Rheumatoid Arthritis

Key clinical point: A 2-week methotrexate withdrawal after each dose of Sinovac-CoronaVac vaccine may improve anti-SARS-CoV-2 immunogenicity in patients with rheumatoid arthritis (RA) with low disease activity (LDA) or remission. However, this may increase flare rates, thereby requiring close surveillance of disease activity.

Major finding: At 6 weeks after the second vaccine dose, patients who withheld vs. maintained methotrexate after both vaccine shots had a significantly higher seroconversion (P = .019) with a parallel increase in geometric mean titer (P = .006). However, the flare rate (Clinical Disease Activity Index >10) was higher in the group that withheld vs. continued methotrexate (P = .011).

Study details: Findings are from the single-center, prospective CoronavRheum study that included 138 patients with RA with LDA/remission at first vaccine dose who were randomly assigned to maintain (n = 69) methotrexate use or institute a 2-week withdrawal (n = 60) of methotrexate after each dose of Sinovac-CoronaVac vaccine.

Disclosures: This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3 - Bolsa de Valores do Brasil. No conflicts of interest were declared.

Source: Renner Araujo CS et al. Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: A randomised clinical trial. Ann Rheum Dis. 2022 (Feb 22). Doi: 10.1136/annrheumdis-2021-221916

Key clinical point: A 2-week methotrexate withdrawal after each dose of Sinovac-CoronaVac vaccine may improve anti-SARS-CoV-2 immunogenicity in patients with rheumatoid arthritis (RA) with low disease activity (LDA) or remission. However, this may increase flare rates, thereby requiring close surveillance of disease activity.

Major finding: At 6 weeks after the second vaccine dose, patients who withheld vs. maintained methotrexate after both vaccine shots had a significantly higher seroconversion (P = .019) with a parallel increase in geometric mean titer (P = .006). However, the flare rate (Clinical Disease Activity Index >10) was higher in the group that withheld vs. continued methotrexate (P = .011).

Study details: Findings are from the single-center, prospective CoronavRheum study that included 138 patients with RA with LDA/remission at first vaccine dose who were randomly assigned to maintain (n = 69) methotrexate use or institute a 2-week withdrawal (n = 60) of methotrexate after each dose of Sinovac-CoronaVac vaccine.

Disclosures: This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3 - Bolsa de Valores do Brasil. No conflicts of interest were declared.

Source: Renner Araujo CS et al. Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: A randomised clinical trial. Ann Rheum Dis. 2022 (Feb 22). Doi: 10.1136/annrheumdis-2021-221916

Key clinical point: A 2-week methotrexate withdrawal after each dose of Sinovac-CoronaVac vaccine may improve anti-SARS-CoV-2 immunogenicity in patients with rheumatoid arthritis (RA) with low disease activity (LDA) or remission. However, this may increase flare rates, thereby requiring close surveillance of disease activity.

Major finding: At 6 weeks after the second vaccine dose, patients who withheld vs. maintained methotrexate after both vaccine shots had a significantly higher seroconversion (P = .019) with a parallel increase in geometric mean titer (P = .006). However, the flare rate (Clinical Disease Activity Index >10) was higher in the group that withheld vs. continued methotrexate (P = .011).

Study details: Findings are from the single-center, prospective CoronavRheum study that included 138 patients with RA with LDA/remission at first vaccine dose who were randomly assigned to maintain (n = 69) methotrexate use or institute a 2-week withdrawal (n = 60) of methotrexate after each dose of Sinovac-CoronaVac vaccine.

Disclosures: This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3 - Bolsa de Valores do Brasil. No conflicts of interest were declared.

Source: Renner Araujo CS et al. Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: A randomised clinical trial. Ann Rheum Dis. 2022 (Feb 22). Doi: 10.1136/annrheumdis-2021-221916

Key clinical point: Patient physical function and magnetic resonance imaging (MRI) measures of inflammation and damage at the time of treatment withdrawal (tWD) were independent predictors of flare at 6 and 12 months after tWD in patients with early rheumatoid arthritis (RA).

Major finding: At 6 and 12 months after tWD, a Health Assessment Questionnaire-Disability Index score of >0.5 (adjusted odds ratio [aOR] 3.97; P = .0060 and aOR 5.09; P = .0048, respectively) and an MRI erosion score of >2 (aOR 2.81; P = .0176 and aOR 2.38; P = .0495, respectively) were independently associated with flare.

Study details: This was a post hoc analysis of phase 3b AVERT study involving 172 patients with early RA who achieved remission with methotrexate or abatacept at 1 year and entered a 12-month tWD period.

Disclosures: The study was supported by Bristol Myers Squibb. The authors reported receiving grant/research funding and speaking and consulting fees from various sources, including Bristol Myers Squibb. Dr. Ahmad and Dr. Banerjee reported being employees or shareholders of Bristol Myers Squibb.

Source: Ahmad HA et al. Prediction of flare following remission and treatment withdrawal in early rheumatoid arthritis: Post hoc analysis of a phase IIIb trial with abatacept. Arthritis Res Ther. 2022;24:47 (Feb 16). Doi: 10.1186/s13075-022-02735-8

Key clinical point: Patient physical function and magnetic resonance imaging (MRI) measures of inflammation and damage at the time of treatment withdrawal (tWD) were independent predictors of flare at 6 and 12 months after tWD in patients with early rheumatoid arthritis (RA).

Major finding: At 6 and 12 months after tWD, a Health Assessment Questionnaire-Disability Index score of >0.5 (adjusted odds ratio [aOR] 3.97; P = .0060 and aOR 5.09; P = .0048, respectively) and an MRI erosion score of >2 (aOR 2.81; P = .0176 and aOR 2.38; P = .0495, respectively) were independently associated with flare.

Study details: This was a post hoc analysis of phase 3b AVERT study involving 172 patients with early RA who achieved remission with methotrexate or abatacept at 1 year and entered a 12-month tWD period.

Disclosures: The study was supported by Bristol Myers Squibb. The authors reported receiving grant/research funding and speaking and consulting fees from various sources, including Bristol Myers Squibb. Dr. Ahmad and Dr. Banerjee reported being employees or shareholders of Bristol Myers Squibb.

Source: Ahmad HA et al. Prediction of flare following remission and treatment withdrawal in early rheumatoid arthritis: Post hoc analysis of a phase IIIb trial with abatacept. Arthritis Res Ther. 2022;24:47 (Feb 16). Doi: 10.1186/s13075-022-02735-8

Key clinical point: Patient physical function and magnetic resonance imaging (MRI) measures of inflammation and damage at the time of treatment withdrawal (tWD) were independent predictors of flare at 6 and 12 months after tWD in patients with early rheumatoid arthritis (RA).

Major finding: At 6 and 12 months after tWD, a Health Assessment Questionnaire-Disability Index score of >0.5 (adjusted odds ratio [aOR] 3.97; P = .0060 and aOR 5.09; P = .0048, respectively) and an MRI erosion score of >2 (aOR 2.81; P = .0176 and aOR 2.38; P = .0495, respectively) were independently associated with flare.

Study details: This was a post hoc analysis of phase 3b AVERT study involving 172 patients with early RA who achieved remission with methotrexate or abatacept at 1 year and entered a 12-month tWD period.

Disclosures: The study was supported by Bristol Myers Squibb. The authors reported receiving grant/research funding and speaking and consulting fees from various sources, including Bristol Myers Squibb. Dr. Ahmad and Dr. Banerjee reported being employees or shareholders of Bristol Myers Squibb.

Source: Ahmad HA et al. Prediction of flare following remission and treatment withdrawal in early rheumatoid arthritis: Post hoc analysis of a phase IIIb trial with abatacept. Arthritis Res Ther. 2022;24:47 (Feb 16). Doi: 10.1186/s13075-022-02735-8

Key clinical point: Approximately two-thirds of patients with rheumatoid arthritis (RA) receiving 15 mg upadacitinib and methotrexate attained a satisfactory humoral response to pneumococcal 13-valent conjugate vaccine (PCV-13) through 12 weeks postvaccination.

Major finding: At 4 weeks, 67.5% (95% CI 57.4%-77.5%) of patients receiving 15 mg upadacitinib and methotrexate attained a satisfactory humoral response to PCV-13, which was sustained until week 12 (64.6%; 95% CI 54.0%-75.1%), with response being similar irrespective of concomitant corticosteroids. Adverse events were mostly mild in severity.

Study details: Findings are from a phase 2 open-label extension trial, Balance-Extend, including 111 patients with RA receiving a stable dose of 15 mg upadacitinib (n = 87) or 30 mg (n = 24) once daily with background methotrexate who were administered PCV-13.

Disclosures: This study was supported by AbbVie. A Friedman, B Hendrickson, Y Li, and J Klaff reported being employees or shareholders of AbbVie, and others declared serving as editorial board members or receiving grants, consulting fees, or honoraria from various sources, including AbbVie.

Source: Winthrop K et al. Evaluation of response to 13-valent conjugated pneumococcal vaccination in patients with rheumatoid arthritis receiving upadacitinib: Results from a phase 2 open-label extension study. RMD Open. 2022;8:e002110 (Mar 4). Doi: 10.1136/rmdopen-2021-002110

Key clinical point: Approximately two-thirds of patients with rheumatoid arthritis (RA) receiving 15 mg upadacitinib and methotrexate attained a satisfactory humoral response to pneumococcal 13-valent conjugate vaccine (PCV-13) through 12 weeks postvaccination.

Major finding: At 4 weeks, 67.5% (95% CI 57.4%-77.5%) of patients receiving 15 mg upadacitinib and methotrexate attained a satisfactory humoral response to PCV-13, which was sustained until week 12 (64.6%; 95% CI 54.0%-75.1%), with response being similar irrespective of concomitant corticosteroids. Adverse events were mostly mild in severity.

Study details: Findings are from a phase 2 open-label extension trial, Balance-Extend, including 111 patients with RA receiving a stable dose of 15 mg upadacitinib (n = 87) or 30 mg (n = 24) once daily with background methotrexate who were administered PCV-13.

Disclosures: This study was supported by AbbVie. A Friedman, B Hendrickson, Y Li, and J Klaff reported being employees or shareholders of AbbVie, and others declared serving as editorial board members or receiving grants, consulting fees, or honoraria from various sources, including AbbVie.

Source: Winthrop K et al. Evaluation of response to 13-valent conjugated pneumococcal vaccination in patients with rheumatoid arthritis receiving upadacitinib: Results from a phase 2 open-label extension study. RMD Open. 2022;8:e002110 (Mar 4). Doi: 10.1136/rmdopen-2021-002110

Key clinical point: Approximately two-thirds of patients with rheumatoid arthritis (RA) receiving 15 mg upadacitinib and methotrexate attained a satisfactory humoral response to pneumococcal 13-valent conjugate vaccine (PCV-13) through 12 weeks postvaccination.

Major finding: At 4 weeks, 67.5% (95% CI 57.4%-77.5%) of patients receiving 15 mg upadacitinib and methotrexate attained a satisfactory humoral response to PCV-13, which was sustained until week 12 (64.6%; 95% CI 54.0%-75.1%), with response being similar irrespective of concomitant corticosteroids. Adverse events were mostly mild in severity.

Study details: Findings are from a phase 2 open-label extension trial, Balance-Extend, including 111 patients with RA receiving a stable dose of 15 mg upadacitinib (n = 87) or 30 mg (n = 24) once daily with background methotrexate who were administered PCV-13.

Disclosures: This study was supported by AbbVie. A Friedman, B Hendrickson, Y Li, and J Klaff reported being employees or shareholders of AbbVie, and others declared serving as editorial board members or receiving grants, consulting fees, or honoraria from various sources, including AbbVie.

Source: Winthrop K et al. Evaluation of response to 13-valent conjugated pneumococcal vaccination in patients with rheumatoid arthritis receiving upadacitinib: Results from a phase 2 open-label extension study. RMD Open. 2022;8:e002110 (Mar 4). Doi: 10.1136/rmdopen-2021-002110

Key clinical point: An additional COVID-19 vaccine dose (AddDose) had no effect on rheumatoid arthritis (RA) disease activity, regardless of whether patients withheld or continued disease-modifying antirheumatic drugs (DMARD).

Major finding: The mean RA Disease Activity Index-5 was not significantly different pre- vs. post-AddDose (3.20 vs. 3.25; P = .51), with no difference observed among patients who withheld at least 1 DMARD or those who continued all DMARDs.

Study details: This was a prospective observational study including 71 patients with RA who had previously received either 2 doses of an mRNA COVID-19 vaccine or 1 dose of an adenovirus vector COVID-19 vaccine and planned for an AddDose.

Disclosures: ModernaTx supported Brigham and Women’s Hospital for an Investigator Sponsored Study, with additional support received from the US National Institutes of Health. The authors declared serving as scientific advisory board members or receiving research support and consulting fees from various sources, including ModernaTx.

Source: Tedeschi SK et al. Rheumatoid arthritis disease activity assessed by patient-reported outcomes and flow cytometry before and after an additional dose of COVID-19 vaccine. Ann Rheum Dis. 2022 (Feb 15). Doi: 10.1136/annrheumdis-2022-222232

Key clinical point: An additional COVID-19 vaccine dose (AddDose) had no effect on rheumatoid arthritis (RA) disease activity, regardless of whether patients withheld or continued disease-modifying antirheumatic drugs (DMARD).

Major finding: The mean RA Disease Activity Index-5 was not significantly different pre- vs. post-AddDose (3.20 vs. 3.25; P = .51), with no difference observed among patients who withheld at least 1 DMARD or those who continued all DMARDs.

Study details: This was a prospective observational study including 71 patients with RA who had previously received either 2 doses of an mRNA COVID-19 vaccine or 1 dose of an adenovirus vector COVID-19 vaccine and planned for an AddDose.

Disclosures: ModernaTx supported Brigham and Women’s Hospital for an Investigator Sponsored Study, with additional support received from the US National Institutes of Health. The authors declared serving as scientific advisory board members or receiving research support and consulting fees from various sources, including ModernaTx.

Source: Tedeschi SK et al. Rheumatoid arthritis disease activity assessed by patient-reported outcomes and flow cytometry before and after an additional dose of COVID-19 vaccine. Ann Rheum Dis. 2022 (Feb 15). Doi: 10.1136/annrheumdis-2022-222232

Key clinical point: An additional COVID-19 vaccine dose (AddDose) had no effect on rheumatoid arthritis (RA) disease activity, regardless of whether patients withheld or continued disease-modifying antirheumatic drugs (DMARD).

Major finding: The mean RA Disease Activity Index-5 was not significantly different pre- vs. post-AddDose (3.20 vs. 3.25; P = .51), with no difference observed among patients who withheld at least 1 DMARD or those who continued all DMARDs.

Study details: This was a prospective observational study including 71 patients with RA who had previously received either 2 doses of an mRNA COVID-19 vaccine or 1 dose of an adenovirus vector COVID-19 vaccine and planned for an AddDose.

Disclosures: ModernaTx supported Brigham and Women’s Hospital for an Investigator Sponsored Study, with additional support received from the US National Institutes of Health. The authors declared serving as scientific advisory board members or receiving research support and consulting fees from various sources, including ModernaTx.

Source: Tedeschi SK et al. Rheumatoid arthritis disease activity assessed by patient-reported outcomes and flow cytometry before and after an additional dose of COVID-19 vaccine. Ann Rheum Dis. 2022 (Feb 15). Doi: 10.1136/annrheumdis-2022-222232

Key clinical point: Baricitinib inhibited the progression of structural joint damage in patients with rheumatoid arthritis (RA) even if they continued to have high or moderate disease activity (DA).

Major finding: Structural damage progression was not significantly different based on DA among patients with inadequate response to methotrexate (methotrexate-IR) receiving baricitinib (P = .6), whereas a clear dependence on DA was observed among patients receiving placebo (P = .02), with patients with moderate/high DA receiving baricitinib vs. placebo showing less disease progression (P < .001).

Study details: The study included patients with established RA who were either methotrexate-IR (RA-BEAM) or naive to conventional synthetic disease-modifying antirheumatic drugs (RA-BEGIN).

Disclosures: Eli Lilly and Company and Incyte Corporation provided funding for the RA-BEGIN and RA-BEAM trials. P Lopez-Romero, I de la Torre, and E Haladyj reported being employees of Eli Lilly and Company, and others declared serving as an advisor or speaker or receiving grants/contracts from various sources, including Eli Lilly.

Source: Lopez-Romero P et al. Baricitinib further enhances disease-modifying effects by uncoupling the link between disease activity and joint structural progression in patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Feb 22). Doi: 10.1136/annrheumdis-2021-221323

Key clinical point: Baricitinib inhibited the progression of structural joint damage in patients with rheumatoid arthritis (RA) even if they continued to have high or moderate disease activity (DA).

Major finding: Structural damage progression was not significantly different based on DA among patients with inadequate response to methotrexate (methotrexate-IR) receiving baricitinib (P = .6), whereas a clear dependence on DA was observed among patients receiving placebo (P = .02), with patients with moderate/high DA receiving baricitinib vs. placebo showing less disease progression (P < .001).

Study details: The study included patients with established RA who were either methotrexate-IR (RA-BEAM) or naive to conventional synthetic disease-modifying antirheumatic drugs (RA-BEGIN).

Disclosures: Eli Lilly and Company and Incyte Corporation provided funding for the RA-BEGIN and RA-BEAM trials. P Lopez-Romero, I de la Torre, and E Haladyj reported being employees of Eli Lilly and Company, and others declared serving as an advisor or speaker or receiving grants/contracts from various sources, including Eli Lilly.

Source: Lopez-Romero P et al. Baricitinib further enhances disease-modifying effects by uncoupling the link between disease activity and joint structural progression in patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Feb 22). Doi: 10.1136/annrheumdis-2021-221323

Key clinical point: Baricitinib inhibited the progression of structural joint damage in patients with rheumatoid arthritis (RA) even if they continued to have high or moderate disease activity (DA).

Major finding: Structural damage progression was not significantly different based on DA among patients with inadequate response to methotrexate (methotrexate-IR) receiving baricitinib (P = .6), whereas a clear dependence on DA was observed among patients receiving placebo (P = .02), with patients with moderate/high DA receiving baricitinib vs. placebo showing less disease progression (P < .001).

Study details: The study included patients with established RA who were either methotrexate-IR (RA-BEAM) or naive to conventional synthetic disease-modifying antirheumatic drugs (RA-BEGIN).

Disclosures: Eli Lilly and Company and Incyte Corporation provided funding for the RA-BEGIN and RA-BEAM trials. P Lopez-Romero, I de la Torre, and E Haladyj reported being employees of Eli Lilly and Company, and others declared serving as an advisor or speaker or receiving grants/contracts from various sources, including Eli Lilly.

Source: Lopez-Romero P et al. Baricitinib further enhances disease-modifying effects by uncoupling the link between disease activity and joint structural progression in patients with rheumatoid arthritis. Ann Rheum Dis. 2022 (Feb 22). Doi: 10.1136/annrheumdis-2021-221323

Key clinical point: Patients with early rheumatoid arthritis (RA) treated with baricitinib monotherapy or baricitinib plus methotrexate vs. methotrexate monotherapy (MM) experienced significantly greater and more rapid pain relief along with more weeks of limited to no pain.

Major finding: Patients treated with baricitinib monotherapy or baricitinib+methotrexate vs. MM reported a significant improvement in pain as early as 2 weeks with sustained improvements and an additional 9-10 weeks of pain-free life over the 52-week treatment period (all P < .001).

Study details: This was a post hoc analysis of the phase 3 study, RA-BEGIN including 588 patients with early RA randomly assigned to receive MM, baricitinib monotherapy, or baricitinib+methotrexate for 52 weeks.

Disclosures: This work was sponsored by Eli Lilly and Company under license from Incyte Corporation. Five authors declared being employees or shareholders of Eli Lilly and Company, and some others declared receiving research grants, consultation fees, honoraria, or speaking fees from various sources, including Eli Lilly and Company.

Source: Taylor PC et al. Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy. RMD Open. 2022;8:e001994 (Mar 9). Doi: 10.1136/rmdopen-2021-001994

Key clinical point: Patients with early rheumatoid arthritis (RA) treated with baricitinib monotherapy or baricitinib plus methotrexate vs. methotrexate monotherapy (MM) experienced significantly greater and more rapid pain relief along with more weeks of limited to no pain.

Major finding: Patients treated with baricitinib monotherapy or baricitinib+methotrexate vs. MM reported a significant improvement in pain as early as 2 weeks with sustained improvements and an additional 9-10 weeks of pain-free life over the 52-week treatment period (all P < .001).

Study details: This was a post hoc analysis of the phase 3 study, RA-BEGIN including 588 patients with early RA randomly assigned to receive MM, baricitinib monotherapy, or baricitinib+methotrexate for 52 weeks.

Disclosures: This work was sponsored by Eli Lilly and Company under license from Incyte Corporation. Five authors declared being employees or shareholders of Eli Lilly and Company, and some others declared receiving research grants, consultation fees, honoraria, or speaking fees from various sources, including Eli Lilly and Company.

Source: Taylor PC et al. Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy. RMD Open. 2022;8:e001994 (Mar 9). Doi: 10.1136/rmdopen-2021-001994

Key clinical point: Patients with early rheumatoid arthritis (RA) treated with baricitinib monotherapy or baricitinib plus methotrexate vs. methotrexate monotherapy (MM) experienced significantly greater and more rapid pain relief along with more weeks of limited to no pain.

Major finding: Patients treated with baricitinib monotherapy or baricitinib+methotrexate vs. MM reported a significant improvement in pain as early as 2 weeks with sustained improvements and an additional 9-10 weeks of pain-free life over the 52-week treatment period (all P < .001).

Study details: This was a post hoc analysis of the phase 3 study, RA-BEGIN including 588 patients with early RA randomly assigned to receive MM, baricitinib monotherapy, or baricitinib+methotrexate for 52 weeks.

Disclosures: This work was sponsored by Eli Lilly and Company under license from Incyte Corporation. Five authors declared being employees or shareholders of Eli Lilly and Company, and some others declared receiving research grants, consultation fees, honoraria, or speaking fees from various sources, including Eli Lilly and Company.

Source: Taylor PC et al. Achieving pain control in early rheumatoid arthritis with baricitinib monotherapy or in combination with methotrexate versus methotrexate monotherapy. RMD Open. 2022;8:e001994 (Mar 9). Doi: 10.1136/rmdopen-2021-001994

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Survival rates of biologics and other novel immunomodulatory drugs vary substantially across chronic inflammatory diseases, and rates are highest for rituximab in rheumatoid arthritis (RA) and golimumab in axial spondyloarthritis (axSpA), but with similar rates seen for most drugs used in the treatment of psoriasis and psoriatic arthritis (PsA), according to findings from a study of two Danish registries.

Drug survival refers to “the probability that patients will remain on a given drug, and is a proxy for efficacy as well as safety in daily clinical practice,” wrote Alexander Egeberg, MD, PhD, of the department of dermatology at Copenhagen University Hospital–Bispebjerg, and colleagues. Although the use of biologics has expanded for inflammatory diseases, real-world data on drug survival in newer agents such as interleukin (IL)-17, IL-23, and Janus kinase inhibitors are lacking, they said.

In a study published in Seminars in Arthritis and Rheumatism, the researchers reviewed data from the DANBIO and DERMBIO registries of patients in Denmark with inflammatory diseases including rheumatoid arthritis (RA), axial spondyloarthritis (AxSpA), psoriatic arthritis (PsA), and psoriasis.

The study population included 12,089 adults: 5,104 with RA, 2,157 with AxSpA, 2,251 with PsA, and 2,577 with psoriasis. Patients’ mean age at the time of first treatment for these conditions was 57.8 years, 42.3 years, 49 years, and 45 years, respectively. Participants were treated with biologics or novel small molecule therapies for RA, AxSpA, PsA, or psoriasis between January 2015 and May 2021 (from the DANBIO database) and November 2009 to November 2019 (DERMBIO database).

In adjusted models, drug survival in RA was highest for rituximab followed by baricitinib, etanercept, and tocilizumab. Drug survival in AxSpA was highest for golimumab, compared with all other drugs, followed by secukinumab and etanercept. Survival was lowest for infliximab. In PsA, drug survival was roughly equal for most drugs, including golimumab, secukinumab, and ixekizumab, with the lowest survival observed for tofacitinib and infliximab, compared with all other drugs. Drug survival in psoriasis was highest with guselkumab, followed by ustekinumab and IL-17 inhibitors.

However, the number of treatment series “was low for some drugs, and not all differences were statistically significant, which could influence the overall interpretability of these findings,” the researchers noted in their discussion.

Notably, the high treatment persistence for rituximab in RA patients needs further confirmation, the researchers said. “In Denmark, rituximab is often the biologic drug of choice in RA patients with a history of cancer while there is a reluctancy to use TNF [tumor necrosis factor] inhibitors in such patients; this may have prolonged the drug survival for rituximab treated patients due to limited treatment alternatives,” they said.

The findings were limited by several factors, including the observational study design and changes in guidelines over the course of the study, the researchers noted. Other limitations included the inability to adjust for certain variables, such as antibody status, body weight, and smoking, because of missing data, and a lack of data on the underlying reasons for drug discontinuation, they said.

However, the results were strengthened by the large number of patients and completeness of the registries, the researchers emphasized. The range in responses to different drug types across diseases supports the need for individualized treatments with attention to underlying disease, patient profile, and treatment history, they concluded.

The study received no outside funding. Eight coauthors reported financial ties to a number of pharmaceutical companies.

Patients with undifferentiated arthritis (UA) that is defined according to contemporary criteria don’t appear to have the same excess mortality that is associated with rheumatoid arthritis, despite links between the two conditions.

UA has long been considered an earlier phase of RA, so similar management strategies are often used based on the assumption that outcomes and elevated mortality risk were similar between the two, but new findings reported in a research letter published in Annals of the Rheumatic Diseases challenge that assumption.

The change in the definition of UA that accompanied the introduction of new RA criteria in 2010 meant that some of the patients who previously met the criteria for UA now were classified as having RA, and “the remaining contemporary UA population (not fulfilling the 1987/2010 RA criteria) is largely autoantibody negative, presents with monoarthritis or oligoarthritis, and progresses less frequently to RA,” PhD candidate Marloes Verstappen of Leiden (Netherlands) University Medical Center, and coauthors wrote.

As the first large study on excess mortality in patients meeting contemporary criteria for UA, the authors said it suggests that the change in criteria for UA has served to increase the differences in mortality between it and RA.

“Further research and discussions are needed as to whether the management of contemporary UA should be similar to or different from that of RA,” they wrote.

The researchers conducted a longitudinal cohort study of 860 patients who met the conventional criteria for UA – they did not meet the 1987 RA criteria or other diagnosis – at baseline and 561 who met contemporary criteria for UA based on the fact that they did not meet the 1987 or 2010 RA criteria. There were also 762 patients who were diagnosed with RA according to the 1987 criteria, and 828 diagnosed according to the 2010 criteria. All of these patients were diagnosed between 1993 and 2008 and their median follow-up times ranged from 16.0 to 17.3 years, with a minimum of 10 years of follow-up.

The study found that, while there was a trend toward excess mortality in the conventional UA group (standardized mortality ratio, 1.11; 95% confidence interval, 0.96-1.27), there was no significant excess mortality in the contemporary UA patients (SMR, 1.05; 95% CI, 0.87-1.26).

In comparison, patients in both the 1987 RA criteria group and the 2010 criteria group showed significantly higher mortality. Among patients with anti–citrullinated protein antibody–positive disease, even early treatment with disease-modifying antirheumatic drugs and treat-to-target strategies didn’t reduce the excess mortality.

The study did find some suggestion of excess mortality among patients with contemporary UA and who were anti–citrullinated protein antibody positive, but the number of patients was small.

“Only a few percent of patients presenting with contemporary UA are autoantibody positive; these patients may be considered at increased risk to progress to RA,” the authors wrote.

The data also suggested that disease-modifying antirheumatic drugs didn’t alter excess mortality among patients with contemporary UA.

The study was supported by the Dutch Arthritis Foundation and the European Research Council. No conflicts of interest were declared.

Patients with undifferentiated arthritis (UA) that is defined according to contemporary criteria don’t appear to have the same excess mortality that is associated with rheumatoid arthritis, despite links between the two conditions.

UA has long been considered an earlier phase of RA, so similar management strategies are often used based on the assumption that outcomes and elevated mortality risk were similar between the two, but new findings reported in a research letter published in Annals of the Rheumatic Diseases challenge that assumption.

The change in the definition of UA that accompanied the introduction of new RA criteria in 2010 meant that some of the patients who previously met the criteria for UA now were classified as having RA, and “the remaining contemporary UA population (not fulfilling the 1987/2010 RA criteria) is largely autoantibody negative, presents with monoarthritis or oligoarthritis, and progresses less frequently to RA,” PhD candidate Marloes Verstappen of Leiden (Netherlands) University Medical Center, and coauthors wrote.

As the first large study on excess mortality in patients meeting contemporary criteria for UA, the authors said it suggests that the change in criteria for UA has served to increase the differences in mortality between it and RA.

“Further research and discussions are needed as to whether the management of contemporary UA should be similar to or different from that of RA,” they wrote.

The researchers conducted a longitudinal cohort study of 860 patients who met the conventional criteria for UA – they did not meet the 1987 RA criteria or other diagnosis – at baseline and 561 who met contemporary criteria for UA based on the fact that they did not meet the 1987 or 2010 RA criteria. There were also 762 patients who were diagnosed with RA according to the 1987 criteria, and 828 diagnosed according to the 2010 criteria. All of these patients were diagnosed between 1993 and 2008 and their median follow-up times ranged from 16.0 to 17.3 years, with a minimum of 10 years of follow-up.

The study found that, while there was a trend toward excess mortality in the conventional UA group (standardized mortality ratio, 1.11; 95% confidence interval, 0.96-1.27), there was no significant excess mortality in the contemporary UA patients (SMR, 1.05; 95% CI, 0.87-1.26).

In comparison, patients in both the 1987 RA criteria group and the 2010 criteria group showed significantly higher mortality. Among patients with anti–citrullinated protein antibody–positive disease, even early treatment with disease-modifying antirheumatic drugs and treat-to-target strategies didn’t reduce the excess mortality.

The study did find some suggestion of excess mortality among patients with contemporary UA and who were anti–citrullinated protein antibody positive, but the number of patients was small.

“Only a few percent of patients presenting with contemporary UA are autoantibody positive; these patients may be considered at increased risk to progress to RA,” the authors wrote.

The data also suggested that disease-modifying antirheumatic drugs didn’t alter excess mortality among patients with contemporary UA.

The study was supported by the Dutch Arthritis Foundation and the European Research Council. No conflicts of interest were declared.

Patients with undifferentiated arthritis (UA) that is defined according to contemporary criteria don’t appear to have the same excess mortality that is associated with rheumatoid arthritis, despite links between the two conditions.

UA has long been considered an earlier phase of RA, so similar management strategies are often used based on the assumption that outcomes and elevated mortality risk were similar between the two, but new findings reported in a research letter published in Annals of the Rheumatic Diseases challenge that assumption.

The change in the definition of UA that accompanied the introduction of new RA criteria in 2010 meant that some of the patients who previously met the criteria for UA now were classified as having RA, and “the remaining contemporary UA population (not fulfilling the 1987/2010 RA criteria) is largely autoantibody negative, presents with monoarthritis or oligoarthritis, and progresses less frequently to RA,” PhD candidate Marloes Verstappen of Leiden (Netherlands) University Medical Center, and coauthors wrote.

As the first large study on excess mortality in patients meeting contemporary criteria for UA, the authors said it suggests that the change in criteria for UA has served to increase the differences in mortality between it and RA.

“Further research and discussions are needed as to whether the management of contemporary UA should be similar to or different from that of RA,” they wrote.

The researchers conducted a longitudinal cohort study of 860 patients who met the conventional criteria for UA – they did not meet the 1987 RA criteria or other diagnosis – at baseline and 561 who met contemporary criteria for UA based on the fact that they did not meet the 1987 or 2010 RA criteria. There were also 762 patients who were diagnosed with RA according to the 1987 criteria, and 828 diagnosed according to the 2010 criteria. All of these patients were diagnosed between 1993 and 2008 and their median follow-up times ranged from 16.0 to 17.3 years, with a minimum of 10 years of follow-up.

The study found that, while there was a trend toward excess mortality in the conventional UA group (standardized mortality ratio, 1.11; 95% confidence interval, 0.96-1.27), there was no significant excess mortality in the contemporary UA patients (SMR, 1.05; 95% CI, 0.87-1.26).

In comparison, patients in both the 1987 RA criteria group and the 2010 criteria group showed significantly higher mortality. Among patients with anti–citrullinated protein antibody–positive disease, even early treatment with disease-modifying antirheumatic drugs and treat-to-target strategies didn’t reduce the excess mortality.

The study did find some suggestion of excess mortality among patients with contemporary UA and who were anti–citrullinated protein antibody positive, but the number of patients was small.

“Only a few percent of patients presenting with contemporary UA are autoantibody positive; these patients may be considered at increased risk to progress to RA,” the authors wrote.

The data also suggested that disease-modifying antirheumatic drugs didn’t alter excess mortality among patients with contemporary UA.

The study was supported by the Dutch Arthritis Foundation and the European Research Council. No conflicts of interest were declared.

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have released updated guidelines regarding whether to withhold drugs such as biologics and immunosuppressives for patients with inflammatory rheumatic disease who are scheduled to undergo elective total hip or knee replacement surgery.

The guidelines, published in a summary by the societies on Feb. 28, include revised and new recommendations about biologics and Janus kinase (JAK) inhibitors for patients with several types of inflammatory arthritis and systemic lupus erythematosus (SLE). In general, the guidelines recommend that the most powerful medications be withheld prior to surgery except for patients whose SLE is so severe that it threatens organs. They also recommend a shorter period of withholding drugs – 3 days instead of 7 – for JAK inhibitors.
 

The previous guidelines were published in 2017.

“These recommendations seek to balance flares of disease that are likely when medications are stopped vs. the risk of infection,” Susan M. Goodman, MD, a rheumatologist at the Hospital for Special Surgery, New York, and co–principal investigator of the guideline, told this news organization. “Patients and physicians may want to be either more conservative or more aggressive with their medications, depending on their personal priorities or specific medical history.”

According to Dr. Goodman, patients with inflammatory rheumatic diseases are especially likely to undergo joint replacement surgery because the conditions can damage the joints. “While the introduction of potent biologics has been linked to a decrease in surgery of soft tissues and small joints, there has been little impact on large-joint surgeries,” she said.

The risk of infection in these patients is about 50% higher than in the general population, she said. However, “it is hard to determine the magnitude of the effect of withholding medications, given the low rate of infection. In fact, using pharmaco-epidemiologic methods in large Medicare databases, no difference was seen in patients whose immunosuppressant medication infusions were close to the time of surgery compared to those patients whose medication infusions were months prior to surgery.”

The guidelines add a recommendation for the first time for apremilast (Otezla), saying that when it is administered twice daily it is okay to schedule surgery at any time.

Withholding drugs in patients with SLE

“We now recommend continuing biologics used to treat SLE – rituximab and belimumab – in patients with severe SLE but continue to recommend withholding them in less severe cases where there is little risk of organ damage,” Bryan D. Springer, MD, an orthopedic surgeon in Charlotte, N.C., first vice president of the AAHKS, and co–principal investigator of the new guidelines, told this news organization.

In severe SLE cases, the guidelines recommend timing total joint replacement surgery for 4-6 months after the latest IV dose of rituximab (Rituxan), which is given every 4-6 months. For patients taking belimumab (Benlysta), time surgery anytime when weekly subcutaneous doses are administered or at week 4 when monthly IV doses are given.

The guidelines also make recommendations regarding two new drugs for the treatment of severe SLE:

• Anifrolumab (Saphnelo): Time surgery at week 4 when IV treatment is given every 4 weeks.
• Voclosporin (Lupkynis): Continue doses when they’re given twice daily.

An ACR statement cautions that there are no published, peer-reviewed data regarding the use of these two drugs prior to total joint surgery. “The medications do increase the risk of infection,” the statement says, “and therefore their use in patients with severe SLE would merit review by the treating rheumatologist in consideration of surgery.”

Timing of stopping and restarting medication

The guidelines also recommend that certain drugs be withheld for patients with rheumatoid arthritis, ankylosing spondylitis, or any type of SLE and then “restarting the antirheumatic therapy once the wound shows evidence of healing, any sutures/staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection, which is typically about 14 days.”

In regard to biologics, “we continue to recommend withholding biologic medications in patients with inflammatory arthritis, withholding the medication for a dosing cycle prior to surgery, and scheduling the surgery after that dose would be due,” Dr. Springer said. “For example, if a patient takes the medication every 4 weeks, the patient would withhold the dose of the medication and schedule surgery in the 5th week.”

The new recommendations for biologics suggest scheduling surgery at week 5 when the interleukin (IL)-17 inhibitor ixekizumab (Taltz) is given once every 4 weeks and at week 9 when the IL-23 inhibitor guselkumab (Tremfya) is given every 8 weeks.

The guidelines also revise the previous recommendation about tofacitinib (Xeljanz): Surgery should be scheduled on day 4 when the drug is given once or twice daily. New recommendations for fellow JAK inhibitors baricitinib (Olumiant, daily) and upadacitinib (Rinvoq, daily) are the same: Withhold for 3 days prior to surgery and perform surgery on the 4th day.

“We shortened the time between the last dose of JAK inhibitors and surgery to 3 days from 7 based on trial data demonstrating early flares when the drug was withheld, suggesting the immunosuppressant effect wears off sooner than we previously thought,” Dr. Springer said.

The guidelines caution that the recommendations for JAK inhibitors are for infection risk but do not consider the risk of cardiac events or venous thromboembolism.

In patients with nonsevere SLE, the guidelines revise the recommendations for mycophenolate mofetil (twice daily), cyclosporine (twice daily), and tacrolimus (twice daily, IV and oral). The new advice is to withhold the drugs for 1 week after last dose prior to surgery. New recommendations offer the same advice for belimumab, both IV and subcutaneous: Withhold for 1 week after last dose prior to surgery.

The board of the ACR approved the guidelines summary; the full manuscript has been submitted for peer review with an eye toward later publication in the journals Arthritis and Rheumatology and Arthritis Care and Research.

The ACR and AAHKS funded the guidelines. Dr. Goodman and Dr. Springer report no relevant financial relationships.

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

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).

The recent ORAL Surveillance trial has raised concerns about the safety of tofacitinib (and potentially other JAK inhibitors) in the treatment of rheumatoid arthritis.¹ JAK inhibitors are known to increase cholesterol levels; however, this was not previously known to increase cardiovascular risk. The ORAL Surveillance trial was an open-label randomized non-inferiority trial comparing 5mg or 10 mg tofacitinib twice daily with tumor necrosis factor (TNF) inhibitor use. Both adverse cardiac events and cancer were increased in the tofacitinib groups (with hazard ratios of 1.33 and 1.48, respectively). The study did not include a control group and so the impact of RA itself on cardiac events and cancer is not known. However, the apparent risk was greatest in patients over the age of 65, suggesting caution should be used in treating older patients with RA with JAK inhibitors. Interestingly, the STAR-RA study, an observational cohort study, looked at claims data from several sources to try to replicate trial results as well as provide real-world evidence on the topic of cardiovascular risk associated with tofacitinib use.² The authors were able to replicate the inclusion/exclusion criteria from the ORAL Surveillance trial and found that the results were similar. However, on “relaxing” inclusion and exclusion criteria, ie, the “real-world evidence” cohort, there was no difference in incidence of cardiovascular outcomes between tofacitinib and TNF-inhibitor groups. Specifically, patients in the real-world cohort who had no cardiovascular risk factors or prior events were not found to have an increased cardiovascular risk with tofacitinib use, a reassuring finding supporting careful attention to cardiovascular risk in patients with RA when evaluating treatment options.

One consideration in the use of rituximab for treatment of RA is the possibility of changing or lowering subsequent or maintenance doses. Past studies have suggested that halving the dose of rituximab to a single 1000 mg infusion was tolerated by RA patients. The REDO trial, published in 2019, looked at even lower doses: 500 mg and 200 mg. The study did not establish non-inferiority of lower doses at 6 months in a per-protocol analysis, only in intention-to-treat. An extension study of REDO presented at the ACR Convergence in 2021 looked at a subset of those patients for up to 4 years and did find non-inferiority in terms of disease activity. Wientjes et al³ present further analysis of the REDO trial with 140 RA patients at 6 months, looking at the association of rituximab dosage with B cell counts as well as the predictive value of different patient characteristics in terms of response to lower dosages. Interestingly, serum drug levels and B cell counts at 3 and 6 months did not predict response to rituximab, nor did patient characteristics, such as age, smoking, disease, duration, or seropositivity for RF and CCP. Though the authors suggest that this implies even lower doses may be effective, it is not clear, and a similar analysis of the extension trial would be of interest. 

Use of methotrexate as a first-line DMARD for RA is cost-effective but often limited by patient fears or intolerance due to adverse events (AE). This observational cohort study by Sherbini et al⁴ evaluates not only the prevalence of AE, but also baseline factors that may predict the development of AE. Over 1,000 patients with early RA initiating methotrexate were included in analysis. More than 75% reported at least one AE in 12 months, with gastrointestinal AE, such as nausea, being most prevalent (42%); 18% developed elevated liver enzyme tests (defined as a single reading above the upper limit of normal). Few strong predictors of AE were identified, though women were overall more likely than men to report AE. Reassuringly, combination conventional synthetic DMARD therapy did not generally lead to more reported AE. Given the few predictive findings from this study, analysis of a comparator group or comparison of AE at different starting and maintenance doses of methotrexate would be of interest.

References

1.  Ytterberg SR et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386:316-326 (Jan 27).
2. Khosrow-Khavar F et al. Tofacitinib and risk of cardiovascular outcomes: results from the Safety of TofAcitinib in Routine care patients with Rheumatoid Arthritis (STAR-RA) study. Ann Rheum Dis. 2022 (Jan 13).
3. Wientjes MHM et al. Drug levels, anti-drug antibodies and B-cell counts were not predictive of response in rheumatoid arthritis patients on (ultra-)low-dose rituximab. Rheumatology (Oxford). 2022 (Jan 12).
4. Sherbini AA et al. Rates and predictors of methotrexate-related adverse events in patients with early rheumatoid arthritis: results from a nationwide UK study. Rheumatology (Oxford). 2022 (Jan 25).