Massimo Sandal

MILAN – The impact of the COVID-19 pandemic on patients with rheumatic and nonrheumatic autoimmune diseases is ongoing and not yet fully comprehended. New data presented at the annual European Congress of Rheumatology, primarily derived from the global COVID-19 in Autoimmune Diseases (COVAD) survey but not limited to it, provide reassurance regarding the protection and safety of COVID-19 vaccines for older and younger adults, as well as for pregnant and breastfeeding women. These data also explore the influence of underlying diseases and medications on breakthrough SARS-CoV-2 infections and infection outcomes.

Safety of vaccines in patients with autoimmune or immune-mediated diseases

Following vaccination, even with low levels of antibodies, the risk of severe COVID-19 remains relatively low for patients who receive immunosuppressive therapy for various immune-mediated inflammatory diseases (IMIDs). This encouraging finding comes from the Nor-vaC study, presented by Hilde Ørbo, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo.

During the presentation, Dr. Ørbo stated: “We did not find any specific diagnosis or medication associated with a significantly higher risk of hospitalization.” Receiving booster doses of the vaccine, having high levels of anti-spike antibodies after vaccination, and achieving hybrid immunity are correlated with further reductions in the risk of breakthrough SARS-CoV-2 infections.

Dr. Hilde Ørbo

Between Feb. 15, 2021, and Feb. 15, 2023, COVID-19 affected a similar proportion among the 729 patients and 350 healthy control persons (67% and 68%, respectively). Among the patients, 22 reported severe COVID-19, whereas none of the healthy control persons did. However, there were no fatalities among the patients. The study cohort consisted of patients with various IMIDs; 70% had an inflammatory joint disease. The use of immunosuppressive medications also varied, with 63% of patients using tumor necrosis factor inhibitors, either as monotherapy or in combination with other treatments, and other patients taking medications such as methotrexate, interleukin inhibitors, Janus kinase inhibitors, vedolizumab (Entyvio), and others.

While being older than 70 years and the presence of comorbidities were identified as risk factors for severe COVID-19, there was a significant reduction in risk with each additional vaccine dose. These results support the protective role of repeated COVID-19 vaccination for patients with IMIDs who are receiving immunosuppressive therapies; they yield a favorable prognosis even with the Omicron variant.

The study further compared the risk of severe COVID-19 between a group with hybrid immunity (having received three vaccine doses and experiencing breakthrough infection with the Omicron variant) and a group that received a fourth vaccine dose within the same time frame. The difference was striking: Hybrid immunity was associated with a 5.8-fold decrease in risk, compared with four-dose vaccination (P < .0001).

The level of antibodies, measured 2-4 weeks after the last vaccination, was predictive of the risk of breakthrough COVID-19. An antibody level above 6000 binding antibody units/mL after vaccination was significantly associated with a reduction in risk. “We can conclude that patients who receive multiple vaccine doses have a lower risk of COVID-19,” Dr. Ørbo said. “In patients who recently experienced breakthrough infections, the administration of a booster vaccine dose might be delayed.”

EULAR

“The virus has undergone changes throughout the pandemic, while the vaccines have remained relatively stable. Are we anticipating more infections over time?” asked Hendrik Schulze-Koops, MD, PhD, of Ludwig Maximilians University of Munich (Germany), the session moderator. In response, Dr. Ørbo stated that 85% of the recorded infections in the study occurred after the emergence of the Omicron variant, and time was considered a covariable in the analysis.

These data shed light on a topic discussed by Pedro Machado, MD, PhD, professor and consultant in rheumatology and neuromuscular diseases at University College London, during his scientific session talk entitled, “Unsolved Issues of COVID Vaccination and Re-vaccination.” Dr. Machado referred to the VROOM study published in 2022, which examined the interruption of methotrexate for 2 weeks following booster administration. Both groups demonstrated a significant antibody response, but the group that stopped taking methotrexate showed double the antibody titers.

However, he emphasized, “what remains unknown is the clinical relevance of these differences in terms of severe infection, hospitalization, or even death. The potential benefit of increased immunogenicity by interrupting conventional synthetic disease-modifying antirheumatic drugs [csDMARDs] such as methotrexate before or after vaccination needs to be balanced against the potential risk of disease flare. Ultimately, decision-making should be individualized based on factors such as comorbidities, disease activity, and other considerations.” The results presented by Dr. Ørbo suggest that, while there may be a clinical difference in terms of severe infection, the overall prognosis for vaccinated patients is reasonably good.

Regarding other DMARDs, such as biologics, the approach may differ. Dr. Machado suggested: “In patients using rituximab or other B cell–depleting therapies, SARS-CoV-2 vaccination should be scheduled in a way that optimizes vaccine immunogenicity. A minimum of 10 B cells/mcL of blood is likely a relevant threshold above which a sufficient cellular and immune response is established.”
 

COVID vaccines are safe for pregnant and breastfeeding women

According to data from the COVAD study, which comprised two global cross-sectional surveys conducted in 2021 and 2022, the COVID-19 vaccine appeared safe for pregnant and breastfeeding women with autoimmune diseases (AID).

Presenter Laura Andreoli, MD, PhD, of the University of Brescia (Italy), said that, although pregnant patients with AID reported more adverse events related to vaccination, these rates were not significantly higher than those among pregnant, healthy control persons who were without AID. No difference in adverse events was observed between breastfeeding women and healthy control persons, and the incidence of disease flares did not significantly differ among all groups.

“In summary, this study provides initial insights into the safety of COVID-19 vaccination during the gestational and postpartum periods in women with autoimmune diseases. These reassuring observations will hopefully improve clinician-patient communication and address hesitancy towards COVID-19 vaccination, as the benefits for the mother and fetus through passive immunization appear to outweigh potential risks,” Dr. Andreoli said in an interview.

“The large number of participants and the global geographical spread of the COVAD survey were very beneficial in gaining access to this important subset of patients,” added Dr. Andreoli. However, she acknowledged that patients with low socioeconomic status and/or high disability were likely underrepresented. While no data on pregnancy outcomes have been collected thus far, Dr. Andreoli expressed the desire to include them in the study’s follow-up.

The COVAD survey data also indicate that, in general, vaccine hesitancy among patients with AID is decreasing; from 2021 to 2022, it declined from 16.5% to 5.1%, as Dr. Machado indicated in his presentation.
 

Multiple factors contribute to breakthrough infections

The risk of breakthrough SARS-CoV-2 infections after vaccination varies among patients with rheumatoid arthritis and rheumatic or nonrheumatic autoimmune diseases, primarily depending on the underlying condition rather than the immunosuppressive medication. Environmental factors also appear to play a role. This complex landscape emerges from a further analysis of the COVAD survey dataset.

Alessia Alunno, MD, PhD, of the University of L’Aquila (Italy), presented a detailed and occasionally counterintuitive picture of similarities and differences among young adult patients (aged 18-35 years), mostly women, with various rheumatic and nonrheumatic diseases in relation to COVID-19. Most notably, the type of disease seemed to have more significance than the immunosuppression resulting from the treatment regimen. This held true for vaccine safety as well as for the risk of breakthrough COVID-19 and symptom profiles.

Patients with rheumatic disease (RMD) and nonrheumatic autoimmune disease (nr-AD) had significantly different therapeutic profiles on average. Before vaccination, 45% of patients with RMD used glucocorticoids (GC), and 91% used immunosuppressants (IS). In contrast, only 9.5% of nr-AD patients used GC, and 21% were taking IS.

Interestingly, the overall prevalence of reported SARS-CoV-2 infections was not influenced by medication and was practically identical (25% to 28%) across all groups. However, there were intriguing differences in the occurrence of infections before and after vaccination between disease groups. Prevaccine infections were less frequent among patients with RMD compared with healthy control persons (adjusted odds ratio, 0.6), while the rates were similar among patients with nr-AD and healthy control persons. On the other hand, breakthrough infections were more frequent in patients with RMD (aOR, 2.7), whereas the rate was similar between healthy control persons and patients with nr-AD.

Despite a much lower rate of GC/IS use, patients with nr-AD experienced repeated infections more frequently. In contrast, patients with RMD were less prone to multiple infections, even compared with healthy control persons (aOR, 0.5).

Regarding the disease profile, fewer than 5% of all infected patients required advanced therapies for SARS-CoV-2 infection. Notably, all SARS-CoV-2 infections in patients with nr-AD were symptomatic, whereas among patients with RMD and healthy control persons, the incidence of asymptomatic infections was 3%. The rate of hospital admissions was 4% for patients with RMD, compared with 2% for patients with nr-AD and 1% for control persons. The RMD group exhibited some differences between prevaccine infections and breakthrough infections, including a significantly lower frequency of loss of smell and taste during breakthrough infections. Overall, patients with RMD and COVID-19 experienced cough, runny nose, throat pain, nausea, and vomiting more frequently. In contrast, patients with nr-AD had a much higher risk of skin rashes during breakthrough infections (aOR, 8.7).

Vaccine adverse events (AEs) were also influenced by the underlying disease. Patients with RMD and those with nr-AD were more likely to experience mild AEs after the first or second dose, compared with healthy control persons (adjusted OR, 2.4 and 2.0, respectively). The most common early, mild AEs across all groups were injection-site pain, headache, and fatigue, but they occurred more frequently in the nr-AD group than in the RMD or healthy control group. Additionally, fever and chills occurred more frequently among the nr-AD group. Late, mild AEs and severe AEs were rare and affected all groups equally.

“The overall incidence of AEs was very low. Our results certainly do not undermine the safety of vaccines,” Dr. Alunno said.

Disease flares were more common after vaccination (10% with RMD and 7% with nr-AD) than after infection (5% with RMD and 1.5% with nr-AD). Furthermore, in many cases, after vaccination, flares required a change of medications, particularly for patients with RMD.

Dr. Naveen Ravichandran

Additional results from the COVAD survey from January to July 2022, presented by Naveen Ravichandran, MD, DM, of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, revealed a higher prevalence (OR, 1.2; P = .001) of breakthrough infections among patients with RA. A total of 22.6% of patients with RA experienced breakthrough infections, compared with 20.6% for patients with other autoimmune rheumatic diseases and 18.4% of healthy control persons. Hospitalizations and the need for advanced treatment were also more common among patients with RA (30.9%) than among healthy control persons (13.9%). Patients with RA who had breakthrough infections tended to be older (closer to 50 years of age on average) and female, and they were more likely to have comorbidities and mental disorders. The human development index of the patient’s country of residence also played a role. Further research is necessary to understand how breakthrough infection outcomes are affected by a patient’s socioeconomic situation.

According to Dr. Ravichandran, medication was not a significant factor, except for the use of steroids and rituximab, which were associated with a higher risk of severe COVID-19 and hospitalization. Patients using rituximab, in particular, faced significantly increased odds for hospitalization (OR, 3.4) and severe breakthrough COVID-19 (OR, 3.0).

Session moderator Kim Lauper, MD, of the University of Geneva, cautioned: “The roles of disease and medication are challenging to separate. Some diseases require a more aggressive immunosuppressive regimen. It’s possible that different diseases affect the immune system differently, but it is not easy to demonstrate.”

The complications observed in the data warrant further study, as mentioned by Dr. Schulze-Koops: “We have a problem tied to the time line of the pandemic, where we had different viruses, different population behaviors, different treatments, and different standards of care over time. We also have differences between ethnic communities and regions of the world. But most importantly, we have different viruses: From the original strain to Delta to Omicron, we know they have very different clinical outcomes. I believe we need more scientific research to unravel these factors.”

Dr. Ørbo, Dr. Ravichandran, Dr. Andreoli, and Dr. Alunno reported no relevant financial relationships. Dr. Machado has received grants and/or honoraria from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Orphazyme, Pfizer, Roche, and UCB.

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

MILAN – The impact of the COVID-19 pandemic on patients with rheumatic and nonrheumatic autoimmune diseases is ongoing and not yet fully comprehended. New data presented at the annual European Congress of Rheumatology, primarily derived from the global COVID-19 in Autoimmune Diseases (COVAD) survey but not limited to it, provide reassurance regarding the protection and safety of COVID-19 vaccines for older and younger adults, as well as for pregnant and breastfeeding women. These data also explore the influence of underlying diseases and medications on breakthrough SARS-CoV-2 infections and infection outcomes.

Safety of vaccines in patients with autoimmune or immune-mediated diseases

Following vaccination, even with low levels of antibodies, the risk of severe COVID-19 remains relatively low for patients who receive immunosuppressive therapy for various immune-mediated inflammatory diseases (IMIDs). This encouraging finding comes from the Nor-vaC study, presented by Hilde Ørbo, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo.

During the presentation, Dr. Ørbo stated: “We did not find any specific diagnosis or medication associated with a significantly higher risk of hospitalization.” Receiving booster doses of the vaccine, having high levels of anti-spike antibodies after vaccination, and achieving hybrid immunity are correlated with further reductions in the risk of breakthrough SARS-CoV-2 infections.

Dr. Hilde Ørbo

Between Feb. 15, 2021, and Feb. 15, 2023, COVID-19 affected a similar proportion among the 729 patients and 350 healthy control persons (67% and 68%, respectively). Among the patients, 22 reported severe COVID-19, whereas none of the healthy control persons did. However, there were no fatalities among the patients. The study cohort consisted of patients with various IMIDs; 70% had an inflammatory joint disease. The use of immunosuppressive medications also varied, with 63% of patients using tumor necrosis factor inhibitors, either as monotherapy or in combination with other treatments, and other patients taking medications such as methotrexate, interleukin inhibitors, Janus kinase inhibitors, vedolizumab (Entyvio), and others.

While being older than 70 years and the presence of comorbidities were identified as risk factors for severe COVID-19, there was a significant reduction in risk with each additional vaccine dose. These results support the protective role of repeated COVID-19 vaccination for patients with IMIDs who are receiving immunosuppressive therapies; they yield a favorable prognosis even with the Omicron variant.

The study further compared the risk of severe COVID-19 between a group with hybrid immunity (having received three vaccine doses and experiencing breakthrough infection with the Omicron variant) and a group that received a fourth vaccine dose within the same time frame. The difference was striking: Hybrid immunity was associated with a 5.8-fold decrease in risk, compared with four-dose vaccination (P < .0001).

The level of antibodies, measured 2-4 weeks after the last vaccination, was predictive of the risk of breakthrough COVID-19. An antibody level above 6000 binding antibody units/mL after vaccination was significantly associated with a reduction in risk. “We can conclude that patients who receive multiple vaccine doses have a lower risk of COVID-19,” Dr. Ørbo said. “In patients who recently experienced breakthrough infections, the administration of a booster vaccine dose might be delayed.”

EULAR

“The virus has undergone changes throughout the pandemic, while the vaccines have remained relatively stable. Are we anticipating more infections over time?” asked Hendrik Schulze-Koops, MD, PhD, of Ludwig Maximilians University of Munich (Germany), the session moderator. In response, Dr. Ørbo stated that 85% of the recorded infections in the study occurred after the emergence of the Omicron variant, and time was considered a covariable in the analysis.

These data shed light on a topic discussed by Pedro Machado, MD, PhD, professor and consultant in rheumatology and neuromuscular diseases at University College London, during his scientific session talk entitled, “Unsolved Issues of COVID Vaccination and Re-vaccination.” Dr. Machado referred to the VROOM study published in 2022, which examined the interruption of methotrexate for 2 weeks following booster administration. Both groups demonstrated a significant antibody response, but the group that stopped taking methotrexate showed double the antibody titers.

However, he emphasized, “what remains unknown is the clinical relevance of these differences in terms of severe infection, hospitalization, or even death. The potential benefit of increased immunogenicity by interrupting conventional synthetic disease-modifying antirheumatic drugs [csDMARDs] such as methotrexate before or after vaccination needs to be balanced against the potential risk of disease flare. Ultimately, decision-making should be individualized based on factors such as comorbidities, disease activity, and other considerations.” The results presented by Dr. Ørbo suggest that, while there may be a clinical difference in terms of severe infection, the overall prognosis for vaccinated patients is reasonably good.

Regarding other DMARDs, such as biologics, the approach may differ. Dr. Machado suggested: “In patients using rituximab or other B cell–depleting therapies, SARS-CoV-2 vaccination should be scheduled in a way that optimizes vaccine immunogenicity. A minimum of 10 B cells/mcL of blood is likely a relevant threshold above which a sufficient cellular and immune response is established.”
 

COVID vaccines are safe for pregnant and breastfeeding women

According to data from the COVAD study, which comprised two global cross-sectional surveys conducted in 2021 and 2022, the COVID-19 vaccine appeared safe for pregnant and breastfeeding women with autoimmune diseases (AID).

Presenter Laura Andreoli, MD, PhD, of the University of Brescia (Italy), said that, although pregnant patients with AID reported more adverse events related to vaccination, these rates were not significantly higher than those among pregnant, healthy control persons who were without AID. No difference in adverse events was observed between breastfeeding women and healthy control persons, and the incidence of disease flares did not significantly differ among all groups.

“In summary, this study provides initial insights into the safety of COVID-19 vaccination during the gestational and postpartum periods in women with autoimmune diseases. These reassuring observations will hopefully improve clinician-patient communication and address hesitancy towards COVID-19 vaccination, as the benefits for the mother and fetus through passive immunization appear to outweigh potential risks,” Dr. Andreoli said in an interview.

“The large number of participants and the global geographical spread of the COVAD survey were very beneficial in gaining access to this important subset of patients,” added Dr. Andreoli. However, she acknowledged that patients with low socioeconomic status and/or high disability were likely underrepresented. While no data on pregnancy outcomes have been collected thus far, Dr. Andreoli expressed the desire to include them in the study’s follow-up.

The COVAD survey data also indicate that, in general, vaccine hesitancy among patients with AID is decreasing; from 2021 to 2022, it declined from 16.5% to 5.1%, as Dr. Machado indicated in his presentation.
 

Multiple factors contribute to breakthrough infections

The risk of breakthrough SARS-CoV-2 infections after vaccination varies among patients with rheumatoid arthritis and rheumatic or nonrheumatic autoimmune diseases, primarily depending on the underlying condition rather than the immunosuppressive medication. Environmental factors also appear to play a role. This complex landscape emerges from a further analysis of the COVAD survey dataset.

Alessia Alunno, MD, PhD, of the University of L’Aquila (Italy), presented a detailed and occasionally counterintuitive picture of similarities and differences among young adult patients (aged 18-35 years), mostly women, with various rheumatic and nonrheumatic diseases in relation to COVID-19. Most notably, the type of disease seemed to have more significance than the immunosuppression resulting from the treatment regimen. This held true for vaccine safety as well as for the risk of breakthrough COVID-19 and symptom profiles.

Patients with rheumatic disease (RMD) and nonrheumatic autoimmune disease (nr-AD) had significantly different therapeutic profiles on average. Before vaccination, 45% of patients with RMD used glucocorticoids (GC), and 91% used immunosuppressants (IS). In contrast, only 9.5% of nr-AD patients used GC, and 21% were taking IS.

Interestingly, the overall prevalence of reported SARS-CoV-2 infections was not influenced by medication and was practically identical (25% to 28%) across all groups. However, there were intriguing differences in the occurrence of infections before and after vaccination between disease groups. Prevaccine infections were less frequent among patients with RMD compared with healthy control persons (adjusted odds ratio, 0.6), while the rates were similar among patients with nr-AD and healthy control persons. On the other hand, breakthrough infections were more frequent in patients with RMD (aOR, 2.7), whereas the rate was similar between healthy control persons and patients with nr-AD.

Despite a much lower rate of GC/IS use, patients with nr-AD experienced repeated infections more frequently. In contrast, patients with RMD were less prone to multiple infections, even compared with healthy control persons (aOR, 0.5).

Regarding the disease profile, fewer than 5% of all infected patients required advanced therapies for SARS-CoV-2 infection. Notably, all SARS-CoV-2 infections in patients with nr-AD were symptomatic, whereas among patients with RMD and healthy control persons, the incidence of asymptomatic infections was 3%. The rate of hospital admissions was 4% for patients with RMD, compared with 2% for patients with nr-AD and 1% for control persons. The RMD group exhibited some differences between prevaccine infections and breakthrough infections, including a significantly lower frequency of loss of smell and taste during breakthrough infections. Overall, patients with RMD and COVID-19 experienced cough, runny nose, throat pain, nausea, and vomiting more frequently. In contrast, patients with nr-AD had a much higher risk of skin rashes during breakthrough infections (aOR, 8.7).

Vaccine adverse events (AEs) were also influenced by the underlying disease. Patients with RMD and those with nr-AD were more likely to experience mild AEs after the first or second dose, compared with healthy control persons (adjusted OR, 2.4 and 2.0, respectively). The most common early, mild AEs across all groups were injection-site pain, headache, and fatigue, but they occurred more frequently in the nr-AD group than in the RMD or healthy control group. Additionally, fever and chills occurred more frequently among the nr-AD group. Late, mild AEs and severe AEs were rare and affected all groups equally.

“The overall incidence of AEs was very low. Our results certainly do not undermine the safety of vaccines,” Dr. Alunno said.

Disease flares were more common after vaccination (10% with RMD and 7% with nr-AD) than after infection (5% with RMD and 1.5% with nr-AD). Furthermore, in many cases, after vaccination, flares required a change of medications, particularly for patients with RMD.

Dr. Naveen Ravichandran

Additional results from the COVAD survey from January to July 2022, presented by Naveen Ravichandran, MD, DM, of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, revealed a higher prevalence (OR, 1.2; P = .001) of breakthrough infections among patients with RA. A total of 22.6% of patients with RA experienced breakthrough infections, compared with 20.6% for patients with other autoimmune rheumatic diseases and 18.4% of healthy control persons. Hospitalizations and the need for advanced treatment were also more common among patients with RA (30.9%) than among healthy control persons (13.9%). Patients with RA who had breakthrough infections tended to be older (closer to 50 years of age on average) and female, and they were more likely to have comorbidities and mental disorders. The human development index of the patient’s country of residence also played a role. Further research is necessary to understand how breakthrough infection outcomes are affected by a patient’s socioeconomic situation.

According to Dr. Ravichandran, medication was not a significant factor, except for the use of steroids and rituximab, which were associated with a higher risk of severe COVID-19 and hospitalization. Patients using rituximab, in particular, faced significantly increased odds for hospitalization (OR, 3.4) and severe breakthrough COVID-19 (OR, 3.0).

Session moderator Kim Lauper, MD, of the University of Geneva, cautioned: “The roles of disease and medication are challenging to separate. Some diseases require a more aggressive immunosuppressive regimen. It’s possible that different diseases affect the immune system differently, but it is not easy to demonstrate.”

The complications observed in the data warrant further study, as mentioned by Dr. Schulze-Koops: “We have a problem tied to the time line of the pandemic, where we had different viruses, different population behaviors, different treatments, and different standards of care over time. We also have differences between ethnic communities and regions of the world. But most importantly, we have different viruses: From the original strain to Delta to Omicron, we know they have very different clinical outcomes. I believe we need more scientific research to unravel these factors.”

Dr. Ørbo, Dr. Ravichandran, Dr. Andreoli, and Dr. Alunno reported no relevant financial relationships. Dr. Machado has received grants and/or honoraria from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Orphazyme, Pfizer, Roche, and UCB.

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

MILAN – The impact of the COVID-19 pandemic on patients with rheumatic and nonrheumatic autoimmune diseases is ongoing and not yet fully comprehended. New data presented at the annual European Congress of Rheumatology, primarily derived from the global COVID-19 in Autoimmune Diseases (COVAD) survey but not limited to it, provide reassurance regarding the protection and safety of COVID-19 vaccines for older and younger adults, as well as for pregnant and breastfeeding women. These data also explore the influence of underlying diseases and medications on breakthrough SARS-CoV-2 infections and infection outcomes.

Safety of vaccines in patients with autoimmune or immune-mediated diseases

Following vaccination, even with low levels of antibodies, the risk of severe COVID-19 remains relatively low for patients who receive immunosuppressive therapy for various immune-mediated inflammatory diseases (IMIDs). This encouraging finding comes from the Nor-vaC study, presented by Hilde Ørbo, MD, of the Center for Treatment of Rheumatic and Musculoskeletal Diseases, Diakonhjemmet Hospital, Oslo.

During the presentation, Dr. Ørbo stated: “We did not find any specific diagnosis or medication associated with a significantly higher risk of hospitalization.” Receiving booster doses of the vaccine, having high levels of anti-spike antibodies after vaccination, and achieving hybrid immunity are correlated with further reductions in the risk of breakthrough SARS-CoV-2 infections.

Dr. Hilde Ørbo

Between Feb. 15, 2021, and Feb. 15, 2023, COVID-19 affected a similar proportion among the 729 patients and 350 healthy control persons (67% and 68%, respectively). Among the patients, 22 reported severe COVID-19, whereas none of the healthy control persons did. However, there were no fatalities among the patients. The study cohort consisted of patients with various IMIDs; 70% had an inflammatory joint disease. The use of immunosuppressive medications also varied, with 63% of patients using tumor necrosis factor inhibitors, either as monotherapy or in combination with other treatments, and other patients taking medications such as methotrexate, interleukin inhibitors, Janus kinase inhibitors, vedolizumab (Entyvio), and others.

While being older than 70 years and the presence of comorbidities were identified as risk factors for severe COVID-19, there was a significant reduction in risk with each additional vaccine dose. These results support the protective role of repeated COVID-19 vaccination for patients with IMIDs who are receiving immunosuppressive therapies; they yield a favorable prognosis even with the Omicron variant.

The study further compared the risk of severe COVID-19 between a group with hybrid immunity (having received three vaccine doses and experiencing breakthrough infection with the Omicron variant) and a group that received a fourth vaccine dose within the same time frame. The difference was striking: Hybrid immunity was associated with a 5.8-fold decrease in risk, compared with four-dose vaccination (P < .0001).

The level of antibodies, measured 2-4 weeks after the last vaccination, was predictive of the risk of breakthrough COVID-19. An antibody level above 6000 binding antibody units/mL after vaccination was significantly associated with a reduction in risk. “We can conclude that patients who receive multiple vaccine doses have a lower risk of COVID-19,” Dr. Ørbo said. “In patients who recently experienced breakthrough infections, the administration of a booster vaccine dose might be delayed.”

EULAR

“The virus has undergone changes throughout the pandemic, while the vaccines have remained relatively stable. Are we anticipating more infections over time?” asked Hendrik Schulze-Koops, MD, PhD, of Ludwig Maximilians University of Munich (Germany), the session moderator. In response, Dr. Ørbo stated that 85% of the recorded infections in the study occurred after the emergence of the Omicron variant, and time was considered a covariable in the analysis.

These data shed light on a topic discussed by Pedro Machado, MD, PhD, professor and consultant in rheumatology and neuromuscular diseases at University College London, during his scientific session talk entitled, “Unsolved Issues of COVID Vaccination and Re-vaccination.” Dr. Machado referred to the VROOM study published in 2022, which examined the interruption of methotrexate for 2 weeks following booster administration. Both groups demonstrated a significant antibody response, but the group that stopped taking methotrexate showed double the antibody titers.

However, he emphasized, “what remains unknown is the clinical relevance of these differences in terms of severe infection, hospitalization, or even death. The potential benefit of increased immunogenicity by interrupting conventional synthetic disease-modifying antirheumatic drugs [csDMARDs] such as methotrexate before or after vaccination needs to be balanced against the potential risk of disease flare. Ultimately, decision-making should be individualized based on factors such as comorbidities, disease activity, and other considerations.” The results presented by Dr. Ørbo suggest that, while there may be a clinical difference in terms of severe infection, the overall prognosis for vaccinated patients is reasonably good.

Regarding other DMARDs, such as biologics, the approach may differ. Dr. Machado suggested: “In patients using rituximab or other B cell–depleting therapies, SARS-CoV-2 vaccination should be scheduled in a way that optimizes vaccine immunogenicity. A minimum of 10 B cells/mcL of blood is likely a relevant threshold above which a sufficient cellular and immune response is established.”
 

COVID vaccines are safe for pregnant and breastfeeding women

According to data from the COVAD study, which comprised two global cross-sectional surveys conducted in 2021 and 2022, the COVID-19 vaccine appeared safe for pregnant and breastfeeding women with autoimmune diseases (AID).

Presenter Laura Andreoli, MD, PhD, of the University of Brescia (Italy), said that, although pregnant patients with AID reported more adverse events related to vaccination, these rates were not significantly higher than those among pregnant, healthy control persons who were without AID. No difference in adverse events was observed between breastfeeding women and healthy control persons, and the incidence of disease flares did not significantly differ among all groups.

“In summary, this study provides initial insights into the safety of COVID-19 vaccination during the gestational and postpartum periods in women with autoimmune diseases. These reassuring observations will hopefully improve clinician-patient communication and address hesitancy towards COVID-19 vaccination, as the benefits for the mother and fetus through passive immunization appear to outweigh potential risks,” Dr. Andreoli said in an interview.

“The large number of participants and the global geographical spread of the COVAD survey were very beneficial in gaining access to this important subset of patients,” added Dr. Andreoli. However, she acknowledged that patients with low socioeconomic status and/or high disability were likely underrepresented. While no data on pregnancy outcomes have been collected thus far, Dr. Andreoli expressed the desire to include them in the study’s follow-up.

The COVAD survey data also indicate that, in general, vaccine hesitancy among patients with AID is decreasing; from 2021 to 2022, it declined from 16.5% to 5.1%, as Dr. Machado indicated in his presentation.
 

Multiple factors contribute to breakthrough infections

The risk of breakthrough SARS-CoV-2 infections after vaccination varies among patients with rheumatoid arthritis and rheumatic or nonrheumatic autoimmune diseases, primarily depending on the underlying condition rather than the immunosuppressive medication. Environmental factors also appear to play a role. This complex landscape emerges from a further analysis of the COVAD survey dataset.

Alessia Alunno, MD, PhD, of the University of L’Aquila (Italy), presented a detailed and occasionally counterintuitive picture of similarities and differences among young adult patients (aged 18-35 years), mostly women, with various rheumatic and nonrheumatic diseases in relation to COVID-19. Most notably, the type of disease seemed to have more significance than the immunosuppression resulting from the treatment regimen. This held true for vaccine safety as well as for the risk of breakthrough COVID-19 and symptom profiles.

Patients with rheumatic disease (RMD) and nonrheumatic autoimmune disease (nr-AD) had significantly different therapeutic profiles on average. Before vaccination, 45% of patients with RMD used glucocorticoids (GC), and 91% used immunosuppressants (IS). In contrast, only 9.5% of nr-AD patients used GC, and 21% were taking IS.

Interestingly, the overall prevalence of reported SARS-CoV-2 infections was not influenced by medication and was practically identical (25% to 28%) across all groups. However, there were intriguing differences in the occurrence of infections before and after vaccination between disease groups. Prevaccine infections were less frequent among patients with RMD compared with healthy control persons (adjusted odds ratio, 0.6), while the rates were similar among patients with nr-AD and healthy control persons. On the other hand, breakthrough infections were more frequent in patients with RMD (aOR, 2.7), whereas the rate was similar between healthy control persons and patients with nr-AD.

Despite a much lower rate of GC/IS use, patients with nr-AD experienced repeated infections more frequently. In contrast, patients with RMD were less prone to multiple infections, even compared with healthy control persons (aOR, 0.5).

Regarding the disease profile, fewer than 5% of all infected patients required advanced therapies for SARS-CoV-2 infection. Notably, all SARS-CoV-2 infections in patients with nr-AD were symptomatic, whereas among patients with RMD and healthy control persons, the incidence of asymptomatic infections was 3%. The rate of hospital admissions was 4% for patients with RMD, compared with 2% for patients with nr-AD and 1% for control persons. The RMD group exhibited some differences between prevaccine infections and breakthrough infections, including a significantly lower frequency of loss of smell and taste during breakthrough infections. Overall, patients with RMD and COVID-19 experienced cough, runny nose, throat pain, nausea, and vomiting more frequently. In contrast, patients with nr-AD had a much higher risk of skin rashes during breakthrough infections (aOR, 8.7).

Vaccine adverse events (AEs) were also influenced by the underlying disease. Patients with RMD and those with nr-AD were more likely to experience mild AEs after the first or second dose, compared with healthy control persons (adjusted OR, 2.4 and 2.0, respectively). The most common early, mild AEs across all groups were injection-site pain, headache, and fatigue, but they occurred more frequently in the nr-AD group than in the RMD or healthy control group. Additionally, fever and chills occurred more frequently among the nr-AD group. Late, mild AEs and severe AEs were rare and affected all groups equally.

“The overall incidence of AEs was very low. Our results certainly do not undermine the safety of vaccines,” Dr. Alunno said.

Disease flares were more common after vaccination (10% with RMD and 7% with nr-AD) than after infection (5% with RMD and 1.5% with nr-AD). Furthermore, in many cases, after vaccination, flares required a change of medications, particularly for patients with RMD.

Dr. Naveen Ravichandran

Additional results from the COVAD survey from January to July 2022, presented by Naveen Ravichandran, MD, DM, of Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India, revealed a higher prevalence (OR, 1.2; P = .001) of breakthrough infections among patients with RA. A total of 22.6% of patients with RA experienced breakthrough infections, compared with 20.6% for patients with other autoimmune rheumatic diseases and 18.4% of healthy control persons. Hospitalizations and the need for advanced treatment were also more common among patients with RA (30.9%) than among healthy control persons (13.9%). Patients with RA who had breakthrough infections tended to be older (closer to 50 years of age on average) and female, and they were more likely to have comorbidities and mental disorders. The human development index of the patient’s country of residence also played a role. Further research is necessary to understand how breakthrough infection outcomes are affected by a patient’s socioeconomic situation.

According to Dr. Ravichandran, medication was not a significant factor, except for the use of steroids and rituximab, which were associated with a higher risk of severe COVID-19 and hospitalization. Patients using rituximab, in particular, faced significantly increased odds for hospitalization (OR, 3.4) and severe breakthrough COVID-19 (OR, 3.0).

Session moderator Kim Lauper, MD, of the University of Geneva, cautioned: “The roles of disease and medication are challenging to separate. Some diseases require a more aggressive immunosuppressive regimen. It’s possible that different diseases affect the immune system differently, but it is not easy to demonstrate.”

The complications observed in the data warrant further study, as mentioned by Dr. Schulze-Koops: “We have a problem tied to the time line of the pandemic, where we had different viruses, different population behaviors, different treatments, and different standards of care over time. We also have differences between ethnic communities and regions of the world. But most importantly, we have different viruses: From the original strain to Delta to Omicron, we know they have very different clinical outcomes. I believe we need more scientific research to unravel these factors.”

Dr. Ørbo, Dr. Ravichandran, Dr. Andreoli, and Dr. Alunno reported no relevant financial relationships. Dr. Machado has received grants and/or honoraria from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Janssen, Merck Sharp & Dohme, Novartis, Orphazyme, Pfizer, Roche, and UCB.

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

MILAN – Dazodalibep, an intravenously administered inhibitor of CD40 ligand, shows promise in reducing disease activity and alleviating key subjective symptoms of Sjögren’s syndrome, compared with placebo. These preliminary findings are from the initial phase of the ALISS trial, a phase 2 randomized, double-blind, placebo-controlled, crossover clinical trial presented at the annul European Congress of Rheumatology.

Over the course of the 169-day trial, both the disease activity score and the patient-reported symptom score dropped significantly for patients who were treated with dazodalibep, also known as VIB4920 or HZN4920, compared with those treated with placebo, meeting both primary endpoints. This benefit was particularly evident for patients who had limited systemic organ involvement but substantial symptom burden.

Dazodalibep is a fusion protein that functions as an inhibitor by blocking the interaction between T cells and CD40-expressing B cells. This inhibition effectively suppresses costimulatory signaling between immune cells. Unlike previous CD40-targeting biologics, dazodalibep does not belong to the antibody class. According to Horizon Thereapeutics, this distinction is expected to help mitigate safety concerns, particularly those related to blood clot formation that were encountered with antibody-based biologics such as ruplizumab, according to Horizon, which acquired the trial’s sponsor, Viela Bio.
 

Patients with moderate to high systemic disease activity

The trial investigated dazodalibep in two patient populations. Wan-Fai Ng, MBBCh, PhD, professor of rheumatology at Newcastle University and honorary consultant rheumatologist at Newcastle upon Tyne Hospitals NHS Foundation Trust, England, presented results from the first group, which comprised 74 adult patients with Sjögren’s syndrome with moderate to high systemic disease activity. Disease activity was defined as a score of ≥ 5 on the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI).

A post hoc responder analysis demonstrated that dazodalibep outperformed placebo in patients who achieved a 5- or 6-point improvement on the ESSDAI. Response rates for these patients was 61.1% and 60.0%, respectively, compared with 35.1% and 34.3% for patients who received placebo. Patients who received dazodalibep experienced a reduction of –6.3 ± 0.6 points in ESSDAI score, whereas the placebo group experienced a reduction of –4.1 ± 0.6 points, a difference of –2.2 (P = .0167). However, there was no significant change in any symptom-related score in this population.
 

Patients with unacceptable symptom burden but limited systemic involvement

Also at EULAR 2023, Chiara Baldini, MD, of the University of Pisa, Italy, reported the results from the second group of 109 adult patients with Sjögren’s syndrome who had notable symptom burden but limited systemic organ involvement. “These patients represent a significant portion of individuals with reduced quality of life who are largely excluded from other clinical trials,” Dr. Baldini said in an interview. The study population was defined by having a EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) ≥ 5 and, in contrast to the previous group, an ESSDAI score < 5.

In this case, treatment with dazodalibep correlated with a substantial reduction in symptom burden, compared with placebo. Among the patients who received dazodalibep, 66.7% achieved ≥ 1 point or ≥ 15% reduction in symptoms, as measured by ESSPRI, compared with 32.7% in the placebo group. The ESSPRI score decreased by –1.80 ± 0.23 points in the dazodalibep group, while it decreased by –0.53 ± 0.23 points in the placebo group, a difference of −1.27 ± 0.33 points favoring dazodalibep (P = .0002). The reduction in symptoms in the dazodalibep group was evident from the first data point on day 29 and was statistically significant for each of the three symptom components included in the ESSPRI score: dryness, pain, and fatigue.

Additionally, a significant improvement was observed in one of the secondary endpoints, namely, a reduction in the Functional Assessment of Chronic Illness Therapy-Fatigue score. The dazodalibep group exhibited a considerably greater reduction (+8.1 ± 1.4, compared with baseline) than did the placebo group (+2.8 ± 1.4; P = .0095).
 

Dazodalibep safety

“Dazodalibep therapy was generally safe and well tolerated,” Dr. Baldini said in her presentation. Adverse events that were reported for both investigations were generally mild and occurred with similar frequency between the treatment groups. The most commonly reported adverse events, each occurring in more than 5% of patients who received dazodalibep, were COVID-19, diarrhea, anemia, dizziness, ligament sprain, upper respiratory tract infection, and nasopharyngitis. The incidence of COVID-19 and nasopharyngitis was comparable between the treatment and placebo arms.

However, in the patient group with moderate to high systemic disease activity, one patient who was treated with dazodalibep experienced two serious adverse events: a grade 3 SARS-CoV-2 infection, and subsequent death from an unknown cause, which occurred 46 days after the last administration of dazodalibep (12 days after COVID-19 diagnosis). Additionally, there was one case of herpes zoster in a patient treated with dazodalibep. In the group with limited systemic organ involvement, three serious adverse events were reported in the dazodalibep group (pneumonia influenza, postacute COVID-19 syndrome [long COVID], and gammopathy); one serious adverse event (neutropenia) was reported in the placebo group. One patient in the dazodalibep group discontinued participation in the study because of an adverse event, compared with two in the placebo group. Investigators determined that, thus far, all serious adverse events in both populations have been unrelated to the medication.

Throughout the trial, eligible participants in both populations were randomly assigned in a 1:1 ratio to receive either intravenous dazodalibep 1,500 mg or placebo every 2 weeks for three doses, followed by every 4 weeks for an additional four doses, up to day 169. The majority of participants in all populations and treatment arms were women (> 90%). Key inclusion criteria were being aged 18 years or older, meeting the 2016 American College of Rheumatology–EULAR classification criteria for Sjögren’s syndrome, and testing positive for anti-SSA and/or rheumatoid factors. Exclusion criteria were having a medical history of thrombosis or anticoagulant use, as well as prior treatment with B cell–depleting therapies. The proportions of patients who received glucocorticoids, antimalarials, or disease-modifying antirheumatic drugs were consistent between both arms of each population.

“Larger clinical trials are necessary to validate the clinical effectiveness and safety of dazodalibep therapy in this specific subgroup of patients,” Dr. Baldini concluded. Currently, dazodalibep is being studied for the treatment of rheumatoid arthritis and renal transplant rejection, and Horizon Therapeutics has plans to explore its use in focal segmental glomerulosclerosis.

Dr. Ng has served as a consultant to Novartis, GlaxoSmithKline, AbbVie, Bristol-Myers Squibb, Sanofi, MedImmune, Resolves Therapeutics, Janssen, and UCB. Dr. Baldini has served as a consultant to GlaxoSmithKline and Sanofi.

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

MILAN – Dazodalibep, an intravenously administered inhibitor of CD40 ligand, shows promise in reducing disease activity and alleviating key subjective symptoms of Sjögren’s syndrome, compared with placebo. These preliminary findings are from the initial phase of the ALISS trial, a phase 2 randomized, double-blind, placebo-controlled, crossover clinical trial presented at the annul European Congress of Rheumatology.

Over the course of the 169-day trial, both the disease activity score and the patient-reported symptom score dropped significantly for patients who were treated with dazodalibep, also known as VIB4920 or HZN4920, compared with those treated with placebo, meeting both primary endpoints. This benefit was particularly evident for patients who had limited systemic organ involvement but substantial symptom burden.

Dazodalibep is a fusion protein that functions as an inhibitor by blocking the interaction between T cells and CD40-expressing B cells. This inhibition effectively suppresses costimulatory signaling between immune cells. Unlike previous CD40-targeting biologics, dazodalibep does not belong to the antibody class. According to Horizon Thereapeutics, this distinction is expected to help mitigate safety concerns, particularly those related to blood clot formation that were encountered with antibody-based biologics such as ruplizumab, according to Horizon, which acquired the trial’s sponsor, Viela Bio.
 

Patients with moderate to high systemic disease activity

The trial investigated dazodalibep in two patient populations. Wan-Fai Ng, MBBCh, PhD, professor of rheumatology at Newcastle University and honorary consultant rheumatologist at Newcastle upon Tyne Hospitals NHS Foundation Trust, England, presented results from the first group, which comprised 74 adult patients with Sjögren’s syndrome with moderate to high systemic disease activity. Disease activity was defined as a score of ≥ 5 on the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI).

A post hoc responder analysis demonstrated that dazodalibep outperformed placebo in patients who achieved a 5- or 6-point improvement on the ESSDAI. Response rates for these patients was 61.1% and 60.0%, respectively, compared with 35.1% and 34.3% for patients who received placebo. Patients who received dazodalibep experienced a reduction of –6.3 ± 0.6 points in ESSDAI score, whereas the placebo group experienced a reduction of –4.1 ± 0.6 points, a difference of –2.2 (P = .0167). However, there was no significant change in any symptom-related score in this population.
 

Patients with unacceptable symptom burden but limited systemic involvement

Also at EULAR 2023, Chiara Baldini, MD, of the University of Pisa, Italy, reported the results from the second group of 109 adult patients with Sjögren’s syndrome who had notable symptom burden but limited systemic organ involvement. “These patients represent a significant portion of individuals with reduced quality of life who are largely excluded from other clinical trials,” Dr. Baldini said in an interview. The study population was defined by having a EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) ≥ 5 and, in contrast to the previous group, an ESSDAI score < 5.

In this case, treatment with dazodalibep correlated with a substantial reduction in symptom burden, compared with placebo. Among the patients who received dazodalibep, 66.7% achieved ≥ 1 point or ≥ 15% reduction in symptoms, as measured by ESSPRI, compared with 32.7% in the placebo group. The ESSPRI score decreased by –1.80 ± 0.23 points in the dazodalibep group, while it decreased by –0.53 ± 0.23 points in the placebo group, a difference of −1.27 ± 0.33 points favoring dazodalibep (P = .0002). The reduction in symptoms in the dazodalibep group was evident from the first data point on day 29 and was statistically significant for each of the three symptom components included in the ESSPRI score: dryness, pain, and fatigue.

Additionally, a significant improvement was observed in one of the secondary endpoints, namely, a reduction in the Functional Assessment of Chronic Illness Therapy-Fatigue score. The dazodalibep group exhibited a considerably greater reduction (+8.1 ± 1.4, compared with baseline) than did the placebo group (+2.8 ± 1.4; P = .0095).
 

Dazodalibep safety

“Dazodalibep therapy was generally safe and well tolerated,” Dr. Baldini said in her presentation. Adverse events that were reported for both investigations were generally mild and occurred with similar frequency between the treatment groups. The most commonly reported adverse events, each occurring in more than 5% of patients who received dazodalibep, were COVID-19, diarrhea, anemia, dizziness, ligament sprain, upper respiratory tract infection, and nasopharyngitis. The incidence of COVID-19 and nasopharyngitis was comparable between the treatment and placebo arms.

However, in the patient group with moderate to high systemic disease activity, one patient who was treated with dazodalibep experienced two serious adverse events: a grade 3 SARS-CoV-2 infection, and subsequent death from an unknown cause, which occurred 46 days after the last administration of dazodalibep (12 days after COVID-19 diagnosis). Additionally, there was one case of herpes zoster in a patient treated with dazodalibep. In the group with limited systemic organ involvement, three serious adverse events were reported in the dazodalibep group (pneumonia influenza, postacute COVID-19 syndrome [long COVID], and gammopathy); one serious adverse event (neutropenia) was reported in the placebo group. One patient in the dazodalibep group discontinued participation in the study because of an adverse event, compared with two in the placebo group. Investigators determined that, thus far, all serious adverse events in both populations have been unrelated to the medication.

Throughout the trial, eligible participants in both populations were randomly assigned in a 1:1 ratio to receive either intravenous dazodalibep 1,500 mg or placebo every 2 weeks for three doses, followed by every 4 weeks for an additional four doses, up to day 169. The majority of participants in all populations and treatment arms were women (> 90%). Key inclusion criteria were being aged 18 years or older, meeting the 2016 American College of Rheumatology–EULAR classification criteria for Sjögren’s syndrome, and testing positive for anti-SSA and/or rheumatoid factors. Exclusion criteria were having a medical history of thrombosis or anticoagulant use, as well as prior treatment with B cell–depleting therapies. The proportions of patients who received glucocorticoids, antimalarials, or disease-modifying antirheumatic drugs were consistent between both arms of each population.

“Larger clinical trials are necessary to validate the clinical effectiveness and safety of dazodalibep therapy in this specific subgroup of patients,” Dr. Baldini concluded. Currently, dazodalibep is being studied for the treatment of rheumatoid arthritis and renal transplant rejection, and Horizon Therapeutics has plans to explore its use in focal segmental glomerulosclerosis.

Dr. Ng has served as a consultant to Novartis, GlaxoSmithKline, AbbVie, Bristol-Myers Squibb, Sanofi, MedImmune, Resolves Therapeutics, Janssen, and UCB. Dr. Baldini has served as a consultant to GlaxoSmithKline and Sanofi.

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

MILAN – Dazodalibep, an intravenously administered inhibitor of CD40 ligand, shows promise in reducing disease activity and alleviating key subjective symptoms of Sjögren’s syndrome, compared with placebo. These preliminary findings are from the initial phase of the ALISS trial, a phase 2 randomized, double-blind, placebo-controlled, crossover clinical trial presented at the annul European Congress of Rheumatology.

Over the course of the 169-day trial, both the disease activity score and the patient-reported symptom score dropped significantly for patients who were treated with dazodalibep, also known as VIB4920 or HZN4920, compared with those treated with placebo, meeting both primary endpoints. This benefit was particularly evident for patients who had limited systemic organ involvement but substantial symptom burden.

Dazodalibep is a fusion protein that functions as an inhibitor by blocking the interaction between T cells and CD40-expressing B cells. This inhibition effectively suppresses costimulatory signaling between immune cells. Unlike previous CD40-targeting biologics, dazodalibep does not belong to the antibody class. According to Horizon Thereapeutics, this distinction is expected to help mitigate safety concerns, particularly those related to blood clot formation that were encountered with antibody-based biologics such as ruplizumab, according to Horizon, which acquired the trial’s sponsor, Viela Bio.
 

Patients with moderate to high systemic disease activity

The trial investigated dazodalibep in two patient populations. Wan-Fai Ng, MBBCh, PhD, professor of rheumatology at Newcastle University and honorary consultant rheumatologist at Newcastle upon Tyne Hospitals NHS Foundation Trust, England, presented results from the first group, which comprised 74 adult patients with Sjögren’s syndrome with moderate to high systemic disease activity. Disease activity was defined as a score of ≥ 5 on the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI).

A post hoc responder analysis demonstrated that dazodalibep outperformed placebo in patients who achieved a 5- or 6-point improvement on the ESSDAI. Response rates for these patients was 61.1% and 60.0%, respectively, compared with 35.1% and 34.3% for patients who received placebo. Patients who received dazodalibep experienced a reduction of –6.3 ± 0.6 points in ESSDAI score, whereas the placebo group experienced a reduction of –4.1 ± 0.6 points, a difference of –2.2 (P = .0167). However, there was no significant change in any symptom-related score in this population.
 

Patients with unacceptable symptom burden but limited systemic involvement

Also at EULAR 2023, Chiara Baldini, MD, of the University of Pisa, Italy, reported the results from the second group of 109 adult patients with Sjögren’s syndrome who had notable symptom burden but limited systemic organ involvement. “These patients represent a significant portion of individuals with reduced quality of life who are largely excluded from other clinical trials,” Dr. Baldini said in an interview. The study population was defined by having a EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) ≥ 5 and, in contrast to the previous group, an ESSDAI score < 5.

In this case, treatment with dazodalibep correlated with a substantial reduction in symptom burden, compared with placebo. Among the patients who received dazodalibep, 66.7% achieved ≥ 1 point or ≥ 15% reduction in symptoms, as measured by ESSPRI, compared with 32.7% in the placebo group. The ESSPRI score decreased by –1.80 ± 0.23 points in the dazodalibep group, while it decreased by –0.53 ± 0.23 points in the placebo group, a difference of −1.27 ± 0.33 points favoring dazodalibep (P = .0002). The reduction in symptoms in the dazodalibep group was evident from the first data point on day 29 and was statistically significant for each of the three symptom components included in the ESSPRI score: dryness, pain, and fatigue.

Additionally, a significant improvement was observed in one of the secondary endpoints, namely, a reduction in the Functional Assessment of Chronic Illness Therapy-Fatigue score. The dazodalibep group exhibited a considerably greater reduction (+8.1 ± 1.4, compared with baseline) than did the placebo group (+2.8 ± 1.4; P = .0095).
 

Dazodalibep safety

“Dazodalibep therapy was generally safe and well tolerated,” Dr. Baldini said in her presentation. Adverse events that were reported for both investigations were generally mild and occurred with similar frequency between the treatment groups. The most commonly reported adverse events, each occurring in more than 5% of patients who received dazodalibep, were COVID-19, diarrhea, anemia, dizziness, ligament sprain, upper respiratory tract infection, and nasopharyngitis. The incidence of COVID-19 and nasopharyngitis was comparable between the treatment and placebo arms.

However, in the patient group with moderate to high systemic disease activity, one patient who was treated with dazodalibep experienced two serious adverse events: a grade 3 SARS-CoV-2 infection, and subsequent death from an unknown cause, which occurred 46 days after the last administration of dazodalibep (12 days after COVID-19 diagnosis). Additionally, there was one case of herpes zoster in a patient treated with dazodalibep. In the group with limited systemic organ involvement, three serious adverse events were reported in the dazodalibep group (pneumonia influenza, postacute COVID-19 syndrome [long COVID], and gammopathy); one serious adverse event (neutropenia) was reported in the placebo group. One patient in the dazodalibep group discontinued participation in the study because of an adverse event, compared with two in the placebo group. Investigators determined that, thus far, all serious adverse events in both populations have been unrelated to the medication.

Throughout the trial, eligible participants in both populations were randomly assigned in a 1:1 ratio to receive either intravenous dazodalibep 1,500 mg or placebo every 2 weeks for three doses, followed by every 4 weeks for an additional four doses, up to day 169. The majority of participants in all populations and treatment arms were women (> 90%). Key inclusion criteria were being aged 18 years or older, meeting the 2016 American College of Rheumatology–EULAR classification criteria for Sjögren’s syndrome, and testing positive for anti-SSA and/or rheumatoid factors. Exclusion criteria were having a medical history of thrombosis or anticoagulant use, as well as prior treatment with B cell–depleting therapies. The proportions of patients who received glucocorticoids, antimalarials, or disease-modifying antirheumatic drugs were consistent between both arms of each population.

“Larger clinical trials are necessary to validate the clinical effectiveness and safety of dazodalibep therapy in this specific subgroup of patients,” Dr. Baldini concluded. Currently, dazodalibep is being studied for the treatment of rheumatoid arthritis and renal transplant rejection, and Horizon Therapeutics has plans to explore its use in focal segmental glomerulosclerosis.

Dr. Ng has served as a consultant to Novartis, GlaxoSmithKline, AbbVie, Bristol-Myers Squibb, Sanofi, MedImmune, Resolves Therapeutics, Janssen, and UCB. Dr. Baldini has served as a consultant to GlaxoSmithKline and Sanofi.

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

AT EULAR 2023

MILAN – Safety considerations, particularly regarding the use of Janus kinase (JAK) inhibitors, are of utmost importance in the 2023 update to recommendations for managing psoriatic arthritis (PsA) by the European Alliance of Associations for Rheumatology (EULAR). Additionally, the selection of therapy should now take into account the complete clinical presentation, explicitly considering nonmusculoskeletal manifestations.

Safety considerations with JAK inhibitors

Expanding on the existing six overarching principles from the 2019 recommendations, the PsA EULAR recommendations now introduce a seventh principle: “The choice of treatment should consider safety considerations regarding individual modes of action to optimize the benefit-risk profile.”

This addition was prompted by recent safety data on JAK inhibitors, which revealed serious potential side effects, such as heart attacks, blood clots, cancer, and severe infections, that recently prompted the European Medicines Agency to restrict their use. As indicated by the new principle, safety considerations have been incorporated into several recommendations.

For instance, in the context of peripheral arthritis, JAK inhibitors may now be considered if there is an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate, sulfasalazine, or leflunomide, and at least one biologic DMARD (bDMARD).

Alternatively, JAK inhibitors may be utilized when bDMARDs are not suitable for other reasons. However, EULAR now emphasizes caution whenever JAK inhibitors are mentioned. Specifically, “careful consideration is necessary for patients aged 65 or above, current or past long-time smokers, individuals with a history of atherosclerotic cardiovascular disease or other cardiovascular risk factors, those with other malignancy risk factors, or individuals with a known risk for venous thromboembolism.”
 

Consider nonmusculoskeletal manifestations in treatment decisions

In another significant update, EULAR now recommends that the choice of therapy should also consider nonmusculoskeletal manifestations associated with PsA. “There is a notable shift in perspective here,” Dr. Gossec told this news organization. Clinically relevant skin involvement should prompt the use of IL-17A or IL-17A/F or IL-23 or IL-12/23 inhibitors, while uveitis should be treated with tumor necrosis factor (TNF) inhibitors.

In the case of inflammatory bowel disease, EULAR advises the use of anti-TNF agents, IL-12/23 or IL-23 inhibitors, or a JAK inhibitor. The recommended course of action within each treatment category is not ranked in order of preference, but EULAR emphasizes the importance of following EMA recommendations and considering safety.
 

Systemic glucocorticoids removed

Certain medications have been removed from the recommendations, reflecting the heightened focus on treatment safety. The use of systemic glucocorticoids as adjunctive therapy is no longer recommended. “We always had reservations about their use, and now we have eliminated them. We are aware that they are still utilized, with 30% of patients in Germany, for instance, receiving low doses of glucocorticoids. However, the long-term efficacy/safety balance of glucocorticoids is unfavorable in any disease, particularly in patients with psoriatic arthritis and multiple comorbidities,” Dr. Gossec explained.

NSAIDs and local glucocorticoids are now limited to specific patient populations, namely those affected by oligoarthritis without poor prognostic factors, entheseal disease, or predominant axial disease. Their use should be short-term, generally no longer than 4 weeks. Polyarthritis or oligoarthritis with poor prognostic factors should instead be treated directly with csDMARDs.
 

No specific biologic treatment order recommended for peripheral arthritis

Regarding patients with peripheral arthritis, recent efficacy data have led EULAR to refrain from recommending any specific order of preference for the use of bDMARDs, which encompass TNF inhibitors and drugs targeting the IL-17 and IL-12/23 pathways. “We lack the data to propose an order of preference in patients with peripheral arthritis. Different classes of molecules exhibit efficacy in joint inflammation, generally resulting in a 50% response rate and similar overall effects,” said Dr. Gossec, referencing head-to-head trials between biologics that yielded very comparable results, such as the EXCEED trial or SPIRIT-H2H trial.

The updated recommendations now consider two IL-23p19 inhibitors, guselkumab (Tremfya) and risankizumab (Skyrizi), the JAK inhibitor upadacitinib (Rinvoq), and the very recently EMA-approved bimekizumab (Bimzelx), an IL-17A/F double inhibitor.

The recommendation for patients with mono- or oligoarthritis and poor prognostic factors now aligns with the previous recommendations for polyarthritis: A csDMARD should be initiated promptly, with a preference for methotrexate if significant skin involvement is present. New data suggest that methotrexate may be beneficial for enthesitis, achieving resolution in approximately 30% of patients. When considering treatment options, JAK inhibitors may also be taken into account, with safety considerations in mind.

In cases of clinically relevant axial disease and an inadequate response to NSAIDs, therapy with an IL-17A inhibitor, a TNF inhibitor, an IL-17A/F inhibitor, or a JAK inhibitor may be considered. This approach now aligns with the most recent axial spondyloarthritis recommendation from EULAR and the Assessment of SpondyloArthritis international Society (ASAS).
 

Which disease manifestation to treat first?

During the discussion, chairwoman Uta Kiltz, MD, PhD, a rheumatologist at Rheumatism Center Ruhrgebiet, Herne, Germany, and clinical lecturer at Ruhr University Bochum, inquired about identifying the primary manifestation to guide the course of action.

“Psoriatic arthritis is highly heterogeneous, and determining the predominant manifestation is sometimes challenging,” Dr. Gossec said. “However, we believe that a certain order of preference is necessary when making treatment decisions. Starting with peripheral arthritis, which can lead to structural damage, allows for treatment selection based on that aspect. If peripheral arthritis is not present, attention should be directed towards axial disease, ensuring the presence of actual inflammation rather than solely axial pain, as mechanical origin axial pain can occur due to the patient’s age.”

David Liew, MBBS, PhD, consultant rheumatologist and clinical pharmacologist at Austin Health in Melbourne, commented on the update to this news organization: “We are fortunate to have a wide range of targeted therapy options for psoriatic arthritis, and these guidelines reflect this abundance of choices. They emphasize the importance of selecting therapies based on specific disease manifestations and tailoring care to each patient’s unique type of psoriatic arthritis. It’s worth noting that some changes in these guidelines were influenced by regulatory changes following ORAL Surveillance. In an era of numerous options, we can afford to be selective at times.”

Regarding safety concerns and JAK inhibitors, Dr. Liew added: “It is not surprising to see these guidelines impose certain restrictions on the use of JAK inhibitors, especially in psoriatic arthritis, where other therapies offer distinct advantages. Until high-quality evidence convincingly points away from a class effect, we can expect to see similar provisions in many more guidelines.”

Many of the recommendations’ authors report financial relationships with one or more pharmaceutical companies. These include AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Chugai, Galapagos, Gilead, GlaxoSmithKline, Janssen, Leo, Lilly, Medac, Merck, Merck Sharp & Dohme, Novartis, Pfizer, R-Pharma, Regeneron, Roche, Sandoz, Sanofi, Takeda, UCB, and Viatris.

EULAR funded the development of the recommendations.

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

AT EULAR 2023

MILAN – Safety considerations, particularly regarding the use of Janus kinase (JAK) inhibitors, are of utmost importance in the 2023 update to recommendations for managing psoriatic arthritis (PsA) by the European Alliance of Associations for Rheumatology (EULAR). Additionally, the selection of therapy should now take into account the complete clinical presentation, explicitly considering nonmusculoskeletal manifestations.

Safety considerations with JAK inhibitors

Expanding on the existing six overarching principles from the 2019 recommendations, the PsA EULAR recommendations now introduce a seventh principle: “The choice of treatment should consider safety considerations regarding individual modes of action to optimize the benefit-risk profile.”

This addition was prompted by recent safety data on JAK inhibitors, which revealed serious potential side effects, such as heart attacks, blood clots, cancer, and severe infections, that recently prompted the European Medicines Agency to restrict their use. As indicated by the new principle, safety considerations have been incorporated into several recommendations.

For instance, in the context of peripheral arthritis, JAK inhibitors may now be considered if there is an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate, sulfasalazine, or leflunomide, and at least one biologic DMARD (bDMARD).

Alternatively, JAK inhibitors may be utilized when bDMARDs are not suitable for other reasons. However, EULAR now emphasizes caution whenever JAK inhibitors are mentioned. Specifically, “careful consideration is necessary for patients aged 65 or above, current or past long-time smokers, individuals with a history of atherosclerotic cardiovascular disease or other cardiovascular risk factors, those with other malignancy risk factors, or individuals with a known risk for venous thromboembolism.”
 

Consider nonmusculoskeletal manifestations in treatment decisions

In another significant update, EULAR now recommends that the choice of therapy should also consider nonmusculoskeletal manifestations associated with PsA. “There is a notable shift in perspective here,” Dr. Gossec told this news organization. Clinically relevant skin involvement should prompt the use of IL-17A or IL-17A/F or IL-23 or IL-12/23 inhibitors, while uveitis should be treated with tumor necrosis factor (TNF) inhibitors.

In the case of inflammatory bowel disease, EULAR advises the use of anti-TNF agents, IL-12/23 or IL-23 inhibitors, or a JAK inhibitor. The recommended course of action within each treatment category is not ranked in order of preference, but EULAR emphasizes the importance of following EMA recommendations and considering safety.
 

Systemic glucocorticoids removed

Certain medications have been removed from the recommendations, reflecting the heightened focus on treatment safety. The use of systemic glucocorticoids as adjunctive therapy is no longer recommended. “We always had reservations about their use, and now we have eliminated them. We are aware that they are still utilized, with 30% of patients in Germany, for instance, receiving low doses of glucocorticoids. However, the long-term efficacy/safety balance of glucocorticoids is unfavorable in any disease, particularly in patients with psoriatic arthritis and multiple comorbidities,” Dr. Gossec explained.

NSAIDs and local glucocorticoids are now limited to specific patient populations, namely those affected by oligoarthritis without poor prognostic factors, entheseal disease, or predominant axial disease. Their use should be short-term, generally no longer than 4 weeks. Polyarthritis or oligoarthritis with poor prognostic factors should instead be treated directly with csDMARDs.
 

No specific biologic treatment order recommended for peripheral arthritis

Regarding patients with peripheral arthritis, recent efficacy data have led EULAR to refrain from recommending any specific order of preference for the use of bDMARDs, which encompass TNF inhibitors and drugs targeting the IL-17 and IL-12/23 pathways. “We lack the data to propose an order of preference in patients with peripheral arthritis. Different classes of molecules exhibit efficacy in joint inflammation, generally resulting in a 50% response rate and similar overall effects,” said Dr. Gossec, referencing head-to-head trials between biologics that yielded very comparable results, such as the EXCEED trial or SPIRIT-H2H trial.

The updated recommendations now consider two IL-23p19 inhibitors, guselkumab (Tremfya) and risankizumab (Skyrizi), the JAK inhibitor upadacitinib (Rinvoq), and the very recently EMA-approved bimekizumab (Bimzelx), an IL-17A/F double inhibitor.

The recommendation for patients with mono- or oligoarthritis and poor prognostic factors now aligns with the previous recommendations for polyarthritis: A csDMARD should be initiated promptly, with a preference for methotrexate if significant skin involvement is present. New data suggest that methotrexate may be beneficial for enthesitis, achieving resolution in approximately 30% of patients. When considering treatment options, JAK inhibitors may also be taken into account, with safety considerations in mind.

In cases of clinically relevant axial disease and an inadequate response to NSAIDs, therapy with an IL-17A inhibitor, a TNF inhibitor, an IL-17A/F inhibitor, or a JAK inhibitor may be considered. This approach now aligns with the most recent axial spondyloarthritis recommendation from EULAR and the Assessment of SpondyloArthritis international Society (ASAS).
 

Which disease manifestation to treat first?

During the discussion, chairwoman Uta Kiltz, MD, PhD, a rheumatologist at Rheumatism Center Ruhrgebiet, Herne, Germany, and clinical lecturer at Ruhr University Bochum, inquired about identifying the primary manifestation to guide the course of action.

“Psoriatic arthritis is highly heterogeneous, and determining the predominant manifestation is sometimes challenging,” Dr. Gossec said. “However, we believe that a certain order of preference is necessary when making treatment decisions. Starting with peripheral arthritis, which can lead to structural damage, allows for treatment selection based on that aspect. If peripheral arthritis is not present, attention should be directed towards axial disease, ensuring the presence of actual inflammation rather than solely axial pain, as mechanical origin axial pain can occur due to the patient’s age.”

David Liew, MBBS, PhD, consultant rheumatologist and clinical pharmacologist at Austin Health in Melbourne, commented on the update to this news organization: “We are fortunate to have a wide range of targeted therapy options for psoriatic arthritis, and these guidelines reflect this abundance of choices. They emphasize the importance of selecting therapies based on specific disease manifestations and tailoring care to each patient’s unique type of psoriatic arthritis. It’s worth noting that some changes in these guidelines were influenced by regulatory changes following ORAL Surveillance. In an era of numerous options, we can afford to be selective at times.”

Regarding safety concerns and JAK inhibitors, Dr. Liew added: “It is not surprising to see these guidelines impose certain restrictions on the use of JAK inhibitors, especially in psoriatic arthritis, where other therapies offer distinct advantages. Until high-quality evidence convincingly points away from a class effect, we can expect to see similar provisions in many more guidelines.”

Many of the recommendations’ authors report financial relationships with one or more pharmaceutical companies. These include AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Chugai, Galapagos, Gilead, GlaxoSmithKline, Janssen, Leo, Lilly, Medac, Merck, Merck Sharp & Dohme, Novartis, Pfizer, R-Pharma, Regeneron, Roche, Sandoz, Sanofi, Takeda, UCB, and Viatris.

EULAR funded the development of the recommendations.

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

AT EULAR 2023

MILAN – Safety considerations, particularly regarding the use of Janus kinase (JAK) inhibitors, are of utmost importance in the 2023 update to recommendations for managing psoriatic arthritis (PsA) by the European Alliance of Associations for Rheumatology (EULAR). Additionally, the selection of therapy should now take into account the complete clinical presentation, explicitly considering nonmusculoskeletal manifestations.

Safety considerations with JAK inhibitors

Expanding on the existing six overarching principles from the 2019 recommendations, the PsA EULAR recommendations now introduce a seventh principle: “The choice of treatment should consider safety considerations regarding individual modes of action to optimize the benefit-risk profile.”

This addition was prompted by recent safety data on JAK inhibitors, which revealed serious potential side effects, such as heart attacks, blood clots, cancer, and severe infections, that recently prompted the European Medicines Agency to restrict their use. As indicated by the new principle, safety considerations have been incorporated into several recommendations.

For instance, in the context of peripheral arthritis, JAK inhibitors may now be considered if there is an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as methotrexate, sulfasalazine, or leflunomide, and at least one biologic DMARD (bDMARD).

Alternatively, JAK inhibitors may be utilized when bDMARDs are not suitable for other reasons. However, EULAR now emphasizes caution whenever JAK inhibitors are mentioned. Specifically, “careful consideration is necessary for patients aged 65 or above, current or past long-time smokers, individuals with a history of atherosclerotic cardiovascular disease or other cardiovascular risk factors, those with other malignancy risk factors, or individuals with a known risk for venous thromboembolism.”
 

Consider nonmusculoskeletal manifestations in treatment decisions

In another significant update, EULAR now recommends that the choice of therapy should also consider nonmusculoskeletal manifestations associated with PsA. “There is a notable shift in perspective here,” Dr. Gossec told this news organization. Clinically relevant skin involvement should prompt the use of IL-17A or IL-17A/F or IL-23 or IL-12/23 inhibitors, while uveitis should be treated with tumor necrosis factor (TNF) inhibitors.

In the case of inflammatory bowel disease, EULAR advises the use of anti-TNF agents, IL-12/23 or IL-23 inhibitors, or a JAK inhibitor. The recommended course of action within each treatment category is not ranked in order of preference, but EULAR emphasizes the importance of following EMA recommendations and considering safety.
 

Systemic glucocorticoids removed

Certain medications have been removed from the recommendations, reflecting the heightened focus on treatment safety. The use of systemic glucocorticoids as adjunctive therapy is no longer recommended. “We always had reservations about their use, and now we have eliminated them. We are aware that they are still utilized, with 30% of patients in Germany, for instance, receiving low doses of glucocorticoids. However, the long-term efficacy/safety balance of glucocorticoids is unfavorable in any disease, particularly in patients with psoriatic arthritis and multiple comorbidities,” Dr. Gossec explained.

NSAIDs and local glucocorticoids are now limited to specific patient populations, namely those affected by oligoarthritis without poor prognostic factors, entheseal disease, or predominant axial disease. Their use should be short-term, generally no longer than 4 weeks. Polyarthritis or oligoarthritis with poor prognostic factors should instead be treated directly with csDMARDs.
 

No specific biologic treatment order recommended for peripheral arthritis

Regarding patients with peripheral arthritis, recent efficacy data have led EULAR to refrain from recommending any specific order of preference for the use of bDMARDs, which encompass TNF inhibitors and drugs targeting the IL-17 and IL-12/23 pathways. “We lack the data to propose an order of preference in patients with peripheral arthritis. Different classes of molecules exhibit efficacy in joint inflammation, generally resulting in a 50% response rate and similar overall effects,” said Dr. Gossec, referencing head-to-head trials between biologics that yielded very comparable results, such as the EXCEED trial or SPIRIT-H2H trial.

The updated recommendations now consider two IL-23p19 inhibitors, guselkumab (Tremfya) and risankizumab (Skyrizi), the JAK inhibitor upadacitinib (Rinvoq), and the very recently EMA-approved bimekizumab (Bimzelx), an IL-17A/F double inhibitor.

The recommendation for patients with mono- or oligoarthritis and poor prognostic factors now aligns with the previous recommendations for polyarthritis: A csDMARD should be initiated promptly, with a preference for methotrexate if significant skin involvement is present. New data suggest that methotrexate may be beneficial for enthesitis, achieving resolution in approximately 30% of patients. When considering treatment options, JAK inhibitors may also be taken into account, with safety considerations in mind.

In cases of clinically relevant axial disease and an inadequate response to NSAIDs, therapy with an IL-17A inhibitor, a TNF inhibitor, an IL-17A/F inhibitor, or a JAK inhibitor may be considered. This approach now aligns with the most recent axial spondyloarthritis recommendation from EULAR and the Assessment of SpondyloArthritis international Society (ASAS).
 

Which disease manifestation to treat first?

During the discussion, chairwoman Uta Kiltz, MD, PhD, a rheumatologist at Rheumatism Center Ruhrgebiet, Herne, Germany, and clinical lecturer at Ruhr University Bochum, inquired about identifying the primary manifestation to guide the course of action.

“Psoriatic arthritis is highly heterogeneous, and determining the predominant manifestation is sometimes challenging,” Dr. Gossec said. “However, we believe that a certain order of preference is necessary when making treatment decisions. Starting with peripheral arthritis, which can lead to structural damage, allows for treatment selection based on that aspect. If peripheral arthritis is not present, attention should be directed towards axial disease, ensuring the presence of actual inflammation rather than solely axial pain, as mechanical origin axial pain can occur due to the patient’s age.”

David Liew, MBBS, PhD, consultant rheumatologist and clinical pharmacologist at Austin Health in Melbourne, commented on the update to this news organization: “We are fortunate to have a wide range of targeted therapy options for psoriatic arthritis, and these guidelines reflect this abundance of choices. They emphasize the importance of selecting therapies based on specific disease manifestations and tailoring care to each patient’s unique type of psoriatic arthritis. It’s worth noting that some changes in these guidelines were influenced by regulatory changes following ORAL Surveillance. In an era of numerous options, we can afford to be selective at times.”

Regarding safety concerns and JAK inhibitors, Dr. Liew added: “It is not surprising to see these guidelines impose certain restrictions on the use of JAK inhibitors, especially in psoriatic arthritis, where other therapies offer distinct advantages. Until high-quality evidence convincingly points away from a class effect, we can expect to see similar provisions in many more guidelines.”

Many of the recommendations’ authors report financial relationships with one or more pharmaceutical companies. These include AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Celltrion, Chugai, Galapagos, Gilead, GlaxoSmithKline, Janssen, Leo, Lilly, Medac, Merck, Merck Sharp & Dohme, Novartis, Pfizer, R-Pharma, Regeneron, Roche, Sandoz, Sanofi, Takeda, UCB, and Viatris.

EULAR funded the development of the recommendations.

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

MILAN – Rheumatic disease is not considered a significant risk factor for long COVID, according to the findings of a Dutch prospective cohort study presented at the annual European Congress of Rheumatology.

Although more patients with inflammatory rheumatic diseases (iRD) report symptoms resembling long COVID, the data suggest that many of these symptoms can be attributed to the underlying rheumatic disease. “Overall, we find the data quite reassuring,” said Laura Boekel, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center.

The results were also published in The Lancet Rheumatology.

The risk of developing long COVID after infection with the Omicron variant appeared to be higher in patients with iRD, with 21% meeting the criteria set by the World Health Organization, compared with 13% of healthy individuals (odds ratio, 1.58; P = .037). Fatigue and loss of fitness were the most common long COVID symptoms reported by both iRD patients and controls. However, the difference in risk decreased after accounting for factors that are significantly associated with an increased risk for long COVID, such as body mass index and the severity of the acute COVID-19 infection (adjusted OR, 1.46; P = .081). The duration of symptoms did not show a statistically significant difference.

Kim Lauper, MD, University of Geneva, who chaired the session in which Ms. Boekel reported the study, said in an interview that the data should be interpreted with caution. “The data demonstrate that rheumatic disease itself is not a risk factor for long COVID. However, patients with rheumatic diseases are at a higher risk of severe disease, which in turn increases the likelihood of long COVID. Therefore, as a population, these patients are more susceptible to long COVID overall.”

Moreover, irrespective of their previous COVID-19 infection status, iRD patients often exhibit symptoms similar to those of long COVID even without a prior COVID-19 infection. (There was no history of COVID-19 in 21% of iRD patients vs. 11% of controls.) This suggests that some of the reported long COVID symptoms may actually be clinical manifestations of the underlying rheumatic disease, thereby complicating the diagnosis of long COVID in this population. The study employed the WHO definition of long COVID, which includes persistent symptoms lasting at least 8 weeks, beginning within 3 months of a confirmed SARS-CoV-2 infection, and that cannot be attributed to an alternative diagnosis. However, the data presented in Milan indicate that the WHO definition “is not well suited for patients with iRD due to significant overlap in symptoms and features,” Ms. Boekel concluded.

The cases of Omicron COVID-19 were identified during Jan. 1–April 25, 2022, among iRD patients recruited from the Amsterdam Rheumatology and Immunology Center. The population with confirmed SARS-CoV-2 Omicron infection during this period was monitored for long COVID. The total number of patients included in the study consisted of 77 iRD patients and 23 healthy controls. When asked about the potential risk of selection bias in the survey, Ms. Boekel stated that only approximately 8% of participants declined to respond, and the nonresponders were comparable with the respondents. She concluded that “the risk of selection bias is minimal.”

In an editorial published in The Lancet Rheumatology, Leonard H. Calabrese, DO, Cleveland Clinic, provided his insights on the findings. He emphasized that, “at present, long COVID remains an important reality that significantly impacts the lives of millions of individuals, yet it remains incompletely defined. ... These limitations in defining cases should not in any way undermine the experiences of those suffering from long COVID. Instead, they should serve as a reminder that, at this stage of the pandemic, we unfortunately still lack validated classification criteria for long COVID. It is crucial to include non–SARS-CoV-2–infected controls in all studies to further enhance our understanding.”

Ms. Boekel and coauthors, as well as Dr. Lauper and Dr. Calabrese, reported no relevant financial relationships.

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

MILAN – Rheumatic disease is not considered a significant risk factor for long COVID, according to the findings of a Dutch prospective cohort study presented at the annual European Congress of Rheumatology.

Although more patients with inflammatory rheumatic diseases (iRD) report symptoms resembling long COVID, the data suggest that many of these symptoms can be attributed to the underlying rheumatic disease. “Overall, we find the data quite reassuring,” said Laura Boekel, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center.

The results were also published in The Lancet Rheumatology.

The risk of developing long COVID after infection with the Omicron variant appeared to be higher in patients with iRD, with 21% meeting the criteria set by the World Health Organization, compared with 13% of healthy individuals (odds ratio, 1.58; P = .037). Fatigue and loss of fitness were the most common long COVID symptoms reported by both iRD patients and controls. However, the difference in risk decreased after accounting for factors that are significantly associated with an increased risk for long COVID, such as body mass index and the severity of the acute COVID-19 infection (adjusted OR, 1.46; P = .081). The duration of symptoms did not show a statistically significant difference.

Kim Lauper, MD, University of Geneva, who chaired the session in which Ms. Boekel reported the study, said in an interview that the data should be interpreted with caution. “The data demonstrate that rheumatic disease itself is not a risk factor for long COVID. However, patients with rheumatic diseases are at a higher risk of severe disease, which in turn increases the likelihood of long COVID. Therefore, as a population, these patients are more susceptible to long COVID overall.”

Moreover, irrespective of their previous COVID-19 infection status, iRD patients often exhibit symptoms similar to those of long COVID even without a prior COVID-19 infection. (There was no history of COVID-19 in 21% of iRD patients vs. 11% of controls.) This suggests that some of the reported long COVID symptoms may actually be clinical manifestations of the underlying rheumatic disease, thereby complicating the diagnosis of long COVID in this population. The study employed the WHO definition of long COVID, which includes persistent symptoms lasting at least 8 weeks, beginning within 3 months of a confirmed SARS-CoV-2 infection, and that cannot be attributed to an alternative diagnosis. However, the data presented in Milan indicate that the WHO definition “is not well suited for patients with iRD due to significant overlap in symptoms and features,” Ms. Boekel concluded.

The cases of Omicron COVID-19 were identified during Jan. 1–April 25, 2022, among iRD patients recruited from the Amsterdam Rheumatology and Immunology Center. The population with confirmed SARS-CoV-2 Omicron infection during this period was monitored for long COVID. The total number of patients included in the study consisted of 77 iRD patients and 23 healthy controls. When asked about the potential risk of selection bias in the survey, Ms. Boekel stated that only approximately 8% of participants declined to respond, and the nonresponders were comparable with the respondents. She concluded that “the risk of selection bias is minimal.”

In an editorial published in The Lancet Rheumatology, Leonard H. Calabrese, DO, Cleveland Clinic, provided his insights on the findings. He emphasized that, “at present, long COVID remains an important reality that significantly impacts the lives of millions of individuals, yet it remains incompletely defined. ... These limitations in defining cases should not in any way undermine the experiences of those suffering from long COVID. Instead, they should serve as a reminder that, at this stage of the pandemic, we unfortunately still lack validated classification criteria for long COVID. It is crucial to include non–SARS-CoV-2–infected controls in all studies to further enhance our understanding.”

Ms. Boekel and coauthors, as well as Dr. Lauper and Dr. Calabrese, reported no relevant financial relationships.

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

MILAN – Rheumatic disease is not considered a significant risk factor for long COVID, according to the findings of a Dutch prospective cohort study presented at the annual European Congress of Rheumatology.

Although more patients with inflammatory rheumatic diseases (iRD) report symptoms resembling long COVID, the data suggest that many of these symptoms can be attributed to the underlying rheumatic disease. “Overall, we find the data quite reassuring,” said Laura Boekel, Amsterdam Rheumatology and Immunology Center, Amsterdam University Medical Center.

The results were also published in The Lancet Rheumatology.

The risk of developing long COVID after infection with the Omicron variant appeared to be higher in patients with iRD, with 21% meeting the criteria set by the World Health Organization, compared with 13% of healthy individuals (odds ratio, 1.58; P = .037). Fatigue and loss of fitness were the most common long COVID symptoms reported by both iRD patients and controls. However, the difference in risk decreased after accounting for factors that are significantly associated with an increased risk for long COVID, such as body mass index and the severity of the acute COVID-19 infection (adjusted OR, 1.46; P = .081). The duration of symptoms did not show a statistically significant difference.

Kim Lauper, MD, University of Geneva, who chaired the session in which Ms. Boekel reported the study, said in an interview that the data should be interpreted with caution. “The data demonstrate that rheumatic disease itself is not a risk factor for long COVID. However, patients with rheumatic diseases are at a higher risk of severe disease, which in turn increases the likelihood of long COVID. Therefore, as a population, these patients are more susceptible to long COVID overall.”

Moreover, irrespective of their previous COVID-19 infection status, iRD patients often exhibit symptoms similar to those of long COVID even without a prior COVID-19 infection. (There was no history of COVID-19 in 21% of iRD patients vs. 11% of controls.) This suggests that some of the reported long COVID symptoms may actually be clinical manifestations of the underlying rheumatic disease, thereby complicating the diagnosis of long COVID in this population. The study employed the WHO definition of long COVID, which includes persistent symptoms lasting at least 8 weeks, beginning within 3 months of a confirmed SARS-CoV-2 infection, and that cannot be attributed to an alternative diagnosis. However, the data presented in Milan indicate that the WHO definition “is not well suited for patients with iRD due to significant overlap in symptoms and features,” Ms. Boekel concluded.

The cases of Omicron COVID-19 were identified during Jan. 1–April 25, 2022, among iRD patients recruited from the Amsterdam Rheumatology and Immunology Center. The population with confirmed SARS-CoV-2 Omicron infection during this period was monitored for long COVID. The total number of patients included in the study consisted of 77 iRD patients and 23 healthy controls. When asked about the potential risk of selection bias in the survey, Ms. Boekel stated that only approximately 8% of participants declined to respond, and the nonresponders were comparable with the respondents. She concluded that “the risk of selection bias is minimal.”

In an editorial published in The Lancet Rheumatology, Leonard H. Calabrese, DO, Cleveland Clinic, provided his insights on the findings. He emphasized that, “at present, long COVID remains an important reality that significantly impacts the lives of millions of individuals, yet it remains incompletely defined. ... These limitations in defining cases should not in any way undermine the experiences of those suffering from long COVID. Instead, they should serve as a reminder that, at this stage of the pandemic, we unfortunately still lack validated classification criteria for long COVID. It is crucial to include non–SARS-CoV-2–infected controls in all studies to further enhance our understanding.”

Ms. Boekel and coauthors, as well as Dr. Lauper and Dr. Calabrese, reported no relevant financial relationships.

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

MILAN – The oral Janus kinase (JAK) 1/2 inhibitor baricitinib (Olumiant) demonstrated significantly better efficacy than cyclophosphamide infusions in the treatment of lupus nephritis in a small, independently funded, phase 3, double-blind clinical trial, Manal Hassanien, MD, reported at the annual European Congress of Rheumatology.

Baricitinib, licensed by Eli Lilly, has been recognized as a potential therapeutic option in systemic lupus, and is approved in the United States to treat RA, alopecia areata, and COVID-19 in certain hospitalized adults. It is also approved to treat atopic dermatitis in Europe. However, it previously yielded disappointing results in phase 3 clinical trials SLE-BRAVE-I and SLE-BRAVE-II for systemic lupus erythematosus. The trial results presented at EULAR suggest that baricitinib could be beneficial in the treatment of lupus nephritis, further establishing the role of JAK inhibitors in autoimmune disease therapy.

“Lupus nephritis typically develops within 5 years of initial lupus symptoms,” said Dr. Hassanien, of the rheumatology research and advanced therapeutics department at Assiut (Egypt) University. “Research has shown that up to 60% of lupus patients will eventually develop lupus nephritis. The management of proliferative lupus nephritis usually involves an initial phase focused on preventing the development of irreversible damage, followed by a maintenance phase to control lupus activity. Despite significant progress, lupus nephritis still carries an increased risk of end-stage renal disease and mortality.”

The study’s primary endpoint of 24-hour proteinuria response rate (≥ 50% reduction from baseline) at week 12 was significantly greater with baricitinib 4 mg daily, compared with monthly cyclophosphamide infusions at 0.7 mg/m² (70% vs. 43%; P < .0001). At week 24, 76.6% of the baricitinib group met the primary endpoint, compared with 50% in the cyclophosphamide group. Two multiplicity-controlled secondary endpoints, C3 serum level and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), also showed statistical significance at 12 weeks (P < .01).

The 6-month trial included 60 adult patients (age 18 years and older) with a clinical diagnosis of lupus nephritis fulfilling classification criteria for LN grade III and IV. Patients needed to demonstrate objective signs of active nephritis consistent with persistent proteinuria greater than 0.5 g/day and/or cellular casts at screening to be included. Additional inclusion criteria were SLEDAI-2K greater than 4 and assessment of anti–double-stranded DNA and C3 serum levels at study entry. The patients were randomly assigned to two equal-sized groups, with one group receiving baricitinib 4 mg daily and a monthly placebo saline infusion, and the other group receiving monthly cyclophosphamide infusions and oral placebo tablets.

The incidence of adverse events was comparable between the two treatment groups, with 48% of patients in the baricitinib group and 46% in the cyclophosphamide group experiencing adverse events. Only three serious adverse events, specifically serious infection or herpes zoster, were recorded, leading to treatment discontinuation.

Two patients (6.6%) in the baricitinib group and one patient (3.3%) in the cyclophosphamide group were affected. The researchers recorded no major adverse cardiovascular or venous thromboembolic events, which are known to occur at higher rates among some users of baricitinib and other JAK inhibitors. The safety profile of baricitinib was consistent with observations made in other inflammatory musculoskeletal diseases, and no new risks were identified.

However, there were some concerns expressed by audience members during the presentation.

“The primary endpoint is limited at proteinuria, while biopsy is considered the gold standard for measuring efficacy,” said Eric F. Morand, MD, head of the Monash Health rheumatology unit, Melbourne. This was not the only critical comment regarding the study that emerged during the discussion. The use of a 4-mg dosage regimen throughout the entire study duration (despite official recommendations suggesting a 2-mg dosage in the long run) and the positive outcomes observed in the control group treated with cyclophosphamide were also mentioned.

Dr. Hassanien acknowledged that this is a small and relatively short study and disclosed plans to extend the follow-up period to 1 year and conduct a renal biopsy.

Dr. Hassanien reported no relevant financial relationships. Assiut University funded the trial.

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

MILAN – The oral Janus kinase (JAK) 1/2 inhibitor baricitinib (Olumiant) demonstrated significantly better efficacy than cyclophosphamide infusions in the treatment of lupus nephritis in a small, independently funded, phase 3, double-blind clinical trial, Manal Hassanien, MD, reported at the annual European Congress of Rheumatology.

Baricitinib, licensed by Eli Lilly, has been recognized as a potential therapeutic option in systemic lupus, and is approved in the United States to treat RA, alopecia areata, and COVID-19 in certain hospitalized adults. It is also approved to treat atopic dermatitis in Europe. However, it previously yielded disappointing results in phase 3 clinical trials SLE-BRAVE-I and SLE-BRAVE-II for systemic lupus erythematosus. The trial results presented at EULAR suggest that baricitinib could be beneficial in the treatment of lupus nephritis, further establishing the role of JAK inhibitors in autoimmune disease therapy.

“Lupus nephritis typically develops within 5 years of initial lupus symptoms,” said Dr. Hassanien, of the rheumatology research and advanced therapeutics department at Assiut (Egypt) University. “Research has shown that up to 60% of lupus patients will eventually develop lupus nephritis. The management of proliferative lupus nephritis usually involves an initial phase focused on preventing the development of irreversible damage, followed by a maintenance phase to control lupus activity. Despite significant progress, lupus nephritis still carries an increased risk of end-stage renal disease and mortality.”

The study’s primary endpoint of 24-hour proteinuria response rate (≥ 50% reduction from baseline) at week 12 was significantly greater with baricitinib 4 mg daily, compared with monthly cyclophosphamide infusions at 0.7 mg/m² (70% vs. 43%; P < .0001). At week 24, 76.6% of the baricitinib group met the primary endpoint, compared with 50% in the cyclophosphamide group. Two multiplicity-controlled secondary endpoints, C3 serum level and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), also showed statistical significance at 12 weeks (P < .01).

The 6-month trial included 60 adult patients (age 18 years and older) with a clinical diagnosis of lupus nephritis fulfilling classification criteria for LN grade III and IV. Patients needed to demonstrate objective signs of active nephritis consistent with persistent proteinuria greater than 0.5 g/day and/or cellular casts at screening to be included. Additional inclusion criteria were SLEDAI-2K greater than 4 and assessment of anti–double-stranded DNA and C3 serum levels at study entry. The patients were randomly assigned to two equal-sized groups, with one group receiving baricitinib 4 mg daily and a monthly placebo saline infusion, and the other group receiving monthly cyclophosphamide infusions and oral placebo tablets.

The incidence of adverse events was comparable between the two treatment groups, with 48% of patients in the baricitinib group and 46% in the cyclophosphamide group experiencing adverse events. Only three serious adverse events, specifically serious infection or herpes zoster, were recorded, leading to treatment discontinuation.

Two patients (6.6%) in the baricitinib group and one patient (3.3%) in the cyclophosphamide group were affected. The researchers recorded no major adverse cardiovascular or venous thromboembolic events, which are known to occur at higher rates among some users of baricitinib and other JAK inhibitors. The safety profile of baricitinib was consistent with observations made in other inflammatory musculoskeletal diseases, and no new risks were identified.

However, there were some concerns expressed by audience members during the presentation.

“The primary endpoint is limited at proteinuria, while biopsy is considered the gold standard for measuring efficacy,” said Eric F. Morand, MD, head of the Monash Health rheumatology unit, Melbourne. This was not the only critical comment regarding the study that emerged during the discussion. The use of a 4-mg dosage regimen throughout the entire study duration (despite official recommendations suggesting a 2-mg dosage in the long run) and the positive outcomes observed in the control group treated with cyclophosphamide were also mentioned.

Dr. Hassanien acknowledged that this is a small and relatively short study and disclosed plans to extend the follow-up period to 1 year and conduct a renal biopsy.

Dr. Hassanien reported no relevant financial relationships. Assiut University funded the trial.

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

MILAN – The oral Janus kinase (JAK) 1/2 inhibitor baricitinib (Olumiant) demonstrated significantly better efficacy than cyclophosphamide infusions in the treatment of lupus nephritis in a small, independently funded, phase 3, double-blind clinical trial, Manal Hassanien, MD, reported at the annual European Congress of Rheumatology.

Baricitinib, licensed by Eli Lilly, has been recognized as a potential therapeutic option in systemic lupus, and is approved in the United States to treat RA, alopecia areata, and COVID-19 in certain hospitalized adults. It is also approved to treat atopic dermatitis in Europe. However, it previously yielded disappointing results in phase 3 clinical trials SLE-BRAVE-I and SLE-BRAVE-II for systemic lupus erythematosus. The trial results presented at EULAR suggest that baricitinib could be beneficial in the treatment of lupus nephritis, further establishing the role of JAK inhibitors in autoimmune disease therapy.

“Lupus nephritis typically develops within 5 years of initial lupus symptoms,” said Dr. Hassanien, of the rheumatology research and advanced therapeutics department at Assiut (Egypt) University. “Research has shown that up to 60% of lupus patients will eventually develop lupus nephritis. The management of proliferative lupus nephritis usually involves an initial phase focused on preventing the development of irreversible damage, followed by a maintenance phase to control lupus activity. Despite significant progress, lupus nephritis still carries an increased risk of end-stage renal disease and mortality.”

The study’s primary endpoint of 24-hour proteinuria response rate (≥ 50% reduction from baseline) at week 12 was significantly greater with baricitinib 4 mg daily, compared with monthly cyclophosphamide infusions at 0.7 mg/m² (70% vs. 43%; P < .0001). At week 24, 76.6% of the baricitinib group met the primary endpoint, compared with 50% in the cyclophosphamide group. Two multiplicity-controlled secondary endpoints, C3 serum level and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), also showed statistical significance at 12 weeks (P < .01).

The 6-month trial included 60 adult patients (age 18 years and older) with a clinical diagnosis of lupus nephritis fulfilling classification criteria for LN grade III and IV. Patients needed to demonstrate objective signs of active nephritis consistent with persistent proteinuria greater than 0.5 g/day and/or cellular casts at screening to be included. Additional inclusion criteria were SLEDAI-2K greater than 4 and assessment of anti–double-stranded DNA and C3 serum levels at study entry. The patients were randomly assigned to two equal-sized groups, with one group receiving baricitinib 4 mg daily and a monthly placebo saline infusion, and the other group receiving monthly cyclophosphamide infusions and oral placebo tablets.

The incidence of adverse events was comparable between the two treatment groups, with 48% of patients in the baricitinib group and 46% in the cyclophosphamide group experiencing adverse events. Only three serious adverse events, specifically serious infection or herpes zoster, were recorded, leading to treatment discontinuation.

Two patients (6.6%) in the baricitinib group and one patient (3.3%) in the cyclophosphamide group were affected. The researchers recorded no major adverse cardiovascular or venous thromboembolic events, which are known to occur at higher rates among some users of baricitinib and other JAK inhibitors. The safety profile of baricitinib was consistent with observations made in other inflammatory musculoskeletal diseases, and no new risks were identified.

However, there were some concerns expressed by audience members during the presentation.

“The primary endpoint is limited at proteinuria, while biopsy is considered the gold standard for measuring efficacy,” said Eric F. Morand, MD, head of the Monash Health rheumatology unit, Melbourne. This was not the only critical comment regarding the study that emerged during the discussion. The use of a 4-mg dosage regimen throughout the entire study duration (despite official recommendations suggesting a 2-mg dosage in the long run) and the positive outcomes observed in the control group treated with cyclophosphamide were also mentioned.

Dr. Hassanien acknowledged that this is a small and relatively short study and disclosed plans to extend the follow-up period to 1 year and conduct a renal biopsy.

Dr. Hassanien reported no relevant financial relationships. Assiut University funded the trial.

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