Clinical Edge Journal Scan

Key clinical point: Inflammatory bowel disease (IBD) may be a risk factor for stroke.

Major finding: IBD was associated with an increased risk for stroke (odds ratio/relative risk [OR/RR], 1.21; P less than .001). Additionally, both Crohn's disease (OR/RR, 1.25; P less than .001) and ulcerative colitis (OR/RR, 1.09; P = .051) were associated with an increased risk for stroke.

Study details: Findings are from a meta-analysis of 9 studies involving 791,010 patients with IBD or stroke.

Disclosures: The study was supported by the General Project of Chongqing Natural Science Foundation and the National Natural Science Foundation of China. All authors declared no conflicts of interest.

Source: Chen Y et al. Brain Behav. 2021 May 7. doi: 10.1002/brb3.2159.

Key clinical point: Inflammatory bowel disease (IBD) may be a risk factor for stroke.

Major finding: IBD was associated with an increased risk for stroke (odds ratio/relative risk [OR/RR], 1.21; P less than .001). Additionally, both Crohn's disease (OR/RR, 1.25; P less than .001) and ulcerative colitis (OR/RR, 1.09; P = .051) were associated with an increased risk for stroke.

Study details: Findings are from a meta-analysis of 9 studies involving 791,010 patients with IBD or stroke.

Disclosures: The study was supported by the General Project of Chongqing Natural Science Foundation and the National Natural Science Foundation of China. All authors declared no conflicts of interest.

Source: Chen Y et al. Brain Behav. 2021 May 7. doi: 10.1002/brb3.2159.

Key clinical point: Inflammatory bowel disease (IBD) may be a risk factor for stroke.

Major finding: IBD was associated with an increased risk for stroke (odds ratio/relative risk [OR/RR], 1.21; P less than .001). Additionally, both Crohn's disease (OR/RR, 1.25; P less than .001) and ulcerative colitis (OR/RR, 1.09; P = .051) were associated with an increased risk for stroke.

Study details: Findings are from a meta-analysis of 9 studies involving 791,010 patients with IBD or stroke.

Disclosures: The study was supported by the General Project of Chongqing Natural Science Foundation and the National Natural Science Foundation of China. All authors declared no conflicts of interest.

Source: Chen Y et al. Brain Behav. 2021 May 7. doi: 10.1002/brb3.2159.

Key clinical point: Prenatal exposure to tobacco smoke and antibiotics and early life otitis media were risk factors for inflammatory bowel disease (IBD).

Major finding: Prenatal exposure to tobacco smoke (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17-1.90) and antibiotics (OR, 1.75; 95% CI, 1.22-2.51), and early life otitis media (OR, 2.11; 95% CI, 1.22-3.62) were positively associated with IBD.

Study details: Findings are from a meta-analysis of 39 studies that evaluated the association between early life (prenatal life to 5 years of age) exposures and subsequent risk for IBD.

Disclosures: The study did not receive any funding. Some of the authors reported receiving grants, speaker fees, advisory board fees, personal fees, consultancy, and/or lectures, and/or honoraria from multiple sources. All other authors had no disclosures.

Source: Agrawal M et al. EClinicalMedicine. 2021 May 15. doi: 10.1016/j.eclinm.2021.100884.

Key clinical point: Prenatal exposure to tobacco smoke and antibiotics and early life otitis media were risk factors for inflammatory bowel disease (IBD).

Major finding: Prenatal exposure to tobacco smoke (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17-1.90) and antibiotics (OR, 1.75; 95% CI, 1.22-2.51), and early life otitis media (OR, 2.11; 95% CI, 1.22-3.62) were positively associated with IBD.

Study details: Findings are from a meta-analysis of 39 studies that evaluated the association between early life (prenatal life to 5 years of age) exposures and subsequent risk for IBD.

Disclosures: The study did not receive any funding. Some of the authors reported receiving grants, speaker fees, advisory board fees, personal fees, consultancy, and/or lectures, and/or honoraria from multiple sources. All other authors had no disclosures.

Source: Agrawal M et al. EClinicalMedicine. 2021 May 15. doi: 10.1016/j.eclinm.2021.100884.

Key clinical point: Prenatal exposure to tobacco smoke and antibiotics and early life otitis media were risk factors for inflammatory bowel disease (IBD).

Major finding: Prenatal exposure to tobacco smoke (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17-1.90) and antibiotics (OR, 1.75; 95% CI, 1.22-2.51), and early life otitis media (OR, 2.11; 95% CI, 1.22-3.62) were positively associated with IBD.

Study details: Findings are from a meta-analysis of 39 studies that evaluated the association between early life (prenatal life to 5 years of age) exposures and subsequent risk for IBD.

Disclosures: The study did not receive any funding. Some of the authors reported receiving grants, speaker fees, advisory board fees, personal fees, consultancy, and/or lectures, and/or honoraria from multiple sources. All other authors had no disclosures.

Source: Agrawal M et al. EClinicalMedicine. 2021 May 15. doi: 10.1016/j.eclinm.2021.100884.

Key clinical point: Ustekinumab showed higher short- and long-term efficacy than vedolizumab in patients with Crohn's disease with prior antitumor necrosis factor (TNF) therapy failure.

Major finding: Ustekinumab vs. vedolizumab was more effective in achieving corticosteroid-free clinical remission at week 54 (50.6% vs. 40.6%; P = .047) and deep remission at week 14 (17.9% vs. 5.7%; P = .047). Patients treated with ustekinumab vs. vedolizumab had a lower rate of primary nonresponse (6.7% vs. 14.8%, P = .034), a longer time to therapeutic escalation (hazard ratio [HR], 1.35; P = .043), and lower risk for drug discontinuation (HR, 1.53; P = .029).

Study details: This was a retrospective cohort study of 312 patients with Crohn's disease treated with ustekinumab (n=224) or vedolizumab (n=88) after exposure to at least 1 anti-TNF agent.

Disclosures: No information on funding was available. A Buisson reported receiving consulting and lecture fees from multiple sources. The other authors had no disclosures.

Source: Manlay L et al. Aliment Pharmacol Ther. 2021 Apr 28. doi: 10.1111/apt.16377.

Key clinical point: Ustekinumab showed higher short- and long-term efficacy than vedolizumab in patients with Crohn's disease with prior antitumor necrosis factor (TNF) therapy failure.

Major finding: Ustekinumab vs. vedolizumab was more effective in achieving corticosteroid-free clinical remission at week 54 (50.6% vs. 40.6%; P = .047) and deep remission at week 14 (17.9% vs. 5.7%; P = .047). Patients treated with ustekinumab vs. vedolizumab had a lower rate of primary nonresponse (6.7% vs. 14.8%, P = .034), a longer time to therapeutic escalation (hazard ratio [HR], 1.35; P = .043), and lower risk for drug discontinuation (HR, 1.53; P = .029).

Study details: This was a retrospective cohort study of 312 patients with Crohn's disease treated with ustekinumab (n=224) or vedolizumab (n=88) after exposure to at least 1 anti-TNF agent.

Disclosures: No information on funding was available. A Buisson reported receiving consulting and lecture fees from multiple sources. The other authors had no disclosures.

Source: Manlay L et al. Aliment Pharmacol Ther. 2021 Apr 28. doi: 10.1111/apt.16377.

Key clinical point: Ustekinumab showed higher short- and long-term efficacy than vedolizumab in patients with Crohn's disease with prior antitumor necrosis factor (TNF) therapy failure.

Major finding: Ustekinumab vs. vedolizumab was more effective in achieving corticosteroid-free clinical remission at week 54 (50.6% vs. 40.6%; P = .047) and deep remission at week 14 (17.9% vs. 5.7%; P = .047). Patients treated with ustekinumab vs. vedolizumab had a lower rate of primary nonresponse (6.7% vs. 14.8%, P = .034), a longer time to therapeutic escalation (hazard ratio [HR], 1.35; P = .043), and lower risk for drug discontinuation (HR, 1.53; P = .029).

Study details: This was a retrospective cohort study of 312 patients with Crohn's disease treated with ustekinumab (n=224) or vedolizumab (n=88) after exposure to at least 1 anti-TNF agent.

Disclosures: No information on funding was available. A Buisson reported receiving consulting and lecture fees from multiple sources. The other authors had no disclosures.

Source: Manlay L et al. Aliment Pharmacol Ther. 2021 Apr 28. doi: 10.1111/apt.16377.

Key clinical point: Patients with Crohn’s disease (CD) who responded to antitumor necrosis factor (anti-TNF) treatment showed partial restoration of intestinal microbiome characteristics of healthy individuals.

Major finding: Patients with CD vs. healthy cohort showed a decrease in genera of the class Clostridia and an increase in the phylum Proteobacteria (P less than .01). Anti-TNF treatment allowed restoration of bacteria belonging to the class Clostridia in responders. The genus Escherichia/Shigella reduced significantly vs. baseline but did not reach statistical significance in responders vs. healthy control.

Study details: Data come from a prospective multicenter observational study of 27 patients with CD who initiated anti-TNF treatment and 16 healthy individuals. Based on inflammatory activity, patients were classified into responders and nonresponders.

Disclosures: No information on funding was available. The authors declared no conflicts of interest.

Source: Sanchis-Artero L et al. Sci Rep. 2021 May 11. doi: 10.1038/s41598-021-88823-2.

Key clinical point: Patients with Crohn’s disease (CD) who responded to antitumor necrosis factor (anti-TNF) treatment showed partial restoration of intestinal microbiome characteristics of healthy individuals.

Major finding: Patients with CD vs. healthy cohort showed a decrease in genera of the class Clostridia and an increase in the phylum Proteobacteria (P less than .01). Anti-TNF treatment allowed restoration of bacteria belonging to the class Clostridia in responders. The genus Escherichia/Shigella reduced significantly vs. baseline but did not reach statistical significance in responders vs. healthy control.

Study details: Data come from a prospective multicenter observational study of 27 patients with CD who initiated anti-TNF treatment and 16 healthy individuals. Based on inflammatory activity, patients were classified into responders and nonresponders.

Disclosures: No information on funding was available. The authors declared no conflicts of interest.

Source: Sanchis-Artero L et al. Sci Rep. 2021 May 11. doi: 10.1038/s41598-021-88823-2.

Key clinical point: Patients with Crohn’s disease (CD) who responded to antitumor necrosis factor (anti-TNF) treatment showed partial restoration of intestinal microbiome characteristics of healthy individuals.

Major finding: Patients with CD vs. healthy cohort showed a decrease in genera of the class Clostridia and an increase in the phylum Proteobacteria (P less than .01). Anti-TNF treatment allowed restoration of bacteria belonging to the class Clostridia in responders. The genus Escherichia/Shigella reduced significantly vs. baseline but did not reach statistical significance in responders vs. healthy control.

Study details: Data come from a prospective multicenter observational study of 27 patients with CD who initiated anti-TNF treatment and 16 healthy individuals. Based on inflammatory activity, patients were classified into responders and nonresponders.

Disclosures: No information on funding was available. The authors declared no conflicts of interest.

Source: Sanchis-Artero L et al. Sci Rep. 2021 May 11. doi: 10.1038/s41598-021-88823-2.

Key clinical point: Ustekinumab was effective and relatively safe in a real-world cohort of patients with Crohn’s disease (CD).

Major finding: After 104 weeks of ustekinumab treatment, 34.0% of patients were in corticosteroid-free clinical remission (Cf-CR). Among patients who were in Cf-CR at week 24, 48.1% remained at Cf-CR at week 104. Lack of response (61.7%) and loss of response (18.3%) were the main reasons for treatment discontinuation. No new safety signals were identified.

Study details: Findings are from a cohort study of 252 patients with CD who initiated ustekinumab and completed at least 2 years of follow-up.

Disclosures: No information on funding was available. The authors declared serving as a speaker, consultant, principal investigator, advisory board member for and/or receiving sponsorship, grants/honoraria, advisory, and/or speaker fees from multiple sources.

Source: Straatmijer T et al. J Crohns Colitis. 2021 Apr 28. doi: 10.1093/ecco-jcc/jjab081.

Key clinical point: Ustekinumab was effective and relatively safe in a real-world cohort of patients with Crohn’s disease (CD).

Major finding: After 104 weeks of ustekinumab treatment, 34.0% of patients were in corticosteroid-free clinical remission (Cf-CR). Among patients who were in Cf-CR at week 24, 48.1% remained at Cf-CR at week 104. Lack of response (61.7%) and loss of response (18.3%) were the main reasons for treatment discontinuation. No new safety signals were identified.

Study details: Findings are from a cohort study of 252 patients with CD who initiated ustekinumab and completed at least 2 years of follow-up.

Disclosures: No information on funding was available. The authors declared serving as a speaker, consultant, principal investigator, advisory board member for and/or receiving sponsorship, grants/honoraria, advisory, and/or speaker fees from multiple sources.

Source: Straatmijer T et al. J Crohns Colitis. 2021 Apr 28. doi: 10.1093/ecco-jcc/jjab081.

Key clinical point: Ustekinumab was effective and relatively safe in a real-world cohort of patients with Crohn’s disease (CD).

Major finding: After 104 weeks of ustekinumab treatment, 34.0% of patients were in corticosteroid-free clinical remission (Cf-CR). Among patients who were in Cf-CR at week 24, 48.1% remained at Cf-CR at week 104. Lack of response (61.7%) and loss of response (18.3%) were the main reasons for treatment discontinuation. No new safety signals were identified.

Study details: Findings are from a cohort study of 252 patients with CD who initiated ustekinumab and completed at least 2 years of follow-up.

Disclosures: No information on funding was available. The authors declared serving as a speaker, consultant, principal investigator, advisory board member for and/or receiving sponsorship, grants/honoraria, advisory, and/or speaker fees from multiple sources.

Source: Straatmijer T et al. J Crohns Colitis. 2021 Apr 28. doi: 10.1093/ecco-jcc/jjab081.

Key clinical point: Patients with an acute flare of inflammatory bowel disease (IBD) treated with intravenous methylprednisolone (IVMP) required significantly more rescue biologics or cyclosporine. Additionally, IVMP significantly reduced rates of hypokalemia compared with intravenous hydrocortisone (IVHC).

Major finding: IVMP was associated with a greater requirement for rescue biologics or cyclosporine (odds ratio [OR], 2.79; P less than .001) and lower rates of hypokalemia (OR, 0.49; P = .005) than IVHC.

Study details: This was a multicenter cohort study of 359 patients hospitalized with an acute flare of IBD and treated with either IVMP 60 mg daily (n=129) or IVHC 100 mg 4 times daily (n=230).

Disclosures: The study did not receive any funding. All the authors declared no conflicts of interest.

Source: Schauer C et al. J Gastroenterol Hepatol. 2021 May 3. doi: 10.1111/jgh.15535.

Key clinical point: Patients with an acute flare of inflammatory bowel disease (IBD) treated with intravenous methylprednisolone (IVMP) required significantly more rescue biologics or cyclosporine. Additionally, IVMP significantly reduced rates of hypokalemia compared with intravenous hydrocortisone (IVHC).

Major finding: IVMP was associated with a greater requirement for rescue biologics or cyclosporine (odds ratio [OR], 2.79; P less than .001) and lower rates of hypokalemia (OR, 0.49; P = .005) than IVHC.

Study details: This was a multicenter cohort study of 359 patients hospitalized with an acute flare of IBD and treated with either IVMP 60 mg daily (n=129) or IVHC 100 mg 4 times daily (n=230).

Disclosures: The study did not receive any funding. All the authors declared no conflicts of interest.

Source: Schauer C et al. J Gastroenterol Hepatol. 2021 May 3. doi: 10.1111/jgh.15535.

Key clinical point: Patients with an acute flare of inflammatory bowel disease (IBD) treated with intravenous methylprednisolone (IVMP) required significantly more rescue biologics or cyclosporine. Additionally, IVMP significantly reduced rates of hypokalemia compared with intravenous hydrocortisone (IVHC).

Major finding: IVMP was associated with a greater requirement for rescue biologics or cyclosporine (odds ratio [OR], 2.79; P less than .001) and lower rates of hypokalemia (OR, 0.49; P = .005) than IVHC.

Study details: This was a multicenter cohort study of 359 patients hospitalized with an acute flare of IBD and treated with either IVMP 60 mg daily (n=129) or IVHC 100 mg 4 times daily (n=230).

Disclosures: The study did not receive any funding. All the authors declared no conflicts of interest.

Source: Schauer C et al. J Gastroenterol Hepatol. 2021 May 3. doi: 10.1111/jgh.15535.

Key clinical point: A significant proportion of patients with inflammatory bowel disease (IBD) remain in remission after discontinuation of antitumor necrosis factor-alpha (anti-TNF) post clinical remission.

Major finding: After a median follow-up of 34 months, incidence rate of relapse was 12% per patient-year (95% confidence interval [CI], 11-14) and the cumulative incidence of relapse was 50% (95% CI, 47-53) with 19%, 31%, 38%, 44%, and 48% at 1, 2, 3, 4, and 5 years of follow-up.

Study details: Data come from an extension of the EVODIS study that included 1,055 patients with Crohn's disease or ulcerative colitis who discontinued anti-TNF therapy after achieving clinical remission.

Disclosures: The study did not receive any funding. Some of the authors reported serving as a speaker, consultant, advisory member, and receiving research and/or education funding from multiple sources.

Source: Casanova MJ et al. Aliment Pharmacol Ther. 2021 May 7. doi: 10.1111/apt.16361.

Key clinical point: A significant proportion of patients with inflammatory bowel disease (IBD) remain in remission after discontinuation of antitumor necrosis factor-alpha (anti-TNF) post clinical remission.

Major finding: After a median follow-up of 34 months, incidence rate of relapse was 12% per patient-year (95% confidence interval [CI], 11-14) and the cumulative incidence of relapse was 50% (95% CI, 47-53) with 19%, 31%, 38%, 44%, and 48% at 1, 2, 3, 4, and 5 years of follow-up.

Study details: Data come from an extension of the EVODIS study that included 1,055 patients with Crohn's disease or ulcerative colitis who discontinued anti-TNF therapy after achieving clinical remission.

Disclosures: The study did not receive any funding. Some of the authors reported serving as a speaker, consultant, advisory member, and receiving research and/or education funding from multiple sources.

Source: Casanova MJ et al. Aliment Pharmacol Ther. 2021 May 7. doi: 10.1111/apt.16361.

Key clinical point: A significant proportion of patients with inflammatory bowel disease (IBD) remain in remission after discontinuation of antitumor necrosis factor-alpha (anti-TNF) post clinical remission.

Major finding: After a median follow-up of 34 months, incidence rate of relapse was 12% per patient-year (95% confidence interval [CI], 11-14) and the cumulative incidence of relapse was 50% (95% CI, 47-53) with 19%, 31%, 38%, 44%, and 48% at 1, 2, 3, 4, and 5 years of follow-up.

Study details: Data come from an extension of the EVODIS study that included 1,055 patients with Crohn's disease or ulcerative colitis who discontinued anti-TNF therapy after achieving clinical remission.

Disclosures: The study did not receive any funding. Some of the authors reported serving as a speaker, consultant, advisory member, and receiving research and/or education funding from multiple sources.

Source: Casanova MJ et al. Aliment Pharmacol Ther. 2021 May 7. doi: 10.1111/apt.16361.

Key clinical point: Patients with inflammatory bowel disease (IBD) treated with infliximab vs. vedolizumab showed attenuated immunogenicity to a single dose of BNT162b2 and adenovirus-ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Reassuringly, second dose of the vaccine led to seroconversion in most patients.

Major finding: Anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab vs. vedolizumab following vaccination with a single dose of either BNT162b2 (fold change [FC], 0.29; P less than .0001) or ChAdOx1 nCoV-19 (FC, 0.39; P less than .0001). After second vaccine dose, 85% of infliximab- and 86% of vedolizumab-treated patients seroconverted (P = .68).

Study details: Findings are from the CLARITY IBD study that included patients with IBD without evidence of prior SARS-CoV-2 infection who were treated with infliximab (n=865) or vedolizumab (n=428).

Disclosures: The study was funded by F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea), and others. Some of the authors reported receiving grants, personal fees, and/or financial or nonfinancial support from multiple sources.

Source: Kennedy NA et al. Gut. 2021 Apr 26. doi: 10.1136/gutjnl-2021-324789.

Key clinical point: Patients with inflammatory bowel disease (IBD) treated with infliximab vs. vedolizumab showed attenuated immunogenicity to a single dose of BNT162b2 and adenovirus-ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Reassuringly, second dose of the vaccine led to seroconversion in most patients.

Major finding: Anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab vs. vedolizumab following vaccination with a single dose of either BNT162b2 (fold change [FC], 0.29; P less than .0001) or ChAdOx1 nCoV-19 (FC, 0.39; P less than .0001). After second vaccine dose, 85% of infliximab- and 86% of vedolizumab-treated patients seroconverted (P = .68).

Study details: Findings are from the CLARITY IBD study that included patients with IBD without evidence of prior SARS-CoV-2 infection who were treated with infliximab (n=865) or vedolizumab (n=428).

Disclosures: The study was funded by F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea), and others. Some of the authors reported receiving grants, personal fees, and/or financial or nonfinancial support from multiple sources.

Source: Kennedy NA et al. Gut. 2021 Apr 26. doi: 10.1136/gutjnl-2021-324789.

Key clinical point: Patients with inflammatory bowel disease (IBD) treated with infliximab vs. vedolizumab showed attenuated immunogenicity to a single dose of BNT162b2 and adenovirus-ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Reassuringly, second dose of the vaccine led to seroconversion in most patients.

Major finding: Anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab vs. vedolizumab following vaccination with a single dose of either BNT162b2 (fold change [FC], 0.29; P less than .0001) or ChAdOx1 nCoV-19 (FC, 0.39; P less than .0001). After second vaccine dose, 85% of infliximab- and 86% of vedolizumab-treated patients seroconverted (P = .68).

Study details: Findings are from the CLARITY IBD study that included patients with IBD without evidence of prior SARS-CoV-2 infection who were treated with infliximab (n=865) or vedolizumab (n=428).

Disclosures: The study was funded by F. Hoffmann-La Roche AG (Switzerland), Biogen GmbH (Switzerland), Celltrion Healthcare (South Korea), and others. Some of the authors reported receiving grants, personal fees, and/or financial or nonfinancial support from multiple sources.

Source: Kennedy NA et al. Gut. 2021 Apr 26. doi: 10.1136/gutjnl-2021-324789.

In the approach to treatment of patients with rheumatoid arthritis (RA), methotrexate monotherapy is often followed by addition of a biologic disease modifying anti-rheumatic drugs (bDMARDs) for best disease outcomes. Combination DMARDs therapy with methotrexate, hydroxychloroquine, and sulfasalazine (triple therapy) has been proposed as an alternative to biologic therapy. Combination methotrexate and leflunomide is not as frequently addressed in the literature, perhaps due in part to concerns about hepatotoxicity. Bredemeier et al address safety concerns regarding combination methotrexate and leflunomide in the treatment of patients with RA. In this multicenter Brazilian registry study, they compared adverse events (including infection) among patients receiving bDMARDs or JAK inhibitors. Patients treated with combination methotrexate and leflunomide had comparable rates of adverse effects as patients treated with either medication alone; infectious and serious adverse events were fewer compared to patients treated with bDMARDs or JAK inhibitors. Given this reassuring information, further study of the efficacy and durability of combination methotrexate and leflunomide therapy would be helpful to firmly establish its place in treatment of RA, especially among newer biologic choices.

Tofacitinib and tocilizumab, for example, have been under investigation for safety and efficacy, alone and in combination with conventional synthetic DMARDs (csDMARDs). Prior studies have suggested that tofacitinib is more effective in bDMARD-naïve patients than patients who have had inadequate efficacy with one or more bDMARDs. In this multicenter Japanese cohort study, Mori et al examine RA outcomes in new users of tofacitinib and tocilizumab. Clinical disease activity index (CDAI) responses and remission rates were significantly better among bDMARD-naïve patients receiving tofacitinib compared to those receiving tocilizumab; interestingly, this difference was not seen in patients who had previously received bDMARDs. Interpretation of these results is somewhat hampered by the use of the lower every-other-week tocilizimab injection dose, but they still raise the question as to whether timing and sequence of biologics can affect future response to therapy.

The role of conventional DMARDs has also been questioned in the converse role: tapering of therapy. Lillegraven et al compare tapering of csDMARDs to continuing therapy in this randomized multicenter Norwegian study. The possibility of biologic tapering in RA has previously been addressed with some evidence of success in the form of reduced frequency of administration. Unfortunately, despite being in stable remission, patients assigned to reduce csDMARDs to half-dose had more flares than those continuing therapy, suggesting that reducing csDMARDs to half-dose in RA patients in remission may not be easily accomplished. Whether this changes in patients with prolonged or “deep” remission is as yet unknown.

Finally, with all of these options for tailored therapy, how does our treatment of early RA fare? Combe et al report the 10-year outcomes of a French early RA cohort (ESPOIR), including patients with RA for <6 months recruited from 2003-2005. 521 patients were followed; at year 10, half were in DAS28 remission, and 14% in drug-free remission. Compared to outcomes from an earlier community- based study, patients in the ESPOIR cohort have better outcomes, possibly due to more aggressive treatment for RA, use of bDMARDs, or perhaps even earlier identification of patients for treatment. Due to the sizeable proportion of patients in drug-free remission, the impact of stringency of entry criteria should be considered, and a comparison to a later cohort with patients identified using 2019 ACR/EULAR criteria would be of great interest.

In the approach to treatment of patients with rheumatoid arthritis (RA), methotrexate monotherapy is often followed by addition of a biologic disease modifying anti-rheumatic drugs (bDMARDs) for best disease outcomes. Combination DMARDs therapy with methotrexate, hydroxychloroquine, and sulfasalazine (triple therapy) has been proposed as an alternative to biologic therapy. Combination methotrexate and leflunomide is not as frequently addressed in the literature, perhaps due in part to concerns about hepatotoxicity. Bredemeier et al address safety concerns regarding combination methotrexate and leflunomide in the treatment of patients with RA. In this multicenter Brazilian registry study, they compared adverse events (including infection) among patients receiving bDMARDs or JAK inhibitors. Patients treated with combination methotrexate and leflunomide had comparable rates of adverse effects as patients treated with either medication alone; infectious and serious adverse events were fewer compared to patients treated with bDMARDs or JAK inhibitors. Given this reassuring information, further study of the efficacy and durability of combination methotrexate and leflunomide therapy would be helpful to firmly establish its place in treatment of RA, especially among newer biologic choices.

Tofacitinib and tocilizumab, for example, have been under investigation for safety and efficacy, alone and in combination with conventional synthetic DMARDs (csDMARDs). Prior studies have suggested that tofacitinib is more effective in bDMARD-naïve patients than patients who have had inadequate efficacy with one or more bDMARDs. In this multicenter Japanese cohort study, Mori et al examine RA outcomes in new users of tofacitinib and tocilizumab. Clinical disease activity index (CDAI) responses and remission rates were significantly better among bDMARD-naïve patients receiving tofacitinib compared to those receiving tocilizumab; interestingly, this difference was not seen in patients who had previously received bDMARDs. Interpretation of these results is somewhat hampered by the use of the lower every-other-week tocilizimab injection dose, but they still raise the question as to whether timing and sequence of biologics can affect future response to therapy.

The role of conventional DMARDs has also been questioned in the converse role: tapering of therapy. Lillegraven et al compare tapering of csDMARDs to continuing therapy in this randomized multicenter Norwegian study. The possibility of biologic tapering in RA has previously been addressed with some evidence of success in the form of reduced frequency of administration. Unfortunately, despite being in stable remission, patients assigned to reduce csDMARDs to half-dose had more flares than those continuing therapy, suggesting that reducing csDMARDs to half-dose in RA patients in remission may not be easily accomplished. Whether this changes in patients with prolonged or “deep” remission is as yet unknown.

Finally, with all of these options for tailored therapy, how does our treatment of early RA fare? Combe et al report the 10-year outcomes of a French early RA cohort (ESPOIR), including patients with RA for <6 months recruited from 2003-2005. 521 patients were followed; at year 10, half were in DAS28 remission, and 14% in drug-free remission. Compared to outcomes from an earlier community- based study, patients in the ESPOIR cohort have better outcomes, possibly due to more aggressive treatment for RA, use of bDMARDs, or perhaps even earlier identification of patients for treatment. Due to the sizeable proportion of patients in drug-free remission, the impact of stringency of entry criteria should be considered, and a comparison to a later cohort with patients identified using 2019 ACR/EULAR criteria would be of great interest.

In the approach to treatment of patients with rheumatoid arthritis (RA), methotrexate monotherapy is often followed by addition of a biologic disease modifying anti-rheumatic drugs (bDMARDs) for best disease outcomes. Combination DMARDs therapy with methotrexate, hydroxychloroquine, and sulfasalazine (triple therapy) has been proposed as an alternative to biologic therapy. Combination methotrexate and leflunomide is not as frequently addressed in the literature, perhaps due in part to concerns about hepatotoxicity. Bredemeier et al address safety concerns regarding combination methotrexate and leflunomide in the treatment of patients with RA. In this multicenter Brazilian registry study, they compared adverse events (including infection) among patients receiving bDMARDs or JAK inhibitors. Patients treated with combination methotrexate and leflunomide had comparable rates of adverse effects as patients treated with either medication alone; infectious and serious adverse events were fewer compared to patients treated with bDMARDs or JAK inhibitors. Given this reassuring information, further study of the efficacy and durability of combination methotrexate and leflunomide therapy would be helpful to firmly establish its place in treatment of RA, especially among newer biologic choices.

Tofacitinib and tocilizumab, for example, have been under investigation for safety and efficacy, alone and in combination with conventional synthetic DMARDs (csDMARDs). Prior studies have suggested that tofacitinib is more effective in bDMARD-naïve patients than patients who have had inadequate efficacy with one or more bDMARDs. In this multicenter Japanese cohort study, Mori et al examine RA outcomes in new users of tofacitinib and tocilizumab. Clinical disease activity index (CDAI) responses and remission rates were significantly better among bDMARD-naïve patients receiving tofacitinib compared to those receiving tocilizumab; interestingly, this difference was not seen in patients who had previously received bDMARDs. Interpretation of these results is somewhat hampered by the use of the lower every-other-week tocilizimab injection dose, but they still raise the question as to whether timing and sequence of biologics can affect future response to therapy.

The role of conventional DMARDs has also been questioned in the converse role: tapering of therapy. Lillegraven et al compare tapering of csDMARDs to continuing therapy in this randomized multicenter Norwegian study. The possibility of biologic tapering in RA has previously been addressed with some evidence of success in the form of reduced frequency of administration. Unfortunately, despite being in stable remission, patients assigned to reduce csDMARDs to half-dose had more flares than those continuing therapy, suggesting that reducing csDMARDs to half-dose in RA patients in remission may not be easily accomplished. Whether this changes in patients with prolonged or “deep” remission is as yet unknown.

Finally, with all of these options for tailored therapy, how does our treatment of early RA fare? Combe et al report the 10-year outcomes of a French early RA cohort (ESPOIR), including patients with RA for <6 months recruited from 2003-2005. 521 patients were followed; at year 10, half were in DAS28 remission, and 14% in drug-free remission. Compared to outcomes from an earlier community- based study, patients in the ESPOIR cohort have better outcomes, possibly due to more aggressive treatment for RA, use of bDMARDs, or perhaps even earlier identification of patients for treatment. Due to the sizeable proportion of patients in drug-free remission, the impact of stringency of entry criteria should be considered, and a comparison to a later cohort with patients identified using 2019 ACR/EULAR criteria would be of great interest.