MDedge Rheumatology

Key clinical point: Minimal important change (MIC) of the Psoriatic Arthritis Disease Activity Score (PASDAS) could help physicians understand patients' perspectives of disease activity and provide an additional tool for the treatment of psoriatic arthritis (PsA).

Major finding: The overall MIC of the PASDAS was 0.67 (95% CI 0.55-0.79) and results for improvement and deterioration were 0.65 (95% CI 0.46-0.83) and 0.71 (95% CI 0.49-0.93), respectively.

Study details: Findings are from a retrospective cohort study that evaluated routine practice data of 408 patients with PsA.

Disclosures: This work was supported by the Regional Junior Researcher Grant from the Sint Maartenskliniek, Nijmegen, and the Radboudumc, Nijmegen, the Netherlands. The authors declared no conflicts of interest.

Source: Mulder MLM et al. Rheumatology (Oxford). 2022 (Jan 13). Doi: 10.1093/rheumatology/keac025.

Key clinical point: Minimal important change (MIC) of the Psoriatic Arthritis Disease Activity Score (PASDAS) could help physicians understand patients' perspectives of disease activity and provide an additional tool for the treatment of psoriatic arthritis (PsA).

Major finding: The overall MIC of the PASDAS was 0.67 (95% CI 0.55-0.79) and results for improvement and deterioration were 0.65 (95% CI 0.46-0.83) and 0.71 (95% CI 0.49-0.93), respectively.

Study details: Findings are from a retrospective cohort study that evaluated routine practice data of 408 patients with PsA.

Disclosures: This work was supported by the Regional Junior Researcher Grant from the Sint Maartenskliniek, Nijmegen, and the Radboudumc, Nijmegen, the Netherlands. The authors declared no conflicts of interest.

Source: Mulder MLM et al. Rheumatology (Oxford). 2022 (Jan 13). Doi: 10.1093/rheumatology/keac025.

Key clinical point: Minimal important change (MIC) of the Psoriatic Arthritis Disease Activity Score (PASDAS) could help physicians understand patients' perspectives of disease activity and provide an additional tool for the treatment of psoriatic arthritis (PsA).

Major finding: The overall MIC of the PASDAS was 0.67 (95% CI 0.55-0.79) and results for improvement and deterioration were 0.65 (95% CI 0.46-0.83) and 0.71 (95% CI 0.49-0.93), respectively.

Study details: Findings are from a retrospective cohort study that evaluated routine practice data of 408 patients with PsA.

Disclosures: This work was supported by the Regional Junior Researcher Grant from the Sint Maartenskliniek, Nijmegen, and the Radboudumc, Nijmegen, the Netherlands. The authors declared no conflicts of interest.

Source: Mulder MLM et al. Rheumatology (Oxford). 2022 (Jan 13). Doi: 10.1093/rheumatology/keac025.

Key clinical point: Entheseal power Doppler (PD) signal, entheseal bone erosions, and gray scale (GS) joint synovitis were indicative of severe psoriatic arthritis (PsA) in terms of ultrasound (US)-detected joint bone erosion.

Major finding: At least 1 joint bone erosion was found in 45.2% of patients and was associated with PD signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and GS synovitis (OR 2.59; P = .02).

Study details: Findings are from a cross-sectional study including 104 patients with PsA.

Disclosures: This study did not receive any specific funding. E Filippucci and W Grassi declared receiving speaker fees from various sources.

Source: Smerilli G et al. J Rheumatol. 2022 (Feb 1). Doi: 10.3899/jrheum.210974.

Key clinical point: Entheseal power Doppler (PD) signal, entheseal bone erosions, and gray scale (GS) joint synovitis were indicative of severe psoriatic arthritis (PsA) in terms of ultrasound (US)-detected joint bone erosion.

Major finding: At least 1 joint bone erosion was found in 45.2% of patients and was associated with PD signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and GS synovitis (OR 2.59; P = .02).

Study details: Findings are from a cross-sectional study including 104 patients with PsA.

Disclosures: This study did not receive any specific funding. E Filippucci and W Grassi declared receiving speaker fees from various sources.

Source: Smerilli G et al. J Rheumatol. 2022 (Feb 1). Doi: 10.3899/jrheum.210974.

Key clinical point: Entheseal power Doppler (PD) signal, entheseal bone erosions, and gray scale (GS) joint synovitis were indicative of severe psoriatic arthritis (PsA) in terms of ultrasound (US)-detected joint bone erosion.

Major finding: At least 1 joint bone erosion was found in 45.2% of patients and was associated with PD signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and GS synovitis (OR 2.59; P = .02).

Study details: Findings are from a cross-sectional study including 104 patients with PsA.

Disclosures: This study did not receive any specific funding. E Filippucci and W Grassi declared receiving speaker fees from various sources.

Source: Smerilli G et al. J Rheumatol. 2022 (Feb 1). Doi: 10.3899/jrheum.210974.

Key clinical point: Patients with psoriatic arthritis (PsA) receiving tofacitinib experienced a shorter time to initial clinically meaningful response than those who switched from placebo to tofacitinib.

Major finding: Median time to the initial Health Assessment Questionnaire-Disability Index score response was shorter in patients receiving 5 mg tofacitinib (29-30 days) and 10 mg tofacitinib (53.5 days) than in those switching from placebo to 5 mg tofacitinib (162 days) or 10 mg tofacitinib (112 days; P < .01). The initial Functional Assessment of Chronic Illness Therapy-Fatigue total score response was achieved faster with 5 mg tofacitinib vs. other treatment groups.

Study details: Findings are from a post hoc analysis of 2 phase 3 trials (OPAL BROADEN and OPAL BEYOND) including 816 patients with PsA randomly assigned to 5 mg tofacitinib, 10 mg tofacitinib, 40 mg adalimumab, or placebo switching to 5 or 10 mg tofacitinib at month 3.

Disclosures: This study was funded by Pfizer. The authors declared receiving research grants, consulting fees, and honoraria from Pfizer and other sources. Four authors declared being employees and stockholders of Pfizer.

Source: Gladman DD et al. Arthritis Res Ther. 2022;24:40 (Feb 9). Doi: 10.1186/s13075-022-02721-0.

Key clinical point: Patients with psoriatic arthritis (PsA) receiving tofacitinib experienced a shorter time to initial clinically meaningful response than those who switched from placebo to tofacitinib.

Major finding: Median time to the initial Health Assessment Questionnaire-Disability Index score response was shorter in patients receiving 5 mg tofacitinib (29-30 days) and 10 mg tofacitinib (53.5 days) than in those switching from placebo to 5 mg tofacitinib (162 days) or 10 mg tofacitinib (112 days; P < .01). The initial Functional Assessment of Chronic Illness Therapy-Fatigue total score response was achieved faster with 5 mg tofacitinib vs. other treatment groups.

Study details: Findings are from a post hoc analysis of 2 phase 3 trials (OPAL BROADEN and OPAL BEYOND) including 816 patients with PsA randomly assigned to 5 mg tofacitinib, 10 mg tofacitinib, 40 mg adalimumab, or placebo switching to 5 or 10 mg tofacitinib at month 3.

Disclosures: This study was funded by Pfizer. The authors declared receiving research grants, consulting fees, and honoraria from Pfizer and other sources. Four authors declared being employees and stockholders of Pfizer.

Source: Gladman DD et al. Arthritis Res Ther. 2022;24:40 (Feb 9). Doi: 10.1186/s13075-022-02721-0.

Key clinical point: Patients with psoriatic arthritis (PsA) receiving tofacitinib experienced a shorter time to initial clinically meaningful response than those who switched from placebo to tofacitinib.

Major finding: Median time to the initial Health Assessment Questionnaire-Disability Index score response was shorter in patients receiving 5 mg tofacitinib (29-30 days) and 10 mg tofacitinib (53.5 days) than in those switching from placebo to 5 mg tofacitinib (162 days) or 10 mg tofacitinib (112 days; P < .01). The initial Functional Assessment of Chronic Illness Therapy-Fatigue total score response was achieved faster with 5 mg tofacitinib vs. other treatment groups.

Study details: Findings are from a post hoc analysis of 2 phase 3 trials (OPAL BROADEN and OPAL BEYOND) including 816 patients with PsA randomly assigned to 5 mg tofacitinib, 10 mg tofacitinib, 40 mg adalimumab, or placebo switching to 5 or 10 mg tofacitinib at month 3.

Disclosures: This study was funded by Pfizer. The authors declared receiving research grants, consulting fees, and honoraria from Pfizer and other sources. Four authors declared being employees and stockholders of Pfizer.

Source: Gladman DD et al. Arthritis Res Ther. 2022;24:40 (Feb 9). Doi: 10.1186/s13075-022-02721-0.

Key clinical point: Increased risk for venous thromboembolism (VTE) in patients with psoriatic arthritis (PsA) seemed to be associated with underlying comorbidities and not independently associated with PsA.

Major finding: During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and  history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE after multivariate adjustment.

Study details: This retrospective cohort study included 5,275 patients with newly diagnosed PsA who were matched with 21,011 control individuals without PsA.

Disclosures: The study did not report any source of funding. The authors declared no conflicts of interest.

Source: Gazitt T et al. Arthritis Res Ther. 2022;24:16 (Jan 7). Doi: 10.1186/s13075-021-02703-8.

Key clinical point: Increased risk for venous thromboembolism (VTE) in patients with psoriatic arthritis (PsA) seemed to be associated with underlying comorbidities and not independently associated with PsA.

Major finding: During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and  history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE after multivariate adjustment.

Study details: This retrospective cohort study included 5,275 patients with newly diagnosed PsA who were matched with 21,011 control individuals without PsA.

Disclosures: The study did not report any source of funding. The authors declared no conflicts of interest.

Source: Gazitt T et al. Arthritis Res Ther. 2022;24:16 (Jan 7). Doi: 10.1186/s13075-021-02703-8.

Key clinical point: Increased risk for venous thromboembolism (VTE) in patients with psoriatic arthritis (PsA) seemed to be associated with underlying comorbidities and not independently associated with PsA.

Major finding: During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and  history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE after multivariate adjustment.

Study details: This retrospective cohort study included 5,275 patients with newly diagnosed PsA who were matched with 21,011 control individuals without PsA.

Disclosures: The study did not report any source of funding. The authors declared no conflicts of interest.

Source: Gazitt T et al. Arthritis Res Ther. 2022;24:16 (Jan 7). Doi: 10.1186/s13075-021-02703-8.

Key clinical point: Patients with juvenile psoriatic arthritis (JPsA) were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody (ANA) positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

Major finding: Patients with JPsA with vs. without uveitis were younger at JPsA onset (5.3 years vs. 9.3 years) and were more frequently positive for ANA (60.3% vs. 37%; both P < .001). The mean clinical Juvenile Arthritis Disease Activity Score 10 was the only factor significantly associated with the development of uveitis in patients with JPsA (hazard ratio 1.16; P = .025).

Study details: This was an analysis of cross-sectional data from 1,862 patients with JPsA from the National Pediatric Rheumatological Database. Of the patients in the study, 122 developed uveitis.

Disclosures: This study was funded by the Federal Ministry for Research and Education, Deutsche Kinderrheuma-Stiftung, and others. Some of the authors declared receiving honoraria and research grants from several sources.

Source: Walscheid K et al. J Rheumatol. 2022 (Jan 15). Doi: 10.3899/jrheum.210755.

Key clinical point: Patients with juvenile psoriatic arthritis (JPsA) were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody (ANA) positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

Major finding: Patients with JPsA with vs. without uveitis were younger at JPsA onset (5.3 years vs. 9.3 years) and were more frequently positive for ANA (60.3% vs. 37%; both P < .001). The mean clinical Juvenile Arthritis Disease Activity Score 10 was the only factor significantly associated with the development of uveitis in patients with JPsA (hazard ratio 1.16; P = .025).

Study details: This was an analysis of cross-sectional data from 1,862 patients with JPsA from the National Pediatric Rheumatological Database. Of the patients in the study, 122 developed uveitis.

Disclosures: This study was funded by the Federal Ministry for Research and Education, Deutsche Kinderrheuma-Stiftung, and others. Some of the authors declared receiving honoraria and research grants from several sources.

Source: Walscheid K et al. J Rheumatol. 2022 (Jan 15). Doi: 10.3899/jrheum.210755.

Key clinical point: Patients with juvenile psoriatic arthritis (JPsA) were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody (ANA) positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

Major finding: Patients with JPsA with vs. without uveitis were younger at JPsA onset (5.3 years vs. 9.3 years) and were more frequently positive for ANA (60.3% vs. 37%; both P < .001). The mean clinical Juvenile Arthritis Disease Activity Score 10 was the only factor significantly associated with the development of uveitis in patients with JPsA (hazard ratio 1.16; P = .025).

Study details: This was an analysis of cross-sectional data from 1,862 patients with JPsA from the National Pediatric Rheumatological Database. Of the patients in the study, 122 developed uveitis.

Disclosures: This study was funded by the Federal Ministry for Research and Education, Deutsche Kinderrheuma-Stiftung, and others. Some of the authors declared receiving honoraria and research grants from several sources.

Source: Walscheid K et al. J Rheumatol. 2022 (Jan 15). Doi: 10.3899/jrheum.210755.

Key clinical point: Patients with psoriasis and concomitant psoriatic arthritis (PsA) were at greater risk of developing endometriosis.

Major finding: A history of psoriasis with concomitant PsA was associated with an increased risk for subsequent endometriosis diagnosis (hazard ratio [HR] 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease (HR 1.94; 95% CI 1.18-3.18).

Study details: Findings are from an analysis of 4,112 patients with laparoscopically confirmed endometriosis and 767 patients with psoriasis, of which 140 had concomitant PsA from the Nurses’ Health Study II.

Disclosures: This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The authors reported no conflicts of interest.

Source: Harris HR et al. Am J Epidemiol. 2022 (Jan 13). Doi: 10.1093/aje/kwac009.

Key clinical point: Patients with psoriasis and concomitant psoriatic arthritis (PsA) were at greater risk of developing endometriosis.

Major finding: A history of psoriasis with concomitant PsA was associated with an increased risk for subsequent endometriosis diagnosis (hazard ratio [HR] 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease (HR 1.94; 95% CI 1.18-3.18).

Study details: Findings are from an analysis of 4,112 patients with laparoscopically confirmed endometriosis and 767 patients with psoriasis, of which 140 had concomitant PsA from the Nurses’ Health Study II.

Disclosures: This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The authors reported no conflicts of interest.

Source: Harris HR et al. Am J Epidemiol. 2022 (Jan 13). Doi: 10.1093/aje/kwac009.

Key clinical point: Patients with psoriasis and concomitant psoriatic arthritis (PsA) were at greater risk of developing endometriosis.

Major finding: A history of psoriasis with concomitant PsA was associated with an increased risk for subsequent endometriosis diagnosis (hazard ratio [HR] 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities such as hypertension, hypercholesterolemia, and cardiovascular disease (HR 1.94; 95% CI 1.18-3.18).

Study details: Findings are from an analysis of 4,112 patients with laparoscopically confirmed endometriosis and 767 patients with psoriasis, of which 140 had concomitant PsA from the Nurses’ Health Study II.

Disclosures: This study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The authors reported no conflicts of interest.

Source: Harris HR et al. Am J Epidemiol. 2022 (Jan 13). Doi: 10.1093/aje/kwac009.

Key clinical point: Secukinumab showed early and clinically meaningful improvements in patient-reported outcomes (PRO) in adults with psoriatic arthritis (PsA).

Major finding: At week 16, patients in all secukinumab treatment groups vs. placebo showed significant improvement in all PRO (P ≤ .0001) except for the 36-item Short-Form Health Survey mental component summary. Patients receiving 300 mg secukinumab showed significant and clinically meaningful improvements as early as week 1 (P < .05).

Study details: Findings are from the phase 3 FUTURE 5 trial including 996 adults with active PsA who were randomly assigned to 300 mg secukinumab, 150 mg secukinumab  (with/without loading dose), or placebo.

Disclosures: This study was funded by Novartis Pharma. Some of the authors declared receiving research grants or consulting and speaker’s bureau fees from various sources including Novartis. Four authors declared being past/current employees or shareholders of Novartis.

Source: Strand V et al. Lancet Rheumatol. 2022 (Feb 1). Doi: 10.1016/S2665-9913(21)00354-4.

Key clinical point: Secukinumab showed early and clinically meaningful improvements in patient-reported outcomes (PRO) in adults with psoriatic arthritis (PsA).

Major finding: At week 16, patients in all secukinumab treatment groups vs. placebo showed significant improvement in all PRO (P ≤ .0001) except for the 36-item Short-Form Health Survey mental component summary. Patients receiving 300 mg secukinumab showed significant and clinically meaningful improvements as early as week 1 (P < .05).

Study details: Findings are from the phase 3 FUTURE 5 trial including 996 adults with active PsA who were randomly assigned to 300 mg secukinumab, 150 mg secukinumab  (with/without loading dose), or placebo.

Disclosures: This study was funded by Novartis Pharma. Some of the authors declared receiving research grants or consulting and speaker’s bureau fees from various sources including Novartis. Four authors declared being past/current employees or shareholders of Novartis.

Source: Strand V et al. Lancet Rheumatol. 2022 (Feb 1). Doi: 10.1016/S2665-9913(21)00354-4.

Key clinical point: Secukinumab showed early and clinically meaningful improvements in patient-reported outcomes (PRO) in adults with psoriatic arthritis (PsA).

Major finding: At week 16, patients in all secukinumab treatment groups vs. placebo showed significant improvement in all PRO (P ≤ .0001) except for the 36-item Short-Form Health Survey mental component summary. Patients receiving 300 mg secukinumab showed significant and clinically meaningful improvements as early as week 1 (P < .05).

Study details: Findings are from the phase 3 FUTURE 5 trial including 996 adults with active PsA who were randomly assigned to 300 mg secukinumab, 150 mg secukinumab  (with/without loading dose), or placebo.

Disclosures: This study was funded by Novartis Pharma. Some of the authors declared receiving research grants or consulting and speaker’s bureau fees from various sources including Novartis. Four authors declared being past/current employees or shareholders of Novartis.

Source: Strand V et al. Lancet Rheumatol. 2022 (Feb 1). Doi: 10.1016/S2665-9913(21)00354-4.

The roots of treat-to-target (T2T) in rheumatology extend back over 30 years to the development of the 28-joint Disease Activity Score. Although it has been shown to be effective in clinical trials and has been included in guidelines, it has yet to be widely adopted in practice. The question remains: What is the role of T2T in rheumatology?

That’s what Jack Cush, MD, and Martin Bergman, MD, sought to answer in a point-counterpoint session at the 2022 Rheumatology Winter Clinical Symposium.

RWCS 2022 screenshot

“I do think that this is a concept we need to keep in mind, and it is a concept whose time is long overdue,” Dr. Bergman said in his presentation arguing in favor of T2T. “As good as you think you are – your ability to see the patient and determine how they’re doing – you’re not.”

But metrics alone are not enough to make clinical decisions, said Dr. Bergman, clinical professor of medicine at Drexel University, Philadelphia, citing a recommendation from 2014 recommendations on T2T published in Annals of the Rheumatic Diseases. “You don’t just follow a number. You have to take into consideration structural changes, functional impairment, comorbidities – and that’s going to adjust how you approach your patient and what you do with them.”

However, implementation of T2T to make changes in clinical practice in RA has been inconsistent. Referencing an abstract from the 2021 American College of Rheumatology annual meeting on 15-year follow-up for changing therapy in RA, Dr. Bergman argued it is not the patient who is unwilling to switch treatments. Between 2006 and 2021, patient unwillingness to change therapies decreased from 64% to 51%.

“What’s driving it mostly here [is] the doctor’s recommendation,” Dr. Bergman said. “And we know this is true because we’ve seen it in other studies.”

Many rheumatologists are “asleep at the wheel” when it comes to administering T2T, he said. “What we need to do is, after we wake up from this nap, we need to get back on the highway and drive to where we should be, which is treat-to-target.”

Dr. Bergman also shared his paradigm for administering T2T, which he noted does not typically take more than a few minutes to administer regardless of the measure chosen. “Pick a measure. I don’t care which measure you take. I personally use two: I like the RAPID3 and the CDAI,” he said. “But then, after you have the measure, evaluate the entire patient. Don’t just look at the number. Look at the patient, what’s going on, solid history, solid physical. And most importantly: Be a doctor, don’t be a computer screen.”

Problems in measurement of RA remission and adoption of T2T

Dr. Cush, who admitted early in his presentation that he is in favor of T2T, delivered his counterpoint somewhat tongue-in-cheek. However, he pointed out that there are several concerns about the goals in measuring outcomes in RA with T2T.

The goal in RA is disease remission, but how you define remission can vary, especially since sometimes there is evidence of synovitis or other disease activity visible through an exam or imaging, said Dr. Cush, a rheumatologist based in Dallas, and executive editor of RheumNow.com. Most of the evidence for T2T is in clinical trials, but adoption is inconsistent in clinical practice, and patients in general appear to be improving without widespread adoption, he argued.

“Are clinical trials the same as clinical practice?” he asked. “I think that this boils down to: Is this a quest for remissions, or the best-you-can-get, low disease activity state? Or is this a quest for physician change, which is actually the path you have to go through to get to remissions?”

“In the end, evidence that the metrics should drive prescribing, especially in private practice is, I think, lacking,” he said.

RWCS 2022 screenshot

Roy Fleischmann, MD, agreed with Dr. Cush’s point of how one defines disease remission, as well as Dr. Bergman’s paradigm for T2T. “If you’re a good rheumatologist, you really do examine joints,” but you also “take a look at patient function, patient global [assessment], your global [assessment], joint count,” he said. “You can put a number to it, but you have to take a look at all of that. Really, treat-to-target – it is all of that. It isn’t just looking at a number, it’s looking at everything. And the better that the patient can do, assuming comorbidities and everything else, the better it is.”

“The problem isn’t the patient. The problem isn’t the metric. The problem is the rheumatologist, because the rheumatologist isn’t putting in enough effort in order to reach that goal,” added Dr. Fleischmann, clinical professor of medicine at the University of Texas, Dallas, and codirector of the Metroplex Clinical Research Center, also in in Dallas.

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, commented that T2T is “great for somebody who’s been doing it for a while, and seeing a lot of patients and has that comfort zone,” but he questioned whether new rheumatologists without a lot of clinical experience could apply the approach. “What information do they use to integrate, and how do they get to that point?” he asked. “I don’t have the answer to that.”

During a rebuttal, Dr. Bergman pushed back on the idea that clinical experience alone was enough. “You need something. You need a benchmark. You need something more than, ‘I say so.’ ”

“The problem is, we still haven’t convinced people to adopt them,” Dr. Bergman said. “And I think it’s failure of training because, in my opinion, I don’t know how you can do a modern current fellowship program and not teach metrics.”

Dr. Cush and Dr. Bergman used the same trials to argue for their side. “I think that us using the same slides, but maybe having different points, speaks to the problem,” Dr. Cush said. “And I choose not to make it the problem of the rheumatologists.”

“You’re in the field of pattern recognition,” Dr. Cush argued. “It’s a visual art. You can have all the numbers you want. You make the most of your decisions based on pattern recognition, which is not rooted in metrics, and that’s why you’re successful at what you do.

“I am a big believer in T2T, but I think you have to measure something, and you have to use it,” Dr. Cush closed. “And the problem is, we can’t be forced into this.”

Dr. Bergman and Dr. Cush reported having financial relationships with numerous pharmaceutical companies.

The roots of treat-to-target (T2T) in rheumatology extend back over 30 years to the development of the 28-joint Disease Activity Score. Although it has been shown to be effective in clinical trials and has been included in guidelines, it has yet to be widely adopted in practice. The question remains: What is the role of T2T in rheumatology?

That’s what Jack Cush, MD, and Martin Bergman, MD, sought to answer in a point-counterpoint session at the 2022 Rheumatology Winter Clinical Symposium.

RWCS 2022 screenshot

“I do think that this is a concept we need to keep in mind, and it is a concept whose time is long overdue,” Dr. Bergman said in his presentation arguing in favor of T2T. “As good as you think you are – your ability to see the patient and determine how they’re doing – you’re not.”

But metrics alone are not enough to make clinical decisions, said Dr. Bergman, clinical professor of medicine at Drexel University, Philadelphia, citing a recommendation from 2014 recommendations on T2T published in Annals of the Rheumatic Diseases. “You don’t just follow a number. You have to take into consideration structural changes, functional impairment, comorbidities – and that’s going to adjust how you approach your patient and what you do with them.”

However, implementation of T2T to make changes in clinical practice in RA has been inconsistent. Referencing an abstract from the 2021 American College of Rheumatology annual meeting on 15-year follow-up for changing therapy in RA, Dr. Bergman argued it is not the patient who is unwilling to switch treatments. Between 2006 and 2021, patient unwillingness to change therapies decreased from 64% to 51%.

“What’s driving it mostly here [is] the doctor’s recommendation,” Dr. Bergman said. “And we know this is true because we’ve seen it in other studies.”

Many rheumatologists are “asleep at the wheel” when it comes to administering T2T, he said. “What we need to do is, after we wake up from this nap, we need to get back on the highway and drive to where we should be, which is treat-to-target.”

Dr. Bergman also shared his paradigm for administering T2T, which he noted does not typically take more than a few minutes to administer regardless of the measure chosen. “Pick a measure. I don’t care which measure you take. I personally use two: I like the RAPID3 and the CDAI,” he said. “But then, after you have the measure, evaluate the entire patient. Don’t just look at the number. Look at the patient, what’s going on, solid history, solid physical. And most importantly: Be a doctor, don’t be a computer screen.”

Problems in measurement of RA remission and adoption of T2T

Dr. Cush, who admitted early in his presentation that he is in favor of T2T, delivered his counterpoint somewhat tongue-in-cheek. However, he pointed out that there are several concerns about the goals in measuring outcomes in RA with T2T.

The goal in RA is disease remission, but how you define remission can vary, especially since sometimes there is evidence of synovitis or other disease activity visible through an exam or imaging, said Dr. Cush, a rheumatologist based in Dallas, and executive editor of RheumNow.com. Most of the evidence for T2T is in clinical trials, but adoption is inconsistent in clinical practice, and patients in general appear to be improving without widespread adoption, he argued.

“Are clinical trials the same as clinical practice?” he asked. “I think that this boils down to: Is this a quest for remissions, or the best-you-can-get, low disease activity state? Or is this a quest for physician change, which is actually the path you have to go through to get to remissions?”

“In the end, evidence that the metrics should drive prescribing, especially in private practice is, I think, lacking,” he said.

RWCS 2022 screenshot

Roy Fleischmann, MD, agreed with Dr. Cush’s point of how one defines disease remission, as well as Dr. Bergman’s paradigm for T2T. “If you’re a good rheumatologist, you really do examine joints,” but you also “take a look at patient function, patient global [assessment], your global [assessment], joint count,” he said. “You can put a number to it, but you have to take a look at all of that. Really, treat-to-target – it is all of that. It isn’t just looking at a number, it’s looking at everything. And the better that the patient can do, assuming comorbidities and everything else, the better it is.”

“The problem isn’t the patient. The problem isn’t the metric. The problem is the rheumatologist, because the rheumatologist isn’t putting in enough effort in order to reach that goal,” added Dr. Fleischmann, clinical professor of medicine at the University of Texas, Dallas, and codirector of the Metroplex Clinical Research Center, also in in Dallas.

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, commented that T2T is “great for somebody who’s been doing it for a while, and seeing a lot of patients and has that comfort zone,” but he questioned whether new rheumatologists without a lot of clinical experience could apply the approach. “What information do they use to integrate, and how do they get to that point?” he asked. “I don’t have the answer to that.”

During a rebuttal, Dr. Bergman pushed back on the idea that clinical experience alone was enough. “You need something. You need a benchmark. You need something more than, ‘I say so.’ ”

“The problem is, we still haven’t convinced people to adopt them,” Dr. Bergman said. “And I think it’s failure of training because, in my opinion, I don’t know how you can do a modern current fellowship program and not teach metrics.”

Dr. Cush and Dr. Bergman used the same trials to argue for their side. “I think that us using the same slides, but maybe having different points, speaks to the problem,” Dr. Cush said. “And I choose not to make it the problem of the rheumatologists.”

“You’re in the field of pattern recognition,” Dr. Cush argued. “It’s a visual art. You can have all the numbers you want. You make the most of your decisions based on pattern recognition, which is not rooted in metrics, and that’s why you’re successful at what you do.

“I am a big believer in T2T, but I think you have to measure something, and you have to use it,” Dr. Cush closed. “And the problem is, we can’t be forced into this.”

Dr. Bergman and Dr. Cush reported having financial relationships with numerous pharmaceutical companies.

The roots of treat-to-target (T2T) in rheumatology extend back over 30 years to the development of the 28-joint Disease Activity Score. Although it has been shown to be effective in clinical trials and has been included in guidelines, it has yet to be widely adopted in practice. The question remains: What is the role of T2T in rheumatology?

That’s what Jack Cush, MD, and Martin Bergman, MD, sought to answer in a point-counterpoint session at the 2022 Rheumatology Winter Clinical Symposium.

RWCS 2022 screenshot

“I do think that this is a concept we need to keep in mind, and it is a concept whose time is long overdue,” Dr. Bergman said in his presentation arguing in favor of T2T. “As good as you think you are – your ability to see the patient and determine how they’re doing – you’re not.”

But metrics alone are not enough to make clinical decisions, said Dr. Bergman, clinical professor of medicine at Drexel University, Philadelphia, citing a recommendation from 2014 recommendations on T2T published in Annals of the Rheumatic Diseases. “You don’t just follow a number. You have to take into consideration structural changes, functional impairment, comorbidities – and that’s going to adjust how you approach your patient and what you do with them.”

However, implementation of T2T to make changes in clinical practice in RA has been inconsistent. Referencing an abstract from the 2021 American College of Rheumatology annual meeting on 15-year follow-up for changing therapy in RA, Dr. Bergman argued it is not the patient who is unwilling to switch treatments. Between 2006 and 2021, patient unwillingness to change therapies decreased from 64% to 51%.

“What’s driving it mostly here [is] the doctor’s recommendation,” Dr. Bergman said. “And we know this is true because we’ve seen it in other studies.”

Many rheumatologists are “asleep at the wheel” when it comes to administering T2T, he said. “What we need to do is, after we wake up from this nap, we need to get back on the highway and drive to where we should be, which is treat-to-target.”

Dr. Bergman also shared his paradigm for administering T2T, which he noted does not typically take more than a few minutes to administer regardless of the measure chosen. “Pick a measure. I don’t care which measure you take. I personally use two: I like the RAPID3 and the CDAI,” he said. “But then, after you have the measure, evaluate the entire patient. Don’t just look at the number. Look at the patient, what’s going on, solid history, solid physical. And most importantly: Be a doctor, don’t be a computer screen.”

Problems in measurement of RA remission and adoption of T2T

Dr. Cush, who admitted early in his presentation that he is in favor of T2T, delivered his counterpoint somewhat tongue-in-cheek. However, he pointed out that there are several concerns about the goals in measuring outcomes in RA with T2T.

The goal in RA is disease remission, but how you define remission can vary, especially since sometimes there is evidence of synovitis or other disease activity visible through an exam or imaging, said Dr. Cush, a rheumatologist based in Dallas, and executive editor of RheumNow.com. Most of the evidence for T2T is in clinical trials, but adoption is inconsistent in clinical practice, and patients in general appear to be improving without widespread adoption, he argued.

“Are clinical trials the same as clinical practice?” he asked. “I think that this boils down to: Is this a quest for remissions, or the best-you-can-get, low disease activity state? Or is this a quest for physician change, which is actually the path you have to go through to get to remissions?”

“In the end, evidence that the metrics should drive prescribing, especially in private practice is, I think, lacking,” he said.

RWCS 2022 screenshot

Roy Fleischmann, MD, agreed with Dr. Cush’s point of how one defines disease remission, as well as Dr. Bergman’s paradigm for T2T. “If you’re a good rheumatologist, you really do examine joints,” but you also “take a look at patient function, patient global [assessment], your global [assessment], joint count,” he said. “You can put a number to it, but you have to take a look at all of that. Really, treat-to-target – it is all of that. It isn’t just looking at a number, it’s looking at everything. And the better that the patient can do, assuming comorbidities and everything else, the better it is.”

“The problem isn’t the patient. The problem isn’t the metric. The problem is the rheumatologist, because the rheumatologist isn’t putting in enough effort in order to reach that goal,” added Dr. Fleischmann, clinical professor of medicine at the University of Texas, Dallas, and codirector of the Metroplex Clinical Research Center, also in in Dallas.

Eric Ruderman, MD, professor of rheumatology at Northwestern University, Chicago, commented that T2T is “great for somebody who’s been doing it for a while, and seeing a lot of patients and has that comfort zone,” but he questioned whether new rheumatologists without a lot of clinical experience could apply the approach. “What information do they use to integrate, and how do they get to that point?” he asked. “I don’t have the answer to that.”

During a rebuttal, Dr. Bergman pushed back on the idea that clinical experience alone was enough. “You need something. You need a benchmark. You need something more than, ‘I say so.’ ”

“The problem is, we still haven’t convinced people to adopt them,” Dr. Bergman said. “And I think it’s failure of training because, in my opinion, I don’t know how you can do a modern current fellowship program and not teach metrics.”

Dr. Cush and Dr. Bergman used the same trials to argue for their side. “I think that us using the same slides, but maybe having different points, speaks to the problem,” Dr. Cush said. “And I choose not to make it the problem of the rheumatologists.”

“You’re in the field of pattern recognition,” Dr. Cush argued. “It’s a visual art. You can have all the numbers you want. You make the most of your decisions based on pattern recognition, which is not rooted in metrics, and that’s why you’re successful at what you do.

“I am a big believer in T2T, but I think you have to measure something, and you have to use it,” Dr. Cush closed. “And the problem is, we can’t be forced into this.”

Dr. Bergman and Dr. Cush reported having financial relationships with numerous pharmaceutical companies.

Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.

Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.

However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
 

Update needed in wake of Omicron

“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.

“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.

“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.

“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”

Diagnostic evaluation

The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.

Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
 

MIS-C and Kawasaki disease phenotypes

Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.

Cardiac management

Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms. 

MIS-C treatment

Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.

When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.

The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
 

COVID-19 and hyperinflammation

The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”

The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.

Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”

The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.

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

Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.

Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.

However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
 

Update needed in wake of Omicron

“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.

“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.

“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.

“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”

Diagnostic evaluation

The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.

Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
 

MIS-C and Kawasaki disease phenotypes

Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.

Cardiac management

Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms. 

MIS-C treatment

Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.

When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.

The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
 

COVID-19 and hyperinflammation

The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”

The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.

Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”

The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.

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

Updated guidance for health care providers on multisystem inflammatory syndrome in children (MIS-C) recognizes the evolving nature of the disease and offers strategies for pediatric rheumatologists, who also may be asked to recommend treatment for hyperinflammation in children with acute COVID-19.

Guidance is needed for many reasons, including the variable case definitions for MIS-C, the presence of MIS-C features in other infections and childhood rheumatic diseases, the extrapolation of treatment strategies from other conditions with similar presentations, and the issue of myocardial dysfunction, wrote Lauren A. Henderson, MD, MMSC, of Boston Children’s Hospital, and members of the American College of Rheumatology MIS-C and COVID-19–Related Hyperinflammation Task Force.

However, “modifications to treatment plans, particularly in patients with complex conditions, are highly disease, patient, geography, and time specific, and therefore must be individualized as part of a shared decision-making process,” the authors said. The updated guidance was published in Arthritis & Rheumatology.
 

Update needed in wake of Omicron

“We continue to see cases of MIS-C across the United States due to the spike in SARS-CoV-2 infections from the Omicron variant,” and therefore updated guidance is important at this time, Dr. Henderson told this news organization.

“MIS-C remains a serious complication of COVID-19 in children and the ACR wanted to continue to provide pediatricians with up-to-date recommendations for the management of MIS-C,” she said.

“Children began to present with MIS-C in April 2020. At that time, little was known about this entity. Most of the recommendations in the first version of the MIS-C guidance were based on expert opinion,” she explained. However, “over the last 2 years, pediatricians have worked very hard to conduct high-quality research studies to better understand MIS-C, so we now have more scientific evidence to guide our recommendations.

“In version three of the MIS-C guidance, there are new recommendations on treatment. Previously, it was unclear what medications should be used for first-line treatment in patients with MIS-C. Some children were given intravenous immunoglobulin while others were given IVIg and steroids together. Several new studies show that children with MIS-C who are treated with a combination of IVIg and steroids have better outcomes. Accordingly, the MIS-C guidance now recommends dual therapy with IVIg and steroids in children with MIS-C.”

Diagnostic evaluation

The guidance calls for maintaining a broad differential diagnosis of MIS-C, given that the condition remains rare, and that most children with COVID-19 present with mild symptoms and have excellent outcomes, the authors noted. The range of clinical features associated with MIS-C include fever, mucocutaneous findings, myocardial dysfunction, cardiac conduction abnormalities, shock, gastrointestinal symptoms, and lymphadenopathy.

Some patients also experience neurologic involvement in the form of severe headache, altered mental status, seizures, cranial nerve palsies, meningismus, cerebral edema, and ischemic or hemorrhagic stroke. Given the nonspecific nature of these symptoms, “it is imperative that a diagnostic evaluation for MIS-C include investigation for other possible causes, as deemed appropriate by the treating provider,” the authors emphasized. Other diagnostic considerations include the prevalence and chronology of COVID-19 in the community, which may change over time.
 

MIS-C and Kawasaki disease phenotypes

Earlier in the pandemic, when MIS-C first emerged, it was compared with Kawasaki disease (KD). “However, a closer examination of the literature shows that only about one-quarter to half of patients with a reported diagnosis of MIS-C meet the full diagnostic criteria for KD,” the authors wrote. Key features that separate MIS-C from KD include the greater incidence of KD among children in Japan and East Asia versus the higher incidence of MIS-C among non-Hispanic Black children. In addition, children with MIS-C have shown a wider age range, more prominent gastrointestinal and neurologic symptoms, and more frequent cardiac dysfunction, compared with those with KD.

Cardiac management

Close follow-up with cardiology is essential for children with MIS-C, according to the authors. The recommendations call for repeat echocardiograms for all children with MIS-C at a minimum of 7-14 days, then again at 4-6 weeks after the initial presentation. The authors also recommended additional echocardiograms for children with left ventricular dysfunction and cardiac aortic aneurysms. 

MIS-C treatment

Current treatment recommendations emphasize that patients under investigation for MIS-C with life-threatening manifestations may need immunomodulatory therapy before a full diagnostic evaluation is complete, the authors said. However, patients without life-threatening manifestations should be evaluated before starting immunomodulatory treatment to avoid potentially harmful therapies for pediatric patients who don’t need them.

When MIS-C is refractory to initial immunomodulatory treatment, a second dose of IVIg is not recommended, but intensification therapy is advised with either high-dose (10-30 mg/kg per day) glucocorticoids, anakinra, or infliximab. However, there is little evidence available for selecting a specific agent for intensification therapy.

The task force also advises giving low-dose aspirin (3-5 mg/kg per day, up to 81 mg once daily) to all MIS-C patients without active bleeding or significant bleeding risk until normalization of the platelet count and confirmed normal coronary arteries at least 4 weeks after diagnosis.
 

COVID-19 and hyperinflammation

The task force also noted a distinction between MIS-C and severe COVID-19 in children. Although many children with MIS-C are previously healthy, most children who develop severe COVID-19 during an initial infection have complex conditions or comorbidities such as developmental delay or genetic anomaly, or chronic conditions such as congenital heart disease, type 1 diabetes, or asthma, the authors said. They recommend that “hospitalized children with COVID-19 requiring supplemental oxygen or respiratory support should be considered for immunomodulatory therapy in addition to supportive care and antiviral medications.”

The authors acknowledged the limitations and evolving nature of the recommendations, which will continue to change and do not replace clinical judgment for the management of individual patients. In the meantime, the ACR will support the task force in reviewing new evidence and providing revised versions of the current document.

Many questions about MIS-C remain, Dr. Henderson said in an interview. “It can be very hard to diagnose children with MIS-C because many of the symptoms are similar to those seen in other febrile illness of childhood. We need to identify better biomarkers to help us make the diagnosis of MIS-C. In addition, we need studies to provide information about what treatments should be used if children fail to respond to IVIg and steroids. Finally, it appears that vaccination [against SARS-CoV-2] protects against severe forms of MIS-C, and studies are needed to see how vaccination protects children from MIS-C.”

The development of the guidance was supported by the American College of Rheumatology. Dr. Henderson disclosed relationships with companies including Sobi, Pfizer, and Adaptive Biotechnologies (less than $10,000) and research support from the Childhood Arthritis and Rheumatology Research Alliance and research grant support from Bristol-Myers Squibb.

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

The Omicron subvariant, BA.2, is not only more transmissible than the original Omicron strain, BA.1, but may cause more severe disease, a lab study from Japan says.

“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.

The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.

“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.

BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.

What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2. 

BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote. 

“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”

If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.

But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.

“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”

“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.

Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants. 

“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”

Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.

It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.

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

The Omicron subvariant, BA.2, is not only more transmissible than the original Omicron strain, BA.1, but may cause more severe disease, a lab study from Japan says.

“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.

The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.

“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.

BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.

What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2. 

BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote. 

“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”

If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.

But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.

“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”

“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.

Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants. 

“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”

Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.

It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.

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

The Omicron subvariant, BA.2, is not only more transmissible than the original Omicron strain, BA.1, but may cause more severe disease, a lab study from Japan says.

“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.

The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.

“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.

BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.

What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2. 

BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote. 

“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”

If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.

But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.

“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”

“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.

Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants. 

“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”

Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.

It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.

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