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Prior bariatric surgery associated with better in-hospital outcomes in patients with RA
Key clinical point: Hospitalized patients with rheumatoid arthritis (RA) with vs without prior bariatric surgery were less likely to have in-hospital deaths, major morbidities, unfavorable discharges, and prolonged length of stay (LOS).
Major finding: Patients with vs without prior bariatric surgery were at a reduced risk for any morbidity (adjusted odds ratio [aOR] 0.45; 95% CI 0.42-0.48), in-hospital mortality (aOR 0.41; 95% CI 0.27-0.61), unfavorable discharge (aOR 0.48; 95% CI 0.44-0.53), and prolonged LOS (aOR 0.43; 95% CI 0.39-0.46).
Study details: This population-based, retrospective study included 33,075 hospitalized patients with morbid obesity and RA, of which 6615 patients with prior bariatric surgery were propensity-score matched with 26,460 patients without prior bariatric surgery.
Disclosures: This study did not declare any source of funding. The authors declared no conflicts of interest.
Source: Lin I-C and Liu H. Impact of bariatric surgery on outcomes of patients with rheumatoid arthritis: A propensity score–matched analysis of US nationwide inpatient sample, 2005–2018. Obes Surg. 2022 (Jun 29). Doi: 10.1007/s11695-022-06177-8
Key clinical point: Hospitalized patients with rheumatoid arthritis (RA) with vs without prior bariatric surgery were less likely to have in-hospital deaths, major morbidities, unfavorable discharges, and prolonged length of stay (LOS).
Major finding: Patients with vs without prior bariatric surgery were at a reduced risk for any morbidity (adjusted odds ratio [aOR] 0.45; 95% CI 0.42-0.48), in-hospital mortality (aOR 0.41; 95% CI 0.27-0.61), unfavorable discharge (aOR 0.48; 95% CI 0.44-0.53), and prolonged LOS (aOR 0.43; 95% CI 0.39-0.46).
Study details: This population-based, retrospective study included 33,075 hospitalized patients with morbid obesity and RA, of which 6615 patients with prior bariatric surgery were propensity-score matched with 26,460 patients without prior bariatric surgery.
Disclosures: This study did not declare any source of funding. The authors declared no conflicts of interest.
Source: Lin I-C and Liu H. Impact of bariatric surgery on outcomes of patients with rheumatoid arthritis: A propensity score–matched analysis of US nationwide inpatient sample, 2005–2018. Obes Surg. 2022 (Jun 29). Doi: 10.1007/s11695-022-06177-8
Key clinical point: Hospitalized patients with rheumatoid arthritis (RA) with vs without prior bariatric surgery were less likely to have in-hospital deaths, major morbidities, unfavorable discharges, and prolonged length of stay (LOS).
Major finding: Patients with vs without prior bariatric surgery were at a reduced risk for any morbidity (adjusted odds ratio [aOR] 0.45; 95% CI 0.42-0.48), in-hospital mortality (aOR 0.41; 95% CI 0.27-0.61), unfavorable discharge (aOR 0.48; 95% CI 0.44-0.53), and prolonged LOS (aOR 0.43; 95% CI 0.39-0.46).
Study details: This population-based, retrospective study included 33,075 hospitalized patients with morbid obesity and RA, of which 6615 patients with prior bariatric surgery were propensity-score matched with 26,460 patients without prior bariatric surgery.
Disclosures: This study did not declare any source of funding. The authors declared no conflicts of interest.
Source: Lin I-C and Liu H. Impact of bariatric surgery on outcomes of patients with rheumatoid arthritis: A propensity score–matched analysis of US nationwide inpatient sample, 2005–2018. Obes Surg. 2022 (Jun 29). Doi: 10.1007/s11695-022-06177-8
Sarcopenia and poor balance increase risk for vertebral spinal osteoporotic fracture in women with RA
Key clinical point: Sarcopenia and poor balance were associated with a higher risk for vertebral spinal osteoporotic fracture (VOPF), disease activity, and joint structure damage in women with rheumatoid arthritis (RA).
Major finding: Women with vs without RA had a significantly higher incidence of sarcopenia (60.0% vs 11.1%; P < .0001), poor balance (44.1% vs 7.9%; P < .0001), and VOPF (21% vs 3.2%; P < .0001). Among women with RA, those with vs without VOPF had a significantly higher incidence of sarcopenia (75.6% vs 55.8%; P < .0001) and poor balance (68.3% vs 37.7%; P < .0001) and those with vs without sarcopenia and poor balance had a higher disease activity, more serious joint damage, and worse joint function (all P < .05).
Study details: This study included 195 women with RA and 126 age- and sex-matched healthy individuals.
Disclosures: This study did not declare any source of funding. The authors declared no competing interests.
Source: Zhang M et al. Effect of sarcopenia and poor balance on vertebral spinal osteoporotic fracture in female rheumatoid arthritis. Sci Rep. 2022;12:9477 (Jun 8). Doi: 10.1038/s41598-022-13339-2
Key clinical point: Sarcopenia and poor balance were associated with a higher risk for vertebral spinal osteoporotic fracture (VOPF), disease activity, and joint structure damage in women with rheumatoid arthritis (RA).
Major finding: Women with vs without RA had a significantly higher incidence of sarcopenia (60.0% vs 11.1%; P < .0001), poor balance (44.1% vs 7.9%; P < .0001), and VOPF (21% vs 3.2%; P < .0001). Among women with RA, those with vs without VOPF had a significantly higher incidence of sarcopenia (75.6% vs 55.8%; P < .0001) and poor balance (68.3% vs 37.7%; P < .0001) and those with vs without sarcopenia and poor balance had a higher disease activity, more serious joint damage, and worse joint function (all P < .05).
Study details: This study included 195 women with RA and 126 age- and sex-matched healthy individuals.
Disclosures: This study did not declare any source of funding. The authors declared no competing interests.
Source: Zhang M et al. Effect of sarcopenia and poor balance on vertebral spinal osteoporotic fracture in female rheumatoid arthritis. Sci Rep. 2022;12:9477 (Jun 8). Doi: 10.1038/s41598-022-13339-2
Key clinical point: Sarcopenia and poor balance were associated with a higher risk for vertebral spinal osteoporotic fracture (VOPF), disease activity, and joint structure damage in women with rheumatoid arthritis (RA).
Major finding: Women with vs without RA had a significantly higher incidence of sarcopenia (60.0% vs 11.1%; P < .0001), poor balance (44.1% vs 7.9%; P < .0001), and VOPF (21% vs 3.2%; P < .0001). Among women with RA, those with vs without VOPF had a significantly higher incidence of sarcopenia (75.6% vs 55.8%; P < .0001) and poor balance (68.3% vs 37.7%; P < .0001) and those with vs without sarcopenia and poor balance had a higher disease activity, more serious joint damage, and worse joint function (all P < .05).
Study details: This study included 195 women with RA and 126 age- and sex-matched healthy individuals.
Disclosures: This study did not declare any source of funding. The authors declared no competing interests.
Source: Zhang M et al. Effect of sarcopenia and poor balance on vertebral spinal osteoporotic fracture in female rheumatoid arthritis. Sci Rep. 2022;12:9477 (Jun 8). Doi: 10.1038/s41598-022-13339-2
RA: Rapid improvements in patient-reported outcomes with upadacitinib vs abatacept
Key clinical point: Upadacitinib vs abatacept treatment resulted in rapid and greater improvements in patient-reported physical function, pain, and overall health in patients with moderate-to-severe rheumatoid arthritis (RA) and an inadequate response to biologic disease modifying antirheumatic drugs (bDMARDs-IR).
Major finding: At 12 weeks, a higher proportion of patients receiving upadacitinib vs abatacept reported clinically meaningful improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI; 74% vs 64%; P < .05), with significant improvements in patient-assessed disease activity (least-squares mean change [LSMC] −33.9 vs −28.4), pain (LSMC −35.3 vs −30.0), HAQ-DI (LSMC −0.65 vs −0.48), and EQ-5D-5L index (LSMC 0.26 vs 0.21; all P < .05) scores.
Study details: Findings are from a post hoc analysis of the SELECT-CHOICE phase 3 trial including 612 patients with moderate-to-severe RA and bDMARDs-IR patients who were randomly assigned to receive upadacitinib or abatacept with concomitant conventional synthetic disease modifying antirheumatic drugs.
Disclosures: This study was funded by AbbVie Inc. Six authors declared being current or former employees or stockholders of AbbVie or a company receiving consulting fees from AbbVie. The other authors reported ties with AbbVie and various sources.
Source: Bergman M et al. Patient-reported outcomes of upadacitinib versus abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs: 12- and 24-week results of a phase 3 trial. Arthritis Res Ther. 2022;24:15 (Jun 24). Doi: 10.1186/s13075-022-02813-x
Key clinical point: Upadacitinib vs abatacept treatment resulted in rapid and greater improvements in patient-reported physical function, pain, and overall health in patients with moderate-to-severe rheumatoid arthritis (RA) and an inadequate response to biologic disease modifying antirheumatic drugs (bDMARDs-IR).
Major finding: At 12 weeks, a higher proportion of patients receiving upadacitinib vs abatacept reported clinically meaningful improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI; 74% vs 64%; P < .05), with significant improvements in patient-assessed disease activity (least-squares mean change [LSMC] −33.9 vs −28.4), pain (LSMC −35.3 vs −30.0), HAQ-DI (LSMC −0.65 vs −0.48), and EQ-5D-5L index (LSMC 0.26 vs 0.21; all P < .05) scores.
Study details: Findings are from a post hoc analysis of the SELECT-CHOICE phase 3 trial including 612 patients with moderate-to-severe RA and bDMARDs-IR patients who were randomly assigned to receive upadacitinib or abatacept with concomitant conventional synthetic disease modifying antirheumatic drugs.
Disclosures: This study was funded by AbbVie Inc. Six authors declared being current or former employees or stockholders of AbbVie or a company receiving consulting fees from AbbVie. The other authors reported ties with AbbVie and various sources.
Source: Bergman M et al. Patient-reported outcomes of upadacitinib versus abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs: 12- and 24-week results of a phase 3 trial. Arthritis Res Ther. 2022;24:15 (Jun 24). Doi: 10.1186/s13075-022-02813-x
Key clinical point: Upadacitinib vs abatacept treatment resulted in rapid and greater improvements in patient-reported physical function, pain, and overall health in patients with moderate-to-severe rheumatoid arthritis (RA) and an inadequate response to biologic disease modifying antirheumatic drugs (bDMARDs-IR).
Major finding: At 12 weeks, a higher proportion of patients receiving upadacitinib vs abatacept reported clinically meaningful improvements in the Health Assessment Questionnaire Disability Index (HAQ-DI; 74% vs 64%; P < .05), with significant improvements in patient-assessed disease activity (least-squares mean change [LSMC] −33.9 vs −28.4), pain (LSMC −35.3 vs −30.0), HAQ-DI (LSMC −0.65 vs −0.48), and EQ-5D-5L index (LSMC 0.26 vs 0.21; all P < .05) scores.
Study details: Findings are from a post hoc analysis of the SELECT-CHOICE phase 3 trial including 612 patients with moderate-to-severe RA and bDMARDs-IR patients who were randomly assigned to receive upadacitinib or abatacept with concomitant conventional synthetic disease modifying antirheumatic drugs.
Disclosures: This study was funded by AbbVie Inc. Six authors declared being current or former employees or stockholders of AbbVie or a company receiving consulting fees from AbbVie. The other authors reported ties with AbbVie and various sources.
Source: Bergman M et al. Patient-reported outcomes of upadacitinib versus abatacept in patients with rheumatoid arthritis and an inadequate response to biologic disease-modifying antirheumatic drugs: 12- and 24-week results of a phase 3 trial. Arthritis Res Ther. 2022;24:15 (Jun 24). Doi: 10.1186/s13075-022-02813-x
RA: Ozoralizumab shows promise in patients with inadequate response to methotrexate
Key clinical point: Ozoralizumab at a dose of 30 or 80 mg significantly improved clinical outcomes compared to placebo and was well tolerated with no new safety signals in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate therapy.
Major finding: A significantly higher proportion of patients receiving 30/80 mg ozoralizumab vs placebo achieved ≥ 20% improvement in American College of Rheumatology criteria (79.6%/75.3% vs 37.3%; P < .001) at 16 weeks and had structural damage nonprogression (73.0%/73.4% vs 56.0%; P < .01) at 24 weeks. No new adverse events were reported.
Study details: The data come from the phase 2/3 OHZORA trial including 381 patients with active RA and an inadequate response to methotrexate who were randomly assigned to receive ozoralizumab (30 or 80 mg) or placebo in combination with methotrexate for 24 weeks.
Disclosures: This trial was sponsored by Taisho Pharmaceutical Co., Ltd. Three authors reported being employees of Taisho Pharmaceutical. Several authors reported receiving grants, consulting fees, or speaking fees from various sources.
Source: Takeuchi T et al. Phase II/III results of the anti-TNF multivalent NANOBODY® compound ‘ozoralizumab’ in patient with rheumatoid arthritis (OHZORA trial). Arthritis Rheumatol. 2022 Jun 21. doi: 10.1002/art.42273.
Key clinical point: Ozoralizumab at a dose of 30 or 80 mg significantly improved clinical outcomes compared to placebo and was well tolerated with no new safety signals in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate therapy.
Major finding: A significantly higher proportion of patients receiving 30/80 mg ozoralizumab vs placebo achieved ≥ 20% improvement in American College of Rheumatology criteria (79.6%/75.3% vs 37.3%; P < .001) at 16 weeks and had structural damage nonprogression (73.0%/73.4% vs 56.0%; P < .01) at 24 weeks. No new adverse events were reported.
Study details: The data come from the phase 2/3 OHZORA trial including 381 patients with active RA and an inadequate response to methotrexate who were randomly assigned to receive ozoralizumab (30 or 80 mg) or placebo in combination with methotrexate for 24 weeks.
Disclosures: This trial was sponsored by Taisho Pharmaceutical Co., Ltd. Three authors reported being employees of Taisho Pharmaceutical. Several authors reported receiving grants, consulting fees, or speaking fees from various sources.
Source: Takeuchi T et al. Phase II/III results of the anti-TNF multivalent NANOBODY® compound ‘ozoralizumab’ in patient with rheumatoid arthritis (OHZORA trial). Arthritis Rheumatol. 2022 Jun 21. doi: 10.1002/art.42273.
Key clinical point: Ozoralizumab at a dose of 30 or 80 mg significantly improved clinical outcomes compared to placebo and was well tolerated with no new safety signals in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate therapy.
Major finding: A significantly higher proportion of patients receiving 30/80 mg ozoralizumab vs placebo achieved ≥ 20% improvement in American College of Rheumatology criteria (79.6%/75.3% vs 37.3%; P < .001) at 16 weeks and had structural damage nonprogression (73.0%/73.4% vs 56.0%; P < .01) at 24 weeks. No new adverse events were reported.
Study details: The data come from the phase 2/3 OHZORA trial including 381 patients with active RA and an inadequate response to methotrexate who were randomly assigned to receive ozoralizumab (30 or 80 mg) or placebo in combination with methotrexate for 24 weeks.
Disclosures: This trial was sponsored by Taisho Pharmaceutical Co., Ltd. Three authors reported being employees of Taisho Pharmaceutical. Several authors reported receiving grants, consulting fees, or speaking fees from various sources.
Source: Takeuchi T et al. Phase II/III results of the anti-TNF multivalent NANOBODY® compound ‘ozoralizumab’ in patient with rheumatoid arthritis (OHZORA trial). Arthritis Rheumatol. 2022 Jun 21. doi: 10.1002/art.42273.
Real-world efficacy and safety of second-line therapies for RA
Key clinical point: The drug discontinuation and 1-year response rates of Janus kinase inhibitors (JAKi), interleukin-6 inhibitors (IL-6i), and abatacept as second-line therapies for rheumatoid arthritis (RA) appeared to be similar to those of tumor necrosis factor-inhibitors (TNFi). However, JAKi and IL-6i were more often discontinued for adverse events and less for ineffectiveness.
Major finding: Compared with TNFi, the 1-year response rate and treatment retention were not significantly different for abatacept, IL-6i, and JAKi, but IL6-i (adjusted hazard ratio [aHR] 0.76; 95% CI 0.67-0.85) and JAKi (aHR 0.75; 95% CI 0.67-0.83) were less frequently discontinued because of inefficacy and often because of adverse events.
Study details: This study evaluated data of 31,846 treatment courses (TNFi: n = 17,522; abatacept: n = 2775; IL-6i: n = 3863; and JAKi: n = 7686) from 19 registers.
Disclosures: The registers were supported by Fundacion Española de Reumatología, the Spanish Medicines and Health Products Agency, and other sources. Several authors reported receiving personal or speaking fees, grants, or honoraria, or serving on speaker’s bureaus for various sources.
Source: Lauper K et al. Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the ‘JAK-pot’ collaboration. Ann Rheum Dis. 2022 (Jun 15. Doi: 10.1136/annrheumdis-2022-222586
Key clinical point: The drug discontinuation and 1-year response rates of Janus kinase inhibitors (JAKi), interleukin-6 inhibitors (IL-6i), and abatacept as second-line therapies for rheumatoid arthritis (RA) appeared to be similar to those of tumor necrosis factor-inhibitors (TNFi). However, JAKi and IL-6i were more often discontinued for adverse events and less for ineffectiveness.
Major finding: Compared with TNFi, the 1-year response rate and treatment retention were not significantly different for abatacept, IL-6i, and JAKi, but IL6-i (adjusted hazard ratio [aHR] 0.76; 95% CI 0.67-0.85) and JAKi (aHR 0.75; 95% CI 0.67-0.83) were less frequently discontinued because of inefficacy and often because of adverse events.
Study details: This study evaluated data of 31,846 treatment courses (TNFi: n = 17,522; abatacept: n = 2775; IL-6i: n = 3863; and JAKi: n = 7686) from 19 registers.
Disclosures: The registers were supported by Fundacion Española de Reumatología, the Spanish Medicines and Health Products Agency, and other sources. Several authors reported receiving personal or speaking fees, grants, or honoraria, or serving on speaker’s bureaus for various sources.
Source: Lauper K et al. Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the ‘JAK-pot’ collaboration. Ann Rheum Dis. 2022 (Jun 15. Doi: 10.1136/annrheumdis-2022-222586
Key clinical point: The drug discontinuation and 1-year response rates of Janus kinase inhibitors (JAKi), interleukin-6 inhibitors (IL-6i), and abatacept as second-line therapies for rheumatoid arthritis (RA) appeared to be similar to those of tumor necrosis factor-inhibitors (TNFi). However, JAKi and IL-6i were more often discontinued for adverse events and less for ineffectiveness.
Major finding: Compared with TNFi, the 1-year response rate and treatment retention were not significantly different for abatacept, IL-6i, and JAKi, but IL6-i (adjusted hazard ratio [aHR] 0.76; 95% CI 0.67-0.85) and JAKi (aHR 0.75; 95% CI 0.67-0.83) were less frequently discontinued because of inefficacy and often because of adverse events.
Study details: This study evaluated data of 31,846 treatment courses (TNFi: n = 17,522; abatacept: n = 2775; IL-6i: n = 3863; and JAKi: n = 7686) from 19 registers.
Disclosures: The registers were supported by Fundacion Española de Reumatología, the Spanish Medicines and Health Products Agency, and other sources. Several authors reported receiving personal or speaking fees, grants, or honoraria, or serving on speaker’s bureaus for various sources.
Source: Lauper K et al. Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the ‘JAK-pot’ collaboration. Ann Rheum Dis. 2022 (Jun 15. Doi: 10.1136/annrheumdis-2022-222586
Higher prevalence of CPPD and chondrocalcinosis in seronegative than seropositive RA
Key clinical point: Calcium pyrophosphate deposition disease (CPPD) and chondrocalcinosis are more prevalent in seronegative vs seropositive rheumatoid arthritis (RA), and the symmetry of arthritis and the acuteness of attack best differentiate CPDD and RA.
Major finding: CPPD (84.9% vs 15.1%) and chondrocalcinosis (32.3% vs 16.6%; P < .001) were more prevalent in seronegative vs seropositive RA, with acute attacks being more frequent in CPDD (67.9%) than seronegative (28.2%) or seropositive (25.9%; P < .001) RA and symmetric arthritis being more prevalent in RA than CPDD (P = .007).
Study details: This was a retrospective cross-sectional study including 503 patients, of which 262 had RA (142 seropositive, 120 seronegative), 181 had CPPD, 30 had gout, and 30 had polymyalgia rheumatica.
Disclosures: This study did not declare any specific source of funding. No competing interests were declared.
Source: Krekeler M et al. High prevalence of chondrocalcinosis and frequent comorbidity with calcium pyrophosphate deposition disease in patients with seronegative rheumatoid arthritis. RMD Open. 2022;8:e002383 (Jun 14). Doi: 10.1136/rmdopen-2022-002383
Key clinical point: Calcium pyrophosphate deposition disease (CPPD) and chondrocalcinosis are more prevalent in seronegative vs seropositive rheumatoid arthritis (RA), and the symmetry of arthritis and the acuteness of attack best differentiate CPDD and RA.
Major finding: CPPD (84.9% vs 15.1%) and chondrocalcinosis (32.3% vs 16.6%; P < .001) were more prevalent in seronegative vs seropositive RA, with acute attacks being more frequent in CPDD (67.9%) than seronegative (28.2%) or seropositive (25.9%; P < .001) RA and symmetric arthritis being more prevalent in RA than CPDD (P = .007).
Study details: This was a retrospective cross-sectional study including 503 patients, of which 262 had RA (142 seropositive, 120 seronegative), 181 had CPPD, 30 had gout, and 30 had polymyalgia rheumatica.
Disclosures: This study did not declare any specific source of funding. No competing interests were declared.
Source: Krekeler M et al. High prevalence of chondrocalcinosis and frequent comorbidity with calcium pyrophosphate deposition disease in patients with seronegative rheumatoid arthritis. RMD Open. 2022;8:e002383 (Jun 14). Doi: 10.1136/rmdopen-2022-002383
Key clinical point: Calcium pyrophosphate deposition disease (CPPD) and chondrocalcinosis are more prevalent in seronegative vs seropositive rheumatoid arthritis (RA), and the symmetry of arthritis and the acuteness of attack best differentiate CPDD and RA.
Major finding: CPPD (84.9% vs 15.1%) and chondrocalcinosis (32.3% vs 16.6%; P < .001) were more prevalent in seronegative vs seropositive RA, with acute attacks being more frequent in CPDD (67.9%) than seronegative (28.2%) or seropositive (25.9%; P < .001) RA and symmetric arthritis being more prevalent in RA than CPDD (P = .007).
Study details: This was a retrospective cross-sectional study including 503 patients, of which 262 had RA (142 seropositive, 120 seronegative), 181 had CPPD, 30 had gout, and 30 had polymyalgia rheumatica.
Disclosures: This study did not declare any specific source of funding. No competing interests were declared.
Source: Krekeler M et al. High prevalence of chondrocalcinosis and frequent comorbidity with calcium pyrophosphate deposition disease in patients with seronegative rheumatoid arthritis. RMD Open. 2022;8:e002383 (Jun 14). Doi: 10.1136/rmdopen-2022-002383
Menopausal status and use of sex hormones influence remission in female patients with RA
Key clinical point: Female reproductive status influences the likelihood of achieving rheumatoid arthritis (RA) remission, with odds being higher in the premenopausal vs perimenopausal status and with the use of exogenous sex hormones.
Major finding: Female patients in perimenopause vs premenopause were less likely to achieve remission (adjusted hazard ratio [aHR] 0.78; 95% CI 0.61-0.99). The use of exogenous sex hormones was significantly associated with a higher likelihood of achieving remission (aHR 1.20; P = .038).
Study details: This study pooled individual patient data from 5 phase 3 trials and evaluated 4455 female patients with moderate-to-severe active RA and varying menopausal status and exogenous sex hormone use who were randomly assigned to receive tocilizumab or conventional synthetic disease-modifying antirheumatic drugs.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Daraghmeh DN et al. Female reproductive status and exogenous sex hormone use in rheumatoid arthritis patients treated with tocilizumab and csDMARDs. Rheumatology (Oxford). 2022 (Jun 22). Doi: 10.1093/rheumatology/keac357
Key clinical point: Female reproductive status influences the likelihood of achieving rheumatoid arthritis (RA) remission, with odds being higher in the premenopausal vs perimenopausal status and with the use of exogenous sex hormones.
Major finding: Female patients in perimenopause vs premenopause were less likely to achieve remission (adjusted hazard ratio [aHR] 0.78; 95% CI 0.61-0.99). The use of exogenous sex hormones was significantly associated with a higher likelihood of achieving remission (aHR 1.20; P = .038).
Study details: This study pooled individual patient data from 5 phase 3 trials and evaluated 4455 female patients with moderate-to-severe active RA and varying menopausal status and exogenous sex hormone use who were randomly assigned to receive tocilizumab or conventional synthetic disease-modifying antirheumatic drugs.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Daraghmeh DN et al. Female reproductive status and exogenous sex hormone use in rheumatoid arthritis patients treated with tocilizumab and csDMARDs. Rheumatology (Oxford). 2022 (Jun 22). Doi: 10.1093/rheumatology/keac357
Key clinical point: Female reproductive status influences the likelihood of achieving rheumatoid arthritis (RA) remission, with odds being higher in the premenopausal vs perimenopausal status and with the use of exogenous sex hormones.
Major finding: Female patients in perimenopause vs premenopause were less likely to achieve remission (adjusted hazard ratio [aHR] 0.78; 95% CI 0.61-0.99). The use of exogenous sex hormones was significantly associated with a higher likelihood of achieving remission (aHR 1.20; P = .038).
Study details: This study pooled individual patient data from 5 phase 3 trials and evaluated 4455 female patients with moderate-to-severe active RA and varying menopausal status and exogenous sex hormone use who were randomly assigned to receive tocilizumab or conventional synthetic disease-modifying antirheumatic drugs.
Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.
Source: Daraghmeh DN et al. Female reproductive status and exogenous sex hormone use in rheumatoid arthritis patients treated with tocilizumab and csDMARDs. Rheumatology (Oxford). 2022 (Jun 22). Doi: 10.1093/rheumatology/keac357
TNF inhibitor use for RA shows beneficial effect in pregnancy
Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.
The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.
Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.
Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
Bigger babies
The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).
The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.
“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth.
Welcomed data
This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.
“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”
The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.
A version of this article first appeared on Medscape.com.
Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.
The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.
Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.
Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
Bigger babies
The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).
The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.
“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth.
Welcomed data
This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.
“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”
The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.
A version of this article first appeared on Medscape.com.
Women with well-controlled rheumatoid arthritis who used a tumor necrosis factor (TNF) inhibitor during pregnancy gave birth to infants with higher birth weight than did other patients, without an increased risk of adverse outcomes, according to findings from a Dutch prospective cohort study published online in Annals of the Rheumatic Diseases.
The study involved 188 patients drawn from the ongoing Preconceptional Counseling in Active RA (PreCARA) study, which followed patients with inflammatory rheumatic diseases before and during pregnancy. Women enrolled in PreCARA were closely monitored and treated with a therapeutic approach that aimed to achieve minimal disease activity, which included the use of TNF inhibitors.
Much research on TNF inhibitors during pregnancy has been limited to the first trimester and focused primarily on congenital malformations. In addition, most previous studies evaluating TNF inhibitors during pregnancy involved patients with different underlying diseases, making it difficult to interpret the results.
Hieronymus T. W. Smeele, MD, and colleagues at Erasmus University Medical Center, Rotterdam, the Netherlands, evaluated participants every 3 months before pregnancy; then again in the first, second, and third trimesters; and at 6, 12, and 26 weeks post partum. At these visits, in addition to undergoing an examination of their joints, patients completed questionnaires and gave blood samples. Disease activity was determined using the Disease Activity Score in 28 joints. Twin births and diagnoses other than RA were excluded.
Bigger babies
The study found that use of TNF inhibitors during pregnancy (n = 92 women) did not increase the risk of birth defects or emergency cesarean sections. While RA is typically associated with small-for-gestational-age (SGA) birth weights, TNF inhibitors were associated with a significant increase in birth weight and fewer infants born SGA, even when the comparison was adjusted for confounders, such as disease activity. At the same time, TNF inhibitors were not associated with high birth weight or with infants who were large for gestational age (LGA).
The results showed that the effects were greatest when TNF inhibitors were used in the third trimester. However, teasing out the effects based on trimester is difficult because participants who used TNF inhibitors during the third trimester were likely to use them in the first and second trimester as well. The study’s authors pointed out that these results need to be replicated.
“The immune system is not only important in the pathogenesis of RA,” the study’s authors wrote, “but also for ensuring and maintaining a normal pregnancy.” They pointed out that many adverse outcomes of pregnancy that are thought to arise from inadequate development of the placenta, such as intrauterine growth restriction, SGA, and hypertensive disorders of pregnancy, can involve an increase in proinflammatory cytokines, such as TNF. “It is tempting to speculate that treatment with [TNF inhibitors] during pregnancy promotes placentation and thereby fetal growth and birth weight by changing the balance between proinflammatory and anti-inflammatory cytokines and by increasing the number and function of [regulatory T cells].” They also hypothesize that treatment with TNF inhibitors induces epigenetic changes in the fetus, which positively influence fetal growth.
Welcomed data
This is a well-done, interesting study that will add to the still-slim body of research on pregnancy in rheumatic diseases, Kevin Byram, MD, assistant professor of medicine in the division of rheumatology and immunology and associate director of the rheumatology training program at Vanderbilt University, Nashville, Tenn., told this news organization.
“Historically, pregnant women have been excluded from clinical trials, not just in rheumatoid arthritis, but in other rheumatic diseases, so we don’t have a lot of great data,” he said, adding that the more interesting part of the study was that it showed there was no increased risk of adverse outcomes. “I’m not sure what to make of the increased birth weight. It will be interesting to see if the hypothesis that there might be a role for this molecule in preventing low birth weight goes anywhere.”
The work was supported by the Dutch Arthritis Foundation. PreCARA is an investigator-initiated study that was financially supported by UCB. The authors declared no competing interests.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF THE RHEUMATIC DISEASES
Methotrexate’s impact on COVID-19 vaccination: New insights made
Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.
In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.
In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
Pausing methotrexate after booster
The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.
Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.
It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.
“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.
In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.
However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.
“Although this finding adds to the evidence base to support interruption of methotrexate after vaccination, a shared decision process is needed to weigh the possible benefit of optimizing protection from COVID-19 and the possible risk of underlying disease flare,” they added.
Dr. Abhishek and colleagues assessed 254 patients with immune-mediated inflammatory disease from dermatology and rheumatology clinics across 26 hospitals in the United Kingdom. Participants had been diagnosed with systemic lupus erythematosus, rheumatoid arthritis, atopic dermatitis, polymyalgia rheumatica, axial spondyloarthritis, and psoriasis without or with arthritis. They had also been taking up to 25 mg of methotrexate per week for 3 months or longer and had received two doses of either the Pfizer/BioNTech BNT162b2 vaccine or AstraZeneca/Oxford viral vector vaccine. The booster dose was most often the Pfizer BNT162b2 vaccine (82%). The patients’ mean age was 59 years, with females comprising 61% of the cohort. Participants were randomly assigned 1:1 to either group.
Investigators performing laboratory analysis were masked to cohort assignment, and clinical research staff, data analysts, participants, and researchers were unmasked.
The elevated antibody response of patients who suspended methotrexate was the same across different kinds of immune-mediated inflammatory disease, primary vaccination platform, SARS-CoV-2 infection history, and age.
Notably, no intervention-associated adverse events were reported, the study team noted.
The conclusions that could be drawn from the booster-dose study were limited by the trial’s modest cohort size, the small number of patients in exploratory subgroup analyses, a lack of information about differences in prescription drug behavior, and early termination’s effect on the researchers’ ability to identify differences between subgroups and in secondary outcomes, the authors noted.
Other limitations included a lack of generalizability to patients with active disease who couldn’t stop therapy and were not included in the investigation, and participants were not blinded to what group they were in, the researchers said.
Expert commentary
This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.
“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”
Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.
It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
Pausing methotrexate during initial COVID vaccine doses
Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.
Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.
In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.
The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).
The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).
The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.
Expert commentary: MIVAC I and II
Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.
“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.
“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.
Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth and Dr. Colmegna have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.
In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.
In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
Pausing methotrexate after booster
The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.
Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.
It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.
“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.
In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.
However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.
“Although this finding adds to the evidence base to support interruption of methotrexate after vaccination, a shared decision process is needed to weigh the possible benefit of optimizing protection from COVID-19 and the possible risk of underlying disease flare,” they added.
Dr. Abhishek and colleagues assessed 254 patients with immune-mediated inflammatory disease from dermatology and rheumatology clinics across 26 hospitals in the United Kingdom. Participants had been diagnosed with systemic lupus erythematosus, rheumatoid arthritis, atopic dermatitis, polymyalgia rheumatica, axial spondyloarthritis, and psoriasis without or with arthritis. They had also been taking up to 25 mg of methotrexate per week for 3 months or longer and had received two doses of either the Pfizer/BioNTech BNT162b2 vaccine or AstraZeneca/Oxford viral vector vaccine. The booster dose was most often the Pfizer BNT162b2 vaccine (82%). The patients’ mean age was 59 years, with females comprising 61% of the cohort. Participants were randomly assigned 1:1 to either group.
Investigators performing laboratory analysis were masked to cohort assignment, and clinical research staff, data analysts, participants, and researchers were unmasked.
The elevated antibody response of patients who suspended methotrexate was the same across different kinds of immune-mediated inflammatory disease, primary vaccination platform, SARS-CoV-2 infection history, and age.
Notably, no intervention-associated adverse events were reported, the study team noted.
The conclusions that could be drawn from the booster-dose study were limited by the trial’s modest cohort size, the small number of patients in exploratory subgroup analyses, a lack of information about differences in prescription drug behavior, and early termination’s effect on the researchers’ ability to identify differences between subgroups and in secondary outcomes, the authors noted.
Other limitations included a lack of generalizability to patients with active disease who couldn’t stop therapy and were not included in the investigation, and participants were not blinded to what group they were in, the researchers said.
Expert commentary
This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.
“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”
Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.
It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
Pausing methotrexate during initial COVID vaccine doses
Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.
Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.
In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.
The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).
The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).
The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.
Expert commentary: MIVAC I and II
Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.
“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.
“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.
Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth and Dr. Colmegna have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Patients who take methotrexate for a variety of immune-mediated inflammatory diseases and pause taking the drug following receipt of a COVID-19 vaccine dose did not have a higher risk of disease flare and had higher antireceptor binding domain (anti-RBD) antibody titers and increased immunogenicity when compared with continuing the drug, three recent studies suggest.
In one study, British researchers examined the effects of a 2-week break in methotrexate therapy on anti-RBD titers following receipt of a third COVID-19 vaccine dose. In their paper published in The Lancet: Respiratory Medicine, they reported results from a randomized, open-label, superiority trial that suggested pausing the drug improved immunogenicity, compared with no break.
In two trials presented at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, a team from India set out to determine whether holding methotrexate after receiving both doses of a COVID-19 vaccine, or holding it only after the second dose, was safe and effective. They found that pausing methotrexate only following the second dose contributed to a lower flare risk, and that patients had higher anti-RBD titers when holding methotrexate for 2 weeks following each dose.
Pausing methotrexate after booster
The 2-week methotrexate break and booster vaccine dose data in the Vaccine Response On Off Methotrexate (VROOM) trial showed that after a month, the geometric mean antispike 1 (S1)-RBD antibody titer was 10,798 U/mL (95% confidence interval [CI], 8,970-12,997) in the group that continued methotrexate and 22,750 U/mL (95% CI, 19,314-26,796) in the group that suspended methotrexate; the geometric mean ratio was 2.19 (P < .0001; mixed-effects model), reported Abhishek Abhishek, MD, PhD, professor of rheumatology at the University of Nottingham in Nottingham, England, and colleagues.
Prior research showed that stopping methotrexate therapy for 2 weeks following the seasonal influenza vaccine contributed to better vaccine immunity among patients with rheumatoid arthritis, but there was no impact of stopping the drug for up to 4 weeks before vaccination on vaccine-related immunity, the researchers noted.
It is crucial in maximizing long-lasting vaccine protection in people who are possibly susceptible through immune suppression at this point in the COVID-19 vaccination regimen, the study team noted.
“Evidence from this study will be useful for policymakers, national immunization advisory committees, and specialist societies formulating recommendations on the use of methotrexate around the time of COVID-19 vaccination. This evidence will help patients and clinicians make informed choices about the risks and benefits of interrupting methotrexate treatment around the time of COVID-19 vaccination, with implications for the potential to extend such approaches to other therapeutics,” they wrote.
In American College of Rheumatology (ACR) guidance for COVID-19 vaccination, the organization advised against using standard synthetic disease-modifying antirheumatic medicines such as methotrexate “for 1-2 weeks (as disease activity allows) after each COVID-19 vaccine dose,” given the at-risk population and public health concerns, Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine and associate physician at Brigham and Women’s Hospital and Harvard Medical School, Boston, and Sara K. Tedeschi, MD, MPH, assistant professor of medicine at Harvard Medical School, noted in an accompanying editorial in The Lancet: Respiratory Medicine.
However, when the ACR developed this statement, there was only one trial involving patients with rheumatoid arthritis who paused methotrexate following seasonal influenza vaccination, the editorialists said.
“Although this finding adds to the evidence base to support interruption of methotrexate after vaccination, a shared decision process is needed to weigh the possible benefit of optimizing protection from COVID-19 and the possible risk of underlying disease flare,” they added.
Dr. Abhishek and colleagues assessed 254 patients with immune-mediated inflammatory disease from dermatology and rheumatology clinics across 26 hospitals in the United Kingdom. Participants had been diagnosed with systemic lupus erythematosus, rheumatoid arthritis, atopic dermatitis, polymyalgia rheumatica, axial spondyloarthritis, and psoriasis without or with arthritis. They had also been taking up to 25 mg of methotrexate per week for 3 months or longer and had received two doses of either the Pfizer/BioNTech BNT162b2 vaccine or AstraZeneca/Oxford viral vector vaccine. The booster dose was most often the Pfizer BNT162b2 vaccine (82%). The patients’ mean age was 59 years, with females comprising 61% of the cohort. Participants were randomly assigned 1:1 to either group.
Investigators performing laboratory analysis were masked to cohort assignment, and clinical research staff, data analysts, participants, and researchers were unmasked.
The elevated antibody response of patients who suspended methotrexate was the same across different kinds of immune-mediated inflammatory disease, primary vaccination platform, SARS-CoV-2 infection history, and age.
Notably, no intervention-associated adverse events were reported, the study team noted.
The conclusions that could be drawn from the booster-dose study were limited by the trial’s modest cohort size, the small number of patients in exploratory subgroup analyses, a lack of information about differences in prescription drug behavior, and early termination’s effect on the researchers’ ability to identify differences between subgroups and in secondary outcomes, the authors noted.
Other limitations included a lack of generalizability to patients with active disease who couldn’t stop therapy and were not included in the investigation, and participants were not blinded to what group they were in, the researchers said.
Expert commentary
This current study is consistent with other studies over the last several months showing that methotrexate harms both humoral and cell-mediated COVID-19 responses, noted Kevin Winthrop, MD, MPH, professor of infectious disease and public health at Oregon Health & Science University, Portland, who was not involved in the study. “And so now the new wave of studies are like this one, where they are holding methotrexate experimentally and seeing if it makes a difference,” he said.
“The one shortcoming of this study – and so far, the studies to date – is that no one has looked at whether the experimental hold has resulted in a change in T-cell responses, which ... we are [now] recognizing [the importance of] more and more in long-term protection, particularly in severe disease. Theoretically, holding [methotrexate] might help enhance T-cell responses, but that hasn’t been shown experimentally.”
Dr. Winthrop pointed out that one might get the same benefit from holding methotrexate for 1 week instead of 2 and that there likely is a reduced risk of flare-up from underlying autoimmune disease.
It is still not certain that this benefit extends to other vaccines, Dr. Winthrop noted. “It is probably true for most vaccines that if you hold methotrexate for 1 or 2 weeks, you might see some short-term benefit in responsiveness, but you don’t know that there is any clinical meaningfulness of this. That’s going to take other long-term studies. You don’t know how long this benefit lasts.”
Pausing methotrexate during initial COVID vaccine doses
Patients with either rheumatoid arthritis or psoriatic arthritis had higher anti-RBD antibody titers when methotrexate was stopped after both doses of the AstraZeneca vaccine, or simply after the second dose, than when methotrexate was continued, according to results from two single-center, randomized controlled trials called MIVAC I and II, Anu Sreekanth, MD, of Sree Sudheendra Medical Mission in Kochi, Kerala, India, and colleagues reported at EULAR 2022.
Results from MIVAC I indicated that there was a higher flare rate when methotrexate was stopped after both vaccine doses, but there was no difference in flare rate in MIVAC II when methotrexate was stopped only after the second dose as opposed to stopping it after both doses.
In the MIVAC I trial, 158 unvaccinated patients were randomized 1:1 to a cohort in which methotrexate was held for 2 weeks after both doses and a cohort in which methotrexate was continued despite the vaccine. In MIVAC II, 157 patients continued methotrexate while receiving the first vaccine dose. These patients were subsequently randomized either to continue or to stop methotrexate for 2 weeks following the second dose.
The findings from MIVAC I demonstrated the flare rate was lower in the methotrexate-continue group than in the methotrexate-pause group (8% vs. 25%; P = .005) and that the median anti-RBD titer was significantly higher for the methotrexate-pause group than the methotrexate-continue group (2,484 vs. 1,147; P = .001).
The results from MIVAC II trial indicated that there was no difference in flare rates between the two study groups (7.9% vs. 11.8%; P = .15). Yet, the median anti-RBD titer was significantly higher in the methotrexate-pause cohort than in the methotrexate-continue cohort (2,553 vs. 990; P = .001).
The report suggests there is a flare risk when methotrexate is stopped, Dr. Sreekanth noted. “It appears more logical to hold only after the second dose, as comparable anti-RBD titers are generated” with either approach, Dr. Sreekanth said.
Expert commentary: MIVAC I and II
Inés Colmegna, MD, associate professor at McGill University in Montreal, noted that it was intriguing that the risk of flares in MIVAC II is half of that reported after each of the doses of MIVAC I. “It is also worth emphasizing that despite the reported frequency of flares, the actual disease activity [as measured by the Disease Activity Score in 28 joints] in patients who did or did not withhold methotrexate was similar.
“MIVAC I and II have practical implications as they help to adequately inform patients about the risk and benefit trade of withholding methotrexate post–COVID-19 vaccination,” Dr. Colmegna told this news organization.
“Additional information would help to [further] interpret the findings of these studies, including whether any of the participants were taking any other DMARDs; data on the severity of the flares and functional impact; analysis of factors that predict the risk of flares, such as higher doses of methotrexate; [and change in] disease activity scores pre- and postvaccination,” Dr. Colmegna concluded.
Dr. Abhishek disclosed relationships with Springer, UpTodate, Oxford, Immunotec, AstraZeneca, Inflazome, NGM Biopharmaceuticals, Menarini Pharmaceuticals, and Cadila Pharmaceuticals. Dr. Abhishek is cochair of the ACR/EULAR CPPD Classification Criteria Working Group and the OMERACT CPPD Working Group. Dr. Sparks disclosed relationships with Gilead, Boehringer Ingelheim, Amgen, Bristol-Myers Squibb, and AbbVie, unrelated to this study. Dr. Tedeschi disclosed relationships with ModernaTx and NGM Biopharmaceuticals. Dr. Winthrop disclosed a research grant and serving as a scientific consultant for Pfizer. Dr. Sreekanth and Dr. Colmegna have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Neural networks can distinguish PsA from rheumatoid arthritis on MRI
Hand images are sufficient
NEW YORK – On the basis of MRI images of the hand, a neural network has been trained to distinguish seronegative and seropositive rheumatoid arthritis (RA) from psoriatic arthritis (PsA) as well as from each other, according to a study that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
In the work so far, the neural network was correct about 70% of the time in the absence of any further clinical analyses, according to David Simon, MD, a rheumatologist in the department of internal medicine at Friedrich-Alexander University, Erlangen, Germany.
Previous to this work, “there has been no study that has exclusively used hand MRI data and deep learning without requiring further expert input for the classification of arthritides,” Dr. Simon said.
In fact, when demographic and clinical data were added, there was no improvement in the performance of patient classification relative to the deep learning classification alone, according to the data presented by Dr. Simon.
The images were evaluated with residual neural networks (ResNet), which represents a sophisticated form of deep learning to facilitate the flow of information across the network layers as they form to improve accuracy in their ability to distinguish one form of disease from the other. The training was performed on images from the T1 coronal, T2 corona1, T1 coronal fat suppressed with contrast, T1 axial fat suppressed with contrast, and T2 fat suppressed axial sequences.
The study included hand MRI scans from 135 patients with seronegative RA, 190 with seropositive RA, 177 with PsA, and 147 with psoriasis. The performance was judged on the basis of area under the receiver operating characteristics curve (AUROC) with and without input of clinical characteristics. Patients who had psoriasis without clinical arthritis were included as a control population.
The AUROC for accuracy was 75% for seropositive RA relative to PsA, 74% for seronegative RA relative to PsA, and 67% for seropositive relative to seronegative RA. Of the patients who had psoriasis without arthritis, 98% were classified as PsA and 2% as RA.
Subsequent to the classification of the patients with psoriasis, 14 of the 147 (9.5%) have developed PsA so far over a relatively short follow-up. All of these were among those identified as PsA by neural network evaluation of the hand MRIs.
This suggests that “a PsA-like pattern may be present early in the course of psoriatic disease,” Dr. Simon said.
In the groups with joint disease, who had mean ages ranging from 56 to 65, the mean disease durations were 2.6 years for those with seropositive RA, 1.3 years for those with seronegative RA, and 0.8 years for those with PsA. The patients with psoriasis were younger (mean age, 40.5 years) but had a longer disease duration (mean 4.2 years).
All of the MRI sequences were relevant for classification, but contrast did not appear to help with accuracy.
“If the images with contrast enhancement were deleted, the loss of performance was only marginal,” Dr. Simon reported.
The accuracy of neural networks increases with data, making it likely that further refinements in methodology will lead to a greater degree of accuracy, according to Dr. Simon. While the methodology is not yet ready for routine use in the clinic, the study demonstrates that neural network analysis of hand MRI to distinguish forms of arthritis “is possible.” Further studies are planned toward the goal of creating a viable clinical tool.
“Of course, if we could create an accurate tool with ultrasound, this would be even more practical,” said Dr. Simon, recognizing the value of an office tool, but he cautioned that this would be far more challenging.
“The precision of MRI is an important factor for effective neural network training,” he said.
Utility: ‘In challenging cases if the accuracy improves’?
A viable method for objectively and rapidly distinguishing inflammatory joint diseases, particularly in patients with an ambiguous clinical presentation, is an unmet need, according to Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center, Seattle.
Although the data presented are promising, Dr. Mease said in an interview that he believes there is a fair amount of work to be done before imaging analysis based on deep learning makes its way into routine clinical care. He is also hoping for methods to distinguish RA from PsA that are easier and less expensive, such as serum biomarkers. However, he agreed that a MRI-based tool could be useful when differentiating disease that is challenging.
“MRI is an expensive way for routine classification of disease, but this approach could be useful in challenging cases if the accuracy improves,” he said.
Meanwhile, other clinical researchers might want to test the principle. “You can try it,” said Dr. Simon, who reported that his team has made the methodology publicly available.
Dr. Simon reported no conflicts of interest. Dr. Mease reported financial relationships with more than 10 pharmaceutical companies, most of which make products used for the treatment of inflammatory joint diseases.
Hand images are sufficient
Hand images are sufficient
NEW YORK – On the basis of MRI images of the hand, a neural network has been trained to distinguish seronegative and seropositive rheumatoid arthritis (RA) from psoriatic arthritis (PsA) as well as from each other, according to a study that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
In the work so far, the neural network was correct about 70% of the time in the absence of any further clinical analyses, according to David Simon, MD, a rheumatologist in the department of internal medicine at Friedrich-Alexander University, Erlangen, Germany.
Previous to this work, “there has been no study that has exclusively used hand MRI data and deep learning without requiring further expert input for the classification of arthritides,” Dr. Simon said.
In fact, when demographic and clinical data were added, there was no improvement in the performance of patient classification relative to the deep learning classification alone, according to the data presented by Dr. Simon.
The images were evaluated with residual neural networks (ResNet), which represents a sophisticated form of deep learning to facilitate the flow of information across the network layers as they form to improve accuracy in their ability to distinguish one form of disease from the other. The training was performed on images from the T1 coronal, T2 corona1, T1 coronal fat suppressed with contrast, T1 axial fat suppressed with contrast, and T2 fat suppressed axial sequences.
The study included hand MRI scans from 135 patients with seronegative RA, 190 with seropositive RA, 177 with PsA, and 147 with psoriasis. The performance was judged on the basis of area under the receiver operating characteristics curve (AUROC) with and without input of clinical characteristics. Patients who had psoriasis without clinical arthritis were included as a control population.
The AUROC for accuracy was 75% for seropositive RA relative to PsA, 74% for seronegative RA relative to PsA, and 67% for seropositive relative to seronegative RA. Of the patients who had psoriasis without arthritis, 98% were classified as PsA and 2% as RA.
Subsequent to the classification of the patients with psoriasis, 14 of the 147 (9.5%) have developed PsA so far over a relatively short follow-up. All of these were among those identified as PsA by neural network evaluation of the hand MRIs.
This suggests that “a PsA-like pattern may be present early in the course of psoriatic disease,” Dr. Simon said.
In the groups with joint disease, who had mean ages ranging from 56 to 65, the mean disease durations were 2.6 years for those with seropositive RA, 1.3 years for those with seronegative RA, and 0.8 years for those with PsA. The patients with psoriasis were younger (mean age, 40.5 years) but had a longer disease duration (mean 4.2 years).
All of the MRI sequences were relevant for classification, but contrast did not appear to help with accuracy.
“If the images with contrast enhancement were deleted, the loss of performance was only marginal,” Dr. Simon reported.
The accuracy of neural networks increases with data, making it likely that further refinements in methodology will lead to a greater degree of accuracy, according to Dr. Simon. While the methodology is not yet ready for routine use in the clinic, the study demonstrates that neural network analysis of hand MRI to distinguish forms of arthritis “is possible.” Further studies are planned toward the goal of creating a viable clinical tool.
“Of course, if we could create an accurate tool with ultrasound, this would be even more practical,” said Dr. Simon, recognizing the value of an office tool, but he cautioned that this would be far more challenging.
“The precision of MRI is an important factor for effective neural network training,” he said.
Utility: ‘In challenging cases if the accuracy improves’?
A viable method for objectively and rapidly distinguishing inflammatory joint diseases, particularly in patients with an ambiguous clinical presentation, is an unmet need, according to Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center, Seattle.
Although the data presented are promising, Dr. Mease said in an interview that he believes there is a fair amount of work to be done before imaging analysis based on deep learning makes its way into routine clinical care. He is also hoping for methods to distinguish RA from PsA that are easier and less expensive, such as serum biomarkers. However, he agreed that a MRI-based tool could be useful when differentiating disease that is challenging.
“MRI is an expensive way for routine classification of disease, but this approach could be useful in challenging cases if the accuracy improves,” he said.
Meanwhile, other clinical researchers might want to test the principle. “You can try it,” said Dr. Simon, who reported that his team has made the methodology publicly available.
Dr. Simon reported no conflicts of interest. Dr. Mease reported financial relationships with more than 10 pharmaceutical companies, most of which make products used for the treatment of inflammatory joint diseases.
NEW YORK – On the basis of MRI images of the hand, a neural network has been trained to distinguish seronegative and seropositive rheumatoid arthritis (RA) from psoriatic arthritis (PsA) as well as from each other, according to a study that was presented at the annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis.
In the work so far, the neural network was correct about 70% of the time in the absence of any further clinical analyses, according to David Simon, MD, a rheumatologist in the department of internal medicine at Friedrich-Alexander University, Erlangen, Germany.
Previous to this work, “there has been no study that has exclusively used hand MRI data and deep learning without requiring further expert input for the classification of arthritides,” Dr. Simon said.
In fact, when demographic and clinical data were added, there was no improvement in the performance of patient classification relative to the deep learning classification alone, according to the data presented by Dr. Simon.
The images were evaluated with residual neural networks (ResNet), which represents a sophisticated form of deep learning to facilitate the flow of information across the network layers as they form to improve accuracy in their ability to distinguish one form of disease from the other. The training was performed on images from the T1 coronal, T2 corona1, T1 coronal fat suppressed with contrast, T1 axial fat suppressed with contrast, and T2 fat suppressed axial sequences.
The study included hand MRI scans from 135 patients with seronegative RA, 190 with seropositive RA, 177 with PsA, and 147 with psoriasis. The performance was judged on the basis of area under the receiver operating characteristics curve (AUROC) with and without input of clinical characteristics. Patients who had psoriasis without clinical arthritis were included as a control population.
The AUROC for accuracy was 75% for seropositive RA relative to PsA, 74% for seronegative RA relative to PsA, and 67% for seropositive relative to seronegative RA. Of the patients who had psoriasis without arthritis, 98% were classified as PsA and 2% as RA.
Subsequent to the classification of the patients with psoriasis, 14 of the 147 (9.5%) have developed PsA so far over a relatively short follow-up. All of these were among those identified as PsA by neural network evaluation of the hand MRIs.
This suggests that “a PsA-like pattern may be present early in the course of psoriatic disease,” Dr. Simon said.
In the groups with joint disease, who had mean ages ranging from 56 to 65, the mean disease durations were 2.6 years for those with seropositive RA, 1.3 years for those with seronegative RA, and 0.8 years for those with PsA. The patients with psoriasis were younger (mean age, 40.5 years) but had a longer disease duration (mean 4.2 years).
All of the MRI sequences were relevant for classification, but contrast did not appear to help with accuracy.
“If the images with contrast enhancement were deleted, the loss of performance was only marginal,” Dr. Simon reported.
The accuracy of neural networks increases with data, making it likely that further refinements in methodology will lead to a greater degree of accuracy, according to Dr. Simon. While the methodology is not yet ready for routine use in the clinic, the study demonstrates that neural network analysis of hand MRI to distinguish forms of arthritis “is possible.” Further studies are planned toward the goal of creating a viable clinical tool.
“Of course, if we could create an accurate tool with ultrasound, this would be even more practical,” said Dr. Simon, recognizing the value of an office tool, but he cautioned that this would be far more challenging.
“The precision of MRI is an important factor for effective neural network training,” he said.
Utility: ‘In challenging cases if the accuracy improves’?
A viable method for objectively and rapidly distinguishing inflammatory joint diseases, particularly in patients with an ambiguous clinical presentation, is an unmet need, according to Philip J. Mease, MD, director of rheumatology research at Swedish Medical Center, Seattle.
Although the data presented are promising, Dr. Mease said in an interview that he believes there is a fair amount of work to be done before imaging analysis based on deep learning makes its way into routine clinical care. He is also hoping for methods to distinguish RA from PsA that are easier and less expensive, such as serum biomarkers. However, he agreed that a MRI-based tool could be useful when differentiating disease that is challenging.
“MRI is an expensive way for routine classification of disease, but this approach could be useful in challenging cases if the accuracy improves,” he said.
Meanwhile, other clinical researchers might want to test the principle. “You can try it,” said Dr. Simon, who reported that his team has made the methodology publicly available.
Dr. Simon reported no conflicts of interest. Dr. Mease reported financial relationships with more than 10 pharmaceutical companies, most of which make products used for the treatment of inflammatory joint diseases.
AT GRAPPA 2022