Clinical Edge Journal Scan

Key clinical point: Low cardiorespiratory fitness (CRF) is an important mediator of increased long-term all-cause mortality among patients with rheumatoid arthritis (RA).

Major finding: Patients with RA having CRF below sex-specific and age-specific median had a 28% excess relative risk of mortality (P = .035), of which 5% was associated with the disease itself and 23% was mediated by direct and indirect effects of low CRF.

Study details: Data come from an analysis of patients with RA (n=348) and controls (n=60,938) who participated in the second and third waves of the longitudinal population-based Trøndelag Health Study.

Disclosures: This project was funded by a grant to MH Liff from the Central Norway Regional Health Authority, allocated via the Liaison Committee for Education, Research and Innovation in Central Norway. All the authors declared no conflicts of interest.

Source: Liff MH et al. RMD Open. 2021 March 8. doi: 10.1136/rmdopen-2020-001545.

Key clinical point: Low cardiorespiratory fitness (CRF) is an important mediator of increased long-term all-cause mortality among patients with rheumatoid arthritis (RA).

Major finding: Patients with RA having CRF below sex-specific and age-specific median had a 28% excess relative risk of mortality (P = .035), of which 5% was associated with the disease itself and 23% was mediated by direct and indirect effects of low CRF.

Study details: Data come from an analysis of patients with RA (n=348) and controls (n=60,938) who participated in the second and third waves of the longitudinal population-based Trøndelag Health Study.

Disclosures: This project was funded by a grant to MH Liff from the Central Norway Regional Health Authority, allocated via the Liaison Committee for Education, Research and Innovation in Central Norway. All the authors declared no conflicts of interest.

Source: Liff MH et al. RMD Open. 2021 March 8. doi: 10.1136/rmdopen-2020-001545.

Key clinical point: Low cardiorespiratory fitness (CRF) is an important mediator of increased long-term all-cause mortality among patients with rheumatoid arthritis (RA).

Major finding: Patients with RA having CRF below sex-specific and age-specific median had a 28% excess relative risk of mortality (P = .035), of which 5% was associated with the disease itself and 23% was mediated by direct and indirect effects of low CRF.

Study details: Data come from an analysis of patients with RA (n=348) and controls (n=60,938) who participated in the second and third waves of the longitudinal population-based Trøndelag Health Study.

Disclosures: This project was funded by a grant to MH Liff from the Central Norway Regional Health Authority, allocated via the Liaison Committee for Education, Research and Innovation in Central Norway. All the authors declared no conflicts of interest.

Source: Liff MH et al. RMD Open. 2021 March 8. doi: 10.1136/rmdopen-2020-001545.

Key clinical point: Frailty is positively associated with disease activity in rheumatoid arthritis (RA), and habitual fish intake may help prevent progression of frailty and RA.

Major finding: The presence of frailty was significantly associated with the disease activity score (Disease Activity Score 28-erythrocyte sedimentation rate; odds ratio [OR], 1.70; P less than .0001). Patients who consumed fish more than twice per week had a lower prevalence of frailty than those who consumed fish twice per week or lesser (OR, 0.35; P = .00060).

Study details: The data come from a cross-sectional study of 306 female outpatients with RA from the KURAMA cohort database.

Disclosures: KURAMA cohort study was supported by AMED and a grant from the Daiichi Sankyo Co. Ltd. M. Hashimoto, R Watanabe, K Nishitani, H Ito, K Ohmura, and S Matsuda reported to receive grants and/or speaker fees from various pharmaceutical companies including Bristol-Meyers, Mitsubishi Tanabe Pharma, Asahi-Kasei Pharma, Daiichi-Sankyo, etc. Some of the authors declared no conflicts of interest.

Source: Minamino H et al. Sci Rep. 2021 Mar 3. doi: 10.1038/s41598-021-84479-0.

Key clinical point: Frailty is positively associated with disease activity in rheumatoid arthritis (RA), and habitual fish intake may help prevent progression of frailty and RA.

Major finding: The presence of frailty was significantly associated with the disease activity score (Disease Activity Score 28-erythrocyte sedimentation rate; odds ratio [OR], 1.70; P less than .0001). Patients who consumed fish more than twice per week had a lower prevalence of frailty than those who consumed fish twice per week or lesser (OR, 0.35; P = .00060).

Study details: The data come from a cross-sectional study of 306 female outpatients with RA from the KURAMA cohort database.

Disclosures: KURAMA cohort study was supported by AMED and a grant from the Daiichi Sankyo Co. Ltd. M. Hashimoto, R Watanabe, K Nishitani, H Ito, K Ohmura, and S Matsuda reported to receive grants and/or speaker fees from various pharmaceutical companies including Bristol-Meyers, Mitsubishi Tanabe Pharma, Asahi-Kasei Pharma, Daiichi-Sankyo, etc. Some of the authors declared no conflicts of interest.

Source: Minamino H et al. Sci Rep. 2021 Mar 3. doi: 10.1038/s41598-021-84479-0.

Key clinical point: Frailty is positively associated with disease activity in rheumatoid arthritis (RA), and habitual fish intake may help prevent progression of frailty and RA.

Major finding: The presence of frailty was significantly associated with the disease activity score (Disease Activity Score 28-erythrocyte sedimentation rate; odds ratio [OR], 1.70; P less than .0001). Patients who consumed fish more than twice per week had a lower prevalence of frailty than those who consumed fish twice per week or lesser (OR, 0.35; P = .00060).

Study details: The data come from a cross-sectional study of 306 female outpatients with RA from the KURAMA cohort database.

Disclosures: KURAMA cohort study was supported by AMED and a grant from the Daiichi Sankyo Co. Ltd. M. Hashimoto, R Watanabe, K Nishitani, H Ito, K Ohmura, and S Matsuda reported to receive grants and/or speaker fees from various pharmaceutical companies including Bristol-Meyers, Mitsubishi Tanabe Pharma, Asahi-Kasei Pharma, Daiichi-Sankyo, etc. Some of the authors declared no conflicts of interest.

Source: Minamino H et al. Sci Rep. 2021 Mar 3. doi: 10.1038/s41598-021-84479-0.

Key clinical point: Rheumatoid arthritis (RA) is associated with poor long-term prognosis after myocardial infarction (MI).

Major finding: At 14-year follow-up after MI, the cumulative all-cause mortality risk was significantly higher among patients with vs. without RA (80.4% vs. 72.3%; hazard ratio [HR], 1.25; P less than .0001). Patients with RA had a higher risk for new MI (HR, 1.22; P = .0001) and revascularization (HR, 1.27; P = .002) after discharge from index MI.

Study details: This was a nationwide, multicenter, cohort register study of real-life MI patients with RA (n=1,614) retrospectively compared with propensity score-matched MI patients without RA (n=8,070).

Disclosures: This study was supported by grant funding from the Finnish Cultural Foundation, the Paulo Foundation, and the Finnish Governmental VTR-funding. A Palomäki, AM Kerola, M Malmberg, and V Kytö reported relevant relationships with various pharmaceutical companies and/or research organizations. The other author declared no conflicts of interest.

Source: Palomäki A et al. Rheumatology (Oxford). 2021 Mar 1. doi: 10.1093/rheumatology/keab204.

Key clinical point: Rheumatoid arthritis (RA) is associated with poor long-term prognosis after myocardial infarction (MI).

Major finding: At 14-year follow-up after MI, the cumulative all-cause mortality risk was significantly higher among patients with vs. without RA (80.4% vs. 72.3%; hazard ratio [HR], 1.25; P less than .0001). Patients with RA had a higher risk for new MI (HR, 1.22; P = .0001) and revascularization (HR, 1.27; P = .002) after discharge from index MI.

Study details: This was a nationwide, multicenter, cohort register study of real-life MI patients with RA (n=1,614) retrospectively compared with propensity score-matched MI patients without RA (n=8,070).

Disclosures: This study was supported by grant funding from the Finnish Cultural Foundation, the Paulo Foundation, and the Finnish Governmental VTR-funding. A Palomäki, AM Kerola, M Malmberg, and V Kytö reported relevant relationships with various pharmaceutical companies and/or research organizations. The other author declared no conflicts of interest.

Source: Palomäki A et al. Rheumatology (Oxford). 2021 Mar 1. doi: 10.1093/rheumatology/keab204.

Key clinical point: Rheumatoid arthritis (RA) is associated with poor long-term prognosis after myocardial infarction (MI).

Major finding: At 14-year follow-up after MI, the cumulative all-cause mortality risk was significantly higher among patients with vs. without RA (80.4% vs. 72.3%; hazard ratio [HR], 1.25; P less than .0001). Patients with RA had a higher risk for new MI (HR, 1.22; P = .0001) and revascularization (HR, 1.27; P = .002) after discharge from index MI.

Study details: This was a nationwide, multicenter, cohort register study of real-life MI patients with RA (n=1,614) retrospectively compared with propensity score-matched MI patients without RA (n=8,070).

Disclosures: This study was supported by grant funding from the Finnish Cultural Foundation, the Paulo Foundation, and the Finnish Governmental VTR-funding. A Palomäki, AM Kerola, M Malmberg, and V Kytö reported relevant relationships with various pharmaceutical companies and/or research organizations. The other author declared no conflicts of interest.

Source: Palomäki A et al. Rheumatology (Oxford). 2021 Mar 1. doi: 10.1093/rheumatology/keab204.

Key clinical point: Multi-Biomarker Disease Activity (MBDA) should not be preferred to assess clinically meaningful improvements in disease activity after repository corticotropin injection (RCI) therapy in patients with active rheumatoid arthritis (RA).

Major finding: RCI-mediated improvements in Disease Activity Score 28-erythrocyte sedimentation rate and Clinical Disease Activity Index scores suggested clinically meaningful improvement with more than 84% of patients meeting the minimal clinically important difference/minimally important difference criteria, which ranged from 26.3% to 34.7% for MBDA.

Study details: The data come from a multicenter, randomized, placebo-controlled study of 259 patients with active RA despite treatment with stable glucocorticoid dose and 1 or 2 disease-modifying anti-rheumatic drugs. Patients achieving low disease activity during open-label period were randomly assigned to either 80 U of RCI (n=77) or placebo (n=76) during the 12-week double-blind period.

Disclosures: This study was funded by Mallinckrodt Pharmaceuticals. R Fleischmann, DE Furst, and OG Segurado reported receiving clinical trial grants and consulting fees from various pharmaceutical companies including Mallinckrodt Pharmaceuticals. J Liu and J Zhu declared being employees of Mallinckrodt Pharmaceuticals.

Source: Fleischmann R et al. Arthritis Care Res (Hoboken). 2021 Feb 28. doi: 10.1002/acr.24583.

Key clinical point: Multi-Biomarker Disease Activity (MBDA) should not be preferred to assess clinically meaningful improvements in disease activity after repository corticotropin injection (RCI) therapy in patients with active rheumatoid arthritis (RA).

Major finding: RCI-mediated improvements in Disease Activity Score 28-erythrocyte sedimentation rate and Clinical Disease Activity Index scores suggested clinically meaningful improvement with more than 84% of patients meeting the minimal clinically important difference/minimally important difference criteria, which ranged from 26.3% to 34.7% for MBDA.

Study details: The data come from a multicenter, randomized, placebo-controlled study of 259 patients with active RA despite treatment with stable glucocorticoid dose and 1 or 2 disease-modifying anti-rheumatic drugs. Patients achieving low disease activity during open-label period were randomly assigned to either 80 U of RCI (n=77) or placebo (n=76) during the 12-week double-blind period.

Disclosures: This study was funded by Mallinckrodt Pharmaceuticals. R Fleischmann, DE Furst, and OG Segurado reported receiving clinical trial grants and consulting fees from various pharmaceutical companies including Mallinckrodt Pharmaceuticals. J Liu and J Zhu declared being employees of Mallinckrodt Pharmaceuticals.

Source: Fleischmann R et al. Arthritis Care Res (Hoboken). 2021 Feb 28. doi: 10.1002/acr.24583.

Key clinical point: Multi-Biomarker Disease Activity (MBDA) should not be preferred to assess clinically meaningful improvements in disease activity after repository corticotropin injection (RCI) therapy in patients with active rheumatoid arthritis (RA).

Major finding: RCI-mediated improvements in Disease Activity Score 28-erythrocyte sedimentation rate and Clinical Disease Activity Index scores suggested clinically meaningful improvement with more than 84% of patients meeting the minimal clinically important difference/minimally important difference criteria, which ranged from 26.3% to 34.7% for MBDA.

Study details: The data come from a multicenter, randomized, placebo-controlled study of 259 patients with active RA despite treatment with stable glucocorticoid dose and 1 or 2 disease-modifying anti-rheumatic drugs. Patients achieving low disease activity during open-label period were randomly assigned to either 80 U of RCI (n=77) or placebo (n=76) during the 12-week double-blind period.

Disclosures: This study was funded by Mallinckrodt Pharmaceuticals. R Fleischmann, DE Furst, and OG Segurado reported receiving clinical trial grants and consulting fees from various pharmaceutical companies including Mallinckrodt Pharmaceuticals. J Liu and J Zhu declared being employees of Mallinckrodt Pharmaceuticals.

Source: Fleischmann R et al. Arthritis Care Res (Hoboken). 2021 Feb 28. doi: 10.1002/acr.24583.

Key clinical point: Median durability of tocilizumab (TCZ) response was more than 3 years when measured as maintenance of minimum clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) score in patients with RA initiating TCZ.

Major finding: Overall, durability of response among patients who initiated TCZ and achieved MCID in CDAI remained more than 50% after 3 years of follow-up. The proportion of patients maintaining MCID durability at 1, 2, and 3 years was 64.4% (95% CI, 59.2%-69.6%), 56.0% (95% CI, 50.0%-62.0%), and 51.8% (95% CI, 44.7%-58.9%), respectively.

Study details: The findings are from an observational study of 1,789 patients with RA who initiated TCZ and were enrolled in the US-based Corrona RA Registry.

Disclosures: This study was sponsored by Corrona LLC, and the analysis was funded by Genentech, Inc. DA Pappas, T Blachley, and K Emeanuru declared being employees and/or shareholders of Corrona, LLC. JH Best, WG Reiss, and S Zlotnick declared being current/former employees and/or shareholders of Genentech, Inc.

Source: Pappas DA et al. Rheumatol Ther. 2021 Feb 25. doi: 10.1007/s40744-021-00285-0.

Key clinical point: Median durability of tocilizumab (TCZ) response was more than 3 years when measured as maintenance of minimum clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) score in patients with RA initiating TCZ.

Major finding: Overall, durability of response among patients who initiated TCZ and achieved MCID in CDAI remained more than 50% after 3 years of follow-up. The proportion of patients maintaining MCID durability at 1, 2, and 3 years was 64.4% (95% CI, 59.2%-69.6%), 56.0% (95% CI, 50.0%-62.0%), and 51.8% (95% CI, 44.7%-58.9%), respectively.

Study details: The findings are from an observational study of 1,789 patients with RA who initiated TCZ and were enrolled in the US-based Corrona RA Registry.

Disclosures: This study was sponsored by Corrona LLC, and the analysis was funded by Genentech, Inc. DA Pappas, T Blachley, and K Emeanuru declared being employees and/or shareholders of Corrona, LLC. JH Best, WG Reiss, and S Zlotnick declared being current/former employees and/or shareholders of Genentech, Inc.

Source: Pappas DA et al. Rheumatol Ther. 2021 Feb 25. doi: 10.1007/s40744-021-00285-0.

Key clinical point: Median durability of tocilizumab (TCZ) response was more than 3 years when measured as maintenance of minimum clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) score in patients with RA initiating TCZ.

Major finding: Overall, durability of response among patients who initiated TCZ and achieved MCID in CDAI remained more than 50% after 3 years of follow-up. The proportion of patients maintaining MCID durability at 1, 2, and 3 years was 64.4% (95% CI, 59.2%-69.6%), 56.0% (95% CI, 50.0%-62.0%), and 51.8% (95% CI, 44.7%-58.9%), respectively.

Study details: The findings are from an observational study of 1,789 patients with RA who initiated TCZ and were enrolled in the US-based Corrona RA Registry.

Disclosures: This study was sponsored by Corrona LLC, and the analysis was funded by Genentech, Inc. DA Pappas, T Blachley, and K Emeanuru declared being employees and/or shareholders of Corrona, LLC. JH Best, WG Reiss, and S Zlotnick declared being current/former employees and/or shareholders of Genentech, Inc.

Source: Pappas DA et al. Rheumatol Ther. 2021 Feb 25. doi: 10.1007/s40744-021-00285-0.

Key clinical point: The addition of iguratimod (IGU) can effectively reduce methotrexate (MTX) dose required by rheumatoid arthritis (RA) patients with long-term clinical remission.

Major finding: MTX dose could be reduced from 8.6±2.4 mg/week to 4.7±2.2 mg/week at 36 weeks. Despite MTX dose reduction, disease activity score 28-erythrocyte sedimentation rate was maintained at 1.48 at baseline and 1.69 at 36 weeks (P = .911). Other than drug discontinuation by 2 patients in the IGU addition group, no other adverse events were observed.

Study details: Findings are from a prospective analysis of 47 patients with RA who had sustained clinical remission with MTX for more than 24 weeks. Patients either continued constant MTX dose (n=25) or were treated with additional IGU and tapered MTX dose (n=22).

Disclosures: No source of funding was declared. The authors declared no conflicts of interest.

Source: Yoshikawa A et al. Mod Rheumatol. 2021 Mar 16. doi: 10.1080/14397595.2021.1892945.

Key clinical point: The addition of iguratimod (IGU) can effectively reduce methotrexate (MTX) dose required by rheumatoid arthritis (RA) patients with long-term clinical remission.

Major finding: MTX dose could be reduced from 8.6±2.4 mg/week to 4.7±2.2 mg/week at 36 weeks. Despite MTX dose reduction, disease activity score 28-erythrocyte sedimentation rate was maintained at 1.48 at baseline and 1.69 at 36 weeks (P = .911). Other than drug discontinuation by 2 patients in the IGU addition group, no other adverse events were observed.

Study details: Findings are from a prospective analysis of 47 patients with RA who had sustained clinical remission with MTX for more than 24 weeks. Patients either continued constant MTX dose (n=25) or were treated with additional IGU and tapered MTX dose (n=22).

Disclosures: No source of funding was declared. The authors declared no conflicts of interest.

Source: Yoshikawa A et al. Mod Rheumatol. 2021 Mar 16. doi: 10.1080/14397595.2021.1892945.

Key clinical point: The addition of iguratimod (IGU) can effectively reduce methotrexate (MTX) dose required by rheumatoid arthritis (RA) patients with long-term clinical remission.

Major finding: MTX dose could be reduced from 8.6±2.4 mg/week to 4.7±2.2 mg/week at 36 weeks. Despite MTX dose reduction, disease activity score 28-erythrocyte sedimentation rate was maintained at 1.48 at baseline and 1.69 at 36 weeks (P = .911). Other than drug discontinuation by 2 patients in the IGU addition group, no other adverse events were observed.

Study details: Findings are from a prospective analysis of 47 patients with RA who had sustained clinical remission with MTX for more than 24 weeks. Patients either continued constant MTX dose (n=25) or were treated with additional IGU and tapered MTX dose (n=22).

Disclosures: No source of funding was declared. The authors declared no conflicts of interest.

Source: Yoshikawa A et al. Mod Rheumatol. 2021 Mar 16. doi: 10.1080/14397595.2021.1892945.

Key clinical point: Janus kinase inhibitors (JAKis: baricitinib or tofacitinib) vs. rituximab for the treatment of rheumatoid arthritis (RA) in patients with concurrent interstitial lung disease (ILD) or bronchiectasis did not increase the rate of hospitalization or mortality because of a respiratory cause.

Major finding: Respiratory events were reported in 5 patients treated with JAKi (18%; 7 hospitalizations, 2 of whom died) and 4 patients treated with rituximab (21%; 4 hospitalizations, 1 of whom died). Respiratory event survival (hazard ratio [HR], 1.38; P = .64) and the rate of drug discontinuation HR, 1.9; P = .251) did not differ significantly between groups.

Study details: A retrospective analysis of patients with RA and concurrent ILD or bronchiectasis who received JAKis (n=28: baricitinib, n=26; tofacitinib, n=2) or rituximab (n=19) for a mean of 1.1 and 2.14 years, respectively.

Disclosures: The study did not receive any funding. The lead author received sponsorship from Lilly and Pfizer to attend educational conferences. The other authors declared no conflicts of interest.

Citation: Cronin O et al. Rheumatol Int. 2021 Mar 15. doi: 10.1007/s00296-021-04835-1.

Key clinical point: Janus kinase inhibitors (JAKis: baricitinib or tofacitinib) vs. rituximab for the treatment of rheumatoid arthritis (RA) in patients with concurrent interstitial lung disease (ILD) or bronchiectasis did not increase the rate of hospitalization or mortality because of a respiratory cause.

Major finding: Respiratory events were reported in 5 patients treated with JAKi (18%; 7 hospitalizations, 2 of whom died) and 4 patients treated with rituximab (21%; 4 hospitalizations, 1 of whom died). Respiratory event survival (hazard ratio [HR], 1.38; P = .64) and the rate of drug discontinuation HR, 1.9; P = .251) did not differ significantly between groups.

Study details: A retrospective analysis of patients with RA and concurrent ILD or bronchiectasis who received JAKis (n=28: baricitinib, n=26; tofacitinib, n=2) or rituximab (n=19) for a mean of 1.1 and 2.14 years, respectively.

Disclosures: The study did not receive any funding. The lead author received sponsorship from Lilly and Pfizer to attend educational conferences. The other authors declared no conflicts of interest.

Citation: Cronin O et al. Rheumatol Int. 2021 Mar 15. doi: 10.1007/s00296-021-04835-1.

Key clinical point: Janus kinase inhibitors (JAKis: baricitinib or tofacitinib) vs. rituximab for the treatment of rheumatoid arthritis (RA) in patients with concurrent interstitial lung disease (ILD) or bronchiectasis did not increase the rate of hospitalization or mortality because of a respiratory cause.

Major finding: Respiratory events were reported in 5 patients treated with JAKi (18%; 7 hospitalizations, 2 of whom died) and 4 patients treated with rituximab (21%; 4 hospitalizations, 1 of whom died). Respiratory event survival (hazard ratio [HR], 1.38; P = .64) and the rate of drug discontinuation HR, 1.9; P = .251) did not differ significantly between groups.

Study details: A retrospective analysis of patients with RA and concurrent ILD or bronchiectasis who received JAKis (n=28: baricitinib, n=26; tofacitinib, n=2) or rituximab (n=19) for a mean of 1.1 and 2.14 years, respectively.

Disclosures: The study did not receive any funding. The lead author received sponsorship from Lilly and Pfizer to attend educational conferences. The other authors declared no conflicts of interest.

Citation: Cronin O et al. Rheumatol Int. 2021 Mar 15. doi: 10.1007/s00296-021-04835-1.

Key clinical point: Peficitinib (ASP015K) showed improvement in clinical outcomes, which was maintained throughout the treatment duration of 32 months along with a generally tolerable safety profile in patients with rheumatoid arthritis (RA).

Major finding: The American College of Rheumatology (ACR)20, ACR50, and ACR70 response rates were maintained throughout from baseline (71.6%, 52.1%, and 34.7%, respectively) to the end of treatment (78.7%, 63.3%, and 44.1%, respectively). Treatment-emergent adverse events, mostly grade 1 or 2 in severity, were experienced by 94.4% of patients, leading to drug discontinuation in 16.6% of patients. 

Study details: Findings are from the final analysis of an open-label long-term extension study involving 843 Asian patients with RA who previously completed phase 2b and phase 3 studies of peficitinib.

Disclosures: This work was funded by the Astellas Pharma, Inc. The authors including the lead author reported receiving grants, speaker’s fees, consultancy fees, personal fees, and/or honoraria from various sources including Astellas Pharma, Inc. Four of the authors reported being employees of Astellas Pharma, Inc.

Source: Takeuchi T et al. Rheumatol Ther. 2021 Mar 3. doi: 10.1007/s40744-021-00280-5.

Key clinical point: Peficitinib (ASP015K) showed improvement in clinical outcomes, which was maintained throughout the treatment duration of 32 months along with a generally tolerable safety profile in patients with rheumatoid arthritis (RA).

Major finding: The American College of Rheumatology (ACR)20, ACR50, and ACR70 response rates were maintained throughout from baseline (71.6%, 52.1%, and 34.7%, respectively) to the end of treatment (78.7%, 63.3%, and 44.1%, respectively). Treatment-emergent adverse events, mostly grade 1 or 2 in severity, were experienced by 94.4% of patients, leading to drug discontinuation in 16.6% of patients. 

Study details: Findings are from the final analysis of an open-label long-term extension study involving 843 Asian patients with RA who previously completed phase 2b and phase 3 studies of peficitinib.

Disclosures: This work was funded by the Astellas Pharma, Inc. The authors including the lead author reported receiving grants, speaker’s fees, consultancy fees, personal fees, and/or honoraria from various sources including Astellas Pharma, Inc. Four of the authors reported being employees of Astellas Pharma, Inc.

Source: Takeuchi T et al. Rheumatol Ther. 2021 Mar 3. doi: 10.1007/s40744-021-00280-5.

Key clinical point: Peficitinib (ASP015K) showed improvement in clinical outcomes, which was maintained throughout the treatment duration of 32 months along with a generally tolerable safety profile in patients with rheumatoid arthritis (RA).

Major finding: The American College of Rheumatology (ACR)20, ACR50, and ACR70 response rates were maintained throughout from baseline (71.6%, 52.1%, and 34.7%, respectively) to the end of treatment (78.7%, 63.3%, and 44.1%, respectively). Treatment-emergent adverse events, mostly grade 1 or 2 in severity, were experienced by 94.4% of patients, leading to drug discontinuation in 16.6% of patients. 

Study details: Findings are from the final analysis of an open-label long-term extension study involving 843 Asian patients with RA who previously completed phase 2b and phase 3 studies of peficitinib.

Disclosures: This work was funded by the Astellas Pharma, Inc. The authors including the lead author reported receiving grants, speaker’s fees, consultancy fees, personal fees, and/or honoraria from various sources including Astellas Pharma, Inc. Four of the authors reported being employees of Astellas Pharma, Inc.

Source: Takeuchi T et al. Rheumatol Ther. 2021 Mar 3. doi: 10.1007/s40744-021-00280-5.

Key clinical point: Patients with early rheumatoid arthritis (RA) who initiated biological vs. triple therapy after inadequate response to methotrexate (MTX) were more likely to achieve sustained remission (SR).

Major finding: Patients initiating biological vs. triple therapy were more likely to achieve short-term and long-term SR at 1 year (adjusted odds ratio [aOR], 1.79; 95% confidence interval [CI], 1.18-2.71 and aOR, 1.86; 95% CI, 1.00-3.48, respectively) and 2 years (aOR, 1.92; 95% CI, 1.21-3.06 and aOR, 1.62; 95% CI, 0.94-2.79, respectively) from treatment initiation.

Study details: Findings are from an analysis of 1,502 patients with relatively early RA who initiated biological (biological disease-modifying antirheumatic drugs+MTX; n=1,155) or triple (MTX+sulfasalazine+hydroxychloroquine/chloroquine; n=347) therapy as the first treatment strategy after inadequate response to MTX monotherapy.

Disclosures: This work funded by the Swedish Rheumatism Association, the Medical Faculty of Lund University, Alfred Österlund ́s Foundation, Greta and Johan Kock ́s foundation, the King Gustaf V Foundation, Lund University Hospital, Professor Nanna Svartz Foundation, and Anna-Greta Crafoord Foundation. The authors declared no conflicts of interest.

Source: Källmark H et al. Arthritis Rheumatol. 2021 Mar 7. doi: 10.1002/art.41720.

Key clinical point: Patients with early rheumatoid arthritis (RA) who initiated biological vs. triple therapy after inadequate response to methotrexate (MTX) were more likely to achieve sustained remission (SR).

Major finding: Patients initiating biological vs. triple therapy were more likely to achieve short-term and long-term SR at 1 year (adjusted odds ratio [aOR], 1.79; 95% confidence interval [CI], 1.18-2.71 and aOR, 1.86; 95% CI, 1.00-3.48, respectively) and 2 years (aOR, 1.92; 95% CI, 1.21-3.06 and aOR, 1.62; 95% CI, 0.94-2.79, respectively) from treatment initiation.

Study details: Findings are from an analysis of 1,502 patients with relatively early RA who initiated biological (biological disease-modifying antirheumatic drugs+MTX; n=1,155) or triple (MTX+sulfasalazine+hydroxychloroquine/chloroquine; n=347) therapy as the first treatment strategy after inadequate response to MTX monotherapy.

Disclosures: This work funded by the Swedish Rheumatism Association, the Medical Faculty of Lund University, Alfred Österlund ́s Foundation, Greta and Johan Kock ́s foundation, the King Gustaf V Foundation, Lund University Hospital, Professor Nanna Svartz Foundation, and Anna-Greta Crafoord Foundation. The authors declared no conflicts of interest.

Source: Källmark H et al. Arthritis Rheumatol. 2021 Mar 7. doi: 10.1002/art.41720.

Key clinical point: Patients with early rheumatoid arthritis (RA) who initiated biological vs. triple therapy after inadequate response to methotrexate (MTX) were more likely to achieve sustained remission (SR).

Major finding: Patients initiating biological vs. triple therapy were more likely to achieve short-term and long-term SR at 1 year (adjusted odds ratio [aOR], 1.79; 95% confidence interval [CI], 1.18-2.71 and aOR, 1.86; 95% CI, 1.00-3.48, respectively) and 2 years (aOR, 1.92; 95% CI, 1.21-3.06 and aOR, 1.62; 95% CI, 0.94-2.79, respectively) from treatment initiation.

Study details: Findings are from an analysis of 1,502 patients with relatively early RA who initiated biological (biological disease-modifying antirheumatic drugs+MTX; n=1,155) or triple (MTX+sulfasalazine+hydroxychloroquine/chloroquine; n=347) therapy as the first treatment strategy after inadequate response to MTX monotherapy.

Disclosures: This work funded by the Swedish Rheumatism Association, the Medical Faculty of Lund University, Alfred Österlund ́s Foundation, Greta and Johan Kock ́s foundation, the King Gustaf V Foundation, Lund University Hospital, Professor Nanna Svartz Foundation, and Anna-Greta Crafoord Foundation. The authors declared no conflicts of interest.

Source: Källmark H et al. Arthritis Rheumatol. 2021 Mar 7. doi: 10.1002/art.41720.

ENESTfreedom is an important study that set the current guidelines for TFR. The trial included 190 patients treated with front line nilotinib at 300mg twice daily for two years that had achieved an MR4.5, followed by one year of consolidation maintaining deep molecular response of at least MR4 were allowed to discontinued therapy. A recent 5 year update of the trial showed that 81/190 patients (42.6%) still remained on TFR (MR4) with 76 (40.0%) in MR4.5. From the patients who lost major molecular response (MMR) and were re-treated, 90/91 patients entering this phase (98.9%) regained MMR and 84/91 patients (92.3%) regained MR4.5. More important, no disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously, including a declined incidence of AEs at 96 weeks of the TFR follow up (with low incidence CV AEs), while an expected increase on those in the treatment re-initiation phase.  As previously has been described in other trials, Low Sokal risk score, BCR-ABL1 IS levels at 48 weeks of TFR and stable MR4.5 response for the first year of TFR were associated with higher TFR rates.

When looking at patients who can be candidates for TFR, it is important to take in consideration the likelihood of successful discontinuation and educate patients on certain factors that may contribute to good outcomes. The Australian CML group had previously reported the importance of the initial decline rate of BCR-ABL1 measured as halving time as an important factor associated to deep molecular response. The same group, in a very interesting publication, reported the impact of halving time as a strong predictor of sustained TFR post-tyrosine kinase inhibitor (TKI) cessation in CML patients treated with front line TKI therapies.

Out of 115 patients who attempted TFR and had ≥12 months of follow-up, 55% sustained TFR, defined as remaining in major molecular response off TKI therapy for 12 months, similar percentage seen in other studies. However, when the time taken for the BCR-ABL1 value to halve was applied, it became the strongest independent predictor of sustained TFR with 80% in patients with a halving time of <9.35 days (first quartile) compared with only 4% if the halving time was >21.85 days (last quartile) (P < .001). The e14a2 BCR-ABL1 transcript type and duration of TKI exposure before attempting TFR were also independent predictors of sustained TFR. However, the BCR-ABL1 value measured at 3 months of TKI was not an independent predictor of sustained TFR.

ENESTfreedom is an important study that set the current guidelines for TFR. The trial included 190 patients treated with front line nilotinib at 300mg twice daily for two years that had achieved an MR4.5, followed by one year of consolidation maintaining deep molecular response of at least MR4 were allowed to discontinued therapy. A recent 5 year update of the trial showed that 81/190 patients (42.6%) still remained on TFR (MR4) with 76 (40.0%) in MR4.5. From the patients who lost major molecular response (MMR) and were re-treated, 90/91 patients entering this phase (98.9%) regained MMR and 84/91 patients (92.3%) regained MR4.5. More important, no disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously, including a declined incidence of AEs at 96 weeks of the TFR follow up (with low incidence CV AEs), while an expected increase on those in the treatment re-initiation phase.  As previously has been described in other trials, Low Sokal risk score, BCR-ABL1 IS levels at 48 weeks of TFR and stable MR4.5 response for the first year of TFR were associated with higher TFR rates.

When looking at patients who can be candidates for TFR, it is important to take in consideration the likelihood of successful discontinuation and educate patients on certain factors that may contribute to good outcomes. The Australian CML group had previously reported the importance of the initial decline rate of BCR-ABL1 measured as halving time as an important factor associated to deep molecular response. The same group, in a very interesting publication, reported the impact of halving time as a strong predictor of sustained TFR post-tyrosine kinase inhibitor (TKI) cessation in CML patients treated with front line TKI therapies.

Out of 115 patients who attempted TFR and had ≥12 months of follow-up, 55% sustained TFR, defined as remaining in major molecular response off TKI therapy for 12 months, similar percentage seen in other studies. However, when the time taken for the BCR-ABL1 value to halve was applied, it became the strongest independent predictor of sustained TFR with 80% in patients with a halving time of <9.35 days (first quartile) compared with only 4% if the halving time was >21.85 days (last quartile) (P < .001). The e14a2 BCR-ABL1 transcript type and duration of TKI exposure before attempting TFR were also independent predictors of sustained TFR. However, the BCR-ABL1 value measured at 3 months of TKI was not an independent predictor of sustained TFR.

ENESTfreedom is an important study that set the current guidelines for TFR. The trial included 190 patients treated with front line nilotinib at 300mg twice daily for two years that had achieved an MR4.5, followed by one year of consolidation maintaining deep molecular response of at least MR4 were allowed to discontinued therapy. A recent 5 year update of the trial showed that 81/190 patients (42.6%) still remained on TFR (MR4) with 76 (40.0%) in MR4.5. From the patients who lost major molecular response (MMR) and were re-treated, 90/91 patients entering this phase (98.9%) regained MMR and 84/91 patients (92.3%) regained MR4.5. More important, no disease progression or CML-related deaths were observed, and the adverse event profile was consistent with that reported previously, including a declined incidence of AEs at 96 weeks of the TFR follow up (with low incidence CV AEs), while an expected increase on those in the treatment re-initiation phase.  As previously has been described in other trials, Low Sokal risk score, BCR-ABL1 IS levels at 48 weeks of TFR and stable MR4.5 response for the first year of TFR were associated with higher TFR rates.

When looking at patients who can be candidates for TFR, it is important to take in consideration the likelihood of successful discontinuation and educate patients on certain factors that may contribute to good outcomes. The Australian CML group had previously reported the importance of the initial decline rate of BCR-ABL1 measured as halving time as an important factor associated to deep molecular response. The same group, in a very interesting publication, reported the impact of halving time as a strong predictor of sustained TFR post-tyrosine kinase inhibitor (TKI) cessation in CML patients treated with front line TKI therapies.

Out of 115 patients who attempted TFR and had ≥12 months of follow-up, 55% sustained TFR, defined as remaining in major molecular response off TKI therapy for 12 months, similar percentage seen in other studies. However, when the time taken for the BCR-ABL1 value to halve was applied, it became the strongest independent predictor of sustained TFR with 80% in patients with a halving time of <9.35 days (first quartile) compared with only 4% if the halving time was >21.85 days (last quartile) (P < .001). The e14a2 BCR-ABL1 transcript type and duration of TKI exposure before attempting TFR were also independent predictors of sustained TFR. However, the BCR-ABL1 value measured at 3 months of TKI was not an independent predictor of sustained TFR.