Rheumatoid Arthritis

Key clinical point: Initial treatment with methotrexate (MTX) and glucocorticoids (GC) bridging reduced chronic use of the nonsteroidal anti-inflammatory drug (NSAID) and analgesics compared with MTX treatment alone in patients with early rheumatoid arthritis (eRA) considered to have a favorable prognosis.

Major finding: The number of patients with a daily chronic intake of NSAIDs was significantly lower in MTX monotherapy along with step-down GC vs. MTX monotherapy without oral GC group (14% vs. 40%; P less than .01). Even after correcting for previous chronic analgesic use and baseline pain, patients treated with MTX and step-down GCs had an 83% lower hazard of chronic use of NSAID or analgesic (P less than .001).

Study details: Findings are from a post hoc analysis of the CareRA trial of 90 patients with eRA and favorable risk profile. Patients were randomly allocated to either MTX monotherapy without oral GC (n=47) or MTX monotherapy along with step-down GC (n=43).

Disclosures: The CareRA trial was funded by a Flemish governmental grant. All the authors declared no conflicts of interest.

Source: Pazmino S et al. RMD Open. 2021 May 24. doi: 10.1136/rmdopen-2021-001615.

Key clinical point: Initial treatment with methotrexate (MTX) and glucocorticoids (GC) bridging reduced chronic use of the nonsteroidal anti-inflammatory drug (NSAID) and analgesics compared with MTX treatment alone in patients with early rheumatoid arthritis (eRA) considered to have a favorable prognosis.

Major finding: The number of patients with a daily chronic intake of NSAIDs was significantly lower in MTX monotherapy along with step-down GC vs. MTX monotherapy without oral GC group (14% vs. 40%; P less than .01). Even after correcting for previous chronic analgesic use and baseline pain, patients treated with MTX and step-down GCs had an 83% lower hazard of chronic use of NSAID or analgesic (P less than .001).

Study details: Findings are from a post hoc analysis of the CareRA trial of 90 patients with eRA and favorable risk profile. Patients were randomly allocated to either MTX monotherapy without oral GC (n=47) or MTX monotherapy along with step-down GC (n=43).

Disclosures: The CareRA trial was funded by a Flemish governmental grant. All the authors declared no conflicts of interest.

Source: Pazmino S et al. RMD Open. 2021 May 24. doi: 10.1136/rmdopen-2021-001615.

Key clinical point: Initial treatment with methotrexate (MTX) and glucocorticoids (GC) bridging reduced chronic use of the nonsteroidal anti-inflammatory drug (NSAID) and analgesics compared with MTX treatment alone in patients with early rheumatoid arthritis (eRA) considered to have a favorable prognosis.

Major finding: The number of patients with a daily chronic intake of NSAIDs was significantly lower in MTX monotherapy along with step-down GC vs. MTX monotherapy without oral GC group (14% vs. 40%; P less than .01). Even after correcting for previous chronic analgesic use and baseline pain, patients treated with MTX and step-down GCs had an 83% lower hazard of chronic use of NSAID or analgesic (P less than .001).

Study details: Findings are from a post hoc analysis of the CareRA trial of 90 patients with eRA and favorable risk profile. Patients were randomly allocated to either MTX monotherapy without oral GC (n=47) or MTX monotherapy along with step-down GC (n=43).

Disclosures: The CareRA trial was funded by a Flemish governmental grant. All the authors declared no conflicts of interest.

Source: Pazmino S et al. RMD Open. 2021 May 24. doi: 10.1136/rmdopen-2021-001615.

Key clinical point: Early rheumatoid arthritis (RA) strategies have different risk profiles. Moreover, the use of early steroid-based regimens did not emerge as more harmful.

Major finding: The risk for serious adverse events was higher with biologic monotherapy vs. methotrexate (MTX)+steroid therapy (rate ratio [RR], 3.22; 95% confidence interval [CI], 1.47-7.07) and with biological monotherapy vs. MTX monotherapy (RR, 1.39; 95% CI, 1.12-1.73) and MTX+biologic disease-modifying antirheumatic drugs (DMARD; RR, 1.26; 95% CI, 1.02-1.54).

Study details: Findings are from a network meta-analysis of 20 double-blind randomized clinical trials involving 9,202 adult patients with RA who were initiated on DMARD therapy.

Disclosures: This study received no external funding. The authors received speaker’s fees and honoraria from various pharmaceutical companies including AbbVie. None of the authors reported any conflict of interest.

Source: Adas MA et al. Rheumatology (Oxford). 2021 May 18. doi: 10.1093/rheumatology/keab429.

Key clinical point: Early rheumatoid arthritis (RA) strategies have different risk profiles. Moreover, the use of early steroid-based regimens did not emerge as more harmful.

Major finding: The risk for serious adverse events was higher with biologic monotherapy vs. methotrexate (MTX)+steroid therapy (rate ratio [RR], 3.22; 95% confidence interval [CI], 1.47-7.07) and with biological monotherapy vs. MTX monotherapy (RR, 1.39; 95% CI, 1.12-1.73) and MTX+biologic disease-modifying antirheumatic drugs (DMARD; RR, 1.26; 95% CI, 1.02-1.54).

Study details: Findings are from a network meta-analysis of 20 double-blind randomized clinical trials involving 9,202 adult patients with RA who were initiated on DMARD therapy.

Disclosures: This study received no external funding. The authors received speaker’s fees and honoraria from various pharmaceutical companies including AbbVie. None of the authors reported any conflict of interest.

Source: Adas MA et al. Rheumatology (Oxford). 2021 May 18. doi: 10.1093/rheumatology/keab429.

Key clinical point: Early rheumatoid arthritis (RA) strategies have different risk profiles. Moreover, the use of early steroid-based regimens did not emerge as more harmful.

Major finding: The risk for serious adverse events was higher with biologic monotherapy vs. methotrexate (MTX)+steroid therapy (rate ratio [RR], 3.22; 95% confidence interval [CI], 1.47-7.07) and with biological monotherapy vs. MTX monotherapy (RR, 1.39; 95% CI, 1.12-1.73) and MTX+biologic disease-modifying antirheumatic drugs (DMARD; RR, 1.26; 95% CI, 1.02-1.54).

Study details: Findings are from a network meta-analysis of 20 double-blind randomized clinical trials involving 9,202 adult patients with RA who were initiated on DMARD therapy.

Disclosures: This study received no external funding. The authors received speaker’s fees and honoraria from various pharmaceutical companies including AbbVie. None of the authors reported any conflict of interest.

Source: Adas MA et al. Rheumatology (Oxford). 2021 May 18. doi: 10.1093/rheumatology/keab429.

Key clinical point: Tocilizumab (TCZ) was associated with an increased risk for diverticulitis and gastrointestinal (GI) perforation related to diverticulitis compared with rituximab (RTX) and abatacept (ABA) in patients with rheumatoid arthritis (RA).

Major finding: TCZ vs. RTX or ABA was associated with an increased risk for diverticulitis (hazard ratio [HR], 3.1; P = .002) and GI perforation because of diverticulitis (HR, 2.9; P = .03).

Study details: Data come from an analysis of a real-life cohort of 4,501 patients with RA from 3 observational registries of the French Society of Rheumatology who received RTX (n=1,986), ABA (n=1,019), or TCZ (n=1,496).

Disclosures: The French Society of Rheumatology received unrestricted grants from Bristol Myers Squibb, Roche, and Roche-Chugai. Some of the authors including the lead author declared receiving grants and consulting/speaker/personal fees from various sources including Bristol Myers Squibb. C Rempenault, A Herrero, and I Pane declared no conflicts of interest.

Source: Rempenault C et al. Rheumatology (Oxford). 2021 May 16. doi: 10.1093/rheumatology/keab438.

Key clinical point: Tocilizumab (TCZ) was associated with an increased risk for diverticulitis and gastrointestinal (GI) perforation related to diverticulitis compared with rituximab (RTX) and abatacept (ABA) in patients with rheumatoid arthritis (RA).

Major finding: TCZ vs. RTX or ABA was associated with an increased risk for diverticulitis (hazard ratio [HR], 3.1; P = .002) and GI perforation because of diverticulitis (HR, 2.9; P = .03).

Study details: Data come from an analysis of a real-life cohort of 4,501 patients with RA from 3 observational registries of the French Society of Rheumatology who received RTX (n=1,986), ABA (n=1,019), or TCZ (n=1,496).

Disclosures: The French Society of Rheumatology received unrestricted grants from Bristol Myers Squibb, Roche, and Roche-Chugai. Some of the authors including the lead author declared receiving grants and consulting/speaker/personal fees from various sources including Bristol Myers Squibb. C Rempenault, A Herrero, and I Pane declared no conflicts of interest.

Source: Rempenault C et al. Rheumatology (Oxford). 2021 May 16. doi: 10.1093/rheumatology/keab438.

Key clinical point: Tocilizumab (TCZ) was associated with an increased risk for diverticulitis and gastrointestinal (GI) perforation related to diverticulitis compared with rituximab (RTX) and abatacept (ABA) in patients with rheumatoid arthritis (RA).

Major finding: TCZ vs. RTX or ABA was associated with an increased risk for diverticulitis (hazard ratio [HR], 3.1; P = .002) and GI perforation because of diverticulitis (HR, 2.9; P = .03).

Study details: Data come from an analysis of a real-life cohort of 4,501 patients with RA from 3 observational registries of the French Society of Rheumatology who received RTX (n=1,986), ABA (n=1,019), or TCZ (n=1,496).

Disclosures: The French Society of Rheumatology received unrestricted grants from Bristol Myers Squibb, Roche, and Roche-Chugai. Some of the authors including the lead author declared receiving grants and consulting/speaker/personal fees from various sources including Bristol Myers Squibb. C Rempenault, A Herrero, and I Pane declared no conflicts of interest.

Source: Rempenault C et al. Rheumatology (Oxford). 2021 May 16. doi: 10.1093/rheumatology/keab438.

Key clinical point: Use of methotrexate significantly reduced the risk for cardiovascular disease (CVD) events, particularly heart failure (HF)-related hospitalizations in patients with rheumatoid arthritis (RA).

Major finding: Use of methotrexate was associated with a significant 24% reduced risk for composite CVD events (hazard ratio [HR], 0.76; P = .04), including a 57% lower risk for HF hospitalizations (HR, 0.43; P = .005).

Study details: The data come from a prospective cohort study of 2,044 US veterans with RA.

Disclosures: The work was supported by Centre of Excellence for Suicide Prevention and Joint Department of Veterans Affairs and Department of Defense Mortality Data Repository—National Death Index. MD George reported receiving grant support from Bristol Myers Squibb for unrelated work.

Source: Johnson TM et al. Ann Rheum Dis. 2021 May 28. doi: 10.1136/annrheumdis-2021-220125.

Key clinical point: Use of methotrexate significantly reduced the risk for cardiovascular disease (CVD) events, particularly heart failure (HF)-related hospitalizations in patients with rheumatoid arthritis (RA).

Major finding: Use of methotrexate was associated with a significant 24% reduced risk for composite CVD events (hazard ratio [HR], 0.76; P = .04), including a 57% lower risk for HF hospitalizations (HR, 0.43; P = .005).

Study details: The data come from a prospective cohort study of 2,044 US veterans with RA.

Disclosures: The work was supported by Centre of Excellence for Suicide Prevention and Joint Department of Veterans Affairs and Department of Defense Mortality Data Repository—National Death Index. MD George reported receiving grant support from Bristol Myers Squibb for unrelated work.

Source: Johnson TM et al. Ann Rheum Dis. 2021 May 28. doi: 10.1136/annrheumdis-2021-220125.

Key clinical point: Use of methotrexate significantly reduced the risk for cardiovascular disease (CVD) events, particularly heart failure (HF)-related hospitalizations in patients with rheumatoid arthritis (RA).

Major finding: Use of methotrexate was associated with a significant 24% reduced risk for composite CVD events (hazard ratio [HR], 0.76; P = .04), including a 57% lower risk for HF hospitalizations (HR, 0.43; P = .005).

Study details: The data come from a prospective cohort study of 2,044 US veterans with RA.

Disclosures: The work was supported by Centre of Excellence for Suicide Prevention and Joint Department of Veterans Affairs and Department of Defense Mortality Data Repository—National Death Index. MD George reported receiving grant support from Bristol Myers Squibb for unrelated work.

Source: Johnson TM et al. Ann Rheum Dis. 2021 May 28. doi: 10.1136/annrheumdis-2021-220125.

Key clinical point: Patients with rheumatoid arthritis (RA) treated with rituximab or Janus kinase inhibitors (JAKi) at onset of COVID-19 were more likely to have poor COVID-19 outcomes compared with those treated with tumor necrosis factor inhibitors (TNFi).

Major finding: Odds of worse COVID-19 severity were 4.15 and 2.06 greater in patients on rituximab (odds ratio [OR], 4.15) and JAKi (OR, 2.06; both P less than .01) vs. those on TNFi. Patients on rituximab and JAKi therapy vs. TNFi were more susceptible to hospitalization (OR, 4.53 and 2.40, respectively; P less than .01) and death (OR, 4.57 and 2.04, respectively; P less than .01).

Study details: The data come from the analysis of 2,869 patients with RA and COVID-19 who were on abatacept (n=237), rituximab (n=364), interleukin 6 inhibitors (n=317), Janus kinase inhibitors (n=563), or TNFi (n=1,388) at the time of clinical COVID-19 onset.

Disclosures: The study received support from the American College of Rheumatology and the European Alliance of Associations for Rheumatology. The authors reported receiving research support, grants, and speaker’s/consultancy/personal fees from various sources.

Source: Sparks JA et al. Ann Rheum Dis. 2021 May 28. doi: 10.1136/annrheumdis-2021-220418.

Key clinical point: Patients with rheumatoid arthritis (RA) treated with rituximab or Janus kinase inhibitors (JAKi) at onset of COVID-19 were more likely to have poor COVID-19 outcomes compared with those treated with tumor necrosis factor inhibitors (TNFi).

Major finding: Odds of worse COVID-19 severity were 4.15 and 2.06 greater in patients on rituximab (odds ratio [OR], 4.15) and JAKi (OR, 2.06; both P less than .01) vs. those on TNFi. Patients on rituximab and JAKi therapy vs. TNFi were more susceptible to hospitalization (OR, 4.53 and 2.40, respectively; P less than .01) and death (OR, 4.57 and 2.04, respectively; P less than .01).

Study details: The data come from the analysis of 2,869 patients with RA and COVID-19 who were on abatacept (n=237), rituximab (n=364), interleukin 6 inhibitors (n=317), Janus kinase inhibitors (n=563), or TNFi (n=1,388) at the time of clinical COVID-19 onset.

Disclosures: The study received support from the American College of Rheumatology and the European Alliance of Associations for Rheumatology. The authors reported receiving research support, grants, and speaker’s/consultancy/personal fees from various sources.

Source: Sparks JA et al. Ann Rheum Dis. 2021 May 28. doi: 10.1136/annrheumdis-2021-220418.

Key clinical point: Patients with rheumatoid arthritis (RA) treated with rituximab or Janus kinase inhibitors (JAKi) at onset of COVID-19 were more likely to have poor COVID-19 outcomes compared with those treated with tumor necrosis factor inhibitors (TNFi).

Major finding: Odds of worse COVID-19 severity were 4.15 and 2.06 greater in patients on rituximab (odds ratio [OR], 4.15) and JAKi (OR, 2.06; both P less than .01) vs. those on TNFi. Patients on rituximab and JAKi therapy vs. TNFi were more susceptible to hospitalization (OR, 4.53 and 2.40, respectively; P less than .01) and death (OR, 4.57 and 2.04, respectively; P less than .01).

Study details: The data come from the analysis of 2,869 patients with RA and COVID-19 who were on abatacept (n=237), rituximab (n=364), interleukin 6 inhibitors (n=317), Janus kinase inhibitors (n=563), or TNFi (n=1,388) at the time of clinical COVID-19 onset.

Disclosures: The study received support from the American College of Rheumatology and the European Alliance of Associations for Rheumatology. The authors reported receiving research support, grants, and speaker’s/consultancy/personal fees from various sources.

Source: Sparks JA et al. Ann Rheum Dis. 2021 May 28. doi: 10.1136/annrheumdis-2021-220418.

Key clinical point: ORAL Shift demonstrates safety and efficacy of tofacitinib modified-release 11 mg once daily (OD) plus methotrexate in a global population of patients with rheumatoid arthritis (RA).

Major finding: All efficacy outcomes improved from baseline to week 12 including Disease Activity Score in 28 joints, erythrocyte sedimentation rate (mean change [MC], −2.0), Clinical Disease Activity Index (CDAI; MC, −19.6), Simplified Disease Activity Index (MC, −20.3), and other patient-reported outcomes, which continued to improve through week 24. At week 24, 84.5% of patients achieved CDAI-defined low disease activity. Most adverse events were mild or moderate in severity and no deaths were reported.

Study details: ORAL Shift, a 48-week phase 3b/4 withdrawal study included patients with moderate to severe RA and an inadequate response to methotrexate who received open-label tofacitinib modified-release 11 mg OD and methotrexate.

Disclosures: This study was sponsored by Pfizer Inc. Some of the authors declared receiving research support and honoraria and serving as consultant or on speaker’s bureau for various sources including Pfizer. Seven of the authors declared being employees and shareholders at Pfizer Inc.

Source: Cohen SB et al. RMD Open. 2021 Jun 7. doi: 10.1136/rmdopen-2021-001673.

Key clinical point: ORAL Shift demonstrates safety and efficacy of tofacitinib modified-release 11 mg once daily (OD) plus methotrexate in a global population of patients with rheumatoid arthritis (RA).

Major finding: All efficacy outcomes improved from baseline to week 12 including Disease Activity Score in 28 joints, erythrocyte sedimentation rate (mean change [MC], −2.0), Clinical Disease Activity Index (CDAI; MC, −19.6), Simplified Disease Activity Index (MC, −20.3), and other patient-reported outcomes, which continued to improve through week 24. At week 24, 84.5% of patients achieved CDAI-defined low disease activity. Most adverse events were mild or moderate in severity and no deaths were reported.

Study details: ORAL Shift, a 48-week phase 3b/4 withdrawal study included patients with moderate to severe RA and an inadequate response to methotrexate who received open-label tofacitinib modified-release 11 mg OD and methotrexate.

Disclosures: This study was sponsored by Pfizer Inc. Some of the authors declared receiving research support and honoraria and serving as consultant or on speaker’s bureau for various sources including Pfizer. Seven of the authors declared being employees and shareholders at Pfizer Inc.

Source: Cohen SB et al. RMD Open. 2021 Jun 7. doi: 10.1136/rmdopen-2021-001673.

Key clinical point: ORAL Shift demonstrates safety and efficacy of tofacitinib modified-release 11 mg once daily (OD) plus methotrexate in a global population of patients with rheumatoid arthritis (RA).

Major finding: All efficacy outcomes improved from baseline to week 12 including Disease Activity Score in 28 joints, erythrocyte sedimentation rate (mean change [MC], −2.0), Clinical Disease Activity Index (CDAI; MC, −19.6), Simplified Disease Activity Index (MC, −20.3), and other patient-reported outcomes, which continued to improve through week 24. At week 24, 84.5% of patients achieved CDAI-defined low disease activity. Most adverse events were mild or moderate in severity and no deaths were reported.

Study details: ORAL Shift, a 48-week phase 3b/4 withdrawal study included patients with moderate to severe RA and an inadequate response to methotrexate who received open-label tofacitinib modified-release 11 mg OD and methotrexate.

Disclosures: This study was sponsored by Pfizer Inc. Some of the authors declared receiving research support and honoraria and serving as consultant or on speaker’s bureau for various sources including Pfizer. Seven of the authors declared being employees and shareholders at Pfizer Inc.

Source: Cohen SB et al. RMD Open. 2021 Jun 7. doi: 10.1136/rmdopen-2021-001673.

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.

Key clinical point: Rheumatologists mostly preferred tumor necrosis factor inhibitors (TNFi) for the management of patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate. Abatacept seemed to be the more preferred option for patients with pulmonary involvement or a high risk for infection.

Major finding: TNFi was the preferred strategy in 80% of vignettes, except in cases with a history of infection and pulmonary comorbidity where abatacept was the first choice (global BW score: TNFi, 0.53 and abatacept, 0.38). Tocilizumab was the third most preferred strategy, chosen in 83% of the cases (global BW score: 0.11).

Study details: This was a noninterventional multicenter study involving 64 hypothetical clinical vignettes of patients with RA with an inadequate response to methotrexate. These case vignettes were presented to 211 French rheumatologists to elicit their therapeutic preferences.

Disclosures: The study was funded by Eli Lilly and Company, Indianapolis, IN, USA. Some of the authors declared receiving research grants, consultancy fees, and/or being employees and/or shareholders of Eli Lilly and Company and FAST4.

Source: Senbel E et al. Rheumatol Ther. 2021 May 3. doi: 10.1007/s40744-021-00311-1.

Key clinical point: Rheumatologists mostly preferred tumor necrosis factor inhibitors (TNFi) for the management of patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate. Abatacept seemed to be the more preferred option for patients with pulmonary involvement or a high risk for infection.

Major finding: TNFi was the preferred strategy in 80% of vignettes, except in cases with a history of infection and pulmonary comorbidity where abatacept was the first choice (global BW score: TNFi, 0.53 and abatacept, 0.38). Tocilizumab was the third most preferred strategy, chosen in 83% of the cases (global BW score: 0.11).

Study details: This was a noninterventional multicenter study involving 64 hypothetical clinical vignettes of patients with RA with an inadequate response to methotrexate. These case vignettes were presented to 211 French rheumatologists to elicit their therapeutic preferences.

Disclosures: The study was funded by Eli Lilly and Company, Indianapolis, IN, USA. Some of the authors declared receiving research grants, consultancy fees, and/or being employees and/or shareholders of Eli Lilly and Company and FAST4.

Source: Senbel E et al. Rheumatol Ther. 2021 May 3. doi: 10.1007/s40744-021-00311-1.

Key clinical point: Rheumatologists mostly preferred tumor necrosis factor inhibitors (TNFi) for the management of patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate. Abatacept seemed to be the more preferred option for patients with pulmonary involvement or a high risk for infection.

Major finding: TNFi was the preferred strategy in 80% of vignettes, except in cases with a history of infection and pulmonary comorbidity where abatacept was the first choice (global BW score: TNFi, 0.53 and abatacept, 0.38). Tocilizumab was the third most preferred strategy, chosen in 83% of the cases (global BW score: 0.11).

Study details: This was a noninterventional multicenter study involving 64 hypothetical clinical vignettes of patients with RA with an inadequate response to methotrexate. These case vignettes were presented to 211 French rheumatologists to elicit their therapeutic preferences.

Disclosures: The study was funded by Eli Lilly and Company, Indianapolis, IN, USA. Some of the authors declared receiving research grants, consultancy fees, and/or being employees and/or shareholders of Eli Lilly and Company and FAST4.

Source: Senbel E et al. Rheumatol Ther. 2021 May 3. doi: 10.1007/s40744-021-00311-1.

Key clinical point: Patients with rheumatoid arthritis (RA) have distinct clinical and biomechanical factors that place them at an increased risk for falls.

Major finding: The fallers vs. nonfallers were older (P = .05), had significantly higher pain scores (P less than .01), experienced dizziness (P less than .01), and were taking psychotropic medications (P = .02). The fallers vs. nonfallers had significantly higher anteroposterior sway (P = .03) and sway range (P = .02) and medial-lateral sway (P = .01) and sway range (P = .02) when standing with eyes open and a greater asymmetry during isometric extension at 90° (P = .05) and 60° (P = .02).

Study details: This was a nested case-control biomechanical analysis of 436 patients (aged 60 years or older) with RA who completed a 1-year prospective survey of falls.

Disclosures: This work was supported by the National Institute for Health Research, Research for Patient Benefit, and NIHR Manchester Biomedical Research Centre. The authors declared no conflicts of interest.

Source: Smith TO et al. Rheumatology (Oxford). 2021 Apr 26. doi:10.1093/rheumatology/keab388.

Key clinical point: Patients with rheumatoid arthritis (RA) have distinct clinical and biomechanical factors that place them at an increased risk for falls.

Major finding: The fallers vs. nonfallers were older (P = .05), had significantly higher pain scores (P less than .01), experienced dizziness (P less than .01), and were taking psychotropic medications (P = .02). The fallers vs. nonfallers had significantly higher anteroposterior sway (P = .03) and sway range (P = .02) and medial-lateral sway (P = .01) and sway range (P = .02) when standing with eyes open and a greater asymmetry during isometric extension at 90° (P = .05) and 60° (P = .02).

Study details: This was a nested case-control biomechanical analysis of 436 patients (aged 60 years or older) with RA who completed a 1-year prospective survey of falls.

Disclosures: This work was supported by the National Institute for Health Research, Research for Patient Benefit, and NIHR Manchester Biomedical Research Centre. The authors declared no conflicts of interest.

Source: Smith TO et al. Rheumatology (Oxford). 2021 Apr 26. doi:10.1093/rheumatology/keab388.

Key clinical point: Patients with rheumatoid arthritis (RA) have distinct clinical and biomechanical factors that place them at an increased risk for falls.

Major finding: The fallers vs. nonfallers were older (P = .05), had significantly higher pain scores (P less than .01), experienced dizziness (P less than .01), and were taking psychotropic medications (P = .02). The fallers vs. nonfallers had significantly higher anteroposterior sway (P = .03) and sway range (P = .02) and medial-lateral sway (P = .01) and sway range (P = .02) when standing with eyes open and a greater asymmetry during isometric extension at 90° (P = .05) and 60° (P = .02).

Study details: This was a nested case-control biomechanical analysis of 436 patients (aged 60 years or older) with RA who completed a 1-year prospective survey of falls.

Disclosures: This work was supported by the National Institute for Health Research, Research for Patient Benefit, and NIHR Manchester Biomedical Research Centre. The authors declared no conflicts of interest.

Source: Smith TO et al. Rheumatology (Oxford). 2021 Apr 26. doi:10.1093/rheumatology/keab388.

Key clinical point: Obese patients with established rheumatoid arthritis (RA) were less likely to achieve remission and more likely to experience intensive exposure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) than patients with normal body mass index (BMI).

Major finding: At 6 months, obese patients vs. those with normal BMI were less likely to achieve disease activity score 28 remission (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.28-0.69) and more likely to be treated with combination csDMARD therapy than monotherapy (OR, 1.59; 95% CI, 1.03-2.45).

Study details: The findings are from a real-world analysis of 1,313 patients diagnosed with RA collected from the METEOR database.

Disclosures: No funding was received for this study. The authors declared no conflicts of interest.

Source: Dey M et al. Rheumatology (Oxford). 2021 Apr 30. doi: 10.1093/rheumatology/keab389.

Key clinical point: Obese patients with established rheumatoid arthritis (RA) were less likely to achieve remission and more likely to experience intensive exposure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) than patients with normal body mass index (BMI).

Major finding: At 6 months, obese patients vs. those with normal BMI were less likely to achieve disease activity score 28 remission (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.28-0.69) and more likely to be treated with combination csDMARD therapy than monotherapy (OR, 1.59; 95% CI, 1.03-2.45).

Study details: The findings are from a real-world analysis of 1,313 patients diagnosed with RA collected from the METEOR database.

Disclosures: No funding was received for this study. The authors declared no conflicts of interest.

Source: Dey M et al. Rheumatology (Oxford). 2021 Apr 30. doi: 10.1093/rheumatology/keab389.

Key clinical point: Obese patients with established rheumatoid arthritis (RA) were less likely to achieve remission and more likely to experience intensive exposure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) than patients with normal body mass index (BMI).

Major finding: At 6 months, obese patients vs. those with normal BMI were less likely to achieve disease activity score 28 remission (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.28-0.69) and more likely to be treated with combination csDMARD therapy than monotherapy (OR, 1.59; 95% CI, 1.03-2.45).

Study details: The findings are from a real-world analysis of 1,313 patients diagnosed with RA collected from the METEOR database.

Disclosures: No funding was received for this study. The authors declared no conflicts of interest.

Source: Dey M et al. Rheumatology (Oxford). 2021 Apr 30. doi: 10.1093/rheumatology/keab389.