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TNFi use during pregnancy in women with RA increases birth weight of offspring
Key clinical point: In women with well-controlled rheumatoid arthritis (RA), the use of a tumor necrosis factor inhibitor (TNFi) during pregnancy was associated with increased birth weight of the offspring and the birth of fewer small-for-gestational age (SGA) children without an increase in adverse pregnancy outcomes.
Major finding: Compared with non-use of TNFi, the use of TNFi during pregnancy significantly increased the mean birth weight of the offspring (absolute difference 173 g; P = .03) and led to fewer SGA children being born (9.8% vs 20.0%; P = .05) without increasing the risk for large-for-gestational age and adverse pregnancy outcomes, such as prematurity, low birth weight of offspring, cesarean section, and hypertensive disorders.
Study details: Findings are from a prospective cohort study including 188 women with RA, of which 92 used TNFi during pregnancy.
Disclosures: This study was supported by the Dutch Arthritis Foundation and UCB. No competing interests were declared.
Source: Smeele HTW et al. Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients’ offspring. Ann Rheum Dis. 2022 (Jul 11). Doi: 10.1136/ard-2022-222679
Key clinical point: In women with well-controlled rheumatoid arthritis (RA), the use of a tumor necrosis factor inhibitor (TNFi) during pregnancy was associated with increased birth weight of the offspring and the birth of fewer small-for-gestational age (SGA) children without an increase in adverse pregnancy outcomes.
Major finding: Compared with non-use of TNFi, the use of TNFi during pregnancy significantly increased the mean birth weight of the offspring (absolute difference 173 g; P = .03) and led to fewer SGA children being born (9.8% vs 20.0%; P = .05) without increasing the risk for large-for-gestational age and adverse pregnancy outcomes, such as prematurity, low birth weight of offspring, cesarean section, and hypertensive disorders.
Study details: Findings are from a prospective cohort study including 188 women with RA, of which 92 used TNFi during pregnancy.
Disclosures: This study was supported by the Dutch Arthritis Foundation and UCB. No competing interests were declared.
Source: Smeele HTW et al. Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients’ offspring. Ann Rheum Dis. 2022 (Jul 11). Doi: 10.1136/ard-2022-222679
Key clinical point: In women with well-controlled rheumatoid arthritis (RA), the use of a tumor necrosis factor inhibitor (TNFi) during pregnancy was associated with increased birth weight of the offspring and the birth of fewer small-for-gestational age (SGA) children without an increase in adverse pregnancy outcomes.
Major finding: Compared with non-use of TNFi, the use of TNFi during pregnancy significantly increased the mean birth weight of the offspring (absolute difference 173 g; P = .03) and led to fewer SGA children being born (9.8% vs 20.0%; P = .05) without increasing the risk for large-for-gestational age and adverse pregnancy outcomes, such as prematurity, low birth weight of offspring, cesarean section, and hypertensive disorders.
Study details: Findings are from a prospective cohort study including 188 women with RA, of which 92 used TNFi during pregnancy.
Disclosures: This study was supported by the Dutch Arthritis Foundation and UCB. No competing interests were declared.
Source: Smeele HTW et al. Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients’ offspring. Ann Rheum Dis. 2022 (Jul 11). Doi: 10.1136/ard-2022-222679
Early methotrexate does not prevent progression to arthritis in arthralgia patients at risk for RA
Key clinical point: Early initiation of a single glucocorticoid injection with 1-year methotrexate treatment in patients with arthralgia at risk for rheumatoid arthritis (RA) did not prevent clinical arthritis but improved overall disease burden.
Major finding: At 2 years, the risk of developing clinical arthritis persisting for ≥2 weeks was similar (hazard ratio 0.81; 95% CI 0.45-1.48). However, methotrexate vs placebo showed sustained decrease in magnetic resonance imaging-detected joint inflammation (mean difference [MD] −1.4 points; P < .0001) and improvement in physical functioning (MD −0.09; P = .0042), pain (MD −8; P < .0001) and morning stiffness of joints (MD −12; P < .0001). No new adverse events were reported.
Study details: Findings are from TREAT-EARLIER, a randomized controlled proof-of-concept trial, including 236 patients with arthralgia clinically predisposed to RA who were randomly assigned to receive single glucocorticoid injection+methotrexate or placebo for 1 year.
Disclosures: This study was funded by the Dutch Research Council, supported by the Dutch Arthritis Society. The authors declared no conflicts of interest.
Source: Krijbolder DI et al. Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): A randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet. 2022;400(10348):283-294 (Jul 23). Doi: 10.1016/S0140-6736(22)01193-X
Key clinical point: Early initiation of a single glucocorticoid injection with 1-year methotrexate treatment in patients with arthralgia at risk for rheumatoid arthritis (RA) did not prevent clinical arthritis but improved overall disease burden.
Major finding: At 2 years, the risk of developing clinical arthritis persisting for ≥2 weeks was similar (hazard ratio 0.81; 95% CI 0.45-1.48). However, methotrexate vs placebo showed sustained decrease in magnetic resonance imaging-detected joint inflammation (mean difference [MD] −1.4 points; P < .0001) and improvement in physical functioning (MD −0.09; P = .0042), pain (MD −8; P < .0001) and morning stiffness of joints (MD −12; P < .0001). No new adverse events were reported.
Study details: Findings are from TREAT-EARLIER, a randomized controlled proof-of-concept trial, including 236 patients with arthralgia clinically predisposed to RA who were randomly assigned to receive single glucocorticoid injection+methotrexate or placebo for 1 year.
Disclosures: This study was funded by the Dutch Research Council, supported by the Dutch Arthritis Society. The authors declared no conflicts of interest.
Source: Krijbolder DI et al. Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): A randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet. 2022;400(10348):283-294 (Jul 23). Doi: 10.1016/S0140-6736(22)01193-X
Key clinical point: Early initiation of a single glucocorticoid injection with 1-year methotrexate treatment in patients with arthralgia at risk for rheumatoid arthritis (RA) did not prevent clinical arthritis but improved overall disease burden.
Major finding: At 2 years, the risk of developing clinical arthritis persisting for ≥2 weeks was similar (hazard ratio 0.81; 95% CI 0.45-1.48). However, methotrexate vs placebo showed sustained decrease in magnetic resonance imaging-detected joint inflammation (mean difference [MD] −1.4 points; P < .0001) and improvement in physical functioning (MD −0.09; P = .0042), pain (MD −8; P < .0001) and morning stiffness of joints (MD −12; P < .0001). No new adverse events were reported.
Study details: Findings are from TREAT-EARLIER, a randomized controlled proof-of-concept trial, including 236 patients with arthralgia clinically predisposed to RA who were randomly assigned to receive single glucocorticoid injection+methotrexate or placebo for 1 year.
Disclosures: This study was funded by the Dutch Research Council, supported by the Dutch Arthritis Society. The authors declared no conflicts of interest.
Source: Krijbolder DI et al. Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): A randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet. 2022;400(10348):283-294 (Jul 23). Doi: 10.1016/S0140-6736(22)01193-X
FDA approves adalimumab-bwwd biosimilar (Hadlima) in high-concentration form
The U.S. Food and Drug Administration today approved a citrate-free, high-concentration formulation of adalimumab-bwwd (Hadlima), the manufacturer, Samsung Bioepis, and its commercialization partner Organon said in an announcement.
Hadlima is a biosimilar of the tumor necrosis factor inhibitor reference product adalimumab (Humira).
Hadlima was first approved in July 2019 in a citrated, 50-mg/mL formulation. The new citrate-free, 100-mg/mL version will be available in prefilled syringe and autoinjector options.
The 100-mg/mL formulation is indicated for the same seven conditions as its 50-mg/mL counterpart: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult and pediatric Crohn’s disease, and ulcerative colitis.
The approval was based on clinical data from a randomized, single-blind, two-arm, parallel group, single-dose study that compared the pharmacokinetics, safety, tolerability, and immunogenicity of the 100-mg/mL and 50-mg/mL formulations of Hadlima in healthy volunteers.
Both low- and high-concentration formulations of Humira are currently marketed in the United States. Organon said that it expects to market Hadlima in the United States on or after July 1, 2023, in accordance with a licensing agreement with AbbVie.
The prescribing information for Hadlima includes specific warnings and areas of concern. The drug should not be administered to individuals who are known to be hypersensitive to adalimumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, including serious infections leading to hospitalization or death, such as tuberculosis, bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections attributable to other opportunistic pathogens.
A test for latent TB infection should be given before administration, and treatment of TB should begin before administration of Hadlima.
Patients taking Hadlima should not take a live vaccine.
The most common adverse effects (incidence > 10%) include infections (for example, upper respiratory infections, sinusitis), injection site reactions, headache, and rash.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration today approved a citrate-free, high-concentration formulation of adalimumab-bwwd (Hadlima), the manufacturer, Samsung Bioepis, and its commercialization partner Organon said in an announcement.
Hadlima is a biosimilar of the tumor necrosis factor inhibitor reference product adalimumab (Humira).
Hadlima was first approved in July 2019 in a citrated, 50-mg/mL formulation. The new citrate-free, 100-mg/mL version will be available in prefilled syringe and autoinjector options.
The 100-mg/mL formulation is indicated for the same seven conditions as its 50-mg/mL counterpart: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult and pediatric Crohn’s disease, and ulcerative colitis.
The approval was based on clinical data from a randomized, single-blind, two-arm, parallel group, single-dose study that compared the pharmacokinetics, safety, tolerability, and immunogenicity of the 100-mg/mL and 50-mg/mL formulations of Hadlima in healthy volunteers.
Both low- and high-concentration formulations of Humira are currently marketed in the United States. Organon said that it expects to market Hadlima in the United States on or after July 1, 2023, in accordance with a licensing agreement with AbbVie.
The prescribing information for Hadlima includes specific warnings and areas of concern. The drug should not be administered to individuals who are known to be hypersensitive to adalimumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, including serious infections leading to hospitalization or death, such as tuberculosis, bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections attributable to other opportunistic pathogens.
A test for latent TB infection should be given before administration, and treatment of TB should begin before administration of Hadlima.
Patients taking Hadlima should not take a live vaccine.
The most common adverse effects (incidence > 10%) include infections (for example, upper respiratory infections, sinusitis), injection site reactions, headache, and rash.
A version of this article first appeared on Medscape.com.
The U.S. Food and Drug Administration today approved a citrate-free, high-concentration formulation of adalimumab-bwwd (Hadlima), the manufacturer, Samsung Bioepis, and its commercialization partner Organon said in an announcement.
Hadlima is a biosimilar of the tumor necrosis factor inhibitor reference product adalimumab (Humira).
Hadlima was first approved in July 2019 in a citrated, 50-mg/mL formulation. The new citrate-free, 100-mg/mL version will be available in prefilled syringe and autoinjector options.
The 100-mg/mL formulation is indicated for the same seven conditions as its 50-mg/mL counterpart: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, adult and pediatric Crohn’s disease, and ulcerative colitis.
The approval was based on clinical data from a randomized, single-blind, two-arm, parallel group, single-dose study that compared the pharmacokinetics, safety, tolerability, and immunogenicity of the 100-mg/mL and 50-mg/mL formulations of Hadlima in healthy volunteers.
Both low- and high-concentration formulations of Humira are currently marketed in the United States. Organon said that it expects to market Hadlima in the United States on or after July 1, 2023, in accordance with a licensing agreement with AbbVie.
The prescribing information for Hadlima includes specific warnings and areas of concern. The drug should not be administered to individuals who are known to be hypersensitive to adalimumab. The drug may lower the ability of the immune system to fight infections and may increase risk of infections, including serious infections leading to hospitalization or death, such as tuberculosis, bacterial sepsis, invasive fungal infections (such as histoplasmosis), and infections attributable to other opportunistic pathogens.
A test for latent TB infection should be given before administration, and treatment of TB should begin before administration of Hadlima.
Patients taking Hadlima should not take a live vaccine.
The most common adverse effects (incidence > 10%) include infections (for example, upper respiratory infections, sinusitis), injection site reactions, headache, and rash.
A version of this article first appeared on Medscape.com.
Biosimilar-to-biosimilar switches deemed safe and effective, systematic review reveals
Switching from one biosimilar medication to another is safe and effective, a new systematic review indicates, even though this clinical practice is not governed by current health authority regulations or guidance.
“No reduction in effectiveness or increase in adverse events was detected in biosimilar-to-biosimilar switching studies conducted to date,” the review’s authors noted in their study, published online in BioDrugs.
“The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future. ... Although it is not covered by current health authority regulations or guidance,” added the authors, led by Hillel P. Cohen, PhD, executive director of scientific affairs at Sandoz, a division of Novartis.
The researchers searched electronic databases through December 2021 and found 23 observational studies that met their search criteria, of which 13 were published in peer-reviewed journals; the remainder appeared in abstract form. The studies totaled 3,657 patients. The researchers did not identify any randomized clinical trials.
“The studies were heterogeneous in size, design, and endpoints, providing data on safety, effectiveness, immunogenicity, pharmacokinetics, patient retention, patient and physician perceptions, and drug-use patterns,” the authors wrote.
The authors found that the majority of studies evaluated switches between biosimilars of infliximab, but they also identified switches between biosimilars of adalimumab, etanercept, and rituximab.
“Some health care providers are hesitant to switch patients from one biosimilar to another biosimilar because of a perceived lack of clinical data on such switches,” Dr. Cohen said in an interview.
The review’s findings – that there were no clinically relevant differences when switching patients from one biosimilar to another – are consistent with the science, Dr. Cohen said. “Physicians should have confidence that the data demonstrate that safety and effectiveness are not impacted if patients switch from one biosimilar to another biosimilar of the same reference biologic,” he said.
Currently, the published data include biosimilars to only four reference biologics. “However, I anticipate additional biosimilar-to-biosimilar switching data will become available in the future,” Dr. Cohen said. “In fact, several new studies have been published in recent months, after the cut-off date for inclusion in our systematic review.”
Switching common in rheumatology, dermatology, and gastroenterology
Biosimilar-to-biosimilar switching was observed most commonly in rheumatology practice, but also was seen in the specialties of dermatology and gastroenterology.
Jeffrey Weinberg, MD, clinical professor of dermatology, Icahn School of Medicine at Mount Sinai, New York City, said in an interview that the study is among the best to date showing that switching biosimilars does not compromise efficacy or safety.
“I would hypothesize that the interchangeability would apply to psoriasis patients,” Dr. Weinberg said. However, “over the next few years, we will have an increasing number of biosimilars for an increasing number of different molecules. We will need to be vigilant to observe if similar behavior is observed with the biosimilars yet to come.”
Keith Choate, MD, PhD, professor of dermatology, pathology, and genetics, and associate dean for physician-scientist development at Yale University, New Haven, Conn., said that biosimilars have comparable efficacy to the branded medication they replace. “If response is lost to an individual agent, we would not typically then switch to a biosimilar, but would favor another class of therapy or a distinct therapeutic which targets the same pathway.”
When physicians prescribe a biosimilar for rheumatoid arthritis or psoriatic arthritis, in 9 out 10 people, “it’s going to work as well, and it’s not going to cause any more side effects,” said Stanford Shoor, MD, clinical professor of medicine and rheumatology, Stanford (Calif.) University.
The systematic review, even within its limitations, reinforces confidence in the antitumor necrosis factor biosimilars, said Jean-Frederic Colombel, MD, codirector of the Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, New York, and professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai.
“Still, studies with longer follow-up are needed,” Dr. Colombel said, adding that the remaining questions relate to the efficacy and safety of switching multiple times, which will likely occur in the near future. There will be a “need to provide information to the patient regarding what originator or biosimilar(s) he has been exposed to during the course of his disease.”
Switching will increasingly become the norm, said Miguel Regueiro, MD, chair of the Digestive Disease & Surgery Institute, Cleveland Clinic. In his clinical practice, he has the most experience with Crohn’s disease and ulcerative colitis, and biosimilar-to-biosimilar infliximab switches. “Unless there are data that emerge, I have no concerns with this.”
He added that it’s an “interesting study that affirms my findings in clinical practice – that one can switch from a biosimilar to biosimilar (of the same reference product).”
The review’s results also make sense from an economic standpoint, said Rajat Bhatt, MD, owner of Prime Rheumatology in Richmond, Tex., and an adjunct faculty member at Caribbean Medical University, Willemstad, Curaçao. “Switching to biosimilars will result in cost savings for the health care system.” Patients on certain insurances also will save by switching to a biosimilar with a lower copay.
However, the review is limited by a relatively small number of studies that have provided primary data on this topic, and most of these were switching from infliximab to a biosimilar for inflammatory bowel disease, said Alfred Kim, MD, PhD, an adult rheumatologist at Barnes-Jewish Hospital, St. Louis, and assistant professor of medicine at Washington University in St. Louis.
As with any meta-analysis evaluating a small number of studies, “broad applicability to all conditions and reference/biosimilar pair can only be assumed. Also, many of the studies used for this meta-analysis are observational, which can introduce a variety of biases that can be difficult to adjust for,” Dr. Kim said. “Nevertheless, these analyses are an important first step in validating the [Food and Drug Administration’s] approach to evaluating biosimilars, as the clinical outcomes are consistent between different biosimilars.”
This systematic review is not enough to prove that all patients will do fine when switching from one biosimilar to another, said Florence Aslinia, MD, a gastroenterologist at the University of Kansas Health System in Kansas City. It’s possible that some patients may not do as well, she said, noting that, in one study of patients with inflammatory bowel disease, 10% of patients on a biosimilar infliximab needed to switch back to the originator infliximab (Remicade, Janssen) because of side effects attributed to the biosimilar. The same thing may or may not happen with biosimilar-to-biosimilar switching, and it requires further study.
The authors did not receive any funding for writing this review. Dr. Cohen is an employee of Sandoz, a division of Novartis. He may own stock in Novartis. Two coauthors are also employees of Sandoz. The other three coauthors reported having financial relationships with numerous pharmaceutical companies, including Sandoz and/or Novartis. Dr. Colombel reported financial relationships with many pharmaceutical companies, including Novartis and other manufacturers of biosimilars. Dr. Regueiro reports financial relationships with numerous pharmaceutical companies, including some manufacturers of biosimilars. Dr. Weinberg reported financial relationships with Celgene, AbbVie, Eli Lilly, and Novartis. Kim reports financial relationships with GlaxoSmithKline, Pfizer, and AstraZeneca. Dr. Aslinia, Dr. Shoor, Dr. Choate, and Dr. Bhatt reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Switching from one biosimilar medication to another is safe and effective, a new systematic review indicates, even though this clinical practice is not governed by current health authority regulations or guidance.
“No reduction in effectiveness or increase in adverse events was detected in biosimilar-to-biosimilar switching studies conducted to date,” the review’s authors noted in their study, published online in BioDrugs.
“The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future. ... Although it is not covered by current health authority regulations or guidance,” added the authors, led by Hillel P. Cohen, PhD, executive director of scientific affairs at Sandoz, a division of Novartis.
The researchers searched electronic databases through December 2021 and found 23 observational studies that met their search criteria, of which 13 were published in peer-reviewed journals; the remainder appeared in abstract form. The studies totaled 3,657 patients. The researchers did not identify any randomized clinical trials.
“The studies were heterogeneous in size, design, and endpoints, providing data on safety, effectiveness, immunogenicity, pharmacokinetics, patient retention, patient and physician perceptions, and drug-use patterns,” the authors wrote.
The authors found that the majority of studies evaluated switches between biosimilars of infliximab, but they also identified switches between biosimilars of adalimumab, etanercept, and rituximab.
“Some health care providers are hesitant to switch patients from one biosimilar to another biosimilar because of a perceived lack of clinical data on such switches,” Dr. Cohen said in an interview.
The review’s findings – that there were no clinically relevant differences when switching patients from one biosimilar to another – are consistent with the science, Dr. Cohen said. “Physicians should have confidence that the data demonstrate that safety and effectiveness are not impacted if patients switch from one biosimilar to another biosimilar of the same reference biologic,” he said.
Currently, the published data include biosimilars to only four reference biologics. “However, I anticipate additional biosimilar-to-biosimilar switching data will become available in the future,” Dr. Cohen said. “In fact, several new studies have been published in recent months, after the cut-off date for inclusion in our systematic review.”
Switching common in rheumatology, dermatology, and gastroenterology
Biosimilar-to-biosimilar switching was observed most commonly in rheumatology practice, but also was seen in the specialties of dermatology and gastroenterology.
Jeffrey Weinberg, MD, clinical professor of dermatology, Icahn School of Medicine at Mount Sinai, New York City, said in an interview that the study is among the best to date showing that switching biosimilars does not compromise efficacy or safety.
“I would hypothesize that the interchangeability would apply to psoriasis patients,” Dr. Weinberg said. However, “over the next few years, we will have an increasing number of biosimilars for an increasing number of different molecules. We will need to be vigilant to observe if similar behavior is observed with the biosimilars yet to come.”
Keith Choate, MD, PhD, professor of dermatology, pathology, and genetics, and associate dean for physician-scientist development at Yale University, New Haven, Conn., said that biosimilars have comparable efficacy to the branded medication they replace. “If response is lost to an individual agent, we would not typically then switch to a biosimilar, but would favor another class of therapy or a distinct therapeutic which targets the same pathway.”
When physicians prescribe a biosimilar for rheumatoid arthritis or psoriatic arthritis, in 9 out 10 people, “it’s going to work as well, and it’s not going to cause any more side effects,” said Stanford Shoor, MD, clinical professor of medicine and rheumatology, Stanford (Calif.) University.
The systematic review, even within its limitations, reinforces confidence in the antitumor necrosis factor biosimilars, said Jean-Frederic Colombel, MD, codirector of the Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, New York, and professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai.
“Still, studies with longer follow-up are needed,” Dr. Colombel said, adding that the remaining questions relate to the efficacy and safety of switching multiple times, which will likely occur in the near future. There will be a “need to provide information to the patient regarding what originator or biosimilar(s) he has been exposed to during the course of his disease.”
Switching will increasingly become the norm, said Miguel Regueiro, MD, chair of the Digestive Disease & Surgery Institute, Cleveland Clinic. In his clinical practice, he has the most experience with Crohn’s disease and ulcerative colitis, and biosimilar-to-biosimilar infliximab switches. “Unless there are data that emerge, I have no concerns with this.”
He added that it’s an “interesting study that affirms my findings in clinical practice – that one can switch from a biosimilar to biosimilar (of the same reference product).”
The review’s results also make sense from an economic standpoint, said Rajat Bhatt, MD, owner of Prime Rheumatology in Richmond, Tex., and an adjunct faculty member at Caribbean Medical University, Willemstad, Curaçao. “Switching to biosimilars will result in cost savings for the health care system.” Patients on certain insurances also will save by switching to a biosimilar with a lower copay.
However, the review is limited by a relatively small number of studies that have provided primary data on this topic, and most of these were switching from infliximab to a biosimilar for inflammatory bowel disease, said Alfred Kim, MD, PhD, an adult rheumatologist at Barnes-Jewish Hospital, St. Louis, and assistant professor of medicine at Washington University in St. Louis.
As with any meta-analysis evaluating a small number of studies, “broad applicability to all conditions and reference/biosimilar pair can only be assumed. Also, many of the studies used for this meta-analysis are observational, which can introduce a variety of biases that can be difficult to adjust for,” Dr. Kim said. “Nevertheless, these analyses are an important first step in validating the [Food and Drug Administration’s] approach to evaluating biosimilars, as the clinical outcomes are consistent between different biosimilars.”
This systematic review is not enough to prove that all patients will do fine when switching from one biosimilar to another, said Florence Aslinia, MD, a gastroenterologist at the University of Kansas Health System in Kansas City. It’s possible that some patients may not do as well, she said, noting that, in one study of patients with inflammatory bowel disease, 10% of patients on a biosimilar infliximab needed to switch back to the originator infliximab (Remicade, Janssen) because of side effects attributed to the biosimilar. The same thing may or may not happen with biosimilar-to-biosimilar switching, and it requires further study.
The authors did not receive any funding for writing this review. Dr. Cohen is an employee of Sandoz, a division of Novartis. He may own stock in Novartis. Two coauthors are also employees of Sandoz. The other three coauthors reported having financial relationships with numerous pharmaceutical companies, including Sandoz and/or Novartis. Dr. Colombel reported financial relationships with many pharmaceutical companies, including Novartis and other manufacturers of biosimilars. Dr. Regueiro reports financial relationships with numerous pharmaceutical companies, including some manufacturers of biosimilars. Dr. Weinberg reported financial relationships with Celgene, AbbVie, Eli Lilly, and Novartis. Kim reports financial relationships with GlaxoSmithKline, Pfizer, and AstraZeneca. Dr. Aslinia, Dr. Shoor, Dr. Choate, and Dr. Bhatt reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Switching from one biosimilar medication to another is safe and effective, a new systematic review indicates, even though this clinical practice is not governed by current health authority regulations or guidance.
“No reduction in effectiveness or increase in adverse events was detected in biosimilar-to-biosimilar switching studies conducted to date,” the review’s authors noted in their study, published online in BioDrugs.
“The possibility of multiple switches between biosimilars of the same reference biologic is already a reality, and these types of switches are expected to become more common in the future. ... Although it is not covered by current health authority regulations or guidance,” added the authors, led by Hillel P. Cohen, PhD, executive director of scientific affairs at Sandoz, a division of Novartis.
The researchers searched electronic databases through December 2021 and found 23 observational studies that met their search criteria, of which 13 were published in peer-reviewed journals; the remainder appeared in abstract form. The studies totaled 3,657 patients. The researchers did not identify any randomized clinical trials.
“The studies were heterogeneous in size, design, and endpoints, providing data on safety, effectiveness, immunogenicity, pharmacokinetics, patient retention, patient and physician perceptions, and drug-use patterns,” the authors wrote.
The authors found that the majority of studies evaluated switches between biosimilars of infliximab, but they also identified switches between biosimilars of adalimumab, etanercept, and rituximab.
“Some health care providers are hesitant to switch patients from one biosimilar to another biosimilar because of a perceived lack of clinical data on such switches,” Dr. Cohen said in an interview.
The review’s findings – that there were no clinically relevant differences when switching patients from one biosimilar to another – are consistent with the science, Dr. Cohen said. “Physicians should have confidence that the data demonstrate that safety and effectiveness are not impacted if patients switch from one biosimilar to another biosimilar of the same reference biologic,” he said.
Currently, the published data include biosimilars to only four reference biologics. “However, I anticipate additional biosimilar-to-biosimilar switching data will become available in the future,” Dr. Cohen said. “In fact, several new studies have been published in recent months, after the cut-off date for inclusion in our systematic review.”
Switching common in rheumatology, dermatology, and gastroenterology
Biosimilar-to-biosimilar switching was observed most commonly in rheumatology practice, but also was seen in the specialties of dermatology and gastroenterology.
Jeffrey Weinberg, MD, clinical professor of dermatology, Icahn School of Medicine at Mount Sinai, New York City, said in an interview that the study is among the best to date showing that switching biosimilars does not compromise efficacy or safety.
“I would hypothesize that the interchangeability would apply to psoriasis patients,” Dr. Weinberg said. However, “over the next few years, we will have an increasing number of biosimilars for an increasing number of different molecules. We will need to be vigilant to observe if similar behavior is observed with the biosimilars yet to come.”
Keith Choate, MD, PhD, professor of dermatology, pathology, and genetics, and associate dean for physician-scientist development at Yale University, New Haven, Conn., said that biosimilars have comparable efficacy to the branded medication they replace. “If response is lost to an individual agent, we would not typically then switch to a biosimilar, but would favor another class of therapy or a distinct therapeutic which targets the same pathway.”
When physicians prescribe a biosimilar for rheumatoid arthritis or psoriatic arthritis, in 9 out 10 people, “it’s going to work as well, and it’s not going to cause any more side effects,” said Stanford Shoor, MD, clinical professor of medicine and rheumatology, Stanford (Calif.) University.
The systematic review, even within its limitations, reinforces confidence in the antitumor necrosis factor biosimilars, said Jean-Frederic Colombel, MD, codirector of the Feinstein Inflammatory Bowel Disease Clinical Center at Mount Sinai, New York, and professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai.
“Still, studies with longer follow-up are needed,” Dr. Colombel said, adding that the remaining questions relate to the efficacy and safety of switching multiple times, which will likely occur in the near future. There will be a “need to provide information to the patient regarding what originator or biosimilar(s) he has been exposed to during the course of his disease.”
Switching will increasingly become the norm, said Miguel Regueiro, MD, chair of the Digestive Disease & Surgery Institute, Cleveland Clinic. In his clinical practice, he has the most experience with Crohn’s disease and ulcerative colitis, and biosimilar-to-biosimilar infliximab switches. “Unless there are data that emerge, I have no concerns with this.”
He added that it’s an “interesting study that affirms my findings in clinical practice – that one can switch from a biosimilar to biosimilar (of the same reference product).”
The review’s results also make sense from an economic standpoint, said Rajat Bhatt, MD, owner of Prime Rheumatology in Richmond, Tex., and an adjunct faculty member at Caribbean Medical University, Willemstad, Curaçao. “Switching to biosimilars will result in cost savings for the health care system.” Patients on certain insurances also will save by switching to a biosimilar with a lower copay.
However, the review is limited by a relatively small number of studies that have provided primary data on this topic, and most of these were switching from infliximab to a biosimilar for inflammatory bowel disease, said Alfred Kim, MD, PhD, an adult rheumatologist at Barnes-Jewish Hospital, St. Louis, and assistant professor of medicine at Washington University in St. Louis.
As with any meta-analysis evaluating a small number of studies, “broad applicability to all conditions and reference/biosimilar pair can only be assumed. Also, many of the studies used for this meta-analysis are observational, which can introduce a variety of biases that can be difficult to adjust for,” Dr. Kim said. “Nevertheless, these analyses are an important first step in validating the [Food and Drug Administration’s] approach to evaluating biosimilars, as the clinical outcomes are consistent between different biosimilars.”
This systematic review is not enough to prove that all patients will do fine when switching from one biosimilar to another, said Florence Aslinia, MD, a gastroenterologist at the University of Kansas Health System in Kansas City. It’s possible that some patients may not do as well, she said, noting that, in one study of patients with inflammatory bowel disease, 10% of patients on a biosimilar infliximab needed to switch back to the originator infliximab (Remicade, Janssen) because of side effects attributed to the biosimilar. The same thing may or may not happen with biosimilar-to-biosimilar switching, and it requires further study.
The authors did not receive any funding for writing this review. Dr. Cohen is an employee of Sandoz, a division of Novartis. He may own stock in Novartis. Two coauthors are also employees of Sandoz. The other three coauthors reported having financial relationships with numerous pharmaceutical companies, including Sandoz and/or Novartis. Dr. Colombel reported financial relationships with many pharmaceutical companies, including Novartis and other manufacturers of biosimilars. Dr. Regueiro reports financial relationships with numerous pharmaceutical companies, including some manufacturers of biosimilars. Dr. Weinberg reported financial relationships with Celgene, AbbVie, Eli Lilly, and Novartis. Kim reports financial relationships with GlaxoSmithKline, Pfizer, and AstraZeneca. Dr. Aslinia, Dr. Shoor, Dr. Choate, and Dr. Bhatt reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM BIODRUGS
In RA, tofacitinib shows higher infection rate than TNF inhibitors
Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) are more likely to develop infections than are those who take a tumor necrosis factor inhibitor (TNFi), results of an industry-sponsored randomized controlled trial suggest.
The Janus kinase (JAK) inhibitor tofacitinib and TNFi biologics are common RA treatments that, along with factors including age, disease activity, and comorbidities, can put patients with RA at increased risk for infections.
“In this secondary analysis of the ORAL Surveillance trial, infections were increased with tofacitinib, compared with TNFi,” study coauthor Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, both in Boston, explained in an interview.
As reported in Annals of the Rheumatic Diseases, Dr. Bhatt and colleagues performed a subanalysis of the final dataset from the phase 3b/4 open-label safety trial of tofacitinib in RA conducted between March 2014 and July 2020, in 345 study locations worldwide.
Study participants were 50 years of age or older with moderate to severe RA who were taking methotrexate but having inadequate symptom control. They had at least one cardiovascular risk factor such as being a current smoker or having hypertension, past heart attack, family history of coronary heart disease, high cholesterol, diabetes mellitus, or extra-articular RA. Patients with current or recent infection, clinically significant laboratory abnormalities, or pregnancy, were excluded from the study.
In the study, 1,455 participants received oral tofacitinib 5 mg twice per day; 1,456 received oral tofacitinib 10 mg twice per day; and 1,451 were treated with subcutaneous TNFi (40 mg subcutaneous adalimumab [Humira] injection every 2 weeks in the United States, Puerto Rico, and Canada; and 50 mg subcutaneous etanercept [Enbrel] injection every week in all other countries. Participants continued their prestudy stable dose of methotrexate if clinically indicated.
The researchers calculated incidence rates and hazard ratios for infections, overall and by age (50-64 years, compared with 65 years and older). They calculated probabilities of infection using Kaplan-Meier estimates and identified infection risk factors through Cox modeling.
They found higher infection rates, serious infection events (SIEs), and nonserious infections (NSIs) with tofacitinib than with TNFi, including:
- Patients taking tofacitinib 5 mg (HR, 1.17; 95% confidence interval, 0.92-1.50) and 10 mg (HR, 1.48; 95% CI, 1.17-1.87) were at greater risk for SIEs.
- Patients older than 65 who were taking tofacitinib 10 mg had increased IRs and HRs for all infections and for SIEs, compared with those aged 50-64.
- The probability of a SIE rose from month 18 onward in participants taking tofacitinib 5 mg, as well as before month 6 in those taking tofacitinib 10 mg.
- In both tofacitinib groups, the probability of NSI increased before month 6.
The most common risk factors for SIEs were higher age, baseline opioid use, history of chronic lung disease, and time-dependent oral corticosteroid use. Risk factors for NSIs were female sex, history of chronic lung disease or infection, history of smoking, as well as time-dependent higher Disease Activity Score in 28 joints and C-reactive protein score.
‘Best information to date’
Michael George, MD, MSCE, assistant professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, welcomed the study’s results.
“This study provides the best information to date on the risk of infection with the JAK inhibitor tofacitinib, compared to a TNF inhibitor,” Dr. George, who was not involved in the study, said in an interview. “It is rare to have such a large randomized trial with an active comparator focused on safety. This is a major strength.
“Being able to quantify the amount of increased risk will help with shared decision-making when counseling patients,” he added.
Dr. George said that, while the small overall risk may not be clinically meaningful for younger, healthier patients, trying biologics such as TNFi before tofacitinib may be optimal for high-risk patients who are older or have comorbidities.
Dr. Bhatt agreed.
“In deciding on appropriate therapies for RA (or other conditions where tofacitinib is used), it is important for the prescribing physician to explain the risks to the patient and weigh them against the potential benefits,” he advised.
Dr. Bhatt noted that increased infection is not the first risk that’s been linked with tofacitinib.
“ORAL Surveillance was designed primarily to assess cardiovascular safety and showed higher rates of cardiovascular events such as myocardial infarction and pulmonary embolism, as well as cancer, with tofacitinib,” he explained.
He recommended further related research.
“Randomized trials are needed to determine the best ways to treat conditions such as RA while trying to minimize cardiovascular, cancer, and infectious risks,” he said.
The study was sponsored by Pfizer. All authors reported financial involvements with Pfizer; most have financial involvements with other pharmaceutical companies as well; four authors are employees of Pfizer and three are also stockholders in the company. Dr. George reported involvements with the pharmaceutical industry.
Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) are more likely to develop infections than are those who take a tumor necrosis factor inhibitor (TNFi), results of an industry-sponsored randomized controlled trial suggest.
The Janus kinase (JAK) inhibitor tofacitinib and TNFi biologics are common RA treatments that, along with factors including age, disease activity, and comorbidities, can put patients with RA at increased risk for infections.
“In this secondary analysis of the ORAL Surveillance trial, infections were increased with tofacitinib, compared with TNFi,” study coauthor Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, both in Boston, explained in an interview.
As reported in Annals of the Rheumatic Diseases, Dr. Bhatt and colleagues performed a subanalysis of the final dataset from the phase 3b/4 open-label safety trial of tofacitinib in RA conducted between March 2014 and July 2020, in 345 study locations worldwide.
Study participants were 50 years of age or older with moderate to severe RA who were taking methotrexate but having inadequate symptom control. They had at least one cardiovascular risk factor such as being a current smoker or having hypertension, past heart attack, family history of coronary heart disease, high cholesterol, diabetes mellitus, or extra-articular RA. Patients with current or recent infection, clinically significant laboratory abnormalities, or pregnancy, were excluded from the study.
In the study, 1,455 participants received oral tofacitinib 5 mg twice per day; 1,456 received oral tofacitinib 10 mg twice per day; and 1,451 were treated with subcutaneous TNFi (40 mg subcutaneous adalimumab [Humira] injection every 2 weeks in the United States, Puerto Rico, and Canada; and 50 mg subcutaneous etanercept [Enbrel] injection every week in all other countries. Participants continued their prestudy stable dose of methotrexate if clinically indicated.
The researchers calculated incidence rates and hazard ratios for infections, overall and by age (50-64 years, compared with 65 years and older). They calculated probabilities of infection using Kaplan-Meier estimates and identified infection risk factors through Cox modeling.
They found higher infection rates, serious infection events (SIEs), and nonserious infections (NSIs) with tofacitinib than with TNFi, including:
- Patients taking tofacitinib 5 mg (HR, 1.17; 95% confidence interval, 0.92-1.50) and 10 mg (HR, 1.48; 95% CI, 1.17-1.87) were at greater risk for SIEs.
- Patients older than 65 who were taking tofacitinib 10 mg had increased IRs and HRs for all infections and for SIEs, compared with those aged 50-64.
- The probability of a SIE rose from month 18 onward in participants taking tofacitinib 5 mg, as well as before month 6 in those taking tofacitinib 10 mg.
- In both tofacitinib groups, the probability of NSI increased before month 6.
The most common risk factors for SIEs were higher age, baseline opioid use, history of chronic lung disease, and time-dependent oral corticosteroid use. Risk factors for NSIs were female sex, history of chronic lung disease or infection, history of smoking, as well as time-dependent higher Disease Activity Score in 28 joints and C-reactive protein score.
‘Best information to date’
Michael George, MD, MSCE, assistant professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, welcomed the study’s results.
“This study provides the best information to date on the risk of infection with the JAK inhibitor tofacitinib, compared to a TNF inhibitor,” Dr. George, who was not involved in the study, said in an interview. “It is rare to have such a large randomized trial with an active comparator focused on safety. This is a major strength.
“Being able to quantify the amount of increased risk will help with shared decision-making when counseling patients,” he added.
Dr. George said that, while the small overall risk may not be clinically meaningful for younger, healthier patients, trying biologics such as TNFi before tofacitinib may be optimal for high-risk patients who are older or have comorbidities.
Dr. Bhatt agreed.
“In deciding on appropriate therapies for RA (or other conditions where tofacitinib is used), it is important for the prescribing physician to explain the risks to the patient and weigh them against the potential benefits,” he advised.
Dr. Bhatt noted that increased infection is not the first risk that’s been linked with tofacitinib.
“ORAL Surveillance was designed primarily to assess cardiovascular safety and showed higher rates of cardiovascular events such as myocardial infarction and pulmonary embolism, as well as cancer, with tofacitinib,” he explained.
He recommended further related research.
“Randomized trials are needed to determine the best ways to treat conditions such as RA while trying to minimize cardiovascular, cancer, and infectious risks,” he said.
The study was sponsored by Pfizer. All authors reported financial involvements with Pfizer; most have financial involvements with other pharmaceutical companies as well; four authors are employees of Pfizer and three are also stockholders in the company. Dr. George reported involvements with the pharmaceutical industry.
Patients with rheumatoid arthritis treated with tofacitinib (Xeljanz) are more likely to develop infections than are those who take a tumor necrosis factor inhibitor (TNFi), results of an industry-sponsored randomized controlled trial suggest.
The Janus kinase (JAK) inhibitor tofacitinib and TNFi biologics are common RA treatments that, along with factors including age, disease activity, and comorbidities, can put patients with RA at increased risk for infections.
“In this secondary analysis of the ORAL Surveillance trial, infections were increased with tofacitinib, compared with TNFi,” study coauthor Deepak L. Bhatt, MD, MPH, professor of medicine at Harvard Medical School and executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, both in Boston, explained in an interview.
As reported in Annals of the Rheumatic Diseases, Dr. Bhatt and colleagues performed a subanalysis of the final dataset from the phase 3b/4 open-label safety trial of tofacitinib in RA conducted between March 2014 and July 2020, in 345 study locations worldwide.
Study participants were 50 years of age or older with moderate to severe RA who were taking methotrexate but having inadequate symptom control. They had at least one cardiovascular risk factor such as being a current smoker or having hypertension, past heart attack, family history of coronary heart disease, high cholesterol, diabetes mellitus, or extra-articular RA. Patients with current or recent infection, clinically significant laboratory abnormalities, or pregnancy, were excluded from the study.
In the study, 1,455 participants received oral tofacitinib 5 mg twice per day; 1,456 received oral tofacitinib 10 mg twice per day; and 1,451 were treated with subcutaneous TNFi (40 mg subcutaneous adalimumab [Humira] injection every 2 weeks in the United States, Puerto Rico, and Canada; and 50 mg subcutaneous etanercept [Enbrel] injection every week in all other countries. Participants continued their prestudy stable dose of methotrexate if clinically indicated.
The researchers calculated incidence rates and hazard ratios for infections, overall and by age (50-64 years, compared with 65 years and older). They calculated probabilities of infection using Kaplan-Meier estimates and identified infection risk factors through Cox modeling.
They found higher infection rates, serious infection events (SIEs), and nonserious infections (NSIs) with tofacitinib than with TNFi, including:
- Patients taking tofacitinib 5 mg (HR, 1.17; 95% confidence interval, 0.92-1.50) and 10 mg (HR, 1.48; 95% CI, 1.17-1.87) were at greater risk for SIEs.
- Patients older than 65 who were taking tofacitinib 10 mg had increased IRs and HRs for all infections and for SIEs, compared with those aged 50-64.
- The probability of a SIE rose from month 18 onward in participants taking tofacitinib 5 mg, as well as before month 6 in those taking tofacitinib 10 mg.
- In both tofacitinib groups, the probability of NSI increased before month 6.
The most common risk factors for SIEs were higher age, baseline opioid use, history of chronic lung disease, and time-dependent oral corticosteroid use. Risk factors for NSIs were female sex, history of chronic lung disease or infection, history of smoking, as well as time-dependent higher Disease Activity Score in 28 joints and C-reactive protein score.
‘Best information to date’
Michael George, MD, MSCE, assistant professor of medicine and epidemiology at the University of Pennsylvania, Philadelphia, welcomed the study’s results.
“This study provides the best information to date on the risk of infection with the JAK inhibitor tofacitinib, compared to a TNF inhibitor,” Dr. George, who was not involved in the study, said in an interview. “It is rare to have such a large randomized trial with an active comparator focused on safety. This is a major strength.
“Being able to quantify the amount of increased risk will help with shared decision-making when counseling patients,” he added.
Dr. George said that, while the small overall risk may not be clinically meaningful for younger, healthier patients, trying biologics such as TNFi before tofacitinib may be optimal for high-risk patients who are older or have comorbidities.
Dr. Bhatt agreed.
“In deciding on appropriate therapies for RA (or other conditions where tofacitinib is used), it is important for the prescribing physician to explain the risks to the patient and weigh them against the potential benefits,” he advised.
Dr. Bhatt noted that increased infection is not the first risk that’s been linked with tofacitinib.
“ORAL Surveillance was designed primarily to assess cardiovascular safety and showed higher rates of cardiovascular events such as myocardial infarction and pulmonary embolism, as well as cancer, with tofacitinib,” he explained.
He recommended further related research.
“Randomized trials are needed to determine the best ways to treat conditions such as RA while trying to minimize cardiovascular, cancer, and infectious risks,” he said.
The study was sponsored by Pfizer. All authors reported financial involvements with Pfizer; most have financial involvements with other pharmaceutical companies as well; four authors are employees of Pfizer and three are also stockholders in the company. Dr. George reported involvements with the pharmaceutical industry.
FROM ANNALS OF THE RHEUMATIC DISEASES
ACR makes changes to adult, pediatric vaccinations guidance
Patients with rheumatic and musculoskeletal diseases may need additional vaccines or different versions of vaccines they were not previously recommended to receive, according to updated guidelines from the American College of Rheumatology (ACR) on vaccinations for these patients. The new guidelines pertain to routine vaccinations for adults and children and are based on the most current evidence. They include recommendations on whether to hold certain medications before or after vaccination. They do not include recommendations regarding COVID-19 vaccines.
For guidance on COVID-19 vaccine timing and frequency, the ACR directs physicians to the CDC’s recommendations for people with mild or severe immunosuppression and the ACR’s previous clinical guidance summary on the topic, last revised in February 2022. The recommendations in the new guidance differ from ACR’s guidance on COVID-19 vaccines on whether and when to hold immunosuppressive medications when patients receive nonlive vaccines. The new guidelines now align more closely with those of EULAR, the Infectious Diseases Society of America, and the CDC’s recommendations for human papillomavirus (HPV), pneumococcal, and shingles vaccines.
Vaccinations in this population are particularly important because “a leading cause of morbidity and mortality in those with rheumatic diseases is infections, due to the detrimental impact immunosuppression has on the ability for the patient to properly clear the pathogen,” Alfred Kim, MD, PhD, professor of rheumatology at Washington University, St. Louis, told this news organization. While immunosuppressive medications are the most common reason patients with these conditions may have impaired immune function, “some of our patients with autoimmune disease also have a preexisting immunodeficiency that can inherently blunt immune responses to either infection or vaccination,” Dr. Kim explained.
“The authors of the guidelines have done a really nice job of making distinct recommendations based on the mechanism of action of various immunosuppressive medications,” Dr. Kim said. “This helps simplify the process of deciding the timing of vaccination for the health provider, especially for those on multiple immunosuppressives who represent an important proportion of our patients with rheumatic diseases.”
The main change to the guidelines for children, aside from those related to flu vaccination, is in regard to rotavirus vaccination for infants exposed to tumor necrosis factor (TNF) inhibitors or rituximab in utero. Infants prenatally exposed to rituximab should not receive the rotavirus vaccine until they are older than 6 months. Those exposed prenatally to TNF inhibitors should receive the rotavirus vaccine on time, according to the CDC schedule for all infants.
The new rotavirus recommendations follow data showing that immune responses to rotavirus are blunted in those with infliximab exposure, according to Dr. Kim.
“Thus, this poses a serious theoretical risk in newborns with mothers on [a TNF inhibitor] of ineffective clearance of rotavirus infections,” Dr. Kim said in an interview. “While rotavirus infections are quite common with typically self-limiting disease, sometimes requiring hydration to counteract diarrhea-induced dehydration, this can become severe in these newborns that have [a TNF inhibitor] in their system.”
For adults, the ACR issued the following expanded indications for four vaccines for patients currently taking immunosuppressive medication:
- Patients aged 18 and older should receive the recombinant zoster vaccine against shingles.
- For patients aged 27-44 who weren’t previously vaccinated against HPV, the HPV vaccine is “conditionally recommended.”
- Patients younger than 65 should receive the pneumococcal vaccine.
- Patients aged 19-64 are conditionally recommended to receive the high-dose or adjuvanted flu vaccine rather than the regular-dose flu vaccine.
The guidelines also conditionally recommend that all patients aged 65 and older who have rheumatic or musculoskeletal diseases receive the high-dose or adjuvanted flu vaccine, regardless of whether they are taking immunosuppressive medication. Another new conditional recommendation is to give multiple vaccinations to patients on the same day, rather than give individual vaccines on different days.
The guidelines make conditional recommendations regarding flu and nonlive attenuated vaccines for those taking methotrexate, rituximab, or glucocorticoids. Methotrexate should be held for 2 weeks after flu vaccination as long as disease activity allows it, but patients who are taking methotrexate should continue taking it for any other nonlive attenuated vaccinations.
“Non-rheumatology providers, such as general pediatricians and internists, are encouraged to give the influenza vaccination and then consult with the patient’s rheumatology provider about holding methotrexate to avoid a missed vaccination opportunity,” the guidelines state.
Patients taking rituximab should receive the flu vaccine on schedule and continue taking rituximab. However, for these patients, the guidelines recommend to “delay any subsequent rituximab dosing for at least two weeks after influenza vaccination if disease activity allows.”
“Because of the relatively short time period between the rollout of the influenza vaccine and its season, we can’t always wait to time the B-cell depletion dosage,” Dr. Kim said. “Also, it is not always easy to synchronize the patient’s B-cell depletion dosing schedule to the influenza vaccine rollout. Thus, we now just recommend getting the influenza vaccine regardless of the patient’s last B-cell depletion dosage despite its known strong attenuation of optimal immune responses.”
For other nonlive attenuated vaccines, providers should time vaccination for when the next rituximab dose is due and then hold the drug for at least 2 weeks thereafter, providing time for the B cells to mount a response before rituximab depletes B cells again.
Patients taking less than 20 mg of prednisone daily should still receive the flu vaccine and other nonlive attenuated vaccines. Those taking 20 mg or more of prednisone each day should still receive the flu vaccine, but other vaccines should be deferred until their dose of glucocorticoids has been tapered down to less than 20 mg daily.
Patients taking all other immunosuppressive medications should continue taking them for the flu vaccine and other nonlive attenuated vaccinations, but it is conditionally recommended that live attenuated vaccines be deferred. For any patient with a rheumatic and musculoskeletal disease, regardless of disease activity, it is conditionally recommended that all routine nonlive attenuated vaccines be administered.
For live attenuated virus vaccines, the ACR provides a chart on which immunosuppressive medications to hold and for how long. Glucocorticoids, methotrexate, azathioprine, leflunomide, mycophenolate mofetil, calcineurin inhibitors, and oral cyclophosphamide should all be held 4 weeks before and 4 weeks after administration of a live attenuated vaccine. For those taking JAK inhibitors, the medication should be halted 1 week before administration of a live vaccine and should continue to be withheld for 4 weeks after.
For most other biologics, the ACR recommends holding the medication for one dosing interval before the live vaccine and 4 weeks thereafter. The main exception is rituximab, which should be held for 6 months before a live vaccine and then for 4 more weeks thereafter.
For patients receiving intravenous immunoglobulin, the drug should be held for 8-11 months before they are administered a live attenuated vaccine, depending on the dosage, and then 4 weeks after vaccination, regardless of dosage.
To reassure people with rheumatic disease who may have anxiety or concerns about receiving immunizations, whether taking immunosuppressive medication or not, Dr. Kim said it’s important to provide lots of education to patients.
“Fear and emotion have replaced facts, and data as a leading factor in decision-making, as seen with COVID-19,” Dr. Kim said. “The reality is that a small minority of people will have any issues with most vaccines, which include disease flares, adverse events, or acquisition of an autoimmune disease. We are not saying there is zero risk, rather, that the risk is quite small. This is where shared decision-making between the health care provider and the patient must be done effectively to enable the patient to properly weigh risk versus benefit.”
Dr. Kim has relationships with GlaxoSmithKline, Aurinia Pharmaceuticals, Kypha, Pfizer, Alexion Pharmaceuticals, AstraZeneca, Exagen Diagnostics, and Foghorn Therapeutics.
A version of this article first appeared on Medscape.com.
Patients with rheumatic and musculoskeletal diseases may need additional vaccines or different versions of vaccines they were not previously recommended to receive, according to updated guidelines from the American College of Rheumatology (ACR) on vaccinations for these patients. The new guidelines pertain to routine vaccinations for adults and children and are based on the most current evidence. They include recommendations on whether to hold certain medications before or after vaccination. They do not include recommendations regarding COVID-19 vaccines.
For guidance on COVID-19 vaccine timing and frequency, the ACR directs physicians to the CDC’s recommendations for people with mild or severe immunosuppression and the ACR’s previous clinical guidance summary on the topic, last revised in February 2022. The recommendations in the new guidance differ from ACR’s guidance on COVID-19 vaccines on whether and when to hold immunosuppressive medications when patients receive nonlive vaccines. The new guidelines now align more closely with those of EULAR, the Infectious Diseases Society of America, and the CDC’s recommendations for human papillomavirus (HPV), pneumococcal, and shingles vaccines.
Vaccinations in this population are particularly important because “a leading cause of morbidity and mortality in those with rheumatic diseases is infections, due to the detrimental impact immunosuppression has on the ability for the patient to properly clear the pathogen,” Alfred Kim, MD, PhD, professor of rheumatology at Washington University, St. Louis, told this news organization. While immunosuppressive medications are the most common reason patients with these conditions may have impaired immune function, “some of our patients with autoimmune disease also have a preexisting immunodeficiency that can inherently blunt immune responses to either infection or vaccination,” Dr. Kim explained.
“The authors of the guidelines have done a really nice job of making distinct recommendations based on the mechanism of action of various immunosuppressive medications,” Dr. Kim said. “This helps simplify the process of deciding the timing of vaccination for the health provider, especially for those on multiple immunosuppressives who represent an important proportion of our patients with rheumatic diseases.”
The main change to the guidelines for children, aside from those related to flu vaccination, is in regard to rotavirus vaccination for infants exposed to tumor necrosis factor (TNF) inhibitors or rituximab in utero. Infants prenatally exposed to rituximab should not receive the rotavirus vaccine until they are older than 6 months. Those exposed prenatally to TNF inhibitors should receive the rotavirus vaccine on time, according to the CDC schedule for all infants.
The new rotavirus recommendations follow data showing that immune responses to rotavirus are blunted in those with infliximab exposure, according to Dr. Kim.
“Thus, this poses a serious theoretical risk in newborns with mothers on [a TNF inhibitor] of ineffective clearance of rotavirus infections,” Dr. Kim said in an interview. “While rotavirus infections are quite common with typically self-limiting disease, sometimes requiring hydration to counteract diarrhea-induced dehydration, this can become severe in these newborns that have [a TNF inhibitor] in their system.”
For adults, the ACR issued the following expanded indications for four vaccines for patients currently taking immunosuppressive medication:
- Patients aged 18 and older should receive the recombinant zoster vaccine against shingles.
- For patients aged 27-44 who weren’t previously vaccinated against HPV, the HPV vaccine is “conditionally recommended.”
- Patients younger than 65 should receive the pneumococcal vaccine.
- Patients aged 19-64 are conditionally recommended to receive the high-dose or adjuvanted flu vaccine rather than the regular-dose flu vaccine.
The guidelines also conditionally recommend that all patients aged 65 and older who have rheumatic or musculoskeletal diseases receive the high-dose or adjuvanted flu vaccine, regardless of whether they are taking immunosuppressive medication. Another new conditional recommendation is to give multiple vaccinations to patients on the same day, rather than give individual vaccines on different days.
The guidelines make conditional recommendations regarding flu and nonlive attenuated vaccines for those taking methotrexate, rituximab, or glucocorticoids. Methotrexate should be held for 2 weeks after flu vaccination as long as disease activity allows it, but patients who are taking methotrexate should continue taking it for any other nonlive attenuated vaccinations.
“Non-rheumatology providers, such as general pediatricians and internists, are encouraged to give the influenza vaccination and then consult with the patient’s rheumatology provider about holding methotrexate to avoid a missed vaccination opportunity,” the guidelines state.
Patients taking rituximab should receive the flu vaccine on schedule and continue taking rituximab. However, for these patients, the guidelines recommend to “delay any subsequent rituximab dosing for at least two weeks after influenza vaccination if disease activity allows.”
“Because of the relatively short time period between the rollout of the influenza vaccine and its season, we can’t always wait to time the B-cell depletion dosage,” Dr. Kim said. “Also, it is not always easy to synchronize the patient’s B-cell depletion dosing schedule to the influenza vaccine rollout. Thus, we now just recommend getting the influenza vaccine regardless of the patient’s last B-cell depletion dosage despite its known strong attenuation of optimal immune responses.”
For other nonlive attenuated vaccines, providers should time vaccination for when the next rituximab dose is due and then hold the drug for at least 2 weeks thereafter, providing time for the B cells to mount a response before rituximab depletes B cells again.
Patients taking less than 20 mg of prednisone daily should still receive the flu vaccine and other nonlive attenuated vaccines. Those taking 20 mg or more of prednisone each day should still receive the flu vaccine, but other vaccines should be deferred until their dose of glucocorticoids has been tapered down to less than 20 mg daily.
Patients taking all other immunosuppressive medications should continue taking them for the flu vaccine and other nonlive attenuated vaccinations, but it is conditionally recommended that live attenuated vaccines be deferred. For any patient with a rheumatic and musculoskeletal disease, regardless of disease activity, it is conditionally recommended that all routine nonlive attenuated vaccines be administered.
For live attenuated virus vaccines, the ACR provides a chart on which immunosuppressive medications to hold and for how long. Glucocorticoids, methotrexate, azathioprine, leflunomide, mycophenolate mofetil, calcineurin inhibitors, and oral cyclophosphamide should all be held 4 weeks before and 4 weeks after administration of a live attenuated vaccine. For those taking JAK inhibitors, the medication should be halted 1 week before administration of a live vaccine and should continue to be withheld for 4 weeks after.
For most other biologics, the ACR recommends holding the medication for one dosing interval before the live vaccine and 4 weeks thereafter. The main exception is rituximab, which should be held for 6 months before a live vaccine and then for 4 more weeks thereafter.
For patients receiving intravenous immunoglobulin, the drug should be held for 8-11 months before they are administered a live attenuated vaccine, depending on the dosage, and then 4 weeks after vaccination, regardless of dosage.
To reassure people with rheumatic disease who may have anxiety or concerns about receiving immunizations, whether taking immunosuppressive medication or not, Dr. Kim said it’s important to provide lots of education to patients.
“Fear and emotion have replaced facts, and data as a leading factor in decision-making, as seen with COVID-19,” Dr. Kim said. “The reality is that a small minority of people will have any issues with most vaccines, which include disease flares, adverse events, or acquisition of an autoimmune disease. We are not saying there is zero risk, rather, that the risk is quite small. This is where shared decision-making between the health care provider and the patient must be done effectively to enable the patient to properly weigh risk versus benefit.”
Dr. Kim has relationships with GlaxoSmithKline, Aurinia Pharmaceuticals, Kypha, Pfizer, Alexion Pharmaceuticals, AstraZeneca, Exagen Diagnostics, and Foghorn Therapeutics.
A version of this article first appeared on Medscape.com.
Patients with rheumatic and musculoskeletal diseases may need additional vaccines or different versions of vaccines they were not previously recommended to receive, according to updated guidelines from the American College of Rheumatology (ACR) on vaccinations for these patients. The new guidelines pertain to routine vaccinations for adults and children and are based on the most current evidence. They include recommendations on whether to hold certain medications before or after vaccination. They do not include recommendations regarding COVID-19 vaccines.
For guidance on COVID-19 vaccine timing and frequency, the ACR directs physicians to the CDC’s recommendations for people with mild or severe immunosuppression and the ACR’s previous clinical guidance summary on the topic, last revised in February 2022. The recommendations in the new guidance differ from ACR’s guidance on COVID-19 vaccines on whether and when to hold immunosuppressive medications when patients receive nonlive vaccines. The new guidelines now align more closely with those of EULAR, the Infectious Diseases Society of America, and the CDC’s recommendations for human papillomavirus (HPV), pneumococcal, and shingles vaccines.
Vaccinations in this population are particularly important because “a leading cause of morbidity and mortality in those with rheumatic diseases is infections, due to the detrimental impact immunosuppression has on the ability for the patient to properly clear the pathogen,” Alfred Kim, MD, PhD, professor of rheumatology at Washington University, St. Louis, told this news organization. While immunosuppressive medications are the most common reason patients with these conditions may have impaired immune function, “some of our patients with autoimmune disease also have a preexisting immunodeficiency that can inherently blunt immune responses to either infection or vaccination,” Dr. Kim explained.
“The authors of the guidelines have done a really nice job of making distinct recommendations based on the mechanism of action of various immunosuppressive medications,” Dr. Kim said. “This helps simplify the process of deciding the timing of vaccination for the health provider, especially for those on multiple immunosuppressives who represent an important proportion of our patients with rheumatic diseases.”
The main change to the guidelines for children, aside from those related to flu vaccination, is in regard to rotavirus vaccination for infants exposed to tumor necrosis factor (TNF) inhibitors or rituximab in utero. Infants prenatally exposed to rituximab should not receive the rotavirus vaccine until they are older than 6 months. Those exposed prenatally to TNF inhibitors should receive the rotavirus vaccine on time, according to the CDC schedule for all infants.
The new rotavirus recommendations follow data showing that immune responses to rotavirus are blunted in those with infliximab exposure, according to Dr. Kim.
“Thus, this poses a serious theoretical risk in newborns with mothers on [a TNF inhibitor] of ineffective clearance of rotavirus infections,” Dr. Kim said in an interview. “While rotavirus infections are quite common with typically self-limiting disease, sometimes requiring hydration to counteract diarrhea-induced dehydration, this can become severe in these newborns that have [a TNF inhibitor] in their system.”
For adults, the ACR issued the following expanded indications for four vaccines for patients currently taking immunosuppressive medication:
- Patients aged 18 and older should receive the recombinant zoster vaccine against shingles.
- For patients aged 27-44 who weren’t previously vaccinated against HPV, the HPV vaccine is “conditionally recommended.”
- Patients younger than 65 should receive the pneumococcal vaccine.
- Patients aged 19-64 are conditionally recommended to receive the high-dose or adjuvanted flu vaccine rather than the regular-dose flu vaccine.
The guidelines also conditionally recommend that all patients aged 65 and older who have rheumatic or musculoskeletal diseases receive the high-dose or adjuvanted flu vaccine, regardless of whether they are taking immunosuppressive medication. Another new conditional recommendation is to give multiple vaccinations to patients on the same day, rather than give individual vaccines on different days.
The guidelines make conditional recommendations regarding flu and nonlive attenuated vaccines for those taking methotrexate, rituximab, or glucocorticoids. Methotrexate should be held for 2 weeks after flu vaccination as long as disease activity allows it, but patients who are taking methotrexate should continue taking it for any other nonlive attenuated vaccinations.
“Non-rheumatology providers, such as general pediatricians and internists, are encouraged to give the influenza vaccination and then consult with the patient’s rheumatology provider about holding methotrexate to avoid a missed vaccination opportunity,” the guidelines state.
Patients taking rituximab should receive the flu vaccine on schedule and continue taking rituximab. However, for these patients, the guidelines recommend to “delay any subsequent rituximab dosing for at least two weeks after influenza vaccination if disease activity allows.”
“Because of the relatively short time period between the rollout of the influenza vaccine and its season, we can’t always wait to time the B-cell depletion dosage,” Dr. Kim said. “Also, it is not always easy to synchronize the patient’s B-cell depletion dosing schedule to the influenza vaccine rollout. Thus, we now just recommend getting the influenza vaccine regardless of the patient’s last B-cell depletion dosage despite its known strong attenuation of optimal immune responses.”
For other nonlive attenuated vaccines, providers should time vaccination for when the next rituximab dose is due and then hold the drug for at least 2 weeks thereafter, providing time for the B cells to mount a response before rituximab depletes B cells again.
Patients taking less than 20 mg of prednisone daily should still receive the flu vaccine and other nonlive attenuated vaccines. Those taking 20 mg or more of prednisone each day should still receive the flu vaccine, but other vaccines should be deferred until their dose of glucocorticoids has been tapered down to less than 20 mg daily.
Patients taking all other immunosuppressive medications should continue taking them for the flu vaccine and other nonlive attenuated vaccinations, but it is conditionally recommended that live attenuated vaccines be deferred. For any patient with a rheumatic and musculoskeletal disease, regardless of disease activity, it is conditionally recommended that all routine nonlive attenuated vaccines be administered.
For live attenuated virus vaccines, the ACR provides a chart on which immunosuppressive medications to hold and for how long. Glucocorticoids, methotrexate, azathioprine, leflunomide, mycophenolate mofetil, calcineurin inhibitors, and oral cyclophosphamide should all be held 4 weeks before and 4 weeks after administration of a live attenuated vaccine. For those taking JAK inhibitors, the medication should be halted 1 week before administration of a live vaccine and should continue to be withheld for 4 weeks after.
For most other biologics, the ACR recommends holding the medication for one dosing interval before the live vaccine and 4 weeks thereafter. The main exception is rituximab, which should be held for 6 months before a live vaccine and then for 4 more weeks thereafter.
For patients receiving intravenous immunoglobulin, the drug should be held for 8-11 months before they are administered a live attenuated vaccine, depending on the dosage, and then 4 weeks after vaccination, regardless of dosage.
To reassure people with rheumatic disease who may have anxiety or concerns about receiving immunizations, whether taking immunosuppressive medication or not, Dr. Kim said it’s important to provide lots of education to patients.
“Fear and emotion have replaced facts, and data as a leading factor in decision-making, as seen with COVID-19,” Dr. Kim said. “The reality is that a small minority of people will have any issues with most vaccines, which include disease flares, adverse events, or acquisition of an autoimmune disease. We are not saying there is zero risk, rather, that the risk is quite small. This is where shared decision-making between the health care provider and the patient must be done effectively to enable the patient to properly weigh risk versus benefit.”
Dr. Kim has relationships with GlaxoSmithKline, Aurinia Pharmaceuticals, Kypha, Pfizer, Alexion Pharmaceuticals, AstraZeneca, Exagen Diagnostics, and Foghorn Therapeutics.
A version of this article first appeared on Medscape.com.
Commentary: Concomitant Lung Disease, Drug Efficacy, and Potential Misdiagnosis in RA, August 2022
Interstitial lung disease (ILD) is a serious and not infrequent complication of rheumatoid arthritis (RA). Despite the use of several immunosuppressive medications for ILD as well as others for RA, the most effective treatment for both is yet unclear. Prior cross-sectional, retrospective, and open-label registry studies have suggested that abatacept can be used in patients with RA-ILD, with stability or improvement in pulmonary parameters in a majority of patients. Mena-Vazquez and colleagues present the results of a prospective, observational cohort study with 57 patients from multiple centers in Spain. Similar to previously published results, this study found stability or improvement in pulmonary function tests in 70% of patients as well as improvement in RA disease activity. A relatively high proportion of patients (25 in 57) experienced infections. The study lends further weight to the proposal that abatacept is a reasonable choice in patients with RA-ILD for treatment of both joint and pulmonary inflammation, given the lack of randomized controlled trials.
Lauper and colleagues published the results of a large cohort study of more than 30,000 treatment courses in patients with RA, looking at the efficacy of different biologics and a Janus kinase (JAK) inhibitor. Discontinuation of therapy was used as the primary efficacy outcome, and one secondary outcome was low disease activity based on Clinical Disease Activity Index (CDAI) at 12 months. Over 17,000 courses were anti–tumor necrosis factor (TNF) therapy, with about 7000 JAK-inhibitor therapy courses and the remainder an interleukin 6 (IL-6) inhibitor or abatacept therapy; individual data was only available from 13 to 17 registries (depending on the parameter of interest). Overall, IL-6 inhibitors and JAK inhibitors were less frequently stopped for ineffectiveness compared with anti-TNF agents, but were more frequently stopped owing to adverse events. Drug retention rates also varied between different countries, suggesting that prescription pattern differences may affect the primary outcome. In terms of CDAI, response rates at 1 year were similar between anti-TNF agents, JAK inhibitors, and IL-6 inhibitors and was slightly lower for abatacept. This real-world study does support similar efficacy between these classes of medications, though further conclusions are somewhat hampered by the lack of individual data.
A study in Japan by Mori and colleagues looked at biologic disease-modifying antirheumatic drugs (bDMARD) (TNF inhibitors and an IL-6 inhibitor) and tofacitinib discontinuation in a cohort of 97 patients with RA . Patients were required to initially be in a high or moderate disease activity state prior to treatment, then in remission or a low disease activity state with treatment for more than 48 weeks. Mean follow-up was 2.1 years and disease flare occurred in about 75% of patients at about 1.6 years after medication discontinuation. Though bDMARD- or targeted synthetic DMARD (tsDMARD)–free remission was not "durable" for most patients, the majority of those patients who experienced flares improved with resumption of their previous medication. Though it is reassuring that most study patients were able to discontinue their bDMARD or tsDMARD medication for a period of time, the fact that most experienced flares within 2 years suggests that discontinuation of these medications in patients with high disease activity is not a viable long-term approach.
Krekeler and colleagues performed a retrospective analysis of about 500 patients seen in a single rheumatology clinic to evaluate possible misdiagnosis of RA. The diagnosis of calcium pyrophosphate deposition disease (CPPD), as well as the presence of radiographic chondrocalcinosis, were more frequently found among patients diagnosed with seronegative RA vs those diagnosed with seropositive RA, particularly RA in the wrists. The CPPD diagnosis was made by rheumatologists on the basis of the presence of radiographic chondrocalcinosis along with typical joint swelling and signs of inflammation. Because chondrocalcinosis was part of the CPPD diagnosis, it is unsurprising that both followed similar patterns. Whether patients with CPPD were actually misdiagnosed as having seronegative RA is unclear from this retrospective study; as the authors note, chondrocalcinosis itself has been found to be associated with older age and osteoarthritis in prior studies, particularly in the knee. However, the study confirms that alternative diagnoses in seronegative RA should be considered.
Interstitial lung disease (ILD) is a serious and not infrequent complication of rheumatoid arthritis (RA). Despite the use of several immunosuppressive medications for ILD as well as others for RA, the most effective treatment for both is yet unclear. Prior cross-sectional, retrospective, and open-label registry studies have suggested that abatacept can be used in patients with RA-ILD, with stability or improvement in pulmonary parameters in a majority of patients. Mena-Vazquez and colleagues present the results of a prospective, observational cohort study with 57 patients from multiple centers in Spain. Similar to previously published results, this study found stability or improvement in pulmonary function tests in 70% of patients as well as improvement in RA disease activity. A relatively high proportion of patients (25 in 57) experienced infections. The study lends further weight to the proposal that abatacept is a reasonable choice in patients with RA-ILD for treatment of both joint and pulmonary inflammation, given the lack of randomized controlled trials.
Lauper and colleagues published the results of a large cohort study of more than 30,000 treatment courses in patients with RA, looking at the efficacy of different biologics and a Janus kinase (JAK) inhibitor. Discontinuation of therapy was used as the primary efficacy outcome, and one secondary outcome was low disease activity based on Clinical Disease Activity Index (CDAI) at 12 months. Over 17,000 courses were anti–tumor necrosis factor (TNF) therapy, with about 7000 JAK-inhibitor therapy courses and the remainder an interleukin 6 (IL-6) inhibitor or abatacept therapy; individual data was only available from 13 to 17 registries (depending on the parameter of interest). Overall, IL-6 inhibitors and JAK inhibitors were less frequently stopped for ineffectiveness compared with anti-TNF agents, but were more frequently stopped owing to adverse events. Drug retention rates also varied between different countries, suggesting that prescription pattern differences may affect the primary outcome. In terms of CDAI, response rates at 1 year were similar between anti-TNF agents, JAK inhibitors, and IL-6 inhibitors and was slightly lower for abatacept. This real-world study does support similar efficacy between these classes of medications, though further conclusions are somewhat hampered by the lack of individual data.
A study in Japan by Mori and colleagues looked at biologic disease-modifying antirheumatic drugs (bDMARD) (TNF inhibitors and an IL-6 inhibitor) and tofacitinib discontinuation in a cohort of 97 patients with RA . Patients were required to initially be in a high or moderate disease activity state prior to treatment, then in remission or a low disease activity state with treatment for more than 48 weeks. Mean follow-up was 2.1 years and disease flare occurred in about 75% of patients at about 1.6 years after medication discontinuation. Though bDMARD- or targeted synthetic DMARD (tsDMARD)–free remission was not "durable" for most patients, the majority of those patients who experienced flares improved with resumption of their previous medication. Though it is reassuring that most study patients were able to discontinue their bDMARD or tsDMARD medication for a period of time, the fact that most experienced flares within 2 years suggests that discontinuation of these medications in patients with high disease activity is not a viable long-term approach.
Krekeler and colleagues performed a retrospective analysis of about 500 patients seen in a single rheumatology clinic to evaluate possible misdiagnosis of RA. The diagnosis of calcium pyrophosphate deposition disease (CPPD), as well as the presence of radiographic chondrocalcinosis, were more frequently found among patients diagnosed with seronegative RA vs those diagnosed with seropositive RA, particularly RA in the wrists. The CPPD diagnosis was made by rheumatologists on the basis of the presence of radiographic chondrocalcinosis along with typical joint swelling and signs of inflammation. Because chondrocalcinosis was part of the CPPD diagnosis, it is unsurprising that both followed similar patterns. Whether patients with CPPD were actually misdiagnosed as having seronegative RA is unclear from this retrospective study; as the authors note, chondrocalcinosis itself has been found to be associated with older age and osteoarthritis in prior studies, particularly in the knee. However, the study confirms that alternative diagnoses in seronegative RA should be considered.
Interstitial lung disease (ILD) is a serious and not infrequent complication of rheumatoid arthritis (RA). Despite the use of several immunosuppressive medications for ILD as well as others for RA, the most effective treatment for both is yet unclear. Prior cross-sectional, retrospective, and open-label registry studies have suggested that abatacept can be used in patients with RA-ILD, with stability or improvement in pulmonary parameters in a majority of patients. Mena-Vazquez and colleagues present the results of a prospective, observational cohort study with 57 patients from multiple centers in Spain. Similar to previously published results, this study found stability or improvement in pulmonary function tests in 70% of patients as well as improvement in RA disease activity. A relatively high proportion of patients (25 in 57) experienced infections. The study lends further weight to the proposal that abatacept is a reasonable choice in patients with RA-ILD for treatment of both joint and pulmonary inflammation, given the lack of randomized controlled trials.
Lauper and colleagues published the results of a large cohort study of more than 30,000 treatment courses in patients with RA, looking at the efficacy of different biologics and a Janus kinase (JAK) inhibitor. Discontinuation of therapy was used as the primary efficacy outcome, and one secondary outcome was low disease activity based on Clinical Disease Activity Index (CDAI) at 12 months. Over 17,000 courses were anti–tumor necrosis factor (TNF) therapy, with about 7000 JAK-inhibitor therapy courses and the remainder an interleukin 6 (IL-6) inhibitor or abatacept therapy; individual data was only available from 13 to 17 registries (depending on the parameter of interest). Overall, IL-6 inhibitors and JAK inhibitors were less frequently stopped for ineffectiveness compared with anti-TNF agents, but were more frequently stopped owing to adverse events. Drug retention rates also varied between different countries, suggesting that prescription pattern differences may affect the primary outcome. In terms of CDAI, response rates at 1 year were similar between anti-TNF agents, JAK inhibitors, and IL-6 inhibitors and was slightly lower for abatacept. This real-world study does support similar efficacy between these classes of medications, though further conclusions are somewhat hampered by the lack of individual data.
A study in Japan by Mori and colleagues looked at biologic disease-modifying antirheumatic drugs (bDMARD) (TNF inhibitors and an IL-6 inhibitor) and tofacitinib discontinuation in a cohort of 97 patients with RA . Patients were required to initially be in a high or moderate disease activity state prior to treatment, then in remission or a low disease activity state with treatment for more than 48 weeks. Mean follow-up was 2.1 years and disease flare occurred in about 75% of patients at about 1.6 years after medication discontinuation. Though bDMARD- or targeted synthetic DMARD (tsDMARD)–free remission was not "durable" for most patients, the majority of those patients who experienced flares improved with resumption of their previous medication. Though it is reassuring that most study patients were able to discontinue their bDMARD or tsDMARD medication for a period of time, the fact that most experienced flares within 2 years suggests that discontinuation of these medications in patients with high disease activity is not a viable long-term approach.
Krekeler and colleagues performed a retrospective analysis of about 500 patients seen in a single rheumatology clinic to evaluate possible misdiagnosis of RA. The diagnosis of calcium pyrophosphate deposition disease (CPPD), as well as the presence of radiographic chondrocalcinosis, were more frequently found among patients diagnosed with seronegative RA vs those diagnosed with seropositive RA, particularly RA in the wrists. The CPPD diagnosis was made by rheumatologists on the basis of the presence of radiographic chondrocalcinosis along with typical joint swelling and signs of inflammation. Because chondrocalcinosis was part of the CPPD diagnosis, it is unsurprising that both followed similar patterns. Whether patients with CPPD were actually misdiagnosed as having seronegative RA is unclear from this retrospective study; as the authors note, chondrocalcinosis itself has been found to be associated with older age and osteoarthritis in prior studies, particularly in the knee. However, the study confirms that alternative diagnoses in seronegative RA should be considered.
Real-world data on efficacy of abatacept vs TNFi in ACPA-positive RA
Key clinical point: Abatacept significantly improved disease activity compared with tumor necrosis factor inhibitors (TNFi) in a real-world population of patients with established anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA).
Major finding: At 1-year, the mean change in clinical disease activity index (CDAI) score was significantly higher with abatacept vs TNFi (−16.78 vs −13.61; P = .020), with a higher proportion of patients receiving abatacept vs TNFi achieving CDAI remission or low disease activity (68% vs 52.6%; P = .013).
Study details: The data come from an observational cohort study that propensity-score matched 291 patients with ACPA-positive RA who initiated abatacept (n = 97) or TNFi (n = 194).
Disclosures: This study was sponsored by Bristol-Myers Squibb. The authors declared no conflicts of interest.
Source: Kim MJ, Lee S-K, et al. Efficacy of abatacept versus tumor necrosis factor inhibitors in anti-citrullinated protein antibody-positive patients with rheumatoid arthritis: Results from a Korean nationwide biologics registry. Rheumatol Ther. 2022 (Jun 18). Doi: 10.1007/s40744-022-00467-4
Key clinical point: Abatacept significantly improved disease activity compared with tumor necrosis factor inhibitors (TNFi) in a real-world population of patients with established anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA).
Major finding: At 1-year, the mean change in clinical disease activity index (CDAI) score was significantly higher with abatacept vs TNFi (−16.78 vs −13.61; P = .020), with a higher proportion of patients receiving abatacept vs TNFi achieving CDAI remission or low disease activity (68% vs 52.6%; P = .013).
Study details: The data come from an observational cohort study that propensity-score matched 291 patients with ACPA-positive RA who initiated abatacept (n = 97) or TNFi (n = 194).
Disclosures: This study was sponsored by Bristol-Myers Squibb. The authors declared no conflicts of interest.
Source: Kim MJ, Lee S-K, et al. Efficacy of abatacept versus tumor necrosis factor inhibitors in anti-citrullinated protein antibody-positive patients with rheumatoid arthritis: Results from a Korean nationwide biologics registry. Rheumatol Ther. 2022 (Jun 18). Doi: 10.1007/s40744-022-00467-4
Key clinical point: Abatacept significantly improved disease activity compared with tumor necrosis factor inhibitors (TNFi) in a real-world population of patients with established anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA).
Major finding: At 1-year, the mean change in clinical disease activity index (CDAI) score was significantly higher with abatacept vs TNFi (−16.78 vs −13.61; P = .020), with a higher proportion of patients receiving abatacept vs TNFi achieving CDAI remission or low disease activity (68% vs 52.6%; P = .013).
Study details: The data come from an observational cohort study that propensity-score matched 291 patients with ACPA-positive RA who initiated abatacept (n = 97) or TNFi (n = 194).
Disclosures: This study was sponsored by Bristol-Myers Squibb. The authors declared no conflicts of interest.
Source: Kim MJ, Lee S-K, et al. Efficacy of abatacept versus tumor necrosis factor inhibitors in anti-citrullinated protein antibody-positive patients with rheumatoid arthritis: Results from a Korean nationwide biologics registry. Rheumatol Ther. 2022 (Jun 18). Doi: 10.1007/s40744-022-00467-4
Discontinuing bDMARD or tofacitinib appears viable in RA patients achieving stable disease control
Key clinical point: Attempting discontinuation of biologic disease-modifying antirheumatic drugs (bDMARD) or tofacitinib may be a feasible option in patients with rheumatoid arthritis (RA) and can be pursued after achieving stable control of disease activity.
Major finding: During a mean follow-up period of 2.1 years after discontinuing bDMARD or tofacitinib, disease flare occurred in 76.3% of patients (incidence rate 0.36 per person-year), with the median time to flare being 1.6 years (95% CI 0.9-2.6 years) and 89% of patients regaining remission or low disease activity within 1 month of restarting the previous treatment.
Study details: This was a prospective, observational study including 97 patients with RA in sustained remission or low disease activity for ≥ 48 weeks after a stable treatment with bDMARD or tofacitinib who desired drug discontinuation but received a stable methotrexate dose during follow-up.
Disclosures: This study was supported by the National Hospital Organization, Japan. S Mori reported receiving lecture fees from various sources.
Source: Mori S et al. Long-term outcomes after discontinuing biological drugs and tofacitinib in patients with rheumatoid arthritis: A prospective cohort study. PLoS One. 2022;17(6):e0270391 (Jun 23). Doi: 10.1371/journal.pone.0270391
Key clinical point: Attempting discontinuation of biologic disease-modifying antirheumatic drugs (bDMARD) or tofacitinib may be a feasible option in patients with rheumatoid arthritis (RA) and can be pursued after achieving stable control of disease activity.
Major finding: During a mean follow-up period of 2.1 years after discontinuing bDMARD or tofacitinib, disease flare occurred in 76.3% of patients (incidence rate 0.36 per person-year), with the median time to flare being 1.6 years (95% CI 0.9-2.6 years) and 89% of patients regaining remission or low disease activity within 1 month of restarting the previous treatment.
Study details: This was a prospective, observational study including 97 patients with RA in sustained remission or low disease activity for ≥ 48 weeks after a stable treatment with bDMARD or tofacitinib who desired drug discontinuation but received a stable methotrexate dose during follow-up.
Disclosures: This study was supported by the National Hospital Organization, Japan. S Mori reported receiving lecture fees from various sources.
Source: Mori S et al. Long-term outcomes after discontinuing biological drugs and tofacitinib in patients with rheumatoid arthritis: A prospective cohort study. PLoS One. 2022;17(6):e0270391 (Jun 23). Doi: 10.1371/journal.pone.0270391
Key clinical point: Attempting discontinuation of biologic disease-modifying antirheumatic drugs (bDMARD) or tofacitinib may be a feasible option in patients with rheumatoid arthritis (RA) and can be pursued after achieving stable control of disease activity.
Major finding: During a mean follow-up period of 2.1 years after discontinuing bDMARD or tofacitinib, disease flare occurred in 76.3% of patients (incidence rate 0.36 per person-year), with the median time to flare being 1.6 years (95% CI 0.9-2.6 years) and 89% of patients regaining remission or low disease activity within 1 month of restarting the previous treatment.
Study details: This was a prospective, observational study including 97 patients with RA in sustained remission or low disease activity for ≥ 48 weeks after a stable treatment with bDMARD or tofacitinib who desired drug discontinuation but received a stable methotrexate dose during follow-up.
Disclosures: This study was supported by the National Hospital Organization, Japan. S Mori reported receiving lecture fees from various sources.
Source: Mori S et al. Long-term outcomes after discontinuing biological drugs and tofacitinib in patients with rheumatoid arthritis: A prospective cohort study. PLoS One. 2022;17(6):e0270391 (Jun 23). Doi: 10.1371/journal.pone.0270391
Safety and efficacy of abatacept in RA-associated ILD
Key clinical point: Abatacept stabilized pulmonary function and joint inflammation in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and had a favorable safety profile.
Major finding: Abatacept improved or stabilized lung disease in 72% of patients, with the median survival until progression or death being 72 months (95% CI 34-110 months). No significant decrease in the forced vital capacity or diffusing capacity of the lung for carbon monoxide and a significant improvement in 28-joint Disease Activity Score (P = .024) were observed. Overall, 10.5% of patients reported severe adverse events.
Study details: This was a prospective, observational cohort study including 57 patients with RA-ILD who received abatacept as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs, immunosuppressants, antifibrotic agents, or corticosteroids.
Disclosures: This study received grants from Fundación Andaluza de Reumatología and Instituto de Investigación Biomédica de Málaga, Spain. The authors declared no conflicts of interest.
Source: Mena-Vázquez N et al. Safety and effectiveness of abatacept in a prospective cohort of patients with rheumatoid arthritis–associated interstitial lung disease. Biomedicines. 2022;10(7):1480 (Jun 22). Doi: 10.3390/biomedicines10071480
Key clinical point: Abatacept stabilized pulmonary function and joint inflammation in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and had a favorable safety profile.
Major finding: Abatacept improved or stabilized lung disease in 72% of patients, with the median survival until progression or death being 72 months (95% CI 34-110 months). No significant decrease in the forced vital capacity or diffusing capacity of the lung for carbon monoxide and a significant improvement in 28-joint Disease Activity Score (P = .024) were observed. Overall, 10.5% of patients reported severe adverse events.
Study details: This was a prospective, observational cohort study including 57 patients with RA-ILD who received abatacept as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs, immunosuppressants, antifibrotic agents, or corticosteroids.
Disclosures: This study received grants from Fundación Andaluza de Reumatología and Instituto de Investigación Biomédica de Málaga, Spain. The authors declared no conflicts of interest.
Source: Mena-Vázquez N et al. Safety and effectiveness of abatacept in a prospective cohort of patients with rheumatoid arthritis–associated interstitial lung disease. Biomedicines. 2022;10(7):1480 (Jun 22). Doi: 10.3390/biomedicines10071480
Key clinical point: Abatacept stabilized pulmonary function and joint inflammation in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and had a favorable safety profile.
Major finding: Abatacept improved or stabilized lung disease in 72% of patients, with the median survival until progression or death being 72 months (95% CI 34-110 months). No significant decrease in the forced vital capacity or diffusing capacity of the lung for carbon monoxide and a significant improvement in 28-joint Disease Activity Score (P = .024) were observed. Overall, 10.5% of patients reported severe adverse events.
Study details: This was a prospective, observational cohort study including 57 patients with RA-ILD who received abatacept as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs, immunosuppressants, antifibrotic agents, or corticosteroids.
Disclosures: This study received grants from Fundación Andaluza de Reumatología and Instituto de Investigación Biomédica de Málaga, Spain. The authors declared no conflicts of interest.
Source: Mena-Vázquez N et al. Safety and effectiveness of abatacept in a prospective cohort of patients with rheumatoid arthritis–associated interstitial lung disease. Biomedicines. 2022;10(7):1480 (Jun 22). Doi: 10.3390/biomedicines10071480