARDs and 72% in health care workers after the second dose. The mean response after a third dose was 97% in health care workers and 88% in patients.

The average cross-neutralizing response against the Omicron variant was far lower, particularly in those with rheumatic disease: only 11.5%, which rose to 27% after the third dose. Only 39% of the patient sera showed neutralization of Omicron, even after the third dose. Meanwhile, the mean cross-neutralizing response in health care workers was 18% after the second dose and 50% after the third.

When the researchers compared seropositivity rates against the original virus to neutralizing responses against Omicron, the association between these was stronger in health care workers than in those with ARDs. In fact, among patients with ARDs who seroconverted, only 41% showed any response against Omicron. Among all the patients, most of those who didn’t respond to Omicron (93.5%) had initially seroconverted.

The researchers also looked at the ability to neutralize Omicron on the basis of disease in those who received three doses of the vaccine. About half of those with lupus (52%) showed any neutralization against Omicron, compared with 25% of those with rheumatoid arthritis, 37.5% of those with ankylosing spondylitis, 33% of those with Behçet snydrome, and all of those with adult-onset Still’s disease.

The rate of breakthrough infections was lower in patients (19%) than in health care workers (33%). A similar pattern was seen in the more recent study published Sept. 5. Researchers used data from a prospective cohort study in the Netherlands to examine incidence and severity of Omicron breakthrough infections in patients with immune-mediated inflammatory diseases. The researchers compared infection rates and severity among 1,593 vaccinated patients with inflammatory disease who were taking immunosuppressants and 579 vaccinated controls (418 patients with inflammatory disease not on immunosuppressants and 161 healthy controls).

One in five patients with inflammatory disease (21%) were taking immunosuppressants that substantially impair antibodies, such as anti-CD20 therapy, S1P modulators, or mycophenolate mofetil combination therapy, and 48% of these patients seroconverted after primary vaccination, compared with 96% of patients taking other immunosuppressants and 98% of controls.

Breakthrough infection rates were similar between the control group (31%) and those taking immunosuppressants (30%). Only three participants had severe disease requiring hospitalization: one control and two patients taking immunosuppressants.

“In both studies, the controls had similar or higher rates of breakthrough infections, compared with the immunosuppressed,” noted Alfred Kim, MD, an assistant professor of medicine at Washington University, St Louis, but he added, “one has to consider differences in mitigation strategies, such as masking, that may explain these findings.” That is, patients taking immunosuppressants may be taking fewer risks in the community or have fewer potential exposures, especially in the Korean study, wherein the controls were health care workers.

A greater disparity in infections occurred when considering seroconversion rates. Breakthrough incidence was 38% among those taking immunosuppressants who did not seroconvert, compared with 29% among those who did. A similar trend was seen in breakthrough incidence between those taking strongly antibody-impairing immunosuppressants (36% breakthrough rate) and those taking other immunosuppressants (28%).

A version of this article first appeared on Medscape.com.

People with immune-mediated inflammatory diseases who are taking immunosuppressants don’t mount as strong of an immune defense against the Omicron variant as they did against the original SARS-CoV-2 wild-type virus, according to two studies published in Annals of the Rheumatic Diseases. One of the studies further showed that vaccinated individuals taking immunosuppressants have poorer cross-neutralizing responses to Omicron than do healthy vaccinated individuals, even after three doses of the COVID-19 mRNA vaccines.

filadendron/E+/Getty Images

“We carefully suggest that if Omicron-specific vaccination can be administered, it may be an effective way to reduce the risk of breakthrough infections in patients with autoimmune rheumatic disease,” Sang Tae Choi, MD, PhD, of the University College of Medicine, Seoul, Korea, and one of the authors of the study on cross-neutralizing protection, told this news organization. “However, further research is needed on Omicron-specific vaccine effectiveness in patients with immune dysfunctions. We believe that these study results can be of great benefit in determining the strategy of vaccination in the future.”

The earlier study, published in July, examined the ability of COVID-19 vaccines to induce cross-reactive antibody responses against Omicron infections in patients with autoimmune rheumatic diseases (ARDs). The observational study involved 149 patients with ARDs and 94 health care workers as controls, all of whom provided blood samples a median 15 weeks after their second COVID vaccine dose or a median 8 weeks after their third dose. A little more than two-thirds of the patients (68.5%) had received a third mRNA vaccine dose. None of the participants previously had COVID-19.

The researchers compared the rate of breakthrough infections with the Omicron variant to the neutralizing responses in patients’ blood, specifically the cross-neutralizing antibody responses because the original mRNA vaccines targeted a different variant than Omicron. Breakthrough infections were assessed by survey questions.

“Our findings suggested that neither primary series vaccinations nor booster doses are sufficient to induce Omicron-neutralizing responses above the threshold in patients with ARDs, although responses were noticeably increased following the third dose of an mRNA vaccine,” write Woo-Joong Kim, of the Chung-Ang University College of Medicine, Seoul, Korea, and his colleagues. “This impairment of cross-neutralization responses across most of our patients contrasts starkly with a potent elicitation of the Omicron-neutralizing responses after the third vaccination in healthy recipients.”

The average neutralizing responses against the original SARS-CoV-2 strain were similar in both groups: 76% in patients with ARDs and 72% in health care workers after the second dose. The mean response after a third dose was 97% in health care workers and 88% in patients.

The average cross-neutralizing response against the Omicron variant was far lower, particularly in those with rheumatic disease: only 11.5%, which rose to 27% after the third dose. Only 39% of the patient sera showed neutralization of Omicron, even after the third dose. Meanwhile, the mean cross-neutralizing response in health care workers was 18% after the second dose and 50% after the third.

When the researchers compared seropositivity rates against the original virus to neutralizing responses against Omicron, the association between these was stronger in health care workers than in those with ARDs. In fact, among patients with ARDs who seroconverted, only 41% showed any response against Omicron. Among all the patients, most of those who didn’t respond to Omicron (93.5%) had initially seroconverted.

The researchers also looked at the ability to neutralize Omicron on the basis of disease in those who received three doses of the vaccine. About half of those with lupus (52%) showed any neutralization against Omicron, compared with 25% of those with rheumatoid arthritis, 37.5% of those with ankylosing spondylitis, 33% of those with Behçet snydrome, and all of those with adult-onset Still’s disease.

The rate of breakthrough infections was lower in patients (19%) than in health care workers (33%). A similar pattern was seen in the more recent study published Sept. 5. Researchers used data from a prospective cohort study in the Netherlands to examine incidence and severity of Omicron breakthrough infections in patients with immune-mediated inflammatory diseases. The researchers compared infection rates and severity among 1,593 vaccinated patients with inflammatory disease who were taking immunosuppressants and 579 vaccinated controls (418 patients with inflammatory disease not on immunosuppressants and 161 healthy controls).

One in five patients with inflammatory disease (21%) were taking immunosuppressants that substantially impair antibodies, such as anti-CD20 therapy, S1P modulators, or mycophenolate mofetil combination therapy, and 48% of these patients seroconverted after primary vaccination, compared with 96% of patients taking other immunosuppressants and 98% of controls.

Breakthrough infection rates were similar between the control group (31%) and those taking immunosuppressants (30%). Only three participants had severe disease requiring hospitalization: one control and two patients taking immunosuppressants.

“In both studies, the controls had similar or higher rates of breakthrough infections, compared with the immunosuppressed,” noted Alfred Kim, MD, an assistant professor of medicine at Washington University, St Louis, but he added, “one has to consider differences in mitigation strategies, such as masking, that may explain these findings.” That is, patients taking immunosuppressants may be taking fewer risks in the community or have fewer potential exposures, especially in the Korean study, wherein the controls were health care workers.

A greater disparity in infections occurred when considering seroconversion rates. Breakthrough incidence was 38% among those taking immunosuppressants who did not seroconvert, compared with 29% among those who did. A similar trend was seen in breakthrough incidence between those taking strongly antibody-impairing immunosuppressants (36% breakthrough rate) and those taking other immunosuppressants (28%).

A version of this article first appeared on Medscape.com.

Women with inflammatory arthritis (IA) are more likely to use healthcare services than men, a Canadian study found. The results suggest there are biological differences in disease course and sociocultural differences in health care access and patient behavior among the sexes, Sanjana Tarannum said in a presentation at the Lancet Summit on Sex and Gender in Rheumatology.

Ms. Tarannum and colleagues also recently published the study in Annals of the Rheumatic Diseases.

Effectively managing IA patients calls for timely access to and appropriate use of health care resources, said Ms. Tarannum, of the Women’s College Research Institute in Toronto.

Sex and gender are often used interchangeably but they refer to different things. “Sex is the biological characteristic of being male or female. It relates to disease inheritance patterns, pain processing mechanisms, and immune dysregulation in the context of inflammatory arthritis,” Ms. Tarannum said during her presentation.

Gender is a sociocultural construct associated with masculine or feminine traits. In the context of IA, gender relates to coping strategies, pain perception and reporting, and health care–seeking behavior of patients and interaction with care providers.

A patient’s sex relates to healthcare encounters, time to diagnosis, and prescription patterns. These all affect disease outcomes. Previous studies have yielded inconsistent results and mainly focused on rheumatoid arthritis rather than other IA types such as ankylosing spondylitis (AS).

Ms. Tarannum and colleagues sought to compare health care usage between male and female patients for musculoskeletal-related issues before and after IA diagnosis. They used Ontario administrative health data to create three cohorts of patients with RA, AS, and psoriatic arthritis (PsA), the three most common types of IA. The patients were diagnosed during 2010-2017, and outcomes were assessed in each year for 3 years before and after diagnosis.

Health care use indicators included visits to physicians, musculoskeletal imaging, laboratory tests, and dispensation of drugs. Regression models adjusting for sociodemographic factors and comorbidities were used to compare male and female patients.

Sex-related differences emerge in all IA groups

The investigators assessed 41,277 patients with RA (69% female), 8,150 patients with AS (51% female), and 6,446 patients with PsA (54% female). Male patients had more cardiovascular disease, whereas female patients had higher incidences of depression and osteoporosis.

Similar trends of sex-related differences emerged in all three cohorts. Before diagnosis, female patients were more likely to visit rheumatologists or family physicians for musculoskeletal reasons or use musculoskeletal imaging and laboratory tests. Women were also more likely to remain in rheumatology care after diagnosis.

Men were more likely to visit the ED for musculoskeletal reasons immediately before diagnosis.

No sex- or gender-related differences were observed in medication use, although older females with RA or AS were more likely to get prescriptions for NSAIDs and opioids and conventional disease-modifying antirheumatic drugs, respectively.

The findings show that overall musculoskeletal health care use was higher in female patients with IA. “Sex differences were more pronounced the earlier the encounter was from the time of diagnosis and tended to diminish with time,” Ms. Tarannum observed. Sex differences were also more prominent in the RA and AS cohorts.
 

Women seek out care, do repeat visits

Several reasons may explain why utilization was higher in females. Women with IA have a higher overall risk of musculoskeletal conditions such as osteoarthritis, which could have driven the health care encounters. Numerous studies have also reported that female patients have a lower threshold for pain as well as a greater tendency to seek out health care.

Additionally, female patients often present with pain and fatigue, which are often misdiagnosed as fibromyalgia or depression. Therefore, they often require repeated health care encounters to arrive at an IA diagnosis, Ms. Tarannum said.

An early prodromal phase in females could have triggered a health care encounter as well.

Men, by comparison, are more likely to have acute-onset or severe disease. Objective signs and radiologic features can facilitate diagnosis in men, she said. Male patients also show more reluctance in seeking care, have a higher threshold for pain, and are less likely to have a usual source of care such as a family physician.

Higher confidence in hospital-based emergency services also could have resulted in more ED visits and lower health care use in men. Better response to treatments could also have resulted in fewer episodes of rheumatology care after diagnosis.

The results aren’t surprising, said Scott Zashin, MD, a rheumatologist in Dallas who wasn’t a part of the study.

“At least in terms of musculoskeletal disorders, my clinical experience suggests that women are more compliant with their follow-up than male patients. Especially with gout, a common type of arthritis in men, male patients may wait until their symptoms are severe before seeking medical attention,” Dr. Zashin said.

The Enid Walker Graduate Student Award for Research in Women’s Health provided funding for this study.

A version of this article first appeared on Medscape.com.

Women with inflammatory arthritis (IA) are more likely to use healthcare services than men, a Canadian study found. The results suggest there are biological differences in disease course and sociocultural differences in health care access and patient behavior among the sexes, Sanjana Tarannum said in a presentation at the Lancet Summit on Sex and Gender in Rheumatology.

Ms. Tarannum and colleagues also recently published the study in Annals of the Rheumatic Diseases.

Effectively managing IA patients calls for timely access to and appropriate use of health care resources, said Ms. Tarannum, of the Women’s College Research Institute in Toronto.

Sex and gender are often used interchangeably but they refer to different things. “Sex is the biological characteristic of being male or female. It relates to disease inheritance patterns, pain processing mechanisms, and immune dysregulation in the context of inflammatory arthritis,” Ms. Tarannum said during her presentation.

Gender is a sociocultural construct associated with masculine or feminine traits. In the context of IA, gender relates to coping strategies, pain perception and reporting, and health care–seeking behavior of patients and interaction with care providers.

A patient’s sex relates to healthcare encounters, time to diagnosis, and prescription patterns. These all affect disease outcomes. Previous studies have yielded inconsistent results and mainly focused on rheumatoid arthritis rather than other IA types such as ankylosing spondylitis (AS).

Ms. Tarannum and colleagues sought to compare health care usage between male and female patients for musculoskeletal-related issues before and after IA diagnosis. They used Ontario administrative health data to create three cohorts of patients with RA, AS, and psoriatic arthritis (PsA), the three most common types of IA. The patients were diagnosed during 2010-2017, and outcomes were assessed in each year for 3 years before and after diagnosis.

Health care use indicators included visits to physicians, musculoskeletal imaging, laboratory tests, and dispensation of drugs. Regression models adjusting for sociodemographic factors and comorbidities were used to compare male and female patients.

Sex-related differences emerge in all IA groups

The investigators assessed 41,277 patients with RA (69% female), 8,150 patients with AS (51% female), and 6,446 patients with PsA (54% female). Male patients had more cardiovascular disease, whereas female patients had higher incidences of depression and osteoporosis.

Similar trends of sex-related differences emerged in all three cohorts. Before diagnosis, female patients were more likely to visit rheumatologists or family physicians for musculoskeletal reasons or use musculoskeletal imaging and laboratory tests. Women were also more likely to remain in rheumatology care after diagnosis.

Men were more likely to visit the ED for musculoskeletal reasons immediately before diagnosis.

No sex- or gender-related differences were observed in medication use, although older females with RA or AS were more likely to get prescriptions for NSAIDs and opioids and conventional disease-modifying antirheumatic drugs, respectively.

The findings show that overall musculoskeletal health care use was higher in female patients with IA. “Sex differences were more pronounced the earlier the encounter was from the time of diagnosis and tended to diminish with time,” Ms. Tarannum observed. Sex differences were also more prominent in the RA and AS cohorts.
 

Women seek out care, do repeat visits

Several reasons may explain why utilization was higher in females. Women with IA have a higher overall risk of musculoskeletal conditions such as osteoarthritis, which could have driven the health care encounters. Numerous studies have also reported that female patients have a lower threshold for pain as well as a greater tendency to seek out health care.

Additionally, female patients often present with pain and fatigue, which are often misdiagnosed as fibromyalgia or depression. Therefore, they often require repeated health care encounters to arrive at an IA diagnosis, Ms. Tarannum said.

An early prodromal phase in females could have triggered a health care encounter as well.

Men, by comparison, are more likely to have acute-onset or severe disease. Objective signs and radiologic features can facilitate diagnosis in men, she said. Male patients also show more reluctance in seeking care, have a higher threshold for pain, and are less likely to have a usual source of care such as a family physician.

Higher confidence in hospital-based emergency services also could have resulted in more ED visits and lower health care use in men. Better response to treatments could also have resulted in fewer episodes of rheumatology care after diagnosis.

The results aren’t surprising, said Scott Zashin, MD, a rheumatologist in Dallas who wasn’t a part of the study.

“At least in terms of musculoskeletal disorders, my clinical experience suggests that women are more compliant with their follow-up than male patients. Especially with gout, a common type of arthritis in men, male patients may wait until their symptoms are severe before seeking medical attention,” Dr. Zashin said.

The Enid Walker Graduate Student Award for Research in Women’s Health provided funding for this study.

A version of this article first appeared on Medscape.com.

Women with inflammatory arthritis (IA) are more likely to use healthcare services than men, a Canadian study found. The results suggest there are biological differences in disease course and sociocultural differences in health care access and patient behavior among the sexes, Sanjana Tarannum said in a presentation at the Lancet Summit on Sex and Gender in Rheumatology.

Ms. Tarannum and colleagues also recently published the study in Annals of the Rheumatic Diseases.

Effectively managing IA patients calls for timely access to and appropriate use of health care resources, said Ms. Tarannum, of the Women’s College Research Institute in Toronto.

Sex and gender are often used interchangeably but they refer to different things. “Sex is the biological characteristic of being male or female. It relates to disease inheritance patterns, pain processing mechanisms, and immune dysregulation in the context of inflammatory arthritis,” Ms. Tarannum said during her presentation.

Gender is a sociocultural construct associated with masculine or feminine traits. In the context of IA, gender relates to coping strategies, pain perception and reporting, and health care–seeking behavior of patients and interaction with care providers.

A patient’s sex relates to healthcare encounters, time to diagnosis, and prescription patterns. These all affect disease outcomes. Previous studies have yielded inconsistent results and mainly focused on rheumatoid arthritis rather than other IA types such as ankylosing spondylitis (AS).

Ms. Tarannum and colleagues sought to compare health care usage between male and female patients for musculoskeletal-related issues before and after IA diagnosis. They used Ontario administrative health data to create three cohorts of patients with RA, AS, and psoriatic arthritis (PsA), the three most common types of IA. The patients were diagnosed during 2010-2017, and outcomes were assessed in each year for 3 years before and after diagnosis.

Health care use indicators included visits to physicians, musculoskeletal imaging, laboratory tests, and dispensation of drugs. Regression models adjusting for sociodemographic factors and comorbidities were used to compare male and female patients.

Sex-related differences emerge in all IA groups

The investigators assessed 41,277 patients with RA (69% female), 8,150 patients with AS (51% female), and 6,446 patients with PsA (54% female). Male patients had more cardiovascular disease, whereas female patients had higher incidences of depression and osteoporosis.

Similar trends of sex-related differences emerged in all three cohorts. Before diagnosis, female patients were more likely to visit rheumatologists or family physicians for musculoskeletal reasons or use musculoskeletal imaging and laboratory tests. Women were also more likely to remain in rheumatology care after diagnosis.

Men were more likely to visit the ED for musculoskeletal reasons immediately before diagnosis.

No sex- or gender-related differences were observed in medication use, although older females with RA or AS were more likely to get prescriptions for NSAIDs and opioids and conventional disease-modifying antirheumatic drugs, respectively.

The findings show that overall musculoskeletal health care use was higher in female patients with IA. “Sex differences were more pronounced the earlier the encounter was from the time of diagnosis and tended to diminish with time,” Ms. Tarannum observed. Sex differences were also more prominent in the RA and AS cohorts.
 

Women seek out care, do repeat visits

Several reasons may explain why utilization was higher in females. Women with IA have a higher overall risk of musculoskeletal conditions such as osteoarthritis, which could have driven the health care encounters. Numerous studies have also reported that female patients have a lower threshold for pain as well as a greater tendency to seek out health care.

Additionally, female patients often present with pain and fatigue, which are often misdiagnosed as fibromyalgia or depression. Therefore, they often require repeated health care encounters to arrive at an IA diagnosis, Ms. Tarannum said.

An early prodromal phase in females could have triggered a health care encounter as well.

Men, by comparison, are more likely to have acute-onset or severe disease. Objective signs and radiologic features can facilitate diagnosis in men, she said. Male patients also show more reluctance in seeking care, have a higher threshold for pain, and are less likely to have a usual source of care such as a family physician.

Higher confidence in hospital-based emergency services also could have resulted in more ED visits and lower health care use in men. Better response to treatments could also have resulted in fewer episodes of rheumatology care after diagnosis.

The results aren’t surprising, said Scott Zashin, MD, a rheumatologist in Dallas who wasn’t a part of the study.

“At least in terms of musculoskeletal disorders, my clinical experience suggests that women are more compliant with their follow-up than male patients. Especially with gout, a common type of arthritis in men, male patients may wait until their symptoms are severe before seeking medical attention,” Dr. Zashin said.

The Enid Walker Graduate Student Award for Research in Women’s Health provided funding for this study.

A version of this article first appeared on Medscape.com.

Gender-affirming hormone therapy’s effect on transgender patients with rheumatic disease is unclear but does not appear to modulate its course and does not need to be strictly contraindicated in most patients, according to a case series and systematic literature review.

More doctors are practicing transgender medicine, yet a limited amount of information is available on rheumatic disease in transgender and gender diverse (TGGD) individuals, Kristen Mathias, MD, a rheumatology fellow at Johns Hopkins University, Baltimore, said in her presentation of the study at the Lancet Summit on Sex and Gender in Rheumatology.

“This is important, as it is well known that sex hormones affect the pathogenesis and expression of autoimmune diseases,” Dr. Mathias said. Knowing more about the effects of gender-affirming hormone therapy (GAHT) and gender-affirming surgery on disease activity in TGGD individuals could better inform decisions about care in this population.

Dr. Mathias and colleagues identified 7 transgender patients with rheumatic diseases from a pool of 1,053 patients seen at the Los Angeles County and University of Southern California Medical Center, Los Angeles, from June 2019 to June 2021. This included five transgender males and two transgender females. They ranged in age from 13 to 52 years.

All seven were on GAHT, and its impact on disease activity was considered “possible” in two of the seven patients.

In a systematic literature review, investigators found 11 studies that included 11 transgender women and 2 transgender men, ranging in age from 22 to 49 years. All the patients were on GAHT. In 12 of 13 patients, the hormones were considered possibly related to their rheumatic disease activity.

The 20 patients had diagnoses of rheumatoid arthritis, cutaneous and systemic lupus erythematosus, adult-onset Still disease, spondyloarthritis, myositis, and systemic sclerosis.

GAHT should not be a strict contraindication in these patients, based on these findings, Dr. Mathias noted. Information to clarify the effect of GAHT on rheumatic disease is sparse, however. Physicians should adopt a personalized, shared decision-making approach when consulting patients.

“During patient encounters, they should be screened for psychosocial barriers when appropriate,” Dr. Mathias recommended.

Findings could pave way for larger studies, more data

Studies on the impact and consequences of rheumatic disease in TGGD individuals are sorely lacking, said Vagishwari Murugesan, MBBS, a clinical fellow in rheumatology at the University of Toronto.

“While this is a small study of only seven patients and no conclusive results can be drawn, studies like these can help pave the way for larger multicentric studies, which can give us more definitive data on gender-affirming hormone therapy and its consequences on rheumatic diseases,” said Dr. Murugesan, who was not involved in the study.

A registry would be a great way to collaborate with other stakeholders interested in the same topic and conduct larger studies, she said. “I would recommend that not only do we screen for psychosocial barriers but also actively engage as a health care community in addressing how we can overcome the barriers for patients to access effective health care.”

No external funding was obtained for the study.

A version of this article first appeared on Medscape.com.

Gender-affirming hormone therapy’s effect on transgender patients with rheumatic disease is unclear but does not appear to modulate its course and does not need to be strictly contraindicated in most patients, according to a case series and systematic literature review.

More doctors are practicing transgender medicine, yet a limited amount of information is available on rheumatic disease in transgender and gender diverse (TGGD) individuals, Kristen Mathias, MD, a rheumatology fellow at Johns Hopkins University, Baltimore, said in her presentation of the study at the Lancet Summit on Sex and Gender in Rheumatology.

“This is important, as it is well known that sex hormones affect the pathogenesis and expression of autoimmune diseases,” Dr. Mathias said. Knowing more about the effects of gender-affirming hormone therapy (GAHT) and gender-affirming surgery on disease activity in TGGD individuals could better inform decisions about care in this population.

Dr. Mathias and colleagues identified 7 transgender patients with rheumatic diseases from a pool of 1,053 patients seen at the Los Angeles County and University of Southern California Medical Center, Los Angeles, from June 2019 to June 2021. This included five transgender males and two transgender females. They ranged in age from 13 to 52 years.

All seven were on GAHT, and its impact on disease activity was considered “possible” in two of the seven patients.

In a systematic literature review, investigators found 11 studies that included 11 transgender women and 2 transgender men, ranging in age from 22 to 49 years. All the patients were on GAHT. In 12 of 13 patients, the hormones were considered possibly related to their rheumatic disease activity.

The 20 patients had diagnoses of rheumatoid arthritis, cutaneous and systemic lupus erythematosus, adult-onset Still disease, spondyloarthritis, myositis, and systemic sclerosis.

GAHT should not be a strict contraindication in these patients, based on these findings, Dr. Mathias noted. Information to clarify the effect of GAHT on rheumatic disease is sparse, however. Physicians should adopt a personalized, shared decision-making approach when consulting patients.

“During patient encounters, they should be screened for psychosocial barriers when appropriate,” Dr. Mathias recommended.

Findings could pave way for larger studies, more data

Studies on the impact and consequences of rheumatic disease in TGGD individuals are sorely lacking, said Vagishwari Murugesan, MBBS, a clinical fellow in rheumatology at the University of Toronto.

“While this is a small study of only seven patients and no conclusive results can be drawn, studies like these can help pave the way for larger multicentric studies, which can give us more definitive data on gender-affirming hormone therapy and its consequences on rheumatic diseases,” said Dr. Murugesan, who was not involved in the study.

A registry would be a great way to collaborate with other stakeholders interested in the same topic and conduct larger studies, she said. “I would recommend that not only do we screen for psychosocial barriers but also actively engage as a health care community in addressing how we can overcome the barriers for patients to access effective health care.”

No external funding was obtained for the study.

A version of this article first appeared on Medscape.com.

Gender-affirming hormone therapy’s effect on transgender patients with rheumatic disease is unclear but does not appear to modulate its course and does not need to be strictly contraindicated in most patients, according to a case series and systematic literature review.

More doctors are practicing transgender medicine, yet a limited amount of information is available on rheumatic disease in transgender and gender diverse (TGGD) individuals, Kristen Mathias, MD, a rheumatology fellow at Johns Hopkins University, Baltimore, said in her presentation of the study at the Lancet Summit on Sex and Gender in Rheumatology.

“This is important, as it is well known that sex hormones affect the pathogenesis and expression of autoimmune diseases,” Dr. Mathias said. Knowing more about the effects of gender-affirming hormone therapy (GAHT) and gender-affirming surgery on disease activity in TGGD individuals could better inform decisions about care in this population.

Dr. Mathias and colleagues identified 7 transgender patients with rheumatic diseases from a pool of 1,053 patients seen at the Los Angeles County and University of Southern California Medical Center, Los Angeles, from June 2019 to June 2021. This included five transgender males and two transgender females. They ranged in age from 13 to 52 years.

All seven were on GAHT, and its impact on disease activity was considered “possible” in two of the seven patients.

In a systematic literature review, investigators found 11 studies that included 11 transgender women and 2 transgender men, ranging in age from 22 to 49 years. All the patients were on GAHT. In 12 of 13 patients, the hormones were considered possibly related to their rheumatic disease activity.

The 20 patients had diagnoses of rheumatoid arthritis, cutaneous and systemic lupus erythematosus, adult-onset Still disease, spondyloarthritis, myositis, and systemic sclerosis.

GAHT should not be a strict contraindication in these patients, based on these findings, Dr. Mathias noted. Information to clarify the effect of GAHT on rheumatic disease is sparse, however. Physicians should adopt a personalized, shared decision-making approach when consulting patients.

“During patient encounters, they should be screened for psychosocial barriers when appropriate,” Dr. Mathias recommended.

Findings could pave way for larger studies, more data

Studies on the impact and consequences of rheumatic disease in TGGD individuals are sorely lacking, said Vagishwari Murugesan, MBBS, a clinical fellow in rheumatology at the University of Toronto.

“While this is a small study of only seven patients and no conclusive results can be drawn, studies like these can help pave the way for larger multicentric studies, which can give us more definitive data on gender-affirming hormone therapy and its consequences on rheumatic diseases,” said Dr. Murugesan, who was not involved in the study.

A registry would be a great way to collaborate with other stakeholders interested in the same topic and conduct larger studies, she said. “I would recommend that not only do we screen for psychosocial barriers but also actively engage as a health care community in addressing how we can overcome the barriers for patients to access effective health care.”

No external funding was obtained for the study.

A version of this article first appeared on Medscape.com.

GHENT, BELGIUM – Over 10% of patients referred by chiropractors to rheumatology had undiagnosed spondyloarthritis, with axial spondyloarthritis being the most common, according to new data. The U.S. study was aimed at understanding what proportion of back pain patients have undiagnosed spondyloarthritis.

The study also found that the most common cause for which patients see chiropractors is neck/cervical pain.

Atul Deodhar, MD, MRCP, rheumatologist and medical director of rheumatology clinics at Oregon Health & Science University, Portland, was senior author of the poster that was presented at the 13th International Congress of Spondyloarthritides.

“In the U.S., many people with back pain go to chiropractors, but many chiropractors are not aware of axial spondyloarthritis [axSpA] terminology, and very little – if anything – is published in chiropractic literature, “ he said in an interview.

He remarked that the study highlighted the need to develop a better strategy to identify undiagnosed patients, because the yield found in their study was poor (13%). “Patient-reported spondyloarthritis criteria are often poor, and do not match rheumatologist-inquired history,” he noted, adding that, “inflammatory back pain is in fact a poor ‘entry point.’ ”

Ulrich Weber, MD, rheumatologist from the Practice Buchsbaum in Schaffhausen, Switzerland, commented on the findings, saying he often receives delayed referrals from chiropractors, so “it would be very useful if patients could be more easily and accurately identifiable via this route, but the problem is chiropractors do not have a specific training to spot spondyloarthritis.”

He added that he welcomed the study but noted, “the criteria used to identify patients in this study are broad and I’d worry that it would inundate our rheumatology practice. There remains a real need for a good method of identifying the patients.”
 

Referral to rheumatology

Back pain is highly prevalent in the general population, with a global mean lifetime prevalence of 38.9%. Chiropractors treat many patients with back pain of unknown cause.

“In this study, we wanted to see what percentage of patients in chiropractic practice have undiagnosed axial spondyloarthritis, and what are the common complaints. Our hypothesis was that chiropractors may be missing such patients,” Dr. Deodhar explained.

Dr. Deodhar and colleagues recruited chiropractors from four different parts of the city of Portland into the study. “We think Portland, Oregon, is a typical U.S. city, and our results could be generalized. However, this is our impression alone,” he remarked.

Adults, under the age of 45 years who attended a participating chiropractic clinics between November 2020 and November 2021 for chronic back pain and without a prior diagnosis of spondyloarthritis were eligible for inclusion.

If the patient reported at least one feature of spondyloarthritis in the screening questionnaire they were referred to a rheumatologist for a diagnostic assessment. This assessment involved taking history by telephone, both laboratory tests and imaging, and the patients were categorized as radiographic axSpA, nonradiographic axSpA, peripheral SpA, or no SpA.

The screening questionnaire included the following examples: If the patient was under 45 years and had chronic pain in back, hip or buttocks, then they were asked for more information including whether their pain was gradual (insidious) in onset; if the pain started before the age of 40; and if the pain improved with physical activities or movements. Use of drugs was investigated including whether the pain improved significantly with NSAIDs and whether the patient has current or past heel pains, particularly when waking up in the morning. They were also asked if they have experienced skin psoriasis. Other questions were asked about the presence of uveitis, iritis, family history of psoriasis, inflammatory bowel disease, or ankylosing spondylitis, and whether the patient had unexplained joint pains plus joint swelling.
 

Ten percent of patients referred to rheumatology

A total of 3,103 visits to chiropractor clinics were included, of which 115 patients were referred to a rheumatologist. Eventually, 63 patients were fully assessed by a rheumatologist.

Of those patients who were fully assessed, 12.7% has spondyloarthritis, with one having confirmed radiographic axSpA, five having nonradiographic SpA, and two having peripheral spondyloarthritis or psoriatic arthritis.

Based on the referral questionnaire, all patients reported at least four SpA criteria were met, said Dr. Deodhar.

Of those patients diagnosed with SpA, 14% (1) has elevated C-reactive protein (CRP) level, 14% (1) were HLA-B27 positive, and 14% (1) were identified as having both elevated CRP and HLA-B27 positivity. Sacroiliac joint inflammation was found in 14% (1) on MRI and one had sacroiliac joint inflammation according to modified New York criteria. One (14%) had both sacroiliac joint inflammation on MRI and elevated CRP, and 14% (1) had both sacroiliac joint inflammation and was HLA-B27 positive.

The top complaints reported by patients at chiropractor clinics were neck and cervical spine pain/spasm (16.8%); followed by acute low back pain (11.7%); acute upper back (7.1%); and chronic lower back pain (6.9%).
 

No patients with more than 10 SpA criteria

The performance of an initial diagnostic assessment based on patient reported SpA criteria, as compared with the outcome of the full diagnosis (by a rheumatologist) showed that patients with one to four SpA criteria had a sensitivity of 0.50 (95% confidence interval, 0.15-0.85), and specificity of 0.73 (95% CI, 0.61-0.84). This increased to sensitivity of 0.60 (95% CI, 0.17-1.03), and specificity of 0.61 (95% CI, 0.44-0.77) when six SpA criteria were present.

Dr. Deodhar said the results supported a need to further develop the chiropractor’s role in identifying the right patients for referral, and that the study showed that a referral strategy is required to find undiagnosed patients with spondyloarthritis from chiropractic offices. “Chiropractors need education for axSpA, when to suspect, and when to refer,” he asserted. “What referral strategy to use is for debate – the ASAS [Assessment in SpondyloArthritis international Society] strategy is too sensitive and not specific enough.”

Dr. Deodhar noted that SPARTAN (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network) is working on a referral strategy that is likely to be more specific, and that more data would be forthcoming soon.

Dr. Deodhar declared affiliations with multiple companies involved in the field unrelated to the study. Dr. Weber declared no relevant disclosures.

GHENT, BELGIUM – Over 10% of patients referred by chiropractors to rheumatology had undiagnosed spondyloarthritis, with axial spondyloarthritis being the most common, according to new data. The U.S. study was aimed at understanding what proportion of back pain patients have undiagnosed spondyloarthritis.

The study also found that the most common cause for which patients see chiropractors is neck/cervical pain.

Atul Deodhar, MD, MRCP, rheumatologist and medical director of rheumatology clinics at Oregon Health & Science University, Portland, was senior author of the poster that was presented at the 13th International Congress of Spondyloarthritides.

“In the U.S., many people with back pain go to chiropractors, but many chiropractors are not aware of axial spondyloarthritis [axSpA] terminology, and very little – if anything – is published in chiropractic literature, “ he said in an interview.

He remarked that the study highlighted the need to develop a better strategy to identify undiagnosed patients, because the yield found in their study was poor (13%). “Patient-reported spondyloarthritis criteria are often poor, and do not match rheumatologist-inquired history,” he noted, adding that, “inflammatory back pain is in fact a poor ‘entry point.’ ”

Ulrich Weber, MD, rheumatologist from the Practice Buchsbaum in Schaffhausen, Switzerland, commented on the findings, saying he often receives delayed referrals from chiropractors, so “it would be very useful if patients could be more easily and accurately identifiable via this route, but the problem is chiropractors do not have a specific training to spot spondyloarthritis.”

He added that he welcomed the study but noted, “the criteria used to identify patients in this study are broad and I’d worry that it would inundate our rheumatology practice. There remains a real need for a good method of identifying the patients.”
 

Referral to rheumatology

Back pain is highly prevalent in the general population, with a global mean lifetime prevalence of 38.9%. Chiropractors treat many patients with back pain of unknown cause.

“In this study, we wanted to see what percentage of patients in chiropractic practice have undiagnosed axial spondyloarthritis, and what are the common complaints. Our hypothesis was that chiropractors may be missing such patients,” Dr. Deodhar explained.

Dr. Deodhar and colleagues recruited chiropractors from four different parts of the city of Portland into the study. “We think Portland, Oregon, is a typical U.S. city, and our results could be generalized. However, this is our impression alone,” he remarked.

Adults, under the age of 45 years who attended a participating chiropractic clinics between November 2020 and November 2021 for chronic back pain and without a prior diagnosis of spondyloarthritis were eligible for inclusion.

If the patient reported at least one feature of spondyloarthritis in the screening questionnaire they were referred to a rheumatologist for a diagnostic assessment. This assessment involved taking history by telephone, both laboratory tests and imaging, and the patients were categorized as radiographic axSpA, nonradiographic axSpA, peripheral SpA, or no SpA.

The screening questionnaire included the following examples: If the patient was under 45 years and had chronic pain in back, hip or buttocks, then they were asked for more information including whether their pain was gradual (insidious) in onset; if the pain started before the age of 40; and if the pain improved with physical activities or movements. Use of drugs was investigated including whether the pain improved significantly with NSAIDs and whether the patient has current or past heel pains, particularly when waking up in the morning. They were also asked if they have experienced skin psoriasis. Other questions were asked about the presence of uveitis, iritis, family history of psoriasis, inflammatory bowel disease, or ankylosing spondylitis, and whether the patient had unexplained joint pains plus joint swelling.
 

Ten percent of patients referred to rheumatology

A total of 3,103 visits to chiropractor clinics were included, of which 115 patients were referred to a rheumatologist. Eventually, 63 patients were fully assessed by a rheumatologist.

Of those patients who were fully assessed, 12.7% has spondyloarthritis, with one having confirmed radiographic axSpA, five having nonradiographic SpA, and two having peripheral spondyloarthritis or psoriatic arthritis.

Based on the referral questionnaire, all patients reported at least four SpA criteria were met, said Dr. Deodhar.

Of those patients diagnosed with SpA, 14% (1) has elevated C-reactive protein (CRP) level, 14% (1) were HLA-B27 positive, and 14% (1) were identified as having both elevated CRP and HLA-B27 positivity. Sacroiliac joint inflammation was found in 14% (1) on MRI and one had sacroiliac joint inflammation according to modified New York criteria. One (14%) had both sacroiliac joint inflammation on MRI and elevated CRP, and 14% (1) had both sacroiliac joint inflammation and was HLA-B27 positive.

The top complaints reported by patients at chiropractor clinics were neck and cervical spine pain/spasm (16.8%); followed by acute low back pain (11.7%); acute upper back (7.1%); and chronic lower back pain (6.9%).
 

No patients with more than 10 SpA criteria

The performance of an initial diagnostic assessment based on patient reported SpA criteria, as compared with the outcome of the full diagnosis (by a rheumatologist) showed that patients with one to four SpA criteria had a sensitivity of 0.50 (95% confidence interval, 0.15-0.85), and specificity of 0.73 (95% CI, 0.61-0.84). This increased to sensitivity of 0.60 (95% CI, 0.17-1.03), and specificity of 0.61 (95% CI, 0.44-0.77) when six SpA criteria were present.

Dr. Deodhar said the results supported a need to further develop the chiropractor’s role in identifying the right patients for referral, and that the study showed that a referral strategy is required to find undiagnosed patients with spondyloarthritis from chiropractic offices. “Chiropractors need education for axSpA, when to suspect, and when to refer,” he asserted. “What referral strategy to use is for debate – the ASAS [Assessment in SpondyloArthritis international Society] strategy is too sensitive and not specific enough.”

Dr. Deodhar noted that SPARTAN (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network) is working on a referral strategy that is likely to be more specific, and that more data would be forthcoming soon.

Dr. Deodhar declared affiliations with multiple companies involved in the field unrelated to the study. Dr. Weber declared no relevant disclosures.

GHENT, BELGIUM – Over 10% of patients referred by chiropractors to rheumatology had undiagnosed spondyloarthritis, with axial spondyloarthritis being the most common, according to new data. The U.S. study was aimed at understanding what proportion of back pain patients have undiagnosed spondyloarthritis.

The study also found that the most common cause for which patients see chiropractors is neck/cervical pain.

Atul Deodhar, MD, MRCP, rheumatologist and medical director of rheumatology clinics at Oregon Health & Science University, Portland, was senior author of the poster that was presented at the 13th International Congress of Spondyloarthritides.

“In the U.S., many people with back pain go to chiropractors, but many chiropractors are not aware of axial spondyloarthritis [axSpA] terminology, and very little – if anything – is published in chiropractic literature, “ he said in an interview.

He remarked that the study highlighted the need to develop a better strategy to identify undiagnosed patients, because the yield found in their study was poor (13%). “Patient-reported spondyloarthritis criteria are often poor, and do not match rheumatologist-inquired history,” he noted, adding that, “inflammatory back pain is in fact a poor ‘entry point.’ ”

Ulrich Weber, MD, rheumatologist from the Practice Buchsbaum in Schaffhausen, Switzerland, commented on the findings, saying he often receives delayed referrals from chiropractors, so “it would be very useful if patients could be more easily and accurately identifiable via this route, but the problem is chiropractors do not have a specific training to spot spondyloarthritis.”

He added that he welcomed the study but noted, “the criteria used to identify patients in this study are broad and I’d worry that it would inundate our rheumatology practice. There remains a real need for a good method of identifying the patients.”
 

Referral to rheumatology

Back pain is highly prevalent in the general population, with a global mean lifetime prevalence of 38.9%. Chiropractors treat many patients with back pain of unknown cause.

“In this study, we wanted to see what percentage of patients in chiropractic practice have undiagnosed axial spondyloarthritis, and what are the common complaints. Our hypothesis was that chiropractors may be missing such patients,” Dr. Deodhar explained.

Dr. Deodhar and colleagues recruited chiropractors from four different parts of the city of Portland into the study. “We think Portland, Oregon, is a typical U.S. city, and our results could be generalized. However, this is our impression alone,” he remarked.

Adults, under the age of 45 years who attended a participating chiropractic clinics between November 2020 and November 2021 for chronic back pain and without a prior diagnosis of spondyloarthritis were eligible for inclusion.

If the patient reported at least one feature of spondyloarthritis in the screening questionnaire they were referred to a rheumatologist for a diagnostic assessment. This assessment involved taking history by telephone, both laboratory tests and imaging, and the patients were categorized as radiographic axSpA, nonradiographic axSpA, peripheral SpA, or no SpA.

The screening questionnaire included the following examples: If the patient was under 45 years and had chronic pain in back, hip or buttocks, then they were asked for more information including whether their pain was gradual (insidious) in onset; if the pain started before the age of 40; and if the pain improved with physical activities or movements. Use of drugs was investigated including whether the pain improved significantly with NSAIDs and whether the patient has current or past heel pains, particularly when waking up in the morning. They were also asked if they have experienced skin psoriasis. Other questions were asked about the presence of uveitis, iritis, family history of psoriasis, inflammatory bowel disease, or ankylosing spondylitis, and whether the patient had unexplained joint pains plus joint swelling.
 

Ten percent of patients referred to rheumatology

A total of 3,103 visits to chiropractor clinics were included, of which 115 patients were referred to a rheumatologist. Eventually, 63 patients were fully assessed by a rheumatologist.

Of those patients who were fully assessed, 12.7% has spondyloarthritis, with one having confirmed radiographic axSpA, five having nonradiographic SpA, and two having peripheral spondyloarthritis or psoriatic arthritis.

Based on the referral questionnaire, all patients reported at least four SpA criteria were met, said Dr. Deodhar.

Of those patients diagnosed with SpA, 14% (1) has elevated C-reactive protein (CRP) level, 14% (1) were HLA-B27 positive, and 14% (1) were identified as having both elevated CRP and HLA-B27 positivity. Sacroiliac joint inflammation was found in 14% (1) on MRI and one had sacroiliac joint inflammation according to modified New York criteria. One (14%) had both sacroiliac joint inflammation on MRI and elevated CRP, and 14% (1) had both sacroiliac joint inflammation and was HLA-B27 positive.

The top complaints reported by patients at chiropractor clinics were neck and cervical spine pain/spasm (16.8%); followed by acute low back pain (11.7%); acute upper back (7.1%); and chronic lower back pain (6.9%).
 

No patients with more than 10 SpA criteria

The performance of an initial diagnostic assessment based on patient reported SpA criteria, as compared with the outcome of the full diagnosis (by a rheumatologist) showed that patients with one to four SpA criteria had a sensitivity of 0.50 (95% confidence interval, 0.15-0.85), and specificity of 0.73 (95% CI, 0.61-0.84). This increased to sensitivity of 0.60 (95% CI, 0.17-1.03), and specificity of 0.61 (95% CI, 0.44-0.77) when six SpA criteria were present.

Dr. Deodhar said the results supported a need to further develop the chiropractor’s role in identifying the right patients for referral, and that the study showed that a referral strategy is required to find undiagnosed patients with spondyloarthritis from chiropractic offices. “Chiropractors need education for axSpA, when to suspect, and when to refer,” he asserted. “What referral strategy to use is for debate – the ASAS [Assessment in SpondyloArthritis international Society] strategy is too sensitive and not specific enough.”

Dr. Deodhar noted that SPARTAN (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis and the Spondyloarthritis Research & Treatment Network) is working on a referral strategy that is likely to be more specific, and that more data would be forthcoming soon.

Dr. Deodhar declared affiliations with multiple companies involved in the field unrelated to the study. Dr. Weber declared no relevant disclosures.

GHENT, BELGIUM – The Ankylosing Spondylitis Disease Activity Score (ASDAS) should be the preferred tool for disease activity assessment in patients with axial spondyloarthritis (axSpA) because it is not influenced by gender, according to new data on gender and patient outcomes as assessed by commonly used scoring methods and indices across the spectrum of SpA disease subtypes.

In contrast, researchers led by Diego Benavent, MD, a rheumatologist at La Paz University Hospital, Madrid, found that gender influenced the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in all three disease subtypes: axSpA, peripheral SpA (pSpA), and psoriatic arthritis (PsA).

In addition, data show that women with axSpA, pSpA, or PsA reported higher disease activity, functional limitation, and poorer overall health.

Dr. Benavent presented the results at the 13th International Congress on Spondyloarthritides. The study was also published online Sept. 12 in RMD Open.

“The ASDAS is more likely to be the activity score used because we are reassured that it performs well in both men and women. However, there is a need for more appropriate validated indices that are not affected by gender in peripheral spondyloarthropathies and psoriatic arthritis,” Dr. Benavent said.

So far, most data concerning gender differences have been described in patients with axSpA, and with various measurement instruments available to assess disease activity, function, and overall health. Dr. Benavent and his colleagues wanted to investigate the influence of gender on disease outcomes across not only axSpA but pSpA and PsA, too, to see if there were differences in the relationship between gender and these other disease subtypes.

In previous studies, ASDAS has shown better psychometric properties than the BASDAI for disease activity in axSpA. “But there is little validation in pSpA and PsA, and the influence of gender in the outcomes assessed by these instruments is unknown.

“Compared with men, women with an axSpA diagnosis tend to have more frequent peripheral and extramusculoskeletal manifestations, such as enthesitis and inflammatory bowel disease,” Dr. Benavent said in an interview. “However, males with axSpA present more radiographic damage and objective signs of inflammation.”

Martin Rudwaleit, MD, head of the department of internal medicine and rheumatology at Klinikum Bielefeld (Germany), who attended the talk, reflected on the findings.

“Decades ago, ankylosing spondylitis was largely considered a male disease as found in 80%-90% of cases. Later, with MRI, we started to diagnose patients earlier and learned that more females have the disease and that females have less structural damage in the spine than men. As such, male gender is a predictor for worse radiographic progression,” Dr. Rudwaleit said.

“The question is whether the female patients who are considered to have axSpA really have axSpA, or do they have other origins of their back pain?” he continued.

“Also, this study shows us that females report a wider spectrum of symptoms than males. For example, headache, general discomfort, and overall, a broader spectrum of symptoms than men. This might have contributed to the fact that, previously, diagnoses of axSpA might have been made later in females than males.”

Large study across SpA phenotypes and disease-scoring methods

A total of 4,185 patients from 24 countries participated, with 65% having axSpA, 10% pSpA, and 25% PsA. Females totaled 38.8% of patients across all three types of spondyloarthritis. The researchers drew the data from the Assessment of SpondyloArthritis International Society (ASAS)-perSpA study.

The researchers looked for associations between gender and disease activity as measured by ASDAS and BASDAI, C-reactive protein (CRP), physical function with the Bath Ankylosing Spondylitis Functional Index (BASFI), overall health with the ASAS Health Index (ASAS HI), and European Quality of Life Five Dimensions (EQ-5D) outcomes.

In axSpA, there was a split of 68% men vs. 32% women. The researchers observed certain factors that were more common among men: smoking (49% vs. 32%), HLA-B27 positivity (83% vs. 70%), and elevated CRP (75% vs. 66%). Women more often had enthesitis (45% vs. 39%) and fibromyalgia (17% vs. 3%).

In pSpA, the gender split was approximately equal at 47% men and 53% women. But compared with women, men had more inflammatory back pain (62% vs. 50%), HLA-B27 positivity (70% vs. 54%), and elevated CRP (75% vs. 66%). Women more frequently had inflammatory bowel disease (IBD, 8% vs. 3%) and fibromyalgia (18% vs. 3%).

An approximately equal gender split was also found with PsA (48.5% men vs. 51.5% women). Men more frequently reported ever drinking alcohol than did women (63% vs. 26%), whereas women had a greater family history of both spondyloarthritis (41% vs. 32%) and psoriasis (41% vs. 31%). Women also more often reported enthesitis (49% vs. 42%) and fibromyalgia (19% vs. 3%) than men.

“These data strongly suggest that female patients showed significantly more fibromyalgia across all disease subtypes, and the magnitude of the difference with men is notable,” Dr. Benavent said.”Fibromyalgia is associated with pain and worse patient-reported outcomes, which may bias outcomes with disease activity scores.”

When the researchers analyzed outcomes by the different scores and indices for each disease subtype, they found that females had worse scores for most indices (ASDAS, BASDAI, patient’s global assessment (PtGA), BASFI, ASAS HI, and EQ-5D). “However, for CRP, men presented worse scores across axSpA and pSpA, and no differences were found with women in PsA,” Dr. Benavent added.

Although there are differences between the genders according to the scores, these differences may be confounded and this will affect the score outcome: for example, confounding by fibromyalgia in women, he explained.

To avoid the confounding effect, multivariable regression models were used, including the dependent variable as the explored outcome: for example, with BASDAI or ASDAS serving as the dependent variable and gender as the main independent variable, along with adjustments for potential confounders. When the influence of gender on BASDAI was considered, Dr. Benavent and colleagues found that being female increased all scores across the spectrum: axSpA (0.39 units; 95%  confidence interval, 0.2-0.58), pSpA (1.22 units; 95%  CI, 0.77-1.69), and PsA (0.88 units; 95%  CI, 0.59-1.19). When the influence of gender on ASDAS was considered, the researchers found that being female had no effect on axSpA (0.02 units; 95%  CI, –0.07 to 0.11), but did for pSpA (0.36 units; 95%  CI, 0.15-0.58) and PsA (0.25 units; 95%  CI, 0.12-0.38).

“ASDAS is better than BASDAI because it is similar in males and females, but this only holds true in axSpA, not in pSpA or PsA,” Dr. Benavent concluded.

Dr. Benavent declared serving on speakers bureaus for Janssen, Galapagos, and AbbVie, and receiving grant or research support from Novartis outside the submitted work. Dr. Rudwaleit declared financial relationships with AbbVie, UCB, and Lilly.

GHENT, BELGIUM – The Ankylosing Spondylitis Disease Activity Score (ASDAS) should be the preferred tool for disease activity assessment in patients with axial spondyloarthritis (axSpA) because it is not influenced by gender, according to new data on gender and patient outcomes as assessed by commonly used scoring methods and indices across the spectrum of SpA disease subtypes.

In contrast, researchers led by Diego Benavent, MD, a rheumatologist at La Paz University Hospital, Madrid, found that gender influenced the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in all three disease subtypes: axSpA, peripheral SpA (pSpA), and psoriatic arthritis (PsA).

In addition, data show that women with axSpA, pSpA, or PsA reported higher disease activity, functional limitation, and poorer overall health.

Dr. Benavent presented the results at the 13th International Congress on Spondyloarthritides. The study was also published online Sept. 12 in RMD Open.

“The ASDAS is more likely to be the activity score used because we are reassured that it performs well in both men and women. However, there is a need for more appropriate validated indices that are not affected by gender in peripheral spondyloarthropathies and psoriatic arthritis,” Dr. Benavent said.

So far, most data concerning gender differences have been described in patients with axSpA, and with various measurement instruments available to assess disease activity, function, and overall health. Dr. Benavent and his colleagues wanted to investigate the influence of gender on disease outcomes across not only axSpA but pSpA and PsA, too, to see if there were differences in the relationship between gender and these other disease subtypes.

In previous studies, ASDAS has shown better psychometric properties than the BASDAI for disease activity in axSpA. “But there is little validation in pSpA and PsA, and the influence of gender in the outcomes assessed by these instruments is unknown.

“Compared with men, women with an axSpA diagnosis tend to have more frequent peripheral and extramusculoskeletal manifestations, such as enthesitis and inflammatory bowel disease,” Dr. Benavent said in an interview. “However, males with axSpA present more radiographic damage and objective signs of inflammation.”

Martin Rudwaleit, MD, head of the department of internal medicine and rheumatology at Klinikum Bielefeld (Germany), who attended the talk, reflected on the findings.

“Decades ago, ankylosing spondylitis was largely considered a male disease as found in 80%-90% of cases. Later, with MRI, we started to diagnose patients earlier and learned that more females have the disease and that females have less structural damage in the spine than men. As such, male gender is a predictor for worse radiographic progression,” Dr. Rudwaleit said.

“The question is whether the female patients who are considered to have axSpA really have axSpA, or do they have other origins of their back pain?” he continued.

“Also, this study shows us that females report a wider spectrum of symptoms than males. For example, headache, general discomfort, and overall, a broader spectrum of symptoms than men. This might have contributed to the fact that, previously, diagnoses of axSpA might have been made later in females than males.”

Large study across SpA phenotypes and disease-scoring methods

A total of 4,185 patients from 24 countries participated, with 65% having axSpA, 10% pSpA, and 25% PsA. Females totaled 38.8% of patients across all three types of spondyloarthritis. The researchers drew the data from the Assessment of SpondyloArthritis International Society (ASAS)-perSpA study.

The researchers looked for associations between gender and disease activity as measured by ASDAS and BASDAI, C-reactive protein (CRP), physical function with the Bath Ankylosing Spondylitis Functional Index (BASFI), overall health with the ASAS Health Index (ASAS HI), and European Quality of Life Five Dimensions (EQ-5D) outcomes.

In axSpA, there was a split of 68% men vs. 32% women. The researchers observed certain factors that were more common among men: smoking (49% vs. 32%), HLA-B27 positivity (83% vs. 70%), and elevated CRP (75% vs. 66%). Women more often had enthesitis (45% vs. 39%) and fibromyalgia (17% vs. 3%).

In pSpA, the gender split was approximately equal at 47% men and 53% women. But compared with women, men had more inflammatory back pain (62% vs. 50%), HLA-B27 positivity (70% vs. 54%), and elevated CRP (75% vs. 66%). Women more frequently had inflammatory bowel disease (IBD, 8% vs. 3%) and fibromyalgia (18% vs. 3%).

An approximately equal gender split was also found with PsA (48.5% men vs. 51.5% women). Men more frequently reported ever drinking alcohol than did women (63% vs. 26%), whereas women had a greater family history of both spondyloarthritis (41% vs. 32%) and psoriasis (41% vs. 31%). Women also more often reported enthesitis (49% vs. 42%) and fibromyalgia (19% vs. 3%) than men.

“These data strongly suggest that female patients showed significantly more fibromyalgia across all disease subtypes, and the magnitude of the difference with men is notable,” Dr. Benavent said.”Fibromyalgia is associated with pain and worse patient-reported outcomes, which may bias outcomes with disease activity scores.”

When the researchers analyzed outcomes by the different scores and indices for each disease subtype, they found that females had worse scores for most indices (ASDAS, BASDAI, patient’s global assessment (PtGA), BASFI, ASAS HI, and EQ-5D). “However, for CRP, men presented worse scores across axSpA and pSpA, and no differences were found with women in PsA,” Dr. Benavent added.

Although there are differences between the genders according to the scores, these differences may be confounded and this will affect the score outcome: for example, confounding by fibromyalgia in women, he explained.

To avoid the confounding effect, multivariable regression models were used, including the dependent variable as the explored outcome: for example, with BASDAI or ASDAS serving as the dependent variable and gender as the main independent variable, along with adjustments for potential confounders. When the influence of gender on BASDAI was considered, Dr. Benavent and colleagues found that being female increased all scores across the spectrum: axSpA (0.39 units; 95%  confidence interval, 0.2-0.58), pSpA (1.22 units; 95%  CI, 0.77-1.69), and PsA (0.88 units; 95%  CI, 0.59-1.19). When the influence of gender on ASDAS was considered, the researchers found that being female had no effect on axSpA (0.02 units; 95%  CI, –0.07 to 0.11), but did for pSpA (0.36 units; 95%  CI, 0.15-0.58) and PsA (0.25 units; 95%  CI, 0.12-0.38).

“ASDAS is better than BASDAI because it is similar in males and females, but this only holds true in axSpA, not in pSpA or PsA,” Dr. Benavent concluded.

Dr. Benavent declared serving on speakers bureaus for Janssen, Galapagos, and AbbVie, and receiving grant or research support from Novartis outside the submitted work. Dr. Rudwaleit declared financial relationships with AbbVie, UCB, and Lilly.

GHENT, BELGIUM – The Ankylosing Spondylitis Disease Activity Score (ASDAS) should be the preferred tool for disease activity assessment in patients with axial spondyloarthritis (axSpA) because it is not influenced by gender, according to new data on gender and patient outcomes as assessed by commonly used scoring methods and indices across the spectrum of SpA disease subtypes.

In contrast, researchers led by Diego Benavent, MD, a rheumatologist at La Paz University Hospital, Madrid, found that gender influenced the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in all three disease subtypes: axSpA, peripheral SpA (pSpA), and psoriatic arthritis (PsA).

In addition, data show that women with axSpA, pSpA, or PsA reported higher disease activity, functional limitation, and poorer overall health.

Dr. Benavent presented the results at the 13th International Congress on Spondyloarthritides. The study was also published online Sept. 12 in RMD Open.

“The ASDAS is more likely to be the activity score used because we are reassured that it performs well in both men and women. However, there is a need for more appropriate validated indices that are not affected by gender in peripheral spondyloarthropathies and psoriatic arthritis,” Dr. Benavent said.

So far, most data concerning gender differences have been described in patients with axSpA, and with various measurement instruments available to assess disease activity, function, and overall health. Dr. Benavent and his colleagues wanted to investigate the influence of gender on disease outcomes across not only axSpA but pSpA and PsA, too, to see if there were differences in the relationship between gender and these other disease subtypes.

In previous studies, ASDAS has shown better psychometric properties than the BASDAI for disease activity in axSpA. “But there is little validation in pSpA and PsA, and the influence of gender in the outcomes assessed by these instruments is unknown.

“Compared with men, women with an axSpA diagnosis tend to have more frequent peripheral and extramusculoskeletal manifestations, such as enthesitis and inflammatory bowel disease,” Dr. Benavent said in an interview. “However, males with axSpA present more radiographic damage and objective signs of inflammation.”

Martin Rudwaleit, MD, head of the department of internal medicine and rheumatology at Klinikum Bielefeld (Germany), who attended the talk, reflected on the findings.

“Decades ago, ankylosing spondylitis was largely considered a male disease as found in 80%-90% of cases. Later, with MRI, we started to diagnose patients earlier and learned that more females have the disease and that females have less structural damage in the spine than men. As such, male gender is a predictor for worse radiographic progression,” Dr. Rudwaleit said.

“The question is whether the female patients who are considered to have axSpA really have axSpA, or do they have other origins of their back pain?” he continued.

“Also, this study shows us that females report a wider spectrum of symptoms than males. For example, headache, general discomfort, and overall, a broader spectrum of symptoms than men. This might have contributed to the fact that, previously, diagnoses of axSpA might have been made later in females than males.”

Large study across SpA phenotypes and disease-scoring methods

A total of 4,185 patients from 24 countries participated, with 65% having axSpA, 10% pSpA, and 25% PsA. Females totaled 38.8% of patients across all three types of spondyloarthritis. The researchers drew the data from the Assessment of SpondyloArthritis International Society (ASAS)-perSpA study.

The researchers looked for associations between gender and disease activity as measured by ASDAS and BASDAI, C-reactive protein (CRP), physical function with the Bath Ankylosing Spondylitis Functional Index (BASFI), overall health with the ASAS Health Index (ASAS HI), and European Quality of Life Five Dimensions (EQ-5D) outcomes.

In axSpA, there was a split of 68% men vs. 32% women. The researchers observed certain factors that were more common among men: smoking (49% vs. 32%), HLA-B27 positivity (83% vs. 70%), and elevated CRP (75% vs. 66%). Women more often had enthesitis (45% vs. 39%) and fibromyalgia (17% vs. 3%).

In pSpA, the gender split was approximately equal at 47% men and 53% women. But compared with women, men had more inflammatory back pain (62% vs. 50%), HLA-B27 positivity (70% vs. 54%), and elevated CRP (75% vs. 66%). Women more frequently had inflammatory bowel disease (IBD, 8% vs. 3%) and fibromyalgia (18% vs. 3%).

An approximately equal gender split was also found with PsA (48.5% men vs. 51.5% women). Men more frequently reported ever drinking alcohol than did women (63% vs. 26%), whereas women had a greater family history of both spondyloarthritis (41% vs. 32%) and psoriasis (41% vs. 31%). Women also more often reported enthesitis (49% vs. 42%) and fibromyalgia (19% vs. 3%) than men.

“These data strongly suggest that female patients showed significantly more fibromyalgia across all disease subtypes, and the magnitude of the difference with men is notable,” Dr. Benavent said.”Fibromyalgia is associated with pain and worse patient-reported outcomes, which may bias outcomes with disease activity scores.”

When the researchers analyzed outcomes by the different scores and indices for each disease subtype, they found that females had worse scores for most indices (ASDAS, BASDAI, patient’s global assessment (PtGA), BASFI, ASAS HI, and EQ-5D). “However, for CRP, men presented worse scores across axSpA and pSpA, and no differences were found with women in PsA,” Dr. Benavent added.

Although there are differences between the genders according to the scores, these differences may be confounded and this will affect the score outcome: for example, confounding by fibromyalgia in women, he explained.

To avoid the confounding effect, multivariable regression models were used, including the dependent variable as the explored outcome: for example, with BASDAI or ASDAS serving as the dependent variable and gender as the main independent variable, along with adjustments for potential confounders. When the influence of gender on BASDAI was considered, Dr. Benavent and colleagues found that being female increased all scores across the spectrum: axSpA (0.39 units; 95%  confidence interval, 0.2-0.58), pSpA (1.22 units; 95%  CI, 0.77-1.69), and PsA (0.88 units; 95%  CI, 0.59-1.19). When the influence of gender on ASDAS was considered, the researchers found that being female had no effect on axSpA (0.02 units; 95%  CI, –0.07 to 0.11), but did for pSpA (0.36 units; 95%  CI, 0.15-0.58) and PsA (0.25 units; 95%  CI, 0.12-0.38).

“ASDAS is better than BASDAI because it is similar in males and females, but this only holds true in axSpA, not in pSpA or PsA,” Dr. Benavent concluded.

Dr. Benavent declared serving on speakers bureaus for Janssen, Galapagos, and AbbVie, and receiving grant or research support from Novartis outside the submitted work. Dr. Rudwaleit declared financial relationships with AbbVie, UCB, and Lilly.

GHENT, BELGIUM – Filgotinib (Jyseleca), a Janus kinase (JAK) inhibitor, reduced the risk of flare after withdrawal of glucocorticoids in patients with vision-threatening, noninfectious intermediate, posterior, or pan uveitis, data from a phase 2 study show.

Robin Besuyen, MD, clinical development leader in inflammatory diseases at Galapagos BV, Leiden, the Netherlands, presented the phase 2 results of the placebo-controlled HUMBOLDT trial at the 13th International Congress on Spondyloarthritides.

Treatment with filgotinib was well tolerated, with no new safety concerns for the immunosuppressed uveitis population.

Uveitis involves intraocular inflammation of the eye, accounts for 5%-20% of cases of blindness, and frequently requires long-term use of systemic therapy, mostly glucocorticoids or adalimumab (Humira).

Uveitis is documented to occur in 25%-40% of patients with spondyloarthritis, and its management is essential to prevent morbidity caused by vision loss and secondary complications. The majority of patients in HUMBOLDT had idiopathic uveitis (57%). One patient with spondyloarthritis was included.

Filgotinib is being investigated in the treatment of uveitis because Janus kinases have been found to play a role in the complex cytokine-signaling pathways implicated in immune-mediated diseases, including uveitis. “A preferential inhibitor of JAK 1 could play a role in managing this condition,” Dr. Besuyen said.

Session moderator Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany), reflected on what he said was an “important study,” which, to his knowledge, was the first study of its kind in uveitis.

“The fact that they showed a significant decrease in uveitis in such a short period of time is very positive, especially for the uveitis we know of in spondyloarthritides,” he said in an interview. “The posterior uveitis was significantly impacted, and this is a very positive signal to move forward with further JAK studies in uveitis and apply them in patients with active uveitis and spondyloarthritis.”

With respect to patients with spondyloarthritis, he pointed out that, “if uveitis is fluctuating [in patients with spondyloarthritis] then patients can lose their vision. Uveitis is one of the most frequent extraskeletal manifestations of spondyloarthritis.”

However, he noted that the researchers did not show any correlation to HLA-B27 [human leukocyte antigen B27], which is “something we consider when we discuss uveitis in spondyloarthritides, but these data are convincing.”

 

Phase 2, randomized, double-blind trial – one of very few in uveitis

Participants in the randomized, double-blind trial were at least 18 years old and had intermediate, posterior, or pan uveitis that was active despite 2 weeks of treatment with glucocorticoids (oral prednisolone 10-60 mg/day). They were randomized 1:1 to filgotinib (200 mg once daily) or placebo and were assessed for evidence of treatment failure from week 6 onwards. Glucocorticoids in all participants were tapered off over 15 weeks.

The primary endpoint was the proportion of participants with treatment failure by week 24, defined as new, active, inflammatory chorioretinal and/or retinal vascular lesions at week 6 or later; worsening of best corrected visual acuity by 15 or more letters; or inability to achieve an anterior chamber cell or vitreous haze grade less than or equal to 0.5+ at week 6 or a 2-step grade increase after week 6. These effects had to be present in at least one eye.

Patients were stratified by the presence of sarcoidosis-related uveitis, baseline use of immunosuppressants, and prior use of anti–tumor necrosis factor (TNF) therapy. The mean patient age was 46 years, and around 60% were female, 57% had pan uveitis, and 22% had posterior uveitis. The mean number of uveitis flares in the previous 12 months was two.

A total of 37 patients received filgotinib and 35 received placebo, and together they composed the safety analysis set. Of these, 32 on filgotinib and 34 on placebo continued treatment to week 6, so 66 patients entered the efficacy analysis. 

The study sponsor, Gilead, decided to stop the trial early for business reasons after the U.S. Food and Drug Administration rejected its application for filgotinib in the treatment of rheumatoid arthritis, and only 74 patients of the originally planned 248 participants were randomized. “Therefore, the conclusions that have been drawn from the study are limited, and results should be interpreted with caution,” Dr. Besuyen noted.
 

Primary endpoint of treatment failure favored filgotinib

The primary endpoint of treatment failure was met by 12 (38%) of 32 patients taking filgotinib and 23 (67%) of 34 patients taking placebo, generating an odds ratio of 0.23 favoring filgotinib, which was statistically significant (P = .008), Dr. Besuyen reported.

The median time to treatment failure on or after week 6, one of the trial’s secondary endpoints, was 22 weeks for placebo but could not be calculated for filgotinib because fewer than half of these patients failed treatment with filgotinib.

Filgotinib was safe and well tolerated, and the safety profile emerging from this study was similar to that seen in the indications for which it is marketed in the European Union, United Kingdom, and Japan (rheumatoid arthritis and ulcerative colitis). There were no deaths, no major adverse cardiovascular events, no malignancies, and no opportunistic infections. Treatment-emergent serious adverse events were seen in 13.5% with filgotinib and 5.7% with placebo.

Gilead Sciences and Galapagos NV sponsored and collaborated on the trial. Dr. Besuyen is an employee of Galapagos NV. Dr. Baraliakos has declared no relevant financial conflicts of interest.
 

GHENT, BELGIUM – Filgotinib (Jyseleca), a Janus kinase (JAK) inhibitor, reduced the risk of flare after withdrawal of glucocorticoids in patients with vision-threatening, noninfectious intermediate, posterior, or pan uveitis, data from a phase 2 study show.

Robin Besuyen, MD, clinical development leader in inflammatory diseases at Galapagos BV, Leiden, the Netherlands, presented the phase 2 results of the placebo-controlled HUMBOLDT trial at the 13th International Congress on Spondyloarthritides.

Treatment with filgotinib was well tolerated, with no new safety concerns for the immunosuppressed uveitis population.

Uveitis involves intraocular inflammation of the eye, accounts for 5%-20% of cases of blindness, and frequently requires long-term use of systemic therapy, mostly glucocorticoids or adalimumab (Humira).

Uveitis is documented to occur in 25%-40% of patients with spondyloarthritis, and its management is essential to prevent morbidity caused by vision loss and secondary complications. The majority of patients in HUMBOLDT had idiopathic uveitis (57%). One patient with spondyloarthritis was included.

Filgotinib is being investigated in the treatment of uveitis because Janus kinases have been found to play a role in the complex cytokine-signaling pathways implicated in immune-mediated diseases, including uveitis. “A preferential inhibitor of JAK 1 could play a role in managing this condition,” Dr. Besuyen said.

Session moderator Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany), reflected on what he said was an “important study,” which, to his knowledge, was the first study of its kind in uveitis.

“The fact that they showed a significant decrease in uveitis in such a short period of time is very positive, especially for the uveitis we know of in spondyloarthritides,” he said in an interview. “The posterior uveitis was significantly impacted, and this is a very positive signal to move forward with further JAK studies in uveitis and apply them in patients with active uveitis and spondyloarthritis.”

With respect to patients with spondyloarthritis, he pointed out that, “if uveitis is fluctuating [in patients with spondyloarthritis] then patients can lose their vision. Uveitis is one of the most frequent extraskeletal manifestations of spondyloarthritis.”

However, he noted that the researchers did not show any correlation to HLA-B27 [human leukocyte antigen B27], which is “something we consider when we discuss uveitis in spondyloarthritides, but these data are convincing.”

 

Phase 2, randomized, double-blind trial – one of very few in uveitis

Participants in the randomized, double-blind trial were at least 18 years old and had intermediate, posterior, or pan uveitis that was active despite 2 weeks of treatment with glucocorticoids (oral prednisolone 10-60 mg/day). They were randomized 1:1 to filgotinib (200 mg once daily) or placebo and were assessed for evidence of treatment failure from week 6 onwards. Glucocorticoids in all participants were tapered off over 15 weeks.

The primary endpoint was the proportion of participants with treatment failure by week 24, defined as new, active, inflammatory chorioretinal and/or retinal vascular lesions at week 6 or later; worsening of best corrected visual acuity by 15 or more letters; or inability to achieve an anterior chamber cell or vitreous haze grade less than or equal to 0.5+ at week 6 or a 2-step grade increase after week 6. These effects had to be present in at least one eye.

Patients were stratified by the presence of sarcoidosis-related uveitis, baseline use of immunosuppressants, and prior use of anti–tumor necrosis factor (TNF) therapy. The mean patient age was 46 years, and around 60% were female, 57% had pan uveitis, and 22% had posterior uveitis. The mean number of uveitis flares in the previous 12 months was two.

A total of 37 patients received filgotinib and 35 received placebo, and together they composed the safety analysis set. Of these, 32 on filgotinib and 34 on placebo continued treatment to week 6, so 66 patients entered the efficacy analysis. 

The study sponsor, Gilead, decided to stop the trial early for business reasons after the U.S. Food and Drug Administration rejected its application for filgotinib in the treatment of rheumatoid arthritis, and only 74 patients of the originally planned 248 participants were randomized. “Therefore, the conclusions that have been drawn from the study are limited, and results should be interpreted with caution,” Dr. Besuyen noted.
 

Primary endpoint of treatment failure favored filgotinib

The primary endpoint of treatment failure was met by 12 (38%) of 32 patients taking filgotinib and 23 (67%) of 34 patients taking placebo, generating an odds ratio of 0.23 favoring filgotinib, which was statistically significant (P = .008), Dr. Besuyen reported.

The median time to treatment failure on or after week 6, one of the trial’s secondary endpoints, was 22 weeks for placebo but could not be calculated for filgotinib because fewer than half of these patients failed treatment with filgotinib.

Filgotinib was safe and well tolerated, and the safety profile emerging from this study was similar to that seen in the indications for which it is marketed in the European Union, United Kingdom, and Japan (rheumatoid arthritis and ulcerative colitis). There were no deaths, no major adverse cardiovascular events, no malignancies, and no opportunistic infections. Treatment-emergent serious adverse events were seen in 13.5% with filgotinib and 5.7% with placebo.

Gilead Sciences and Galapagos NV sponsored and collaborated on the trial. Dr. Besuyen is an employee of Galapagos NV. Dr. Baraliakos has declared no relevant financial conflicts of interest.
 

GHENT, BELGIUM – Filgotinib (Jyseleca), a Janus kinase (JAK) inhibitor, reduced the risk of flare after withdrawal of glucocorticoids in patients with vision-threatening, noninfectious intermediate, posterior, or pan uveitis, data from a phase 2 study show.

Robin Besuyen, MD, clinical development leader in inflammatory diseases at Galapagos BV, Leiden, the Netherlands, presented the phase 2 results of the placebo-controlled HUMBOLDT trial at the 13th International Congress on Spondyloarthritides.

Treatment with filgotinib was well tolerated, with no new safety concerns for the immunosuppressed uveitis population.

Uveitis involves intraocular inflammation of the eye, accounts for 5%-20% of cases of blindness, and frequently requires long-term use of systemic therapy, mostly glucocorticoids or adalimumab (Humira).

Uveitis is documented to occur in 25%-40% of patients with spondyloarthritis, and its management is essential to prevent morbidity caused by vision loss and secondary complications. The majority of patients in HUMBOLDT had idiopathic uveitis (57%). One patient with spondyloarthritis was included.

Filgotinib is being investigated in the treatment of uveitis because Janus kinases have been found to play a role in the complex cytokine-signaling pathways implicated in immune-mediated diseases, including uveitis. “A preferential inhibitor of JAK 1 could play a role in managing this condition,” Dr. Besuyen said.

Session moderator Xenofon Baraliakos, MD, professor of internal medicine and rheumatology at Ruhr University Bochum (Germany), reflected on what he said was an “important study,” which, to his knowledge, was the first study of its kind in uveitis.

“The fact that they showed a significant decrease in uveitis in such a short period of time is very positive, especially for the uveitis we know of in spondyloarthritides,” he said in an interview. “The posterior uveitis was significantly impacted, and this is a very positive signal to move forward with further JAK studies in uveitis and apply them in patients with active uveitis and spondyloarthritis.”

With respect to patients with spondyloarthritis, he pointed out that, “if uveitis is fluctuating [in patients with spondyloarthritis] then patients can lose their vision. Uveitis is one of the most frequent extraskeletal manifestations of spondyloarthritis.”

However, he noted that the researchers did not show any correlation to HLA-B27 [human leukocyte antigen B27], which is “something we consider when we discuss uveitis in spondyloarthritides, but these data are convincing.”

 

Phase 2, randomized, double-blind trial – one of very few in uveitis

Participants in the randomized, double-blind trial were at least 18 years old and had intermediate, posterior, or pan uveitis that was active despite 2 weeks of treatment with glucocorticoids (oral prednisolone 10-60 mg/day). They were randomized 1:1 to filgotinib (200 mg once daily) or placebo and were assessed for evidence of treatment failure from week 6 onwards. Glucocorticoids in all participants were tapered off over 15 weeks.

The primary endpoint was the proportion of participants with treatment failure by week 24, defined as new, active, inflammatory chorioretinal and/or retinal vascular lesions at week 6 or later; worsening of best corrected visual acuity by 15 or more letters; or inability to achieve an anterior chamber cell or vitreous haze grade less than or equal to 0.5+ at week 6 or a 2-step grade increase after week 6. These effects had to be present in at least one eye.

Patients were stratified by the presence of sarcoidosis-related uveitis, baseline use of immunosuppressants, and prior use of anti–tumor necrosis factor (TNF) therapy. The mean patient age was 46 years, and around 60% were female, 57% had pan uveitis, and 22% had posterior uveitis. The mean number of uveitis flares in the previous 12 months was two.

A total of 37 patients received filgotinib and 35 received placebo, and together they composed the safety analysis set. Of these, 32 on filgotinib and 34 on placebo continued treatment to week 6, so 66 patients entered the efficacy analysis. 

The study sponsor, Gilead, decided to stop the trial early for business reasons after the U.S. Food and Drug Administration rejected its application for filgotinib in the treatment of rheumatoid arthritis, and only 74 patients of the originally planned 248 participants were randomized. “Therefore, the conclusions that have been drawn from the study are limited, and results should be interpreted with caution,” Dr. Besuyen noted.
 

Primary endpoint of treatment failure favored filgotinib

The primary endpoint of treatment failure was met by 12 (38%) of 32 patients taking filgotinib and 23 (67%) of 34 patients taking placebo, generating an odds ratio of 0.23 favoring filgotinib, which was statistically significant (P = .008), Dr. Besuyen reported.

The median time to treatment failure on or after week 6, one of the trial’s secondary endpoints, was 22 weeks for placebo but could not be calculated for filgotinib because fewer than half of these patients failed treatment with filgotinib.

Filgotinib was safe and well tolerated, and the safety profile emerging from this study was similar to that seen in the indications for which it is marketed in the European Union, United Kingdom, and Japan (rheumatoid arthritis and ulcerative colitis). There were no deaths, no major adverse cardiovascular events, no malignancies, and no opportunistic infections. Treatment-emergent serious adverse events were seen in 13.5% with filgotinib and 5.7% with placebo.

Gilead Sciences and Galapagos NV sponsored and collaborated on the trial. Dr. Besuyen is an employee of Galapagos NV. Dr. Baraliakos has declared no relevant financial conflicts of interest.
 

GHENT, BELGIUM – A strong numerical signal suggests the addition of a selective cyclooxygenase-2 (COX-2) inhibitor to a tumor necrosis factor (TNF) inhibitor can reduce spinal radiographic progression in patients with active radiographic axial spondyloarthritis (axSpA) over 2 years, although results are not statistically significant.

Becky McCall/MDedge News

Lead researcher and rheumatologist, Fabian Proft, MD, based at Charité University Medicine, Berlin, presented the findings of the study at the 13th International Congress on Spondyloarthritides.

Only 97 patients completed the study, and its follow-up period lasted 2 years, which is a relatively short period of time in which to determine the effects of an intervention that might affect structural progression of the spine, Dr. Proft said.

“Based on these data, I won’t treat all my patients with celecoxib,” he told this news organization. However, he added that, “If I have a patient with residual symptoms under biological DMARDs [disease-modifying antirheumatic drugs], and I feel they are at high risk of radiographic spinal progression and they still have symptoms, then I would add in an NSAID – and for that I’d choose a selective COX-2 inhibitor based on radiographic spinal progression data.”

Walter P. Maksymowych, MD, rheumatologist from the University of Alberta, Calgary, commented on the study findings in an interview. “This is an important clinical question because we want to know whether we should be adding an anti-inflammatory in patients who are on biologic therapies. There’s been a long debate and investigation into whether anti-inflammatories might prevent new bone formation and thereby prevent disease progression.”

He went on by acknowledging that there was no statistically significant difference in the primary endpoint (change in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]) between the groups, but added that, “there was a sizable numerical difference, and I think this leaves the community somewhat hanging dry without a definitive answer. However, I do have concerns about whether there was an adequate sample size to address the study question.”
 

To add or not to add a selective COX-2 inhibitor to TNF inhibitor in axSpA treatment

The study aimed to investigate the effect of a selective COX-2 inhibitor when added to anti-TNF therapy with golimumab (Simponi), compared with golimumab therapy alone, on the progression of spinal structural damage over 2 years in patients with active radiographic axSpA.

“To date, we don’t have many treatments with evidence of reducing spinal radiographic progression in axSpA,” Dr. Proft said. “There was one study showing an effect of celecoxib, but another with diclofenac that failed to show any effect. As a result, there was a hypothesis that perhaps there was a selective COX-2 inhibitor effect.”

To investigate this further, Dr. Proft selected patients with high radiographic axSpA disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4) and with existing structural changes – both recognized risk factors for further progression. Participants had to have either an elevated C-reactive protein (CRP) > 5 mg/L and/or ≥ 1 syndesmophyte at screening, as well as a history of inadequate response to at least two DMARDs. Other patient risk factors for radiographic spinal progression included male gender and smoking. Duration of axSpA was unlimited.

Three radiographic readers were blinded for all clinical data and chronology. The primary endpoint was the change in mSASSS, while secondary endpoints were the presence of new syndesmophytes and clinical outcomes including activity, function, mobility, and health-related quality of life, as well as safety assessments.

Patients were treated with only golimumab (50 mg subcutaneous every 4 weeks) for the first 12 weeks and then only those patients with a good clinical response (n = 109) went into phase two of the study, at which point they were randomized 1:1 to golimumab monotherapy (control, 50 mg subcutaneous every 4 weeks), or golimumab (50 mg subcutaneous every 4 weeks) plus celecoxib (400 mg once daily) for 2 years. Radiographs were taken at baseline (week 0) and after 2 years. A total of 45 patients completed the combination therapy and 52 completed the monotherapy.
 

No statistical significance but a numerical difference found

“The primary outcome, which was change in mSASSS score, clearly shows a numerical difference between the combination arm at 1.1 and the monotherapy arm at 1.7 points, showing more structural progression in the monotherapy arm, compared to the combination arm,” Dr. Proft reported. However, he stressed that this difference did not reach statistical significance.

New syndesmophytes occurred in 25% with monotherapy and 11.1% with combination treatment. Again, this difference did not reach statistical significance.

“This might be due to sample size but also to the length of follow-up because a longer follow-up [given structural changes occur relatively slowly] might have shown a greater difference,” Dr. Proft pointed out.

Clinical data, according to Ankylosing Spondylitis Disease Activity Score with CRP and BASDAI, showed that both groups responded very well to therapy, and there were no differences seen between the two groups in terms of clinical parameters.

“It is important when we add a drug – and we know that NSAIDs can have safety concerns – that we do not see any statistically significant serious adverse events between patient groups,” Dr. Proft noted.

There were no significant differences in adverse events between monotherapy and combination therapy. There were 162 infections in the combination arm and 150 in the monotherapy arm. Combination therapy led to seven serious adverse events, and monotherapy occurred with five adverse events.

Dr. Proft added that four patients discontinued in the combination arm, compared with only one in the monotherapy arm, with a variety of different reasons for the discontinuations.

The study was supported by a grant from the German Ministry of Education and Research, and golimumab was provided free of charge by Merck Sharp & Dohme. Dr. Proft reported serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; serving as a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly. Dr. Maksymowych declared having no relevant conflicts of interest.

GHENT, BELGIUM – A strong numerical signal suggests the addition of a selective cyclooxygenase-2 (COX-2) inhibitor to a tumor necrosis factor (TNF) inhibitor can reduce spinal radiographic progression in patients with active radiographic axial spondyloarthritis (axSpA) over 2 years, although results are not statistically significant.

Becky McCall/MDedge News

Lead researcher and rheumatologist, Fabian Proft, MD, based at Charité University Medicine, Berlin, presented the findings of the study at the 13th International Congress on Spondyloarthritides.

Only 97 patients completed the study, and its follow-up period lasted 2 years, which is a relatively short period of time in which to determine the effects of an intervention that might affect structural progression of the spine, Dr. Proft said.

“Based on these data, I won’t treat all my patients with celecoxib,” he told this news organization. However, he added that, “If I have a patient with residual symptoms under biological DMARDs [disease-modifying antirheumatic drugs], and I feel they are at high risk of radiographic spinal progression and they still have symptoms, then I would add in an NSAID – and for that I’d choose a selective COX-2 inhibitor based on radiographic spinal progression data.”

Walter P. Maksymowych, MD, rheumatologist from the University of Alberta, Calgary, commented on the study findings in an interview. “This is an important clinical question because we want to know whether we should be adding an anti-inflammatory in patients who are on biologic therapies. There’s been a long debate and investigation into whether anti-inflammatories might prevent new bone formation and thereby prevent disease progression.”

He went on by acknowledging that there was no statistically significant difference in the primary endpoint (change in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]) between the groups, but added that, “there was a sizable numerical difference, and I think this leaves the community somewhat hanging dry without a definitive answer. However, I do have concerns about whether there was an adequate sample size to address the study question.”
 

To add or not to add a selective COX-2 inhibitor to TNF inhibitor in axSpA treatment

The study aimed to investigate the effect of a selective COX-2 inhibitor when added to anti-TNF therapy with golimumab (Simponi), compared with golimumab therapy alone, on the progression of spinal structural damage over 2 years in patients with active radiographic axSpA.

“To date, we don’t have many treatments with evidence of reducing spinal radiographic progression in axSpA,” Dr. Proft said. “There was one study showing an effect of celecoxib, but another with diclofenac that failed to show any effect. As a result, there was a hypothesis that perhaps there was a selective COX-2 inhibitor effect.”

To investigate this further, Dr. Proft selected patients with high radiographic axSpA disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4) and with existing structural changes – both recognized risk factors for further progression. Participants had to have either an elevated C-reactive protein (CRP) > 5 mg/L and/or ≥ 1 syndesmophyte at screening, as well as a history of inadequate response to at least two DMARDs. Other patient risk factors for radiographic spinal progression included male gender and smoking. Duration of axSpA was unlimited.

Three radiographic readers were blinded for all clinical data and chronology. The primary endpoint was the change in mSASSS, while secondary endpoints were the presence of new syndesmophytes and clinical outcomes including activity, function, mobility, and health-related quality of life, as well as safety assessments.

Patients were treated with only golimumab (50 mg subcutaneous every 4 weeks) for the first 12 weeks and then only those patients with a good clinical response (n = 109) went into phase two of the study, at which point they were randomized 1:1 to golimumab monotherapy (control, 50 mg subcutaneous every 4 weeks), or golimumab (50 mg subcutaneous every 4 weeks) plus celecoxib (400 mg once daily) for 2 years. Radiographs were taken at baseline (week 0) and after 2 years. A total of 45 patients completed the combination therapy and 52 completed the monotherapy.
 

No statistical significance but a numerical difference found

“The primary outcome, which was change in mSASSS score, clearly shows a numerical difference between the combination arm at 1.1 and the monotherapy arm at 1.7 points, showing more structural progression in the monotherapy arm, compared to the combination arm,” Dr. Proft reported. However, he stressed that this difference did not reach statistical significance.

New syndesmophytes occurred in 25% with monotherapy and 11.1% with combination treatment. Again, this difference did not reach statistical significance.

“This might be due to sample size but also to the length of follow-up because a longer follow-up [given structural changes occur relatively slowly] might have shown a greater difference,” Dr. Proft pointed out.

Clinical data, according to Ankylosing Spondylitis Disease Activity Score with CRP and BASDAI, showed that both groups responded very well to therapy, and there were no differences seen between the two groups in terms of clinical parameters.

“It is important when we add a drug – and we know that NSAIDs can have safety concerns – that we do not see any statistically significant serious adverse events between patient groups,” Dr. Proft noted.

There were no significant differences in adverse events between monotherapy and combination therapy. There were 162 infections in the combination arm and 150 in the monotherapy arm. Combination therapy led to seven serious adverse events, and monotherapy occurred with five adverse events.

Dr. Proft added that four patients discontinued in the combination arm, compared with only one in the monotherapy arm, with a variety of different reasons for the discontinuations.

The study was supported by a grant from the German Ministry of Education and Research, and golimumab was provided free of charge by Merck Sharp & Dohme. Dr. Proft reported serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; serving as a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly. Dr. Maksymowych declared having no relevant conflicts of interest.

GHENT, BELGIUM – A strong numerical signal suggests the addition of a selective cyclooxygenase-2 (COX-2) inhibitor to a tumor necrosis factor (TNF) inhibitor can reduce spinal radiographic progression in patients with active radiographic axial spondyloarthritis (axSpA) over 2 years, although results are not statistically significant.

Becky McCall/MDedge News

Lead researcher and rheumatologist, Fabian Proft, MD, based at Charité University Medicine, Berlin, presented the findings of the study at the 13th International Congress on Spondyloarthritides.

Only 97 patients completed the study, and its follow-up period lasted 2 years, which is a relatively short period of time in which to determine the effects of an intervention that might affect structural progression of the spine, Dr. Proft said.

“Based on these data, I won’t treat all my patients with celecoxib,” he told this news organization. However, he added that, “If I have a patient with residual symptoms under biological DMARDs [disease-modifying antirheumatic drugs], and I feel they are at high risk of radiographic spinal progression and they still have symptoms, then I would add in an NSAID – and for that I’d choose a selective COX-2 inhibitor based on radiographic spinal progression data.”

Walter P. Maksymowych, MD, rheumatologist from the University of Alberta, Calgary, commented on the study findings in an interview. “This is an important clinical question because we want to know whether we should be adding an anti-inflammatory in patients who are on biologic therapies. There’s been a long debate and investigation into whether anti-inflammatories might prevent new bone formation and thereby prevent disease progression.”

He went on by acknowledging that there was no statistically significant difference in the primary endpoint (change in modified Stoke Ankylosing Spondylitis Spinal Score [mSASSS]) between the groups, but added that, “there was a sizable numerical difference, and I think this leaves the community somewhat hanging dry without a definitive answer. However, I do have concerns about whether there was an adequate sample size to address the study question.”
 

To add or not to add a selective COX-2 inhibitor to TNF inhibitor in axSpA treatment

The study aimed to investigate the effect of a selective COX-2 inhibitor when added to anti-TNF therapy with golimumab (Simponi), compared with golimumab therapy alone, on the progression of spinal structural damage over 2 years in patients with active radiographic axSpA.

“To date, we don’t have many treatments with evidence of reducing spinal radiographic progression in axSpA,” Dr. Proft said. “There was one study showing an effect of celecoxib, but another with diclofenac that failed to show any effect. As a result, there was a hypothesis that perhaps there was a selective COX-2 inhibitor effect.”

To investigate this further, Dr. Proft selected patients with high radiographic axSpA disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] ≥ 4) and with existing structural changes – both recognized risk factors for further progression. Participants had to have either an elevated C-reactive protein (CRP) > 5 mg/L and/or ≥ 1 syndesmophyte at screening, as well as a history of inadequate response to at least two DMARDs. Other patient risk factors for radiographic spinal progression included male gender and smoking. Duration of axSpA was unlimited.

Three radiographic readers were blinded for all clinical data and chronology. The primary endpoint was the change in mSASSS, while secondary endpoints were the presence of new syndesmophytes and clinical outcomes including activity, function, mobility, and health-related quality of life, as well as safety assessments.

Patients were treated with only golimumab (50 mg subcutaneous every 4 weeks) for the first 12 weeks and then only those patients with a good clinical response (n = 109) went into phase two of the study, at which point they were randomized 1:1 to golimumab monotherapy (control, 50 mg subcutaneous every 4 weeks), or golimumab (50 mg subcutaneous every 4 weeks) plus celecoxib (400 mg once daily) for 2 years. Radiographs were taken at baseline (week 0) and after 2 years. A total of 45 patients completed the combination therapy and 52 completed the monotherapy.
 

No statistical significance but a numerical difference found

“The primary outcome, which was change in mSASSS score, clearly shows a numerical difference between the combination arm at 1.1 and the monotherapy arm at 1.7 points, showing more structural progression in the monotherapy arm, compared to the combination arm,” Dr. Proft reported. However, he stressed that this difference did not reach statistical significance.

New syndesmophytes occurred in 25% with monotherapy and 11.1% with combination treatment. Again, this difference did not reach statistical significance.

“This might be due to sample size but also to the length of follow-up because a longer follow-up [given structural changes occur relatively slowly] might have shown a greater difference,” Dr. Proft pointed out.

Clinical data, according to Ankylosing Spondylitis Disease Activity Score with CRP and BASDAI, showed that both groups responded very well to therapy, and there were no differences seen between the two groups in terms of clinical parameters.

“It is important when we add a drug – and we know that NSAIDs can have safety concerns – that we do not see any statistically significant serious adverse events between patient groups,” Dr. Proft noted.

There were no significant differences in adverse events between monotherapy and combination therapy. There were 162 infections in the combination arm and 150 in the monotherapy arm. Combination therapy led to seven serious adverse events, and monotherapy occurred with five adverse events.

Dr. Proft added that four patients discontinued in the combination arm, compared with only one in the monotherapy arm, with a variety of different reasons for the discontinuations.

The study was supported by a grant from the German Ministry of Education and Research, and golimumab was provided free of charge by Merck Sharp & Dohme. Dr. Proft reported serving on speakers bureaus for Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Roche, and UCB; serving as a consultant to Novartis; and receiving grant or research support from Novartis, UCB, and Lilly. Dr. Maksymowych declared having no relevant conflicts of interest.