MDedge Rheumatology

A deep molecular dive into COVID-19 patients found that the presence of autoantibodies in peripheral blood at initial diagnosis was the chief of four risk factors predicting if a patient would experience long COVID.

Other significant early predictors of prolonged COVID symptoms – which the researchers called postacute sequelae – were having type 2 diabetes, SARS-CoV-2 RNAemia, and Epstein-Barr virus (EBV) viremia, Yapeng Su, PhD, of the Institute for Systems Biology (ISB) in Seattle, and colleagues wrote in Cell.

Having EBV viremia suggested that latent EBV has been reactivated, the authors noted.

“The most important postacute sequelae [that is conditions that are consequences of a disease] of COVID is the presence of autoantibodies,” James R. Heath, PhD, president of ISB and a bioengineering professor at the University of Washington, Seattle, said in an interview. “It’s about two times more important than the others.”

Dr. Heath and coauthors said early detection of this and other variables could prompt earlier aggressive treatment in patients susceptible to long COVID and ward off lingering symptoms.

“These predictive measures of long COVID can also help to better inform patients of their possible disease course,” study coauthor Daniel G. Chen, an undergraduate researcher at ISB, said in an interview. “We were also able to partially resolve the immunological underpinnings of some postacute sequelae of COVID in a way that suggested potential therapies, and the timing of those therapies.”

For example, he continued, the use of antivirals very early in the infectious course may mitigate the later development of long COVID. “This will, of course, have to be explored in an appropriately designed clinical trial.

“We also identified biomarkers of certain types of long COVID, such as neurological sequelae. Those biomarkers can help define the condition, which is a first step towards developing treatments.”

Study findings

With COVID patients monitored for 2 or 3 months, the study findings of the international “multiomic profiling” analysis include:

• Subclinical patient autoantibodies that reduce anti–SARS-CoV-2 antibodies suggest there is immune dysregulation during COVID-19 infection.
• Reactivation of latent other viruses during initial infection may be contributing to long COVID.
• Gastrointestinal postacute sequelae of COVID presents with a unique postacute expansion of cytotoxic T cells.
• SARS-CoV-2–specific and cytomegalovirus-specific CD8+ T cells displayed unique dynamics during recovery from infection.

According to the authors, as many as 69% of COVID-19 patients suffer from long COVID – a range of new, recurrent, or ongoing problems 4 or more weeks following initial SARS-CoV-2 infection. These may include memory loss, gastrointestinal distress, fatigue, anosmia, and shortness of breath.

Long COVID has been associated with acute disease severity, and is suspected to be related to autoimmune factors and unresolved viral fragments, according to the paper.
 

Research methods

The international study did a deep and detailed dive into multiple molecular markers of long COVID. It enrolled 209 COVID-19 patients with varying degrees of disease severity and matched them to 457 healthy controls. The researchers’ goal was to identify discrete and quantifiable long COVID factors and guide possible preemptive treatment. 

Patients were assessed at three time points: at initial diagnosis, during the acute disease phase about a week later, and again 2 to 3 months post onset of symptoms after recovery from the acute phase of COVID. At the third assessment, some patients had lingering symptoms such as fatigue (52% ), cough (25%), and loss of taste or sense of smell (18%).

Blood draws were analyzed for autoantibodies and SARS-CoV-2–specific antibodies, global plasma proteomic and metabolomic profiles, and single-cell multiomic characterizations of peripheral blood mononuclear cells.

Each blood draw was paired with nasal-swab and plasma measurements of SARS-CoV-2 viral load and the data sets were integrated with electronic health records and self-reported patient symptoms to guide the interpretation of the molecular signatures of long COVID.
 

Author conclusions

The authors found an association between T2 hyperinflammation and long COVID–anticipating autoantibodies. This association further implies that hyperinflammation-controlling therapies in the acute stage of COVID may influence whether a patient experiences long COVID. “However, the detailed timing and context of these therapies matter, and, thus, future well-controlled studies will be needed to test these and other therapeutic implications,” Dr. Su and colleagues wrote.

Moreover, the negative correlations between anti–SARS-CoV-2 IgG and certain autoantibodies may suggest that patients with elevated autoantibody levels are more susceptible to breakthrough infections, the authors said.

“Many patients with high autoantibodies simultaneously have low protective antibodies that neutralize SARS-CoV-2, and that’s going to make them more susceptible to breakthrough infections,” Mr. Chen explained.*

“Detectability of most [long COVID-19 factors] at COVID diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests [long COVID] treatment strategies,” they wrote.

According to Mr. Chen, there are clear similarities in underlying immunobiology between patients with COVID autoantibodies and patients with systemic lupus erythematosus.

“These findings are also helping us frame our thinking around other chronic autoimmune conditions, such as postacute Lyme syndrome, for example,” said Dr. Heath.

The bottom line, said Mr. Chen, is that measuring early long COVID indicators may result in preventive treatments. “An example is the cortisol deficiency we see in certain long COVID patients. There are known treatments such as cortisol replacement therapy that should be explored for this group.”

Outside expert’s take on findings

Commenting on the study, Sherry Hsiang-Yi Chou, MD, who was not involved in the research, called the study a very important first step in understanding the path of this complex phenomenon and perhaps other conditions with long-term side effects.

“The researchers have done huge amount of innovative scientific work. They’ve shown the DNA signature of how our bodies respond to this disease,” said Dr. Chou, who is chief of the division of neurocritical care at Northwestern Medicine in Chicago.

“This type of research will help us scientifically understand and differentiate the various syndromes within long COVID. It will help identify who’s at risk for different aspects of this syndrome and lead to following them for longer periods in clinical trials,” she added.

The authors acknowledged that lengthier studies in larger cohorts were needed to see which patients will develop long-term chronic postacute sequelae of COVID.

This research was supported by the Wilke Family Foundation, the Parker Institute for Cancer Immunotherapy, Merck, and the Biomedical Advanced Research and Development Authority. Other support came from the National Institutes of Health, the Bill and Melinda Gates Foundation, Saint John’s Cancer Center, Fred Hutchinson Cancer Research Center, and the European Union’s Horizon 2020 research and innovation program. Dr. Heath is a cofounder of Pact Pharma. He and several coauthors disclosed various ties to multiple private-sector companies. Mr. Chen and Dr. Chou had no competing interests.

*Correction, 1/28: An earlier version of this story misidentified Daniel G. Chen, an undergraduate researcher at ISB.

A deep molecular dive into COVID-19 patients found that the presence of autoantibodies in peripheral blood at initial diagnosis was the chief of four risk factors predicting if a patient would experience long COVID.

Other significant early predictors of prolonged COVID symptoms – which the researchers called postacute sequelae – were having type 2 diabetes, SARS-CoV-2 RNAemia, and Epstein-Barr virus (EBV) viremia, Yapeng Su, PhD, of the Institute for Systems Biology (ISB) in Seattle, and colleagues wrote in Cell.

Having EBV viremia suggested that latent EBV has been reactivated, the authors noted.

“The most important postacute sequelae [that is conditions that are consequences of a disease] of COVID is the presence of autoantibodies,” James R. Heath, PhD, president of ISB and a bioengineering professor at the University of Washington, Seattle, said in an interview. “It’s about two times more important than the others.”

Dr. Heath and coauthors said early detection of this and other variables could prompt earlier aggressive treatment in patients susceptible to long COVID and ward off lingering symptoms.

“These predictive measures of long COVID can also help to better inform patients of their possible disease course,” study coauthor Daniel G. Chen, an undergraduate researcher at ISB, said in an interview. “We were also able to partially resolve the immunological underpinnings of some postacute sequelae of COVID in a way that suggested potential therapies, and the timing of those therapies.”

For example, he continued, the use of antivirals very early in the infectious course may mitigate the later development of long COVID. “This will, of course, have to be explored in an appropriately designed clinical trial.

“We also identified biomarkers of certain types of long COVID, such as neurological sequelae. Those biomarkers can help define the condition, which is a first step towards developing treatments.”

Study findings

With COVID patients monitored for 2 or 3 months, the study findings of the international “multiomic profiling” analysis include:

• Subclinical patient autoantibodies that reduce anti–SARS-CoV-2 antibodies suggest there is immune dysregulation during COVID-19 infection.
• Reactivation of latent other viruses during initial infection may be contributing to long COVID.
• Gastrointestinal postacute sequelae of COVID presents with a unique postacute expansion of cytotoxic T cells.
• SARS-CoV-2–specific and cytomegalovirus-specific CD8+ T cells displayed unique dynamics during recovery from infection.

According to the authors, as many as 69% of COVID-19 patients suffer from long COVID – a range of new, recurrent, or ongoing problems 4 or more weeks following initial SARS-CoV-2 infection. These may include memory loss, gastrointestinal distress, fatigue, anosmia, and shortness of breath.

Long COVID has been associated with acute disease severity, and is suspected to be related to autoimmune factors and unresolved viral fragments, according to the paper.
 

Research methods

The international study did a deep and detailed dive into multiple molecular markers of long COVID. It enrolled 209 COVID-19 patients with varying degrees of disease severity and matched them to 457 healthy controls. The researchers’ goal was to identify discrete and quantifiable long COVID factors and guide possible preemptive treatment. 

Patients were assessed at three time points: at initial diagnosis, during the acute disease phase about a week later, and again 2 to 3 months post onset of symptoms after recovery from the acute phase of COVID. At the third assessment, some patients had lingering symptoms such as fatigue (52% ), cough (25%), and loss of taste or sense of smell (18%).

Blood draws were analyzed for autoantibodies and SARS-CoV-2–specific antibodies, global plasma proteomic and metabolomic profiles, and single-cell multiomic characterizations of peripheral blood mononuclear cells.

Each blood draw was paired with nasal-swab and plasma measurements of SARS-CoV-2 viral load and the data sets were integrated with electronic health records and self-reported patient symptoms to guide the interpretation of the molecular signatures of long COVID.
 

Author conclusions

The authors found an association between T2 hyperinflammation and long COVID–anticipating autoantibodies. This association further implies that hyperinflammation-controlling therapies in the acute stage of COVID may influence whether a patient experiences long COVID. “However, the detailed timing and context of these therapies matter, and, thus, future well-controlled studies will be needed to test these and other therapeutic implications,” Dr. Su and colleagues wrote.

Moreover, the negative correlations between anti–SARS-CoV-2 IgG and certain autoantibodies may suggest that patients with elevated autoantibody levels are more susceptible to breakthrough infections, the authors said.

“Many patients with high autoantibodies simultaneously have low protective antibodies that neutralize SARS-CoV-2, and that’s going to make them more susceptible to breakthrough infections,” Mr. Chen explained.*

“Detectability of most [long COVID-19 factors] at COVID diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests [long COVID] treatment strategies,” they wrote.

According to Mr. Chen, there are clear similarities in underlying immunobiology between patients with COVID autoantibodies and patients with systemic lupus erythematosus.

“These findings are also helping us frame our thinking around other chronic autoimmune conditions, such as postacute Lyme syndrome, for example,” said Dr. Heath.

The bottom line, said Mr. Chen, is that measuring early long COVID indicators may result in preventive treatments. “An example is the cortisol deficiency we see in certain long COVID patients. There are known treatments such as cortisol replacement therapy that should be explored for this group.”

Outside expert’s take on findings

Commenting on the study, Sherry Hsiang-Yi Chou, MD, who was not involved in the research, called the study a very important first step in understanding the path of this complex phenomenon and perhaps other conditions with long-term side effects.

“The researchers have done huge amount of innovative scientific work. They’ve shown the DNA signature of how our bodies respond to this disease,” said Dr. Chou, who is chief of the division of neurocritical care at Northwestern Medicine in Chicago.

“This type of research will help us scientifically understand and differentiate the various syndromes within long COVID. It will help identify who’s at risk for different aspects of this syndrome and lead to following them for longer periods in clinical trials,” she added.

The authors acknowledged that lengthier studies in larger cohorts were needed to see which patients will develop long-term chronic postacute sequelae of COVID.

This research was supported by the Wilke Family Foundation, the Parker Institute for Cancer Immunotherapy, Merck, and the Biomedical Advanced Research and Development Authority. Other support came from the National Institutes of Health, the Bill and Melinda Gates Foundation, Saint John’s Cancer Center, Fred Hutchinson Cancer Research Center, and the European Union’s Horizon 2020 research and innovation program. Dr. Heath is a cofounder of Pact Pharma. He and several coauthors disclosed various ties to multiple private-sector companies. Mr. Chen and Dr. Chou had no competing interests.

*Correction, 1/28: An earlier version of this story misidentified Daniel G. Chen, an undergraduate researcher at ISB.

A deep molecular dive into COVID-19 patients found that the presence of autoantibodies in peripheral blood at initial diagnosis was the chief of four risk factors predicting if a patient would experience long COVID.

Other significant early predictors of prolonged COVID symptoms – which the researchers called postacute sequelae – were having type 2 diabetes, SARS-CoV-2 RNAemia, and Epstein-Barr virus (EBV) viremia, Yapeng Su, PhD, of the Institute for Systems Biology (ISB) in Seattle, and colleagues wrote in Cell.

Having EBV viremia suggested that latent EBV has been reactivated, the authors noted.

“The most important postacute sequelae [that is conditions that are consequences of a disease] of COVID is the presence of autoantibodies,” James R. Heath, PhD, president of ISB and a bioengineering professor at the University of Washington, Seattle, said in an interview. “It’s about two times more important than the others.”

Dr. Heath and coauthors said early detection of this and other variables could prompt earlier aggressive treatment in patients susceptible to long COVID and ward off lingering symptoms.

“These predictive measures of long COVID can also help to better inform patients of their possible disease course,” study coauthor Daniel G. Chen, an undergraduate researcher at ISB, said in an interview. “We were also able to partially resolve the immunological underpinnings of some postacute sequelae of COVID in a way that suggested potential therapies, and the timing of those therapies.”

For example, he continued, the use of antivirals very early in the infectious course may mitigate the later development of long COVID. “This will, of course, have to be explored in an appropriately designed clinical trial.

“We also identified biomarkers of certain types of long COVID, such as neurological sequelae. Those biomarkers can help define the condition, which is a first step towards developing treatments.”

Study findings

With COVID patients monitored for 2 or 3 months, the study findings of the international “multiomic profiling” analysis include:

• Subclinical patient autoantibodies that reduce anti–SARS-CoV-2 antibodies suggest there is immune dysregulation during COVID-19 infection.
• Reactivation of latent other viruses during initial infection may be contributing to long COVID.
• Gastrointestinal postacute sequelae of COVID presents with a unique postacute expansion of cytotoxic T cells.
• SARS-CoV-2–specific and cytomegalovirus-specific CD8+ T cells displayed unique dynamics during recovery from infection.

According to the authors, as many as 69% of COVID-19 patients suffer from long COVID – a range of new, recurrent, or ongoing problems 4 or more weeks following initial SARS-CoV-2 infection. These may include memory loss, gastrointestinal distress, fatigue, anosmia, and shortness of breath.

Long COVID has been associated with acute disease severity, and is suspected to be related to autoimmune factors and unresolved viral fragments, according to the paper.
 

Research methods

The international study did a deep and detailed dive into multiple molecular markers of long COVID. It enrolled 209 COVID-19 patients with varying degrees of disease severity and matched them to 457 healthy controls. The researchers’ goal was to identify discrete and quantifiable long COVID factors and guide possible preemptive treatment. 

Patients were assessed at three time points: at initial diagnosis, during the acute disease phase about a week later, and again 2 to 3 months post onset of symptoms after recovery from the acute phase of COVID. At the third assessment, some patients had lingering symptoms such as fatigue (52% ), cough (25%), and loss of taste or sense of smell (18%).

Blood draws were analyzed for autoantibodies and SARS-CoV-2–specific antibodies, global plasma proteomic and metabolomic profiles, and single-cell multiomic characterizations of peripheral blood mononuclear cells.

Each blood draw was paired with nasal-swab and plasma measurements of SARS-CoV-2 viral load and the data sets were integrated with electronic health records and self-reported patient symptoms to guide the interpretation of the molecular signatures of long COVID.
 

Author conclusions

The authors found an association between T2 hyperinflammation and long COVID–anticipating autoantibodies. This association further implies that hyperinflammation-controlling therapies in the acute stage of COVID may influence whether a patient experiences long COVID. “However, the detailed timing and context of these therapies matter, and, thus, future well-controlled studies will be needed to test these and other therapeutic implications,” Dr. Su and colleagues wrote.

Moreover, the negative correlations between anti–SARS-CoV-2 IgG and certain autoantibodies may suggest that patients with elevated autoantibody levels are more susceptible to breakthrough infections, the authors said.

“Many patients with high autoantibodies simultaneously have low protective antibodies that neutralize SARS-CoV-2, and that’s going to make them more susceptible to breakthrough infections,” Mr. Chen explained.*

“Detectability of most [long COVID-19 factors] at COVID diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests [long COVID] treatment strategies,” they wrote.

According to Mr. Chen, there are clear similarities in underlying immunobiology between patients with COVID autoantibodies and patients with systemic lupus erythematosus.

“These findings are also helping us frame our thinking around other chronic autoimmune conditions, such as postacute Lyme syndrome, for example,” said Dr. Heath.

The bottom line, said Mr. Chen, is that measuring early long COVID indicators may result in preventive treatments. “An example is the cortisol deficiency we see in certain long COVID patients. There are known treatments such as cortisol replacement therapy that should be explored for this group.”

Outside expert’s take on findings

Commenting on the study, Sherry Hsiang-Yi Chou, MD, who was not involved in the research, called the study a very important first step in understanding the path of this complex phenomenon and perhaps other conditions with long-term side effects.

“The researchers have done huge amount of innovative scientific work. They’ve shown the DNA signature of how our bodies respond to this disease,” said Dr. Chou, who is chief of the division of neurocritical care at Northwestern Medicine in Chicago.

“This type of research will help us scientifically understand and differentiate the various syndromes within long COVID. It will help identify who’s at risk for different aspects of this syndrome and lead to following them for longer periods in clinical trials,” she added.

The authors acknowledged that lengthier studies in larger cohorts were needed to see which patients will develop long-term chronic postacute sequelae of COVID.

This research was supported by the Wilke Family Foundation, the Parker Institute for Cancer Immunotherapy, Merck, and the Biomedical Advanced Research and Development Authority. Other support came from the National Institutes of Health, the Bill and Melinda Gates Foundation, Saint John’s Cancer Center, Fred Hutchinson Cancer Research Center, and the European Union’s Horizon 2020 research and innovation program. Dr. Heath is a cofounder of Pact Pharma. He and several coauthors disclosed various ties to multiple private-sector companies. Mr. Chen and Dr. Chou had no competing interests.

*Correction, 1/28: An earlier version of this story misidentified Daniel G. Chen, an undergraduate researcher at ISB.

Over the period of 1 year, secukinumab 300 mg every 2 weeks demonstrated superior efficacy compared with secukinumab 300 mg every 4 weeks in overweight patients with moderate to severe plaque psoriasis, results from a multicenter, double-blind, parallel-group trial showed.

The more frequent dosing was also associated with comparable safety, consistent with the established secukinumab safety profile.

“Weight may have an impact on pharmacokinetics and, therefore, on the clinical outcome of biologic treatment for psoriasis,” Matthias Augustin, MD, and colleagues wrote in the study, published recently in the British Journal of Dermatology. “Dose optimization may be highly beneficial for patients with higher body weight,” they noted, adding that their study supports previous study findings and pharmacokinetic/pharmacodynamic modelling data, showing that secukinumab dosed every 2 weeks “leads to a clinically and statistically significant advantage in PASI 90 response,” compared with standard dosing every 4 weeks in patients who weight 90 kg (about 198 pounds) or more, after 16 weeks of treatment, which was maintained until week 52.

For the study, Dr. Augustin, of the Institute for Health Services Research in Dermatology and Nursing at University Medical Center Hamburg-Eppendorf (Germany), and colleagues randomized 331 patients with moderate to severe chronic plaque psoriasis who weighed 90 kg or more to receive secukinumab 300 mg every 2 weeks, or secukinumab 300 mg every 4 weeks. The mean age of the patients was 47 years, 75% were male, 92% were White, and their mean body weight was 111.1 kg, with a mean body mass index of 36.1 kg/m².

Patients who did not achieve a Psoriasis Area and Severity Index (PASI) 90 at week 16 on the monthly regimen (Q4W) either remained on that regimen or were up-titrated to dosing every 2 weeks (Q2W). Of the 331 patients, 165 received Q2W dosing and 166 received Q4W dosing. The researchers found that, at 16 weeks, patients in the Q2W dosing group had significantly higher PASI 90 responses, compared with those in the Q4W group (73.2% vs. 55.5%, respectively; P = .0003; odds ratio estimate, 2.3).

At 52 weeks, a greater proportion of patients in the Q2W group maintained responses to several outcome measures, compared with those in the Q4W group, including PASI 75 (88.9% vs. 74.8%), PASI 90 (76.4% vs. 52.4%), and PASI 100 (46.7% vs. 27.3%) scores; Investigator’s Global Assessment score of 0 or 1 (75.9% vs. 55.6%); and Dermatology Life Quality Index scores of 0 or 1 (66.1% vs. 48.8%).

In addition, those who had not had a PASI 90 response at week 16 who were up-titrated to Q2W dosing demonstrated higher efficacy responses at week 32, compared with those who remained on the Q4W regimen, with PASI 90 scores of 37.7% versus 16.5%, respectively.

Both regimens were well-tolerated, consistent with the known secukinumab safety profile; safety was comparable in the treatment arms, and there was “no clear dose-response relationship seen” for the incidence of overall adverse events, serious AEs, and AEs leading to discontinuation of the study treatment, “or AEs related to the identified risks” of infections, hypersensitivity, neutropenia and potential risk of major adverse cardiovascular events, the authors wrote.

“Despite more frequent dosing, the incidence of Candida infections was numerically lower in the Q2W group versus the Q4W group,” although there were not many cases, three patients versus six patients, respectively.

 

Need for individualized treatment

“Despite a decades-long revolution in development of highly efficacious biologic treatments for psoriasis, we are only in the early stages of developing personalized clinical approaches,” said Raj Chovatiya, MD, PhD, a dermatologist at Northwestern University, Chicago, who was asked to comment on the study. “The need for individualized treatment in psoriasis is very real; not every patient may respond to therapy in the same way. Obesity is one important comorbidity of psoriasis, and increased body mass index may be associated with variable treatment outcomes with systemic therapy.”

The data from this study, he added, “suggest that dose optimization may be an important strategy to enhance psoriasis clearance in patients with suboptimal treatment outcomes on standard dosing, including those with increased weight. Future studies should examine optimal regimen of biologic therapy across a variety of patient factors.”

The study was funded by Novartis, the manufacturer of secukinumab (Cosentyx); several authors were company employees. Dr. Augustin disclosed that he has served as a consultant for or has been a paid speaker for clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Medac, Merck, MSD, Novartis, Pfizer, UCB, and Xenoport. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arcutis, Arena, Incyte, Pfizer, Regeneron, and Sanofi Genzyme.

Over the period of 1 year, secukinumab 300 mg every 2 weeks demonstrated superior efficacy compared with secukinumab 300 mg every 4 weeks in overweight patients with moderate to severe plaque psoriasis, results from a multicenter, double-blind, parallel-group trial showed.

The more frequent dosing was also associated with comparable safety, consistent with the established secukinumab safety profile.

“Weight may have an impact on pharmacokinetics and, therefore, on the clinical outcome of biologic treatment for psoriasis,” Matthias Augustin, MD, and colleagues wrote in the study, published recently in the British Journal of Dermatology. “Dose optimization may be highly beneficial for patients with higher body weight,” they noted, adding that their study supports previous study findings and pharmacokinetic/pharmacodynamic modelling data, showing that secukinumab dosed every 2 weeks “leads to a clinically and statistically significant advantage in PASI 90 response,” compared with standard dosing every 4 weeks in patients who weight 90 kg (about 198 pounds) or more, after 16 weeks of treatment, which was maintained until week 52.

For the study, Dr. Augustin, of the Institute for Health Services Research in Dermatology and Nursing at University Medical Center Hamburg-Eppendorf (Germany), and colleagues randomized 331 patients with moderate to severe chronic plaque psoriasis who weighed 90 kg or more to receive secukinumab 300 mg every 2 weeks, or secukinumab 300 mg every 4 weeks. The mean age of the patients was 47 years, 75% were male, 92% were White, and their mean body weight was 111.1 kg, with a mean body mass index of 36.1 kg/m².

Patients who did not achieve a Psoriasis Area and Severity Index (PASI) 90 at week 16 on the monthly regimen (Q4W) either remained on that regimen or were up-titrated to dosing every 2 weeks (Q2W). Of the 331 patients, 165 received Q2W dosing and 166 received Q4W dosing. The researchers found that, at 16 weeks, patients in the Q2W dosing group had significantly higher PASI 90 responses, compared with those in the Q4W group (73.2% vs. 55.5%, respectively; P = .0003; odds ratio estimate, 2.3).

At 52 weeks, a greater proportion of patients in the Q2W group maintained responses to several outcome measures, compared with those in the Q4W group, including PASI 75 (88.9% vs. 74.8%), PASI 90 (76.4% vs. 52.4%), and PASI 100 (46.7% vs. 27.3%) scores; Investigator’s Global Assessment score of 0 or 1 (75.9% vs. 55.6%); and Dermatology Life Quality Index scores of 0 or 1 (66.1% vs. 48.8%).

In addition, those who had not had a PASI 90 response at week 16 who were up-titrated to Q2W dosing demonstrated higher efficacy responses at week 32, compared with those who remained on the Q4W regimen, with PASI 90 scores of 37.7% versus 16.5%, respectively.

Both regimens were well-tolerated, consistent with the known secukinumab safety profile; safety was comparable in the treatment arms, and there was “no clear dose-response relationship seen” for the incidence of overall adverse events, serious AEs, and AEs leading to discontinuation of the study treatment, “or AEs related to the identified risks” of infections, hypersensitivity, neutropenia and potential risk of major adverse cardiovascular events, the authors wrote.

“Despite more frequent dosing, the incidence of Candida infections was numerically lower in the Q2W group versus the Q4W group,” although there were not many cases, three patients versus six patients, respectively.

 

Need for individualized treatment

“Despite a decades-long revolution in development of highly efficacious biologic treatments for psoriasis, we are only in the early stages of developing personalized clinical approaches,” said Raj Chovatiya, MD, PhD, a dermatologist at Northwestern University, Chicago, who was asked to comment on the study. “The need for individualized treatment in psoriasis is very real; not every patient may respond to therapy in the same way. Obesity is one important comorbidity of psoriasis, and increased body mass index may be associated with variable treatment outcomes with systemic therapy.”

The data from this study, he added, “suggest that dose optimization may be an important strategy to enhance psoriasis clearance in patients with suboptimal treatment outcomes on standard dosing, including those with increased weight. Future studies should examine optimal regimen of biologic therapy across a variety of patient factors.”

The study was funded by Novartis, the manufacturer of secukinumab (Cosentyx); several authors were company employees. Dr. Augustin disclosed that he has served as a consultant for or has been a paid speaker for clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Medac, Merck, MSD, Novartis, Pfizer, UCB, and Xenoport. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arcutis, Arena, Incyte, Pfizer, Regeneron, and Sanofi Genzyme.

Over the period of 1 year, secukinumab 300 mg every 2 weeks demonstrated superior efficacy compared with secukinumab 300 mg every 4 weeks in overweight patients with moderate to severe plaque psoriasis, results from a multicenter, double-blind, parallel-group trial showed.

The more frequent dosing was also associated with comparable safety, consistent with the established secukinumab safety profile.

“Weight may have an impact on pharmacokinetics and, therefore, on the clinical outcome of biologic treatment for psoriasis,” Matthias Augustin, MD, and colleagues wrote in the study, published recently in the British Journal of Dermatology. “Dose optimization may be highly beneficial for patients with higher body weight,” they noted, adding that their study supports previous study findings and pharmacokinetic/pharmacodynamic modelling data, showing that secukinumab dosed every 2 weeks “leads to a clinically and statistically significant advantage in PASI 90 response,” compared with standard dosing every 4 weeks in patients who weight 90 kg (about 198 pounds) or more, after 16 weeks of treatment, which was maintained until week 52.

For the study, Dr. Augustin, of the Institute for Health Services Research in Dermatology and Nursing at University Medical Center Hamburg-Eppendorf (Germany), and colleagues randomized 331 patients with moderate to severe chronic plaque psoriasis who weighed 90 kg or more to receive secukinumab 300 mg every 2 weeks, or secukinumab 300 mg every 4 weeks. The mean age of the patients was 47 years, 75% were male, 92% were White, and their mean body weight was 111.1 kg, with a mean body mass index of 36.1 kg/m².

Patients who did not achieve a Psoriasis Area and Severity Index (PASI) 90 at week 16 on the monthly regimen (Q4W) either remained on that regimen or were up-titrated to dosing every 2 weeks (Q2W). Of the 331 patients, 165 received Q2W dosing and 166 received Q4W dosing. The researchers found that, at 16 weeks, patients in the Q2W dosing group had significantly higher PASI 90 responses, compared with those in the Q4W group (73.2% vs. 55.5%, respectively; P = .0003; odds ratio estimate, 2.3).

At 52 weeks, a greater proportion of patients in the Q2W group maintained responses to several outcome measures, compared with those in the Q4W group, including PASI 75 (88.9% vs. 74.8%), PASI 90 (76.4% vs. 52.4%), and PASI 100 (46.7% vs. 27.3%) scores; Investigator’s Global Assessment score of 0 or 1 (75.9% vs. 55.6%); and Dermatology Life Quality Index scores of 0 or 1 (66.1% vs. 48.8%).

In addition, those who had not had a PASI 90 response at week 16 who were up-titrated to Q2W dosing demonstrated higher efficacy responses at week 32, compared with those who remained on the Q4W regimen, with PASI 90 scores of 37.7% versus 16.5%, respectively.

Both regimens were well-tolerated, consistent with the known secukinumab safety profile; safety was comparable in the treatment arms, and there was “no clear dose-response relationship seen” for the incidence of overall adverse events, serious AEs, and AEs leading to discontinuation of the study treatment, “or AEs related to the identified risks” of infections, hypersensitivity, neutropenia and potential risk of major adverse cardiovascular events, the authors wrote.

“Despite more frequent dosing, the incidence of Candida infections was numerically lower in the Q2W group versus the Q4W group,” although there were not many cases, three patients versus six patients, respectively.

 

Need for individualized treatment

“Despite a decades-long revolution in development of highly efficacious biologic treatments for psoriasis, we are only in the early stages of developing personalized clinical approaches,” said Raj Chovatiya, MD, PhD, a dermatologist at Northwestern University, Chicago, who was asked to comment on the study. “The need for individualized treatment in psoriasis is very real; not every patient may respond to therapy in the same way. Obesity is one important comorbidity of psoriasis, and increased body mass index may be associated with variable treatment outcomes with systemic therapy.”

The data from this study, he added, “suggest that dose optimization may be an important strategy to enhance psoriasis clearance in patients with suboptimal treatment outcomes on standard dosing, including those with increased weight. Future studies should examine optimal regimen of biologic therapy across a variety of patient factors.”

The study was funded by Novartis, the manufacturer of secukinumab (Cosentyx); several authors were company employees. Dr. Augustin disclosed that he has served as a consultant for or has been a paid speaker for clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Medac, Merck, MSD, Novartis, Pfizer, UCB, and Xenoport. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Arcutis, Arena, Incyte, Pfizer, Regeneron, and Sanofi Genzyme.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: A clinically noteworthy improvement in mental health was observed in patients with rheumatoid arthritis (RA) who were treated with Janus kinase (JAK) inhibitors.

Major finding: The pooled incremental mean reduction in short form-36 mental component score with JAK monotherapy was 4.95 (95% CI 4.41-5.48), which was greater than the minimum clinically important difference value of 2.5, indicating significant improvement in mental health following JAK monotherapy.

Study details: This was a meta-analysis of 19 studies involving 14,323 patients with RA.

Disclosures: This study received no specific funding. The authors did not have any potential conflict of interests.

Source: Shamail GMH et al. Rheumatol Ther. 2021 (Dec 13). Doi: 10.1007/s40744-021-00409-6.

Key clinical point: A clinically noteworthy improvement in mental health was observed in patients with rheumatoid arthritis (RA) who were treated with Janus kinase (JAK) inhibitors.

Major finding: The pooled incremental mean reduction in short form-36 mental component score with JAK monotherapy was 4.95 (95% CI 4.41-5.48), which was greater than the minimum clinically important difference value of 2.5, indicating significant improvement in mental health following JAK monotherapy.

Study details: This was a meta-analysis of 19 studies involving 14,323 patients with RA.

Disclosures: This study received no specific funding. The authors did not have any potential conflict of interests.

Source: Shamail GMH et al. Rheumatol Ther. 2021 (Dec 13). Doi: 10.1007/s40744-021-00409-6.

Key clinical point: A clinically noteworthy improvement in mental health was observed in patients with rheumatoid arthritis (RA) who were treated with Janus kinase (JAK) inhibitors.

Major finding: The pooled incremental mean reduction in short form-36 mental component score with JAK monotherapy was 4.95 (95% CI 4.41-5.48), which was greater than the minimum clinically important difference value of 2.5, indicating significant improvement in mental health following JAK monotherapy.

Study details: This was a meta-analysis of 19 studies involving 14,323 patients with RA.

Disclosures: This study received no specific funding. The authors did not have any potential conflict of interests.

Source: Shamail GMH et al. Rheumatol Ther. 2021 (Dec 13). Doi: 10.1007/s40744-021-00409-6.

Key clinical point: In a cohort of patients with early rheumatoid arthritis (RA), illness perceptions and suboptimal psychosocial well-being were associated with a lower likelihood of sustained remission.

Major finding: Among patients who were had a disease activity score in 28 joints-C-reactive protein remission at week 16, those with a low vs. high psychosocial burden profile showed a significantly longer time to first loss-of-remission (hazard ratio 0.51; P < .001).

Study details: This was a post hoc analysis of the CareRA trial involving 379 patients with early RA who received methotrexate ± additional conventional synthetic disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This study was supported in part by a Strategic Basic Research Fellowship grant from Fonds Wetenschappelijk Onderzoek. All the authors declared no conflicts of interest.

Source: Doumen M et al. Arthritis Care Res (Hoboken). 2021 (Dec 20). Doi: 10.1002/acr.24847.

Key clinical point: In a cohort of patients with early rheumatoid arthritis (RA), illness perceptions and suboptimal psychosocial well-being were associated with a lower likelihood of sustained remission.

Major finding: Among patients who were had a disease activity score in 28 joints-C-reactive protein remission at week 16, those with a low vs. high psychosocial burden profile showed a significantly longer time to first loss-of-remission (hazard ratio 0.51; P < .001).

Study details: This was a post hoc analysis of the CareRA trial involving 379 patients with early RA who received methotrexate ± additional conventional synthetic disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This study was supported in part by a Strategic Basic Research Fellowship grant from Fonds Wetenschappelijk Onderzoek. All the authors declared no conflicts of interest.

Source: Doumen M et al. Arthritis Care Res (Hoboken). 2021 (Dec 20). Doi: 10.1002/acr.24847.

Key clinical point: In a cohort of patients with early rheumatoid arthritis (RA), illness perceptions and suboptimal psychosocial well-being were associated with a lower likelihood of sustained remission.

Major finding: Among patients who were had a disease activity score in 28 joints-C-reactive protein remission at week 16, those with a low vs. high psychosocial burden profile showed a significantly longer time to first loss-of-remission (hazard ratio 0.51; P < .001).

Study details: This was a post hoc analysis of the CareRA trial involving 379 patients with early RA who received methotrexate ± additional conventional synthetic disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This study was supported in part by a Strategic Basic Research Fellowship grant from Fonds Wetenschappelijk Onderzoek. All the authors declared no conflicts of interest.

Source: Doumen M et al. Arthritis Care Res (Hoboken). 2021 (Dec 20). Doi: 10.1002/acr.24847.

Key clinical point: Celecoxib appeared to be relatively safer compared with nonselective nonsteroidal anti-inflammatory drugs (NSAID) or placebo in patients with rheumatoid arthritis (RA), regardless of dose or duration.

Major finding: Celecoxib was associated with a lower risk for all-cause mortality (risk ratio [RR] 0.81; 95% CI 0.66-0.98) and cardiovascular morality (RR 0.75; 95% CI 0.57-0.99) compared with NSAIDs and a similar risk for all-cause mortality (RR 0.92; 95% CI 0.26-3.27) and cardiovascular morality (RR 3.02; 95% CI 0.36-25.27) compared with placebo.

Study details: Findings are from a meta-analysis of 21 randomized clinical studies that compared cardiovascular safety of celecoxib with NSAIDs or placebo in patients with RA or osteoarthritis.

Disclosures: This study was supported by the National Natural Science Foundation project and others. No competing interests were declared.

Source: Cheng BR et al. PLoS One. 2021;16(12):e0261239 (Dec 21). Doi:  10.1371/journal.pone.0261239.

Key clinical point: Celecoxib appeared to be relatively safer compared with nonselective nonsteroidal anti-inflammatory drugs (NSAID) or placebo in patients with rheumatoid arthritis (RA), regardless of dose or duration.

Major finding: Celecoxib was associated with a lower risk for all-cause mortality (risk ratio [RR] 0.81; 95% CI 0.66-0.98) and cardiovascular morality (RR 0.75; 95% CI 0.57-0.99) compared with NSAIDs and a similar risk for all-cause mortality (RR 0.92; 95% CI 0.26-3.27) and cardiovascular morality (RR 3.02; 95% CI 0.36-25.27) compared with placebo.

Study details: Findings are from a meta-analysis of 21 randomized clinical studies that compared cardiovascular safety of celecoxib with NSAIDs or placebo in patients with RA or osteoarthritis.

Disclosures: This study was supported by the National Natural Science Foundation project and others. No competing interests were declared.

Source: Cheng BR et al. PLoS One. 2021;16(12):e0261239 (Dec 21). Doi:  10.1371/journal.pone.0261239.

Key clinical point: Celecoxib appeared to be relatively safer compared with nonselective nonsteroidal anti-inflammatory drugs (NSAID) or placebo in patients with rheumatoid arthritis (RA), regardless of dose or duration.

Major finding: Celecoxib was associated with a lower risk for all-cause mortality (risk ratio [RR] 0.81; 95% CI 0.66-0.98) and cardiovascular morality (RR 0.75; 95% CI 0.57-0.99) compared with NSAIDs and a similar risk for all-cause mortality (RR 0.92; 95% CI 0.26-3.27) and cardiovascular morality (RR 3.02; 95% CI 0.36-25.27) compared with placebo.

Study details: Findings are from a meta-analysis of 21 randomized clinical studies that compared cardiovascular safety of celecoxib with NSAIDs or placebo in patients with RA or osteoarthritis.

Disclosures: This study was supported by the National Natural Science Foundation project and others. No competing interests were declared.

Source: Cheng BR et al. PLoS One. 2021;16(12):e0261239 (Dec 21). Doi:  10.1371/journal.pone.0261239.

Key clinical point: Patients with rheumatoid arthritis (RA) experienced robust pain reduction with baricitinib, irrespective of opioid use.

Major finding: Compared with placebo, pain reduction was significantly greater at all time points, starting as early as week 1 (all P < .05) in both opioid users and nonusers receiving 4 mg baricitinib and only in opioid users receiving 2 mg baricitinib. Opioid nonusers receiving 2 mg baricitinib showed greater pain relief than placebo starting at week 4 (P < .05).

Study details: This was a post hoc analysis of 3 randomized controlled trials (RA-BEAM, RA-BUILD, and RA-BEACON) involving patients with RA with an inadequate response to either methotrexate, conventional disease-modifying antirheumatic drugs, or at least 1 tumor necrosis factor inhibitor, who were randomly assigned to either placebo, baricitinib (2 mg/4 mg), or adalimumab (40 mg) in addition to background therapy.

Disclosures: This study was funded by Eli Lilly under license from Incyte Corporation. The authors declared no conflict of interests.

Source: Pope JE et al. ACR Open Rheumatol. 2021 (Dec 16). Doi: 10.1002/acr2.11380.

Key clinical point: Patients with rheumatoid arthritis (RA) experienced robust pain reduction with baricitinib, irrespective of opioid use.

Major finding: Compared with placebo, pain reduction was significantly greater at all time points, starting as early as week 1 (all P < .05) in both opioid users and nonusers receiving 4 mg baricitinib and only in opioid users receiving 2 mg baricitinib. Opioid nonusers receiving 2 mg baricitinib showed greater pain relief than placebo starting at week 4 (P < .05).

Study details: This was a post hoc analysis of 3 randomized controlled trials (RA-BEAM, RA-BUILD, and RA-BEACON) involving patients with RA with an inadequate response to either methotrexate, conventional disease-modifying antirheumatic drugs, or at least 1 tumor necrosis factor inhibitor, who were randomly assigned to either placebo, baricitinib (2 mg/4 mg), or adalimumab (40 mg) in addition to background therapy.

Disclosures: This study was funded by Eli Lilly under license from Incyte Corporation. The authors declared no conflict of interests.

Source: Pope JE et al. ACR Open Rheumatol. 2021 (Dec 16). Doi: 10.1002/acr2.11380.

Key clinical point: Patients with rheumatoid arthritis (RA) experienced robust pain reduction with baricitinib, irrespective of opioid use.

Major finding: Compared with placebo, pain reduction was significantly greater at all time points, starting as early as week 1 (all P < .05) in both opioid users and nonusers receiving 4 mg baricitinib and only in opioid users receiving 2 mg baricitinib. Opioid nonusers receiving 2 mg baricitinib showed greater pain relief than placebo starting at week 4 (P < .05).

Study details: This was a post hoc analysis of 3 randomized controlled trials (RA-BEAM, RA-BUILD, and RA-BEACON) involving patients with RA with an inadequate response to either methotrexate, conventional disease-modifying antirheumatic drugs, or at least 1 tumor necrosis factor inhibitor, who were randomly assigned to either placebo, baricitinib (2 mg/4 mg), or adalimumab (40 mg) in addition to background therapy.

Disclosures: This study was funded by Eli Lilly under license from Incyte Corporation. The authors declared no conflict of interests.

Source: Pope JE et al. ACR Open Rheumatol. 2021 (Dec 16). Doi: 10.1002/acr2.11380.

Key clinical point: Significant improvement in patient-reported outcomes was observed with filgotinib in patients with rheumatoid arthritis (RA) with an insufficient response to methotrexate or biological disease-modifying antirheumatic drugs (DMARD) and those who were methotrexate-naive.

Major finding: Filgotinib at doses of 200 mg or 100 mg in combination with methotrexate/conventional synthetic DMARDs or 200 mg filgotinib monotherapy demonstrated a significant improvement in the health-related quality of life, fatigue, and assessments of disease activity and work impairment vs. comparators (all P < .05).

Study details: This was a post hoc analysis of phase 3 studies including patients with RA with an inadequate response to methotrexate (FINCH 1) or biological DMARDs (FINCH 2) and those who were methotrexate-naive (FINCH 3).

Disclosures: This study was supported by Gilead Sciences, Inc., Foster City, CA. SJ Lee, L Ye, and H Hu reported being employees and shareholders of Gilead Sciences. All the other authors disclosed receiving grants/research support and speaker/consultancy fees from various companies including Gilead Sciences.

Source: Bingham CO III et al. Arthritis Res Ther. 2022;24:11 (Jan 3). Doi: 10.1186/s13075-021-02677-7.

Key clinical point: Significant improvement in patient-reported outcomes was observed with filgotinib in patients with rheumatoid arthritis (RA) with an insufficient response to methotrexate or biological disease-modifying antirheumatic drugs (DMARD) and those who were methotrexate-naive.

Major finding: Filgotinib at doses of 200 mg or 100 mg in combination with methotrexate/conventional synthetic DMARDs or 200 mg filgotinib monotherapy demonstrated a significant improvement in the health-related quality of life, fatigue, and assessments of disease activity and work impairment vs. comparators (all P < .05).

Study details: This was a post hoc analysis of phase 3 studies including patients with RA with an inadequate response to methotrexate (FINCH 1) or biological DMARDs (FINCH 2) and those who were methotrexate-naive (FINCH 3).

Disclosures: This study was supported by Gilead Sciences, Inc., Foster City, CA. SJ Lee, L Ye, and H Hu reported being employees and shareholders of Gilead Sciences. All the other authors disclosed receiving grants/research support and speaker/consultancy fees from various companies including Gilead Sciences.

Source: Bingham CO III et al. Arthritis Res Ther. 2022;24:11 (Jan 3). Doi: 10.1186/s13075-021-02677-7.

Key clinical point: Significant improvement in patient-reported outcomes was observed with filgotinib in patients with rheumatoid arthritis (RA) with an insufficient response to methotrexate or biological disease-modifying antirheumatic drugs (DMARD) and those who were methotrexate-naive.

Major finding: Filgotinib at doses of 200 mg or 100 mg in combination with methotrexate/conventional synthetic DMARDs or 200 mg filgotinib monotherapy demonstrated a significant improvement in the health-related quality of life, fatigue, and assessments of disease activity and work impairment vs. comparators (all P < .05).

Study details: This was a post hoc analysis of phase 3 studies including patients with RA with an inadequate response to methotrexate (FINCH 1) or biological DMARDs (FINCH 2) and those who were methotrexate-naive (FINCH 3).

Disclosures: This study was supported by Gilead Sciences, Inc., Foster City, CA. SJ Lee, L Ye, and H Hu reported being employees and shareholders of Gilead Sciences. All the other authors disclosed receiving grants/research support and speaker/consultancy fees from various companies including Gilead Sciences.

Source: Bingham CO III et al. Arthritis Res Ther. 2022;24:11 (Jan 3). Doi: 10.1186/s13075-021-02677-7.

Key clinical point: Every 1 in 6 individuals with rheumatoid arthritis (RA) develop interstitial lung disease (ILD) within 20 years, with RA-associated ILD (RA-ILD), even when asymptomatic and radiologically limited, being significantly associated with shorter survival.

Major finding: The cumulative incidence of RA-ILD was 15.3% at 20 years after RA diagnosis, with mortality being higher in patients with RA-ILD vs. matched RA comparators (hazard ratio 2.42; 95% CI 1.32-4.41).

Study details: This was a population-based cohort study involving 645 patients with incident RA.

Disclosures: This study was funded by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and others. R Vassallo and JM Davis III reported receiving research grants from various sources.

Source: Samhouri BF et al. Arthritis Care Res (Hoboken). 2022 (Jan 7). Doi: 10.1002/acr.24856.

Key clinical point: Every 1 in 6 individuals with rheumatoid arthritis (RA) develop interstitial lung disease (ILD) within 20 years, with RA-associated ILD (RA-ILD), even when asymptomatic and radiologically limited, being significantly associated with shorter survival.

Major finding: The cumulative incidence of RA-ILD was 15.3% at 20 years after RA diagnosis, with mortality being higher in patients with RA-ILD vs. matched RA comparators (hazard ratio 2.42; 95% CI 1.32-4.41).

Study details: This was a population-based cohort study involving 645 patients with incident RA.

Disclosures: This study was funded by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and others. R Vassallo and JM Davis III reported receiving research grants from various sources.

Source: Samhouri BF et al. Arthritis Care Res (Hoboken). 2022 (Jan 7). Doi: 10.1002/acr.24856.

Key clinical point: Every 1 in 6 individuals with rheumatoid arthritis (RA) develop interstitial lung disease (ILD) within 20 years, with RA-associated ILD (RA-ILD), even when asymptomatic and radiologically limited, being significantly associated with shorter survival.

Major finding: The cumulative incidence of RA-ILD was 15.3% at 20 years after RA diagnosis, with mortality being higher in patients with RA-ILD vs. matched RA comparators (hazard ratio 2.42; 95% CI 1.32-4.41).

Study details: This was a population-based cohort study involving 645 patients with incident RA.

Disclosures: This study was funded by the National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and others. R Vassallo and JM Davis III reported receiving research grants from various sources.

Source: Samhouri BF et al. Arthritis Care Res (Hoboken). 2022 (Jan 7). Doi: 10.1002/acr.24856.