Rheumatoid Arthritis

Key clinical point: Anti-interleukin-6 (aIL-6) receptor antibody was more effective than other biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with knee joint involvement but not in patients without knee joint involvement.

Major finding: At 12 weeks, treatment with aIL-6 significantly increased clinical disease activity index (CDAI) in patients with knee joint involvement compared with other bDMARDs (P = .02). In patients without swollen knee joints, aIL-6 vs. other bDMARDs showed no significant difference in CDAI improvement (P = .61).

Study details: Findings are from a retrospective analysis of 1,059 treatment courses in patients with RA from the ANSWER cohort who were treated with bDMARDs. The patients were categorized into those with (n=275; 323 bDMARDs treatment course) or without (n=561; 736 bDMARDs treatment course) joint knee involvement.

Disclosures: ANSWER Cohort was supported by grants from Abbie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Sanofi, UCB Japan Co. Ltd., and Teijin Healthcare Limited. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Maeda Y et al. Rheumatol Int. 2021 Apr 26. doi: 10.1007/s00296-021-04862-y.

Key clinical point: Anti-interleukin-6 (aIL-6) receptor antibody was more effective than other biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with knee joint involvement but not in patients without knee joint involvement.

Major finding: At 12 weeks, treatment with aIL-6 significantly increased clinical disease activity index (CDAI) in patients with knee joint involvement compared with other bDMARDs (P = .02). In patients without swollen knee joints, aIL-6 vs. other bDMARDs showed no significant difference in CDAI improvement (P = .61).

Study details: Findings are from a retrospective analysis of 1,059 treatment courses in patients with RA from the ANSWER cohort who were treated with bDMARDs. The patients were categorized into those with (n=275; 323 bDMARDs treatment course) or without (n=561; 736 bDMARDs treatment course) joint knee involvement.

Disclosures: ANSWER Cohort was supported by grants from Abbie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Sanofi, UCB Japan Co. Ltd., and Teijin Healthcare Limited. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Maeda Y et al. Rheumatol Int. 2021 Apr 26. doi: 10.1007/s00296-021-04862-y.

Key clinical point: Anti-interleukin-6 (aIL-6) receptor antibody was more effective than other biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) with knee joint involvement but not in patients without knee joint involvement.

Major finding: At 12 weeks, treatment with aIL-6 significantly increased clinical disease activity index (CDAI) in patients with knee joint involvement compared with other bDMARDs (P = .02). In patients without swollen knee joints, aIL-6 vs. other bDMARDs showed no significant difference in CDAI improvement (P = .61).

Study details: Findings are from a retrospective analysis of 1,059 treatment courses in patients with RA from the ANSWER cohort who were treated with bDMARDs. The patients were categorized into those with (n=275; 323 bDMARDs treatment course) or without (n=561; 736 bDMARDs treatment course) joint knee involvement.

Disclosures: ANSWER Cohort was supported by grants from Abbie G.K., Asahi-Kasei Pharma, AYUMI Pharmaceutical Co., Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical K.K., Ono Pharmaceutical Co., Sanofi, UCB Japan Co. Ltd., and Teijin Healthcare Limited. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Maeda Y et al. Rheumatol Int. 2021 Apr 26. doi: 10.1007/s00296-021-04862-y.

Key clinical point: Combination of methotrexate (MTX) and leflunomide (LEF) had a good overall safety profile compared with MTX or LEF alone and other regimens involved in advanced therapy for rheumatoid arthritis (RA).

Major finding: The risk for serious adverse events (SAEs; adjusted hazard ratio, [aHR], 1.00; P = .984) was not higher; however, the risk for any adverse events (aHR, 1.22; P = .013) was higher with MTX+LEF vs. MTX or LEF alone. The risk for SAEs (aHR, 0.56; P = .011) and infectious SAEs (aHR, 0.48; P = .031) was lower with MTX+LEF combo vs. biologic disease-modifying antirheumatic drugs (bDMARD)/JAK inhibitor (JAKi) with MTX or LEF.

Study details: Findings are from an analysis of 1,671 patients with RA from BiobadaBrasil, a multicentric, observational study. Included patients initiated the first treatment course with a conventional synthetic-DMARD or first bDMARD/JAKi.

Disclosures: This study was funded by the Brazilian Society of Rheumatology with funds from various pharmaceutical companies marketing biological compounds. The authors declared no conflicts of interest.

Source: Bredemeier M et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201248.

Key clinical point: Combination of methotrexate (MTX) and leflunomide (LEF) had a good overall safety profile compared with MTX or LEF alone and other regimens involved in advanced therapy for rheumatoid arthritis (RA).

Major finding: The risk for serious adverse events (SAEs; adjusted hazard ratio, [aHR], 1.00; P = .984) was not higher; however, the risk for any adverse events (aHR, 1.22; P = .013) was higher with MTX+LEF vs. MTX or LEF alone. The risk for SAEs (aHR, 0.56; P = .011) and infectious SAEs (aHR, 0.48; P = .031) was lower with MTX+LEF combo vs. biologic disease-modifying antirheumatic drugs (bDMARD)/JAK inhibitor (JAKi) with MTX or LEF.

Study details: Findings are from an analysis of 1,671 patients with RA from BiobadaBrasil, a multicentric, observational study. Included patients initiated the first treatment course with a conventional synthetic-DMARD or first bDMARD/JAKi.

Disclosures: This study was funded by the Brazilian Society of Rheumatology with funds from various pharmaceutical companies marketing biological compounds. The authors declared no conflicts of interest.

Source: Bredemeier M et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201248.

Key clinical point: Combination of methotrexate (MTX) and leflunomide (LEF) had a good overall safety profile compared with MTX or LEF alone and other regimens involved in advanced therapy for rheumatoid arthritis (RA).

Major finding: The risk for serious adverse events (SAEs; adjusted hazard ratio, [aHR], 1.00; P = .984) was not higher; however, the risk for any adverse events (aHR, 1.22; P = .013) was higher with MTX+LEF vs. MTX or LEF alone. The risk for SAEs (aHR, 0.56; P = .011) and infectious SAEs (aHR, 0.48; P = .031) was lower with MTX+LEF combo vs. biologic disease-modifying antirheumatic drugs (bDMARD)/JAK inhibitor (JAKi) with MTX or LEF.

Study details: Findings are from an analysis of 1,671 patients with RA from BiobadaBrasil, a multicentric, observational study. Included patients initiated the first treatment course with a conventional synthetic-DMARD or first bDMARD/JAKi.

Disclosures: This study was funded by the Brazilian Society of Rheumatology with funds from various pharmaceutical companies marketing biological compounds. The authors declared no conflicts of interest.

Source: Bredemeier M et al. J Rheumatol. 2021 May 1. doi: 10.3899/jrheum.201248.

Key clinical point: Rheumatoid meningitis should be considered in adult patients with or without a diagnosis of rheumatoid arthritis (RA). This would help in timely diagnosis and treatment, thus improving its outcomes.

Major finding: Common clinical manifestations of rheumatoid meningitis were transient focal neurologic signs (64.28%), systemic symptoms (51.78%), episodic headaches (50.00%), and neuropsychiatric changes (47.32%). Brain imaging indicated frontal (82.69%) and parietal (77.88%) lobes as the most common lesion location. Laboratory findings included high levels of rheumatoid factor (89.71%), anticyclic citrulline peptide (89.47%), C-reactive protein (82.54%), and erythrocyte deposition rate (81.81%).

Study details: Findings are from a meta-analysis of 103 studies involving 130 cases of rheumatoid meningitis. RA was diagnosed previously in 83% of cases, whereas the remaining 17% of patients were diagnosed with RA during or after the first diagnosis of rheumatoid meningitis.

Disclosures: No outside funding was provided for this study. The authors did not report any conflicts of interest.

Source: Villa E et al. Eur J Neurol. 2021 May 9. doi: 10.1111/ene.14904.

Key clinical point: Rheumatoid meningitis should be considered in adult patients with or without a diagnosis of rheumatoid arthritis (RA). This would help in timely diagnosis and treatment, thus improving its outcomes.

Major finding: Common clinical manifestations of rheumatoid meningitis were transient focal neurologic signs (64.28%), systemic symptoms (51.78%), episodic headaches (50.00%), and neuropsychiatric changes (47.32%). Brain imaging indicated frontal (82.69%) and parietal (77.88%) lobes as the most common lesion location. Laboratory findings included high levels of rheumatoid factor (89.71%), anticyclic citrulline peptide (89.47%), C-reactive protein (82.54%), and erythrocyte deposition rate (81.81%).

Study details: Findings are from a meta-analysis of 103 studies involving 130 cases of rheumatoid meningitis. RA was diagnosed previously in 83% of cases, whereas the remaining 17% of patients were diagnosed with RA during or after the first diagnosis of rheumatoid meningitis.

Disclosures: No outside funding was provided for this study. The authors did not report any conflicts of interest.

Source: Villa E et al. Eur J Neurol. 2021 May 9. doi: 10.1111/ene.14904.

Key clinical point: Rheumatoid meningitis should be considered in adult patients with or without a diagnosis of rheumatoid arthritis (RA). This would help in timely diagnosis and treatment, thus improving its outcomes.

Major finding: Common clinical manifestations of rheumatoid meningitis were transient focal neurologic signs (64.28%), systemic symptoms (51.78%), episodic headaches (50.00%), and neuropsychiatric changes (47.32%). Brain imaging indicated frontal (82.69%) and parietal (77.88%) lobes as the most common lesion location. Laboratory findings included high levels of rheumatoid factor (89.71%), anticyclic citrulline peptide (89.47%), C-reactive protein (82.54%), and erythrocyte deposition rate (81.81%).

Study details: Findings are from a meta-analysis of 103 studies involving 130 cases of rheumatoid meningitis. RA was diagnosed previously in 83% of cases, whereas the remaining 17% of patients were diagnosed with RA during or after the first diagnosis of rheumatoid meningitis.

Disclosures: No outside funding was provided for this study. The authors did not report any conflicts of interest.

Source: Villa E et al. Eur J Neurol. 2021 May 9. doi: 10.1111/ene.14904.

Key clinical point: A recent large cohort of patients with early rheumatoid arthritis (RA) revealed favorable 10-year outcomes, significantly better than the outcomes observed in a previous cohort of patients studied in 1993.

Major finding: At 10 years, disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate remission, DAS28 sustained remission, and drug-free remission were achieved by 52.4%, 40.1%, and 14.1% of patients, respectively. Half of the patients did not have a serious functional disability. Mortality rates were lower than that in the 1993 cohort (4.5% vs. 11.0%) and similar to that in the general population.

Study details: The data come from an analysis of 521 patients from the ESPOIR cohort who were diagnosed with early arthritis between 2003 and 2005 with a probable or certain diagnosis of RA and had never been prescribed disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This work was supported by the Merck Sharp and Dohme, INSERM, French Society of Rheumatology, AbbVie, Pfizer, Lilly, Fresenius, and Galapagos. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Combe B et al. Rheumatology (Oxford). 2021 May 7. doi: 10.1093/rheumatology/keab398.

Key clinical point: A recent large cohort of patients with early rheumatoid arthritis (RA) revealed favorable 10-year outcomes, significantly better than the outcomes observed in a previous cohort of patients studied in 1993.

Major finding: At 10 years, disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate remission, DAS28 sustained remission, and drug-free remission were achieved by 52.4%, 40.1%, and 14.1% of patients, respectively. Half of the patients did not have a serious functional disability. Mortality rates were lower than that in the 1993 cohort (4.5% vs. 11.0%) and similar to that in the general population.

Study details: The data come from an analysis of 521 patients from the ESPOIR cohort who were diagnosed with early arthritis between 2003 and 2005 with a probable or certain diagnosis of RA and had never been prescribed disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This work was supported by the Merck Sharp and Dohme, INSERM, French Society of Rheumatology, AbbVie, Pfizer, Lilly, Fresenius, and Galapagos. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Combe B et al. Rheumatology (Oxford). 2021 May 7. doi: 10.1093/rheumatology/keab398.

Key clinical point: A recent large cohort of patients with early rheumatoid arthritis (RA) revealed favorable 10-year outcomes, significantly better than the outcomes observed in a previous cohort of patients studied in 1993.

Major finding: At 10 years, disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate remission, DAS28 sustained remission, and drug-free remission were achieved by 52.4%, 40.1%, and 14.1% of patients, respectively. Half of the patients did not have a serious functional disability. Mortality rates were lower than that in the 1993 cohort (4.5% vs. 11.0%) and similar to that in the general population.

Study details: The data come from an analysis of 521 patients from the ESPOIR cohort who were diagnosed with early arthritis between 2003 and 2005 with a probable or certain diagnosis of RA and had never been prescribed disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This work was supported by the Merck Sharp and Dohme, INSERM, French Society of Rheumatology, AbbVie, Pfizer, Lilly, Fresenius, and Galapagos. The authors including the lead author reported receiving grants, consulting fees, speaker fees, and/or honoraria from various sources.

Source: Combe B et al. Rheumatology (Oxford). 2021 May 7. doi: 10.1093/rheumatology/keab398.

Key clinical point: Tofacitinib vs. tocilizumab was more likely to induce and maintain improvement in clinical disease activity index (CDAI) and remission during the first 12 months of therapy in biological disease-modifying antirheumatic drugs (bDMARD)-naïve patients with methotrexate-refractory rheumatoid arthritis (RA).

Major finding: Likelihood of achieving and maintaining 85% or more (adjusted odds ratio [aOR], 3.88; P less than .001), 70% or more (aOR, 2.89; P = .003) improvement in CDAI, and remission (aOR, 3.31; P less than .001) in the first 12 months was higher with tofacitinib vs. tocilizumab in bDMARD-naïve patients but not in patients with previous bDMARD failure.

Study details: This was a multicenter cohort study of 464 patients with methotrexate-refractory RA who had high to moderate CDAI and initiated treatment with tofacitinib (n=247) or tocilizumab (n=217).

Disclosures: This study was supported by research funds from the National Hospital Organization, Japan. The authors including the leading author reported receiving lecture fees from various sources.

Source: Mori S et al. RMD Open. 2021 May 6. doi: 10.1136/rmdopen-2021-001601.

Key clinical point: Tofacitinib vs. tocilizumab was more likely to induce and maintain improvement in clinical disease activity index (CDAI) and remission during the first 12 months of therapy in biological disease-modifying antirheumatic drugs (bDMARD)-naïve patients with methotrexate-refractory rheumatoid arthritis (RA).

Major finding: Likelihood of achieving and maintaining 85% or more (adjusted odds ratio [aOR], 3.88; P less than .001), 70% or more (aOR, 2.89; P = .003) improvement in CDAI, and remission (aOR, 3.31; P less than .001) in the first 12 months was higher with tofacitinib vs. tocilizumab in bDMARD-naïve patients but not in patients with previous bDMARD failure.

Study details: This was a multicenter cohort study of 464 patients with methotrexate-refractory RA who had high to moderate CDAI and initiated treatment with tofacitinib (n=247) or tocilizumab (n=217).

Disclosures: This study was supported by research funds from the National Hospital Organization, Japan. The authors including the leading author reported receiving lecture fees from various sources.

Source: Mori S et al. RMD Open. 2021 May 6. doi: 10.1136/rmdopen-2021-001601.

Key clinical point: Tofacitinib vs. tocilizumab was more likely to induce and maintain improvement in clinical disease activity index (CDAI) and remission during the first 12 months of therapy in biological disease-modifying antirheumatic drugs (bDMARD)-naïve patients with methotrexate-refractory rheumatoid arthritis (RA).

Major finding: Likelihood of achieving and maintaining 85% or more (adjusted odds ratio [aOR], 3.88; P less than .001), 70% or more (aOR, 2.89; P = .003) improvement in CDAI, and remission (aOR, 3.31; P less than .001) in the first 12 months was higher with tofacitinib vs. tocilizumab in bDMARD-naïve patients but not in patients with previous bDMARD failure.

Study details: This was a multicenter cohort study of 464 patients with methotrexate-refractory RA who had high to moderate CDAI and initiated treatment with tofacitinib (n=247) or tocilizumab (n=217).

Disclosures: This study was supported by research funds from the National Hospital Organization, Japan. The authors including the leading author reported receiving lecture fees from various sources.

Source: Mori S et al. RMD Open. 2021 May 6. doi: 10.1136/rmdopen-2021-001601.

Key clinical point: A 3-dose regimen of intravenous tranexamic acid (IV-TXA) was more effective than a single dose in reducing postoperative blood loss in patients with rheumatoid arthritis (RA) who underwent primary unilateral total knee arthroplasty (TKA).

Major finding: Decrease in total blood loss (P = .038), hidden blood loss (P = .036), and maximum hemoglobin drop (P less than .001) was significantly lower with 3 vs. a single dose of postoperative IV-TXA. Additionally, levels of D-dimer on postoperative day 1 were significantly lower with 3 vs. a single dose of IV-TXA (P less than .001). Incidences of thromboembolic events were similar between groups.

Study details: This was a single-center, randomized controlled trial of 104 patients who underwent primary unilateral TKA for RA and were randomly allocated to receive either a single dose of IV-TXA (1 g; n=52) 3 hours postoperatively or 3 doses of IV-TXA (1 g; n=52) 3, 6, and 12 hours postoperatively.

Disclosures: This study was supported by the Foundation of Health and Family planning Commission of Shanghai, China. The authors declared no conflicts of interest.

Source: Kang BX et al. BMC Musculoskelet Disord. 2021 May 7. doi: 10.1186/s12891-021-04307-4.

Key clinical point: A 3-dose regimen of intravenous tranexamic acid (IV-TXA) was more effective than a single dose in reducing postoperative blood loss in patients with rheumatoid arthritis (RA) who underwent primary unilateral total knee arthroplasty (TKA).

Major finding: Decrease in total blood loss (P = .038), hidden blood loss (P = .036), and maximum hemoglobin drop (P less than .001) was significantly lower with 3 vs. a single dose of postoperative IV-TXA. Additionally, levels of D-dimer on postoperative day 1 were significantly lower with 3 vs. a single dose of IV-TXA (P less than .001). Incidences of thromboembolic events were similar between groups.

Study details: This was a single-center, randomized controlled trial of 104 patients who underwent primary unilateral TKA for RA and were randomly allocated to receive either a single dose of IV-TXA (1 g; n=52) 3 hours postoperatively or 3 doses of IV-TXA (1 g; n=52) 3, 6, and 12 hours postoperatively.

Disclosures: This study was supported by the Foundation of Health and Family planning Commission of Shanghai, China. The authors declared no conflicts of interest.

Source: Kang BX et al. BMC Musculoskelet Disord. 2021 May 7. doi: 10.1186/s12891-021-04307-4.

Key clinical point: A 3-dose regimen of intravenous tranexamic acid (IV-TXA) was more effective than a single dose in reducing postoperative blood loss in patients with rheumatoid arthritis (RA) who underwent primary unilateral total knee arthroplasty (TKA).

Major finding: Decrease in total blood loss (P = .038), hidden blood loss (P = .036), and maximum hemoglobin drop (P less than .001) was significantly lower with 3 vs. a single dose of postoperative IV-TXA. Additionally, levels of D-dimer on postoperative day 1 were significantly lower with 3 vs. a single dose of IV-TXA (P less than .001). Incidences of thromboembolic events were similar between groups.

Study details: This was a single-center, randomized controlled trial of 104 patients who underwent primary unilateral TKA for RA and were randomly allocated to receive either a single dose of IV-TXA (1 g; n=52) 3 hours postoperatively or 3 doses of IV-TXA (1 g; n=52) 3, 6, and 12 hours postoperatively.

Disclosures: This study was supported by the Foundation of Health and Family planning Commission of Shanghai, China. The authors declared no conflicts of interest.

Source: Kang BX et al. BMC Musculoskelet Disord. 2021 May 7. doi: 10.1186/s12891-021-04307-4.

Key clinical point: Treatment with the half dose vs. stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was associated with increased rates of flares over 12 months in patients with rheumatoid arthritis (RA) in remission.

Major finding: At 12 months, the proportion of patients with at least 1 flare was significantly higher with half-dose vs. stable-dose csDMARDs (25% vs. 6%; risk difference, 18%; P = .003), thereby not meeting the noninferiority criterion of a 20% difference. There were 54 vs. 75 adverse events in the half-dose vs. stable-dose group.

Study details: Findings are from ARCTIC REWIND, a 36-month noninferiority trial of 160 patients with RA in remission for 12 months who were receiving stable csDMARDs. Patients were randomly allocated to either half-dose (n=80) or stable-dose (n=80) csDMARDs.

Disclosures: ARCTIC REWIND study was funded by the Research Council of Norway and South-Eastern Norway Regional Health Authority. The authors including the lead author reported receiving grants, personal fees, and nonfinancial support from various sources.

Source: Lillegraven S et al. JAMA. 2021 May 4. doi: 10.1001/jama.2021.4542.

Key clinical point: Treatment with the half dose vs. stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was associated with increased rates of flares over 12 months in patients with rheumatoid arthritis (RA) in remission.

Major finding: At 12 months, the proportion of patients with at least 1 flare was significantly higher with half-dose vs. stable-dose csDMARDs (25% vs. 6%; risk difference, 18%; P = .003), thereby not meeting the noninferiority criterion of a 20% difference. There were 54 vs. 75 adverse events in the half-dose vs. stable-dose group.

Study details: Findings are from ARCTIC REWIND, a 36-month noninferiority trial of 160 patients with RA in remission for 12 months who were receiving stable csDMARDs. Patients were randomly allocated to either half-dose (n=80) or stable-dose (n=80) csDMARDs.

Disclosures: ARCTIC REWIND study was funded by the Research Council of Norway and South-Eastern Norway Regional Health Authority. The authors including the lead author reported receiving grants, personal fees, and nonfinancial support from various sources.

Source: Lillegraven S et al. JAMA. 2021 May 4. doi: 10.1001/jama.2021.4542.

Key clinical point: Treatment with the half dose vs. stable dose of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was associated with increased rates of flares over 12 months in patients with rheumatoid arthritis (RA) in remission.

Major finding: At 12 months, the proportion of patients with at least 1 flare was significantly higher with half-dose vs. stable-dose csDMARDs (25% vs. 6%; risk difference, 18%; P = .003), thereby not meeting the noninferiority criterion of a 20% difference. There were 54 vs. 75 adverse events in the half-dose vs. stable-dose group.

Study details: Findings are from ARCTIC REWIND, a 36-month noninferiority trial of 160 patients with RA in remission for 12 months who were receiving stable csDMARDs. Patients were randomly allocated to either half-dose (n=80) or stable-dose (n=80) csDMARDs.

Disclosures: ARCTIC REWIND study was funded by the Research Council of Norway and South-Eastern Norway Regional Health Authority. The authors including the lead author reported receiving grants, personal fees, and nonfinancial support from various sources.

Source: Lillegraven S et al. JAMA. 2021 May 4. doi: 10.1001/jama.2021.4542.

In patients with rheumatoid arthritis, exposure to air pollution is associated with both elevated levels of C-reactive protein (CRP) and increased risk of arthritis flares, according to a novel longitudinal study presented at the annual European Congress of Rheumatology.

The data revealed “a striking association between air pollution and increased CRP levels and risk of an arthritis flare,” reported first author Giovanni Adami, MD, DSc, of the rheumatology unit at the University of Verona (Italy).

The excess risk of elevated CRP and flares began “at very low levels of exposure, even those below commonly used thresholds for risk to human health,” he added.
 

Study details

Researchers collected data on 888 patients with RA from numerous patient visits in the context of more than 13,000 air pollution records. The CRP levels and RA flares were evaluated in the context of air pollution monitoring that is performed on a daily basis at several sites in the city of Verona where the study was conducted. Verona is an industrial city in northern Italy that has high but variable levels of air pollution based on factory activity and weather conditions.

Patients with RA who provided clinical data for this study were matched by their proximity to specific air pollution monitoring sites. By linking CRP levels and disease activity to air pollution levels over multiple follow-up visits, the design allowed the RA study participants “to serve as their own controls,” Dr. Adami explained.

At each patient visit during the study, CRP levels were measured and disease activity assessed. Patients were considered to have elevated CRP when levels were 5 mg/L or higher. The presence of an RA flare was defined by a 1.2-point increase or more in 28-joint Disease Activity Score using CRP (DAS28-CRP).

Both the CRP level and the presence or absence of a flare were evaluated in relationship to the patient’s specific local air pollution levels in the prior 60 days.

Increased levels of CRP, a surrogate for inflammatory activity, and increased disease activity, were both associated with elevated exposure to air pollutants prior to an office visit. These associations remained statistically significant when evaluated by specific air pollutants such as carbon monoxide (CO), nitrogen oxides (NO₂, NO), small particulate matter (PM10; particles ≤ 10 mcm), and ozone (O₃).

The relationship between increased exposure to air pollution contaminants and elevated CRP was supported by a dose effect. In the case of PM10, for example, the odds ratio of having elevated CRP was increased by only about 25% (OR, 1.25) when mean levels were 30 mcg/m³ or lower in the period prior to the office visit. This rose incrementally for higher mean levels of PM10, reaching 70% (OR, 1.70) for levels > 50 mcg/m³.

The researchers detected statistically significant differences in mean and area-under-the curve (AUC) values of most air pollutants in the 60 days prior to office visits when patients had a flare versus when disease activity was low. For example, the difference in mean and AUC levels in the period prior to a flare relative to a period with low disease activity was significant for CO (P = .001 for both) and NO and NO₂ (P = .003 for both), and O₃ (P = .002 and P = .001, respectively). For PM10, P values were .011 and .005, respectively.

“Remarkably, we found that the cumulative exposure to NO₂ in the 60 days preceding a flare was approximately 500 mcg/m³ higher than the low disease activity visit, an exposure that equates to approximately 200 passively smoked cigarettes,” Dr. Adami reported.
 

Trying to confirm causality of association

Dr. Adami’s study is not the first study to link air pollution to risk of RA. Several have suggested that air pollution is a risk factor for developing joint disease, but a recently published study conducted in Kuwait associated greater disease activity with NO₂ and another air pollutant, sulfur dioxide (SO₂), although not CO, PM10, or O₃.

A coauthor of that study, which evaluated pollution in regard to disease activity on DAS score, Adeeba Al-Herz, MD, a rheumatology consultant at Al-Amiri Hospital, Kuwait City, said in an interview, “We proved the correlation between them but not the causality.”

However, she believes that this is an important area of inquiry.

“We are working now on another paper in which we studied a causal relationship between the two, meaning that we are evaluating whether SO₂ and NO₂ trigger RA activity,” Dr. Al-Herz said. That study is now complete, and the manuscript is being written.

The magnitude of the association in these two studies suggest that there might be a clinical message if causality can be confirmed, according to Dr. Adami. Although there are many reasons to seek to reduce and avoid air pollution, these data suggest risk of a proinflammatory state might be one of them.

Dr. Adami believes that the evidence of an adverse effect on patients with RA is strong.

“In order to reduce the burden of RA, public and environmental health policy makers should aim to diminish gaseous and particulate matter emissions to a larger extent than currently recommended,” he said.

In an interview after his presentation, Dr. Adami suggested that the risk of an inflammatory response and increases in arthritis flares from air pollution is not surprising. Previous studies have linked cigarette smoking to both.

“The mechanisms underlying the development of inflammation are very similar. Indeed, the toxic components contained in cigarette smoking are largely shared with diesel exhaust and fossil fuel combustion,” he said.

Although causality between air pollution and arthritis flares cannot be confirmed in these data, a basis for suspecting a causal relationship is supported by “plenty of in vitro and animal studies,” according to Dr. Adami.

On the basis of these studies, several mechanisms have been postulated.

“As an example, exposure to air pollution can promote the activation of the bronchus-associated lymphoid tissue (BALT), which can trigger the activation of the transcription factor nuclear factor-kappaB,” he said. This, in turn, can “lead to the secretion of proinflammatory cytokines, such as tumor necrosis factor–alpha and interleukin-1.”

Another theory is that posttranslational modification of proteins in the lung, a process called citrullination, “can lead to production of autoantibodies known to have a pathogenic role in RA,” he added.

Proving a causal relationship, however, is difficult.

“We certainly cannot conduct a randomized clinical trial on that and voluntarily expose some patients to pollution. Thus, we need to rely on observational data,” Dr. Adami said.

Of strategies being considered to generate evidence of a causal relationship between pollution and the exacerbation of RA, “we certainly will try to study those patients that move from a highly polluted area to a greener zone and vice versa,” he said. This will allow us “to explore what happens when the exposure to pollution changes dramatically in a short period of time.”

In the meantime, “given what is known to date, I would certainly advise my RA patients to avoid exposure to air pollution,” Dr. Adami said. He acknowledged there is no proof that this will help patients to reduce the risk of flares, but there are already many good reasons to minimize exposure to air pollution.

Dr. Adami and Dr. Al-Herz report no potential conflicts of interest.

In patients with rheumatoid arthritis, exposure to air pollution is associated with both elevated levels of C-reactive protein (CRP) and increased risk of arthritis flares, according to a novel longitudinal study presented at the annual European Congress of Rheumatology.

The data revealed “a striking association between air pollution and increased CRP levels and risk of an arthritis flare,” reported first author Giovanni Adami, MD, DSc, of the rheumatology unit at the University of Verona (Italy).

The excess risk of elevated CRP and flares began “at very low levels of exposure, even those below commonly used thresholds for risk to human health,” he added.
 

Study details

Researchers collected data on 888 patients with RA from numerous patient visits in the context of more than 13,000 air pollution records. The CRP levels and RA flares were evaluated in the context of air pollution monitoring that is performed on a daily basis at several sites in the city of Verona where the study was conducted. Verona is an industrial city in northern Italy that has high but variable levels of air pollution based on factory activity and weather conditions.

Patients with RA who provided clinical data for this study were matched by their proximity to specific air pollution monitoring sites. By linking CRP levels and disease activity to air pollution levels over multiple follow-up visits, the design allowed the RA study participants “to serve as their own controls,” Dr. Adami explained.

At each patient visit during the study, CRP levels were measured and disease activity assessed. Patients were considered to have elevated CRP when levels were 5 mg/L or higher. The presence of an RA flare was defined by a 1.2-point increase or more in 28-joint Disease Activity Score using CRP (DAS28-CRP).

Both the CRP level and the presence or absence of a flare were evaluated in relationship to the patient’s specific local air pollution levels in the prior 60 days.

Increased levels of CRP, a surrogate for inflammatory activity, and increased disease activity, were both associated with elevated exposure to air pollutants prior to an office visit. These associations remained statistically significant when evaluated by specific air pollutants such as carbon monoxide (CO), nitrogen oxides (NO₂, NO), small particulate matter (PM10; particles ≤ 10 mcm), and ozone (O₃).

The relationship between increased exposure to air pollution contaminants and elevated CRP was supported by a dose effect. In the case of PM10, for example, the odds ratio of having elevated CRP was increased by only about 25% (OR, 1.25) when mean levels were 30 mcg/m³ or lower in the period prior to the office visit. This rose incrementally for higher mean levels of PM10, reaching 70% (OR, 1.70) for levels > 50 mcg/m³.

The researchers detected statistically significant differences in mean and area-under-the curve (AUC) values of most air pollutants in the 60 days prior to office visits when patients had a flare versus when disease activity was low. For example, the difference in mean and AUC levels in the period prior to a flare relative to a period with low disease activity was significant for CO (P = .001 for both) and NO and NO₂ (P = .003 for both), and O₃ (P = .002 and P = .001, respectively). For PM10, P values were .011 and .005, respectively.

“Remarkably, we found that the cumulative exposure to NO₂ in the 60 days preceding a flare was approximately 500 mcg/m³ higher than the low disease activity visit, an exposure that equates to approximately 200 passively smoked cigarettes,” Dr. Adami reported.
 

Trying to confirm causality of association

Dr. Adami’s study is not the first study to link air pollution to risk of RA. Several have suggested that air pollution is a risk factor for developing joint disease, but a recently published study conducted in Kuwait associated greater disease activity with NO₂ and another air pollutant, sulfur dioxide (SO₂), although not CO, PM10, or O₃.

A coauthor of that study, which evaluated pollution in regard to disease activity on DAS score, Adeeba Al-Herz, MD, a rheumatology consultant at Al-Amiri Hospital, Kuwait City, said in an interview, “We proved the correlation between them but not the causality.”

However, she believes that this is an important area of inquiry.

“We are working now on another paper in which we studied a causal relationship between the two, meaning that we are evaluating whether SO₂ and NO₂ trigger RA activity,” Dr. Al-Herz said. That study is now complete, and the manuscript is being written.

The magnitude of the association in these two studies suggest that there might be a clinical message if causality can be confirmed, according to Dr. Adami. Although there are many reasons to seek to reduce and avoid air pollution, these data suggest risk of a proinflammatory state might be one of them.

Dr. Adami believes that the evidence of an adverse effect on patients with RA is strong.

“In order to reduce the burden of RA, public and environmental health policy makers should aim to diminish gaseous and particulate matter emissions to a larger extent than currently recommended,” he said.

In an interview after his presentation, Dr. Adami suggested that the risk of an inflammatory response and increases in arthritis flares from air pollution is not surprising. Previous studies have linked cigarette smoking to both.

“The mechanisms underlying the development of inflammation are very similar. Indeed, the toxic components contained in cigarette smoking are largely shared with diesel exhaust and fossil fuel combustion,” he said.

Although causality between air pollution and arthritis flares cannot be confirmed in these data, a basis for suspecting a causal relationship is supported by “plenty of in vitro and animal studies,” according to Dr. Adami.

On the basis of these studies, several mechanisms have been postulated.

“As an example, exposure to air pollution can promote the activation of the bronchus-associated lymphoid tissue (BALT), which can trigger the activation of the transcription factor nuclear factor-kappaB,” he said. This, in turn, can “lead to the secretion of proinflammatory cytokines, such as tumor necrosis factor–alpha and interleukin-1.”

Another theory is that posttranslational modification of proteins in the lung, a process called citrullination, “can lead to production of autoantibodies known to have a pathogenic role in RA,” he added.

Proving a causal relationship, however, is difficult.

“We certainly cannot conduct a randomized clinical trial on that and voluntarily expose some patients to pollution. Thus, we need to rely on observational data,” Dr. Adami said.

Of strategies being considered to generate evidence of a causal relationship between pollution and the exacerbation of RA, “we certainly will try to study those patients that move from a highly polluted area to a greener zone and vice versa,” he said. This will allow us “to explore what happens when the exposure to pollution changes dramatically in a short period of time.”

In the meantime, “given what is known to date, I would certainly advise my RA patients to avoid exposure to air pollution,” Dr. Adami said. He acknowledged there is no proof that this will help patients to reduce the risk of flares, but there are already many good reasons to minimize exposure to air pollution.

Dr. Adami and Dr. Al-Herz report no potential conflicts of interest.

In patients with rheumatoid arthritis, exposure to air pollution is associated with both elevated levels of C-reactive protein (CRP) and increased risk of arthritis flares, according to a novel longitudinal study presented at the annual European Congress of Rheumatology.

The data revealed “a striking association between air pollution and increased CRP levels and risk of an arthritis flare,” reported first author Giovanni Adami, MD, DSc, of the rheumatology unit at the University of Verona (Italy).

The excess risk of elevated CRP and flares began “at very low levels of exposure, even those below commonly used thresholds for risk to human health,” he added.
 

Study details

Researchers collected data on 888 patients with RA from numerous patient visits in the context of more than 13,000 air pollution records. The CRP levels and RA flares were evaluated in the context of air pollution monitoring that is performed on a daily basis at several sites in the city of Verona where the study was conducted. Verona is an industrial city in northern Italy that has high but variable levels of air pollution based on factory activity and weather conditions.

Patients with RA who provided clinical data for this study were matched by their proximity to specific air pollution monitoring sites. By linking CRP levels and disease activity to air pollution levels over multiple follow-up visits, the design allowed the RA study participants “to serve as their own controls,” Dr. Adami explained.

At each patient visit during the study, CRP levels were measured and disease activity assessed. Patients were considered to have elevated CRP when levels were 5 mg/L or higher. The presence of an RA flare was defined by a 1.2-point increase or more in 28-joint Disease Activity Score using CRP (DAS28-CRP).

Both the CRP level and the presence or absence of a flare were evaluated in relationship to the patient’s specific local air pollution levels in the prior 60 days.

Increased levels of CRP, a surrogate for inflammatory activity, and increased disease activity, were both associated with elevated exposure to air pollutants prior to an office visit. These associations remained statistically significant when evaluated by specific air pollutants such as carbon monoxide (CO), nitrogen oxides (NO₂, NO), small particulate matter (PM10; particles ≤ 10 mcm), and ozone (O₃).

The relationship between increased exposure to air pollution contaminants and elevated CRP was supported by a dose effect. In the case of PM10, for example, the odds ratio of having elevated CRP was increased by only about 25% (OR, 1.25) when mean levels were 30 mcg/m³ or lower in the period prior to the office visit. This rose incrementally for higher mean levels of PM10, reaching 70% (OR, 1.70) for levels > 50 mcg/m³.

The researchers detected statistically significant differences in mean and area-under-the curve (AUC) values of most air pollutants in the 60 days prior to office visits when patients had a flare versus when disease activity was low. For example, the difference in mean and AUC levels in the period prior to a flare relative to a period with low disease activity was significant for CO (P = .001 for both) and NO and NO₂ (P = .003 for both), and O₃ (P = .002 and P = .001, respectively). For PM10, P values were .011 and .005, respectively.

“Remarkably, we found that the cumulative exposure to NO₂ in the 60 days preceding a flare was approximately 500 mcg/m³ higher than the low disease activity visit, an exposure that equates to approximately 200 passively smoked cigarettes,” Dr. Adami reported.
 

Trying to confirm causality of association

Dr. Adami’s study is not the first study to link air pollution to risk of RA. Several have suggested that air pollution is a risk factor for developing joint disease, but a recently published study conducted in Kuwait associated greater disease activity with NO₂ and another air pollutant, sulfur dioxide (SO₂), although not CO, PM10, or O₃.

A coauthor of that study, which evaluated pollution in regard to disease activity on DAS score, Adeeba Al-Herz, MD, a rheumatology consultant at Al-Amiri Hospital, Kuwait City, said in an interview, “We proved the correlation between them but not the causality.”

However, she believes that this is an important area of inquiry.

“We are working now on another paper in which we studied a causal relationship between the two, meaning that we are evaluating whether SO₂ and NO₂ trigger RA activity,” Dr. Al-Herz said. That study is now complete, and the manuscript is being written.

The magnitude of the association in these two studies suggest that there might be a clinical message if causality can be confirmed, according to Dr. Adami. Although there are many reasons to seek to reduce and avoid air pollution, these data suggest risk of a proinflammatory state might be one of them.

Dr. Adami believes that the evidence of an adverse effect on patients with RA is strong.

“In order to reduce the burden of RA, public and environmental health policy makers should aim to diminish gaseous and particulate matter emissions to a larger extent than currently recommended,” he said.

In an interview after his presentation, Dr. Adami suggested that the risk of an inflammatory response and increases in arthritis flares from air pollution is not surprising. Previous studies have linked cigarette smoking to both.

“The mechanisms underlying the development of inflammation are very similar. Indeed, the toxic components contained in cigarette smoking are largely shared with diesel exhaust and fossil fuel combustion,” he said.

Although causality between air pollution and arthritis flares cannot be confirmed in these data, a basis for suspecting a causal relationship is supported by “plenty of in vitro and animal studies,” according to Dr. Adami.

On the basis of these studies, several mechanisms have been postulated.

“As an example, exposure to air pollution can promote the activation of the bronchus-associated lymphoid tissue (BALT), which can trigger the activation of the transcription factor nuclear factor-kappaB,” he said. This, in turn, can “lead to the secretion of proinflammatory cytokines, such as tumor necrosis factor–alpha and interleukin-1.”

Another theory is that posttranslational modification of proteins in the lung, a process called citrullination, “can lead to production of autoantibodies known to have a pathogenic role in RA,” he added.

Proving a causal relationship, however, is difficult.

“We certainly cannot conduct a randomized clinical trial on that and voluntarily expose some patients to pollution. Thus, we need to rely on observational data,” Dr. Adami said.

Of strategies being considered to generate evidence of a causal relationship between pollution and the exacerbation of RA, “we certainly will try to study those patients that move from a highly polluted area to a greener zone and vice versa,” he said. This will allow us “to explore what happens when the exposure to pollution changes dramatically in a short period of time.”

In the meantime, “given what is known to date, I would certainly advise my RA patients to avoid exposure to air pollution,” Dr. Adami said. He acknowledged there is no proof that this will help patients to reduce the risk of flares, but there are already many good reasons to minimize exposure to air pollution.

Dr. Adami and Dr. Al-Herz report no potential conflicts of interest.

Patients with rheumatoid arthritis who were using rituximab at the time of COVID-19 onset had a fourfold higher risk of being hospitalized, needing mechanical ventilation, or dying, compared with patients taking a tumor necrosis factor inhibitor (TNFi), according to a report given at the annual European Congress of Rheumatology.

The use of Janus kinase inhibitors (JAKi) also was associated with a twofold higher risk for these COVID-19 outcomes, said Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, in presenting the analysis from the COVID-19 Global Rheumatology Alliance (GRA) Physician Registry.

“The strong association of rituximab and JAK inhibitor use with poor COVID-19 outcomes highlights the prioritization of risk mitigation strategies for these patients,” Dr. Sparks said at the meeting.

The full findings have now been published in Annals of the Rheumatic Diseases.
 

JAKi association questioned

These findings provide “an important understanding for the risk of our patients in times before vaccination,” said Hendrik Schulze-Koops, MD, of Ludwig Maximilian University of Munich, who chaired the session in which the study was presented.

However, “recently, baricitinib was licensed to prevent particular aspects of severe COVID. What’s the explanation for this discrepancy?” he asked.

“Certainly, the JAK inhibitor finding deserves further study,” Dr. Sparks acknowledged, adding that the data were analyzed by class rather than for individual drugs.

“One possible explanation could be when JAK inhibitors are used,” he suggested. “It might be different for patients who [have been] just infected – that might have different biologic effects – as opposed to choosing to treat patients right when there’s a hyperinflammatory cascade, or there’s oxygen need.”

Regarding the JAK inhibitor finding, Ronald van Vollenhoven, MD, PhD, of the University of Amsterdam, pointed out during the online Q&A that “JAKi have a very short half-life compared to biologics.”

Dr. van Vollenhoven asked: “Could the practice of stopping these drugs upon COVID infection have a negative impact on the course?” To which Dr. Sparks responded: “The different half-life of drugs would be a promising avenue to look at, to see whether increases in disease activity might have imparted some of the effects we saw.”
 

Performing the analysis

As of April 12, 2021, the GRA Physician Registry contained the records of more than 15,000 patients. Dr. Sparks, collaborator Zachary Wallace, MD, of Massachusetts General Hospital, Boston, and associates limited their analysis to 2,869 patients with RA who had been treated with either a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) at the time they were diagnosed with COVID-19.

“We wanted to limit it to a single disease and also limit it to drugs that are considered for that disease,” Dr. Sparks explained in an interview.

“Because patients with rheumatoid arthritis are often treated sequentially, we wanted to further limit the analysis to patients who were on advanced therapies so that they were at a similar disease state, and also had the opportunity to receive advanced therapies.”

This approach hopefully minimizes the possibility of confounding by indication, Dr. Sparks said.

Most of the patients included in the analysis had received a TNFi (n = 1,388), and they were used as the control arm of the analysis. Outcomes associated with treatment with the other b/tsDMARDs, which included abatacept (n = 237), rituximab (n = 364), interleukin-6 inhibitors (IL-6i; n = 317), and JAKi (n = 563), were then compared with TNFi.

Baseline characteristics of patients were broadly similar across the groups. The mean age was 56.7 years and 80.8% of the study population was female. There were a few expected differences among users of rituximab versus TNFi, notably a higher percentage of patients with interstitial lung disease (11% vs. 1.4% of TNFi users) or cancer (7.4% vs. 0.9%) among patients treated with rituximab since it is commonly used in these patients, Dr. Sparks said.

“We did perform a sensitivity analysis where we restricted the population to not having ILD or cancer and we actually found really similar findings,” he added.

Four COVID-19 outcomes assessed

The researchers used a four-point ordinal scale modeled after one set by the World Health Organization to assess four COVID-19 outcomes: not hospitalized, hospitalized without oxygenation, hospitalized with oxygenation or ventilation, and death.

Odds ratios (ORs) comparing rituximab to TNFi for these four COVID-19 outcomes were a respective 4.53, 2.87, 4.05, and 4.57. The ORs for JAKi versus TNFi were a respective 2.4, 1.55, 2.03, and 2.04.

“We found no consistent associations of abatacept or interleukin-6 inhibitors with COVID-19 severity, compared to TNF inhibitors,” which is reassuring, Dr. Sparks said.

ORs for the four COVID-19 outcomes with abatacept were a respective 1.18, 1.12, 1.41, and 1.46, and for IL-6i were 0.84, 0.72, 0.75, and 1.13.

Rituximab use in patients with RA who develop COVID-19

So, should rituximab be stopped in patients with RA if they develop COVID-19? “This is an important question and one that would be decided on a case-by-case basis,” Dr. Sparks said. “Of course, the drug has a very long half-life, so risk mitigation strategies are still of utmost importance,” he added.

“I think everyone’s a bit reticent to want to start rituximab in this environment, but it might also make me pause about starting a JAK inhibitor,” Dr. Sparks added. “Given that this is a first finding, I’m not sure I would necessarily change patients who are doing well on these medications. I think what it really makes me want to do is to try to obviously vaccinate the patients on JAK inhibitors as they do have a short half-life.”

More observational studies would be helpful, Dr. Sparks said, adding that “the most pressing need is to try to figure out how to protect our patients with rituximab.”

The COVID-19 Global Rheumatology Alliance Physician Registry is supported by the American College of Rheumatology and the European Alliance of Associations for Rheumatology. Dr. Sparks disclosed serving as a consultant for Bristol Myers Squibb, Gilead, Inova, Optum, and Pfizer for work unrelated to this study. Dr. Wallace disclosed receiving grant support from Bristol Myers Squibb and Principia/Sanofi and serving as a consultant for Viela Bio and Medpace for work unrelated to this study.

Patients with rheumatoid arthritis who were using rituximab at the time of COVID-19 onset had a fourfold higher risk of being hospitalized, needing mechanical ventilation, or dying, compared with patients taking a tumor necrosis factor inhibitor (TNFi), according to a report given at the annual European Congress of Rheumatology.

The use of Janus kinase inhibitors (JAKi) also was associated with a twofold higher risk for these COVID-19 outcomes, said Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, in presenting the analysis from the COVID-19 Global Rheumatology Alliance (GRA) Physician Registry.

“The strong association of rituximab and JAK inhibitor use with poor COVID-19 outcomes highlights the prioritization of risk mitigation strategies for these patients,” Dr. Sparks said at the meeting.

The full findings have now been published in Annals of the Rheumatic Diseases.
 

JAKi association questioned

These findings provide “an important understanding for the risk of our patients in times before vaccination,” said Hendrik Schulze-Koops, MD, of Ludwig Maximilian University of Munich, who chaired the session in which the study was presented.

However, “recently, baricitinib was licensed to prevent particular aspects of severe COVID. What’s the explanation for this discrepancy?” he asked.

“Certainly, the JAK inhibitor finding deserves further study,” Dr. Sparks acknowledged, adding that the data were analyzed by class rather than for individual drugs.

“One possible explanation could be when JAK inhibitors are used,” he suggested. “It might be different for patients who [have been] just infected – that might have different biologic effects – as opposed to choosing to treat patients right when there’s a hyperinflammatory cascade, or there’s oxygen need.”

Regarding the JAK inhibitor finding, Ronald van Vollenhoven, MD, PhD, of the University of Amsterdam, pointed out during the online Q&A that “JAKi have a very short half-life compared to biologics.”

Dr. van Vollenhoven asked: “Could the practice of stopping these drugs upon COVID infection have a negative impact on the course?” To which Dr. Sparks responded: “The different half-life of drugs would be a promising avenue to look at, to see whether increases in disease activity might have imparted some of the effects we saw.”
 

Performing the analysis

As of April 12, 2021, the GRA Physician Registry contained the records of more than 15,000 patients. Dr. Sparks, collaborator Zachary Wallace, MD, of Massachusetts General Hospital, Boston, and associates limited their analysis to 2,869 patients with RA who had been treated with either a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) at the time they were diagnosed with COVID-19.

“We wanted to limit it to a single disease and also limit it to drugs that are considered for that disease,” Dr. Sparks explained in an interview.

“Because patients with rheumatoid arthritis are often treated sequentially, we wanted to further limit the analysis to patients who were on advanced therapies so that they were at a similar disease state, and also had the opportunity to receive advanced therapies.”

This approach hopefully minimizes the possibility of confounding by indication, Dr. Sparks said.

Most of the patients included in the analysis had received a TNFi (n = 1,388), and they were used as the control arm of the analysis. Outcomes associated with treatment with the other b/tsDMARDs, which included abatacept (n = 237), rituximab (n = 364), interleukin-6 inhibitors (IL-6i; n = 317), and JAKi (n = 563), were then compared with TNFi.

Baseline characteristics of patients were broadly similar across the groups. The mean age was 56.7 years and 80.8% of the study population was female. There were a few expected differences among users of rituximab versus TNFi, notably a higher percentage of patients with interstitial lung disease (11% vs. 1.4% of TNFi users) or cancer (7.4% vs. 0.9%) among patients treated with rituximab since it is commonly used in these patients, Dr. Sparks said.

“We did perform a sensitivity analysis where we restricted the population to not having ILD or cancer and we actually found really similar findings,” he added.

Four COVID-19 outcomes assessed

The researchers used a four-point ordinal scale modeled after one set by the World Health Organization to assess four COVID-19 outcomes: not hospitalized, hospitalized without oxygenation, hospitalized with oxygenation or ventilation, and death.

Odds ratios (ORs) comparing rituximab to TNFi for these four COVID-19 outcomes were a respective 4.53, 2.87, 4.05, and 4.57. The ORs for JAKi versus TNFi were a respective 2.4, 1.55, 2.03, and 2.04.

“We found no consistent associations of abatacept or interleukin-6 inhibitors with COVID-19 severity, compared to TNF inhibitors,” which is reassuring, Dr. Sparks said.

ORs for the four COVID-19 outcomes with abatacept were a respective 1.18, 1.12, 1.41, and 1.46, and for IL-6i were 0.84, 0.72, 0.75, and 1.13.

Rituximab use in patients with RA who develop COVID-19

So, should rituximab be stopped in patients with RA if they develop COVID-19? “This is an important question and one that would be decided on a case-by-case basis,” Dr. Sparks said. “Of course, the drug has a very long half-life, so risk mitigation strategies are still of utmost importance,” he added.

“I think everyone’s a bit reticent to want to start rituximab in this environment, but it might also make me pause about starting a JAK inhibitor,” Dr. Sparks added. “Given that this is a first finding, I’m not sure I would necessarily change patients who are doing well on these medications. I think what it really makes me want to do is to try to obviously vaccinate the patients on JAK inhibitors as they do have a short half-life.”

More observational studies would be helpful, Dr. Sparks said, adding that “the most pressing need is to try to figure out how to protect our patients with rituximab.”

The COVID-19 Global Rheumatology Alliance Physician Registry is supported by the American College of Rheumatology and the European Alliance of Associations for Rheumatology. Dr. Sparks disclosed serving as a consultant for Bristol Myers Squibb, Gilead, Inova, Optum, and Pfizer for work unrelated to this study. Dr. Wallace disclosed receiving grant support from Bristol Myers Squibb and Principia/Sanofi and serving as a consultant for Viela Bio and Medpace for work unrelated to this study.

Patients with rheumatoid arthritis who were using rituximab at the time of COVID-19 onset had a fourfold higher risk of being hospitalized, needing mechanical ventilation, or dying, compared with patients taking a tumor necrosis factor inhibitor (TNFi), according to a report given at the annual European Congress of Rheumatology.

The use of Janus kinase inhibitors (JAKi) also was associated with a twofold higher risk for these COVID-19 outcomes, said Jeffrey A. Sparks, MD, of Brigham and Women’s Hospital and Harvard Medical School, Boston, in presenting the analysis from the COVID-19 Global Rheumatology Alliance (GRA) Physician Registry.

“The strong association of rituximab and JAK inhibitor use with poor COVID-19 outcomes highlights the prioritization of risk mitigation strategies for these patients,” Dr. Sparks said at the meeting.

The full findings have now been published in Annals of the Rheumatic Diseases.
 

JAKi association questioned

These findings provide “an important understanding for the risk of our patients in times before vaccination,” said Hendrik Schulze-Koops, MD, of Ludwig Maximilian University of Munich, who chaired the session in which the study was presented.

However, “recently, baricitinib was licensed to prevent particular aspects of severe COVID. What’s the explanation for this discrepancy?” he asked.

“Certainly, the JAK inhibitor finding deserves further study,” Dr. Sparks acknowledged, adding that the data were analyzed by class rather than for individual drugs.

“One possible explanation could be when JAK inhibitors are used,” he suggested. “It might be different for patients who [have been] just infected – that might have different biologic effects – as opposed to choosing to treat patients right when there’s a hyperinflammatory cascade, or there’s oxygen need.”

Regarding the JAK inhibitor finding, Ronald van Vollenhoven, MD, PhD, of the University of Amsterdam, pointed out during the online Q&A that “JAKi have a very short half-life compared to biologics.”

Dr. van Vollenhoven asked: “Could the practice of stopping these drugs upon COVID infection have a negative impact on the course?” To which Dr. Sparks responded: “The different half-life of drugs would be a promising avenue to look at, to see whether increases in disease activity might have imparted some of the effects we saw.”
 

Performing the analysis

As of April 12, 2021, the GRA Physician Registry contained the records of more than 15,000 patients. Dr. Sparks, collaborator Zachary Wallace, MD, of Massachusetts General Hospital, Boston, and associates limited their analysis to 2,869 patients with RA who had been treated with either a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) at the time they were diagnosed with COVID-19.

“We wanted to limit it to a single disease and also limit it to drugs that are considered for that disease,” Dr. Sparks explained in an interview.

“Because patients with rheumatoid arthritis are often treated sequentially, we wanted to further limit the analysis to patients who were on advanced therapies so that they were at a similar disease state, and also had the opportunity to receive advanced therapies.”

This approach hopefully minimizes the possibility of confounding by indication, Dr. Sparks said.

Most of the patients included in the analysis had received a TNFi (n = 1,388), and they were used as the control arm of the analysis. Outcomes associated with treatment with the other b/tsDMARDs, which included abatacept (n = 237), rituximab (n = 364), interleukin-6 inhibitors (IL-6i; n = 317), and JAKi (n = 563), were then compared with TNFi.

Baseline characteristics of patients were broadly similar across the groups. The mean age was 56.7 years and 80.8% of the study population was female. There were a few expected differences among users of rituximab versus TNFi, notably a higher percentage of patients with interstitial lung disease (11% vs. 1.4% of TNFi users) or cancer (7.4% vs. 0.9%) among patients treated with rituximab since it is commonly used in these patients, Dr. Sparks said.

“We did perform a sensitivity analysis where we restricted the population to not having ILD or cancer and we actually found really similar findings,” he added.

Four COVID-19 outcomes assessed

The researchers used a four-point ordinal scale modeled after one set by the World Health Organization to assess four COVID-19 outcomes: not hospitalized, hospitalized without oxygenation, hospitalized with oxygenation or ventilation, and death.

Odds ratios (ORs) comparing rituximab to TNFi for these four COVID-19 outcomes were a respective 4.53, 2.87, 4.05, and 4.57. The ORs for JAKi versus TNFi were a respective 2.4, 1.55, 2.03, and 2.04.

“We found no consistent associations of abatacept or interleukin-6 inhibitors with COVID-19 severity, compared to TNF inhibitors,” which is reassuring, Dr. Sparks said.

ORs for the four COVID-19 outcomes with abatacept were a respective 1.18, 1.12, 1.41, and 1.46, and for IL-6i were 0.84, 0.72, 0.75, and 1.13.

Rituximab use in patients with RA who develop COVID-19

So, should rituximab be stopped in patients with RA if they develop COVID-19? “This is an important question and one that would be decided on a case-by-case basis,” Dr. Sparks said. “Of course, the drug has a very long half-life, so risk mitigation strategies are still of utmost importance,” he added.

“I think everyone’s a bit reticent to want to start rituximab in this environment, but it might also make me pause about starting a JAK inhibitor,” Dr. Sparks added. “Given that this is a first finding, I’m not sure I would necessarily change patients who are doing well on these medications. I think what it really makes me want to do is to try to obviously vaccinate the patients on JAK inhibitors as they do have a short half-life.”

More observational studies would be helpful, Dr. Sparks said, adding that “the most pressing need is to try to figure out how to protect our patients with rituximab.”

The COVID-19 Global Rheumatology Alliance Physician Registry is supported by the American College of Rheumatology and the European Alliance of Associations for Rheumatology. Dr. Sparks disclosed serving as a consultant for Bristol Myers Squibb, Gilead, Inova, Optum, and Pfizer for work unrelated to this study. Dr. Wallace disclosed receiving grant support from Bristol Myers Squibb and Principia/Sanofi and serving as a consultant for Viela Bio and Medpace for work unrelated to this study.

Secondhand smoke exposure in both childhood and adulthood is associated with an increased risk of rheumatoid arthritis in women, according to a study presented at the annual European Congress of Rheumatology.

“These results suggest that smoking by-products, whether actively or passively inhaled or absorbed, could generate autoimmunity, at least towards antigens involved in rheumatoid arthritis pathogenesis,” said Yann Nguyen, MD, MPH, of the center for research in epidemiology and population health at the University of Paris-Saclay in Villejuif and of Beaujon Hospital at the University of Paris in Clichy, France.

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

Secondhand smoke exposure in both childhood and adulthood is associated with an increased risk of rheumatoid arthritis in women, according to a study presented at the annual European Congress of Rheumatology.

“These results suggest that smoking by-products, whether actively or passively inhaled or absorbed, could generate autoimmunity, at least towards antigens involved in rheumatoid arthritis pathogenesis,” said Yann Nguyen, MD, MPH, of the center for research in epidemiology and population health at the University of Paris-Saclay in Villejuif and of Beaujon Hospital at the University of Paris in Clichy, France.

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

Secondhand smoke exposure in both childhood and adulthood is associated with an increased risk of rheumatoid arthritis in women, according to a study presented at the annual European Congress of Rheumatology.

“These results suggest that smoking by-products, whether actively or passively inhaled or absorbed, could generate autoimmunity, at least towards antigens involved in rheumatoid arthritis pathogenesis,” said Yann Nguyen, MD, MPH, of the center for research in epidemiology and population health at the University of Paris-Saclay in Villejuif and of Beaujon Hospital at the University of Paris in Clichy, France.

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