Worsening Of Disease Activity Research Articles

Comparison of Reference and Biosimilar Medications for Pediatric Noninfectious Uveitis

Objective/purpose: Compare outcomes and costs of TNF-alpha inhibitor biosimilars to reference medications in the treatment of pediatric NIU. Methods: Patients 18 years old or below treated with reference or biosimilar TNF-alpha inhibitor for noninfectious uveitis and had a history of active ocular inflammation with at least 1 month of ophthalmology follow-up from January 1, 2013, to June 1, 2023, were included. Retrospective chart review was performed. Results: Nineteen patients met the inclusion criteria. Mean age was 9.3±4.0 years, and 47.4% (9/19) were female. Of the patients who were on infliximab at any time point in their disease course (n=9), the mean duration on infliximab was 3.6 years (42 mo). Of the patients on biosimilar infliximab (n=10), the mean duration was 0.82 years (9.8 mo). Mean flares/year was 0.22±0.3 on infliximab and 0.15±0.3 on biosimilar infliximab. The average annual cost was $42,298.97 for infliximab (n =9), $41,141 for infliximab-dyyb (n=9), and $40,950 for infliximab-axxq (n=1). Reasons for switching to biosimilar infliximab from adalimumab included a combination of insurance mandate (100%), worsening disease activity (37.5%), or other issues such as noncompliance (37.5%). Conclusions: The most common reason for biosimilar initiation was insurance mandate. Compared with the reference infliximab, pediatric patients had fewer number of flares per year on biosimilar infliximab, but they were also on the biosimilar for a shorter duration of time compared with the reference which may confound an accurate assessment. Biosimilar infliximab had a lower cost profile compared with reference infliximab.

A Canadian Retrospective Chart Review Evaluating Concomitant Methotrexate De-escalation Patterns in Patients with Rheumatoid Arthritis Treated with Biologic or Targeted Synthetic DMARDs.

Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX)-anchored therapy with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); however, tolerability issues often lead to non-adherence. Canadian data on MTX tapering and/or withdrawal following b/tsDMARD initiation are minimal. This chart review assessed frequency of MTX tapering or withdrawal following b/tsDMARD initiation and the impact on disease status in Canadian adults with RA. Eligible patients had received MTX for ≥ 3months before b/tsDMARD initiation. The b/tsDMARD was prescribed continuously for ≥ 18months. Patients taking > 10mg/day oral prednisone or equivalent were excluded. Eight hundred eighty-nine patients (mean baseline MTX dose 19.0mg/week) prescribed b/tsDMARDs (tumor necrosis factor inhibitor 52.1%, Janus kinase inhibitor 18.3%, interleukin-6 inhibitor [IL-6i] 11.9%, other 17.7%) were evaluated at 22 Canadian centers. Within 2years of b/tsDMARD initiation, MTX was tapered in 123 (13.8%) patients and discontinued in 147 (16.5%), most commonly due to planned tapering (36.6%) and patient decision (27.2%), respectively, and most commonly with IL-6i use (34.9%). The MTX dose was unchanged for 582 (65.5%) patients and increased for 37 (4.2%). Missing data limit interpretations of MTX dose effects on some secondary endpoints and challenge the assertion that a disease activity measure-based treat-to-target approach is routinely used in Canadian rheumatology practice. Methotrexate tapering or withdrawal occurred in 30.4% of Canadians with RA within 2years following b/tsDMARD initiation. Baseline disease activity measures were missing from many medical records. However, for patients with baseline assessments, MTX tapering or discontinuation did not worsen disease activity.

Validation of new medication use algorithms as proxies for worsening disease activity in patients with juvenile idiopathic arthritis.

To facilitate claims-based research on populations with juvenile idiopathic arthritis (JIA), we sought to validate an algorithm of new medication use as a proxy for worsening JIA disease activity. Using electronic health record data from three pediatric centers, we defined new JIA medication use as (re)initiation of disease-modifying antirheumatic drugs or glucocorticoids (oral or intra-articular). Data were collected from 201 randomly selected subjects with (101) or without (100) new medication use. We assessed the positive predictive value (PPV) and negative predictive value (NPV) based on a reference standard of documented worsening of JIA disease activity. The algorithm was refined to optimize test characteristics. Overall, the medication-based algorithm had suboptimal performance in representing worsening JIA disease activity (PPV 69.3%, NPV 77.1%). However, algorithm performance improved for definitions specifying longer times after JIA diagnosis (≥1-year post-diagnosis: PPV 82.9%, NPV 80.0%) or after initiation of prior JIA treatment (≥1-year post-treatment: PPV 89.7%, NPV 80.0%). An algorithm for new JIA medication use appears to be a reasonable proxy for worsening JIA disease activity, particularly when specifying new use ≥1 year since initiating a prior JIA medication. This algorithm will be valuable for conducting research on JIA populations within administrative claims databases.

Autoimmune thyroid disease and rheumatoid arthritis: where the twain meet.

Autoimmune thyroid disease (AITD) is the most prevalent autoimmune disease. It shares multiple genetic, clinical, and serologic characteristics with rheumatoid arthritis (RA). Although frequently described as a classic form of single-organ autoimmunity, the AITD disease burden in a subset of patients extends well beyond the thyroid gland. This review explores the complex interaction between the two diseases and the clinical consequences when they overlap. Beyond the well-known effects of AITD on thyroid function in RA, there is mounting evidence of the association of both conditions impacting the presentation and outcomes of diabetes, metabolic syndrome, and cardiovascular disease. An increasing number of studies suggest that there are negative effects of AITD on RA disease activity both in the presence and in the absence of thyroid dysfunction. Recent evidence suggests that AITD may not only worsen the cumulative damage of RA through higher disease activity but may also worsen secondary osteoarthritis changes. Less well-known is the significant association between AITD and chronic widespread pain syndromes including fibromyalgia. Importantly, the presence of fibromyalgia, which is increased in RA patients, appears to be further increased when it overlaps with AITD. Lastly, we probe the possible influence of AITD interacting with RA on fertility and clinical depression. Key Points • Autoimmune thyroid disease is the most common autoimmune disease and is frequently associated with rheumatoid arthritis. • Autoimmune thyroid disease can present with osteoarthritis, inflammatory arthritis, and chronic widespread pain syndromes. • The co-occurrence of autoimmune thyroid disease and rheumatoid arthritis may worsen disease activity and exacerbate other disease manifestations including cardiovascular disease, fertility, and depression. • The overlap of rheumatoid arthritis with autoimmune thyroid disease needs further research and should be sought in general clinical practice.

ASSESSING THE CLINICAL IMPACTS OF IMMUNOMODULATORY WITHDRAWAL FROM ANTI-TNF COMBINATION THERAPY IN PEDIATRIC INFLAMMTORY BOWEL DISEASE

Abstract INTRODUCTION Combination therapy consists of both a monoclonal antibody against tumor necrosis factor (anti-TNF) (infliximab (IFX) or adalimumab (ADA)) and an immunomodulator (IMM) (thiopurines (TP) or methotrexate (MTX)). Although combination therapy improves clinical outcomes, the IMM may be discontinued to mitigate the risk of IMM-related adverse events. However, it is unknown how de-escalation impacts clinical outcomes in children with IBD. METHODS This is a retrospective review of pediatric patients with IBD (<18 years of age) initiated on combination therapy between January 2014 and December 2019. Demographic and laboratory data were recorded at initiation of combination therapy, prior to IMM discontinuation, and between 6-12 months after de-escalation. The primary objectives were to assess the impacts of de-escalation on clinical remission rates, laboratory markers, and anti-TNF trough levels, and to evaluate factors that predict a poor response to de-escalation. Linear mixed effects models with random intercepts accounting for correlated measures with a patient across time were used to compare differences between study groups (and subgroups). Chi-square and Kruskal-Wallis tests were used for comparisons between patients who did and did not require subsequent escalation. Hypothesis testing was conducted at an alpha of 0.05. RESULTS We included 152 pediatric patients, of whom 126 patients had CD and 26 patients had UC/IC. The mean age of initiating combination therapy was 13.76 (± 3.1) years, and the mean duration of combination therapy was 106 (± 56) weeks. De-escalation did not increase the risk of worsening disease activity or affect laboratory values, including albumin, hemoglobin, sedimentation rate, and c-reactive protein. In patients with CD on IFX and TP, calprotectin significantly increased from 107 ug/g to 383 ug/g (p<0.05) and anti-TNF trough levels significantly decreased from 19 ug/ml to 14 ug/ml (p<0.05) after de-escalation. Eighteen percent (27 patients) of patients required subsequent escalation in therapy. Amongst these patients, anti-TNF levels were lower and CRP and ESR were higher prior to de-escalation compared to patients who did not require adjustments (p<0.05). DISCUSSION Only patients with CD on IFX who discontinued the TP had a significant increase in fecal calprotectin and decrease in IFX levels, though the drug levels remained within therapeutic range >10 ug/ml, and there was no increased risk of worsening disease. Lower anti-TNF levels and higher inflammatory markers prior to de-escalation may be predictive of patients requiring escalation in therapy after stopping the IMM. De-escalation in children on combination therapy may be safely considered with close attention to clinical symptoms, inflammatory markers, and anti-TNF drug levels, especially in children with CD on IFX and TP combination therapy.

P712 Effectiveness of switching from intravenous to subcutaneous infliximab in Inflammatory Bowel Disease patients: A combined analysis of real-world evidence

Abstract Background Since approval, numerous inflammatory bowel disease (IBD) patients have been treated with subcutaneous (SC) infliximab (IFX), but real-life data based on a large multi-national population of patients switching from intravenous (IV) to SC IFX is lacking. Methods The ASSEMBLE project is an initiative to combine multi-national real-world cohort datasets and analyse the effectiveness and safety of SC IFX therapy. In the ASSEMBLE-1 analysis, three studies from France and the United Kingdom1-3 were integrated to assess the clinical outcomes up to 6 months (6M) after switching from IV to SC IFX. Clinical remission was defined as Harvey-Bradshaw Index (HBI) or modified HBI (mHBI) <5 for Crohn’s disease (CD) and Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) <3 for ulcerative colitis (UC). Treatment persistence was assessed by Kaplan-Meier survival analysis. Results The data of 428 patients were pooled from the three datasets (70.6% CD, 29.4% UC). 85.4% of patients were in clinical remission before switching with median HBI or mHBI of 1 (IQR 0,2) for CD and median SCCAI of 2 (IQR 1,3) or PMS of 0 (IQR 0,0) for UC. 59.6% of patients were treated with the standard dose of IV IFX (5 mg/kg Q8W) before switching and 54.0% of patients were on concomitant immunomodulator therapy. Patients were switched to SC IFX 120 mg Q2W (94.4%) or 120 mg QW (5.6%) regimen. After switching, the overall clinical remission rates were 83.4% and 84.7% at 3M and 6M, respectively. CD patients were associated with higher remission rate (89.8%) than UC patients (71.9%) at 6M (p<0.001). The disease activity scores and the levels of fecal calprotectin and C-reactive protein of the overall population were maintained stable after switching (Table 1). High persistence was observed in both CD (97.3% at 3M, 94.8% at 6M) and UC patients (96% at 3M, 94.1% at 6M), with no significant difference between indications (p=0.47 at 3M and p=0.78 at 6M). Perianal CD patients (n=89) did not have a significantly worse treatment persistence rate than non-perianal CD patients (p=0.30). The most common reasons leading to drug discontinuation were lost to follow-up, consent withdrawal, worsening of disease activity, and worsening of perianal disease (3 cases for each). Two patients discontinued due to injection-site pain. Conclusion This pooled analysis of ASSEMBLE-1 confirms that switching from IV to SC IFX is effective and safe for CD and UC patients in clinical practice and that the clinical remission is well maintained up to 6M after switching, with no new concerns in safety profiles. [1] Smith et al. J Crohns Colitis 2022 [2] Buisson et al. Clin Gastroenterol Hepatol 2023 [3] Rahmany et al. Gastroenterology 2023.

Lupus nephritis and socioeconomic status: Findings from the Southern California lupus registry.

Lupus nephritis (LN) is a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Despite multiple studies addressing healthcare disparities, disparate outcomes in LN persist. We investigate herein the association between socioeconomic status (SES) and LN as well as the association between SES, SLE disease activity index (SLEDAI), and treatment response. Patients were selected from the Southern California Lupus Registry (SCOLR), a registry enrolling all-comers with SLE. Analysis was completed on individuals with public vs. private insurance. Insurance and ethnicity were used as surrogate variables for SES, and we tested differences in means. After adjusting for age and sex, public insurance was independently associated with the prevalence of LN. Analysis of 35 patients revealed greater proteinuria and mean SLEDAI in patients with public insurance at baseline and 6 months. Baseline, 6-, and 12-month SLEDAI means were significantly lower in Asian/Pacific Islanders (PI) compared to others. While non-Hispanic Whites demonstrated mean SLEDAI improvement over 6 months, Asians/PI, Blacks, and Hispanics demonstrated worsened disease activity on average. Low SES, when defined by insurance, is associated with greater adverse outcomes in SLE. This is the first regional study that compares differences in treatment response in LN patients with low SES as well as association of SES with long-term outcomes in SLE and LN in southern California.

Body mass, neuro-hormonal stress processing, and disease activity in lean to obese people with multiple sclerosis.

Overweight and obesity can worsen disease activity in multiple sclerosis (MS). Although psychobiological stress processing is increasingly recognized as important obesity factor that is tightly connected to proinflammatory metabolic hormones and cytokines, its role for MS obesity remains unexplored. Consequently, we investigated the interplay between body mass index (BMI), neural stress processing (functional connectivity, FC), and immuno-hormonal stress parameters (salivary cortisol and T cell glucocorticoid [GC] sensitivity) in 57 people with MS (six obese, 19 over-, 28 normal-, and four underweight; 37 females, 46.4 ± 10.6years) using an Arterial-Spin-Labeling MRI task comprising a rest and stress stage, along with quantitative PCR. Our findings revealed significant positive connections between BMI and MS disease activity (i.e., higher BMI was accompanied by higher relapse rate). BMI was positively linked to right supramarginal gyrus and anterior insula FC during rest and negatively to right superior parietal lobule and cerebellum FC during stress. BMI showed associations with GC functioning, with higher BMI associated with lower CD8+ FKBP4 expression and higher CD8+ FKBP5 expression on T cells. Finally, the expression of CD8+ FKBP4 positively correlated with the FC of right supramarginal gyrus and left superior parietal lobule during rest. Overall, our study provides evidence that body mass is tied to neuro-hormonal stress processing in people with MS. The observed pattern of associations between BMI, neural networks, and GC functioning suggests partial overlap between neuro-hormonal and neural-body mass networks. Ultimately, the study underscores the clinical importance of understanding multi-system crosstalk in MS obesity.

The association of disease activity with depression and sleep quality in patients with rheumatoid arthritis in Hong Kong.

Patients with rheumatoid arthritis (RA) often experience depression and poor sleep. Depression and poor sleep may, in turn, worsen RA disease activity. This cross-sectional study aimed to investigate the relationship between RA disease activity as measured using the Disease Activity Score-28 (DAS28-ESR), depression measured using the Beck's Depression Inventory-II (BDI-II), and sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI). Anxiety was measured using the Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A). A total of 164 consecutive patients with RA were recruited from the Rheumatology Specialist Clinic of a regional hospital in Hong Kong. They were asked to complete questionnaires that included demographic information, the Health Assessment Questionnaire (HAQ), BDI-II, HADS-A, and PSQI. The DAS28-ESR was assessed by the attending rheumatologists. Clinical information was retrieved from the electronic medical records. The mean DAS28-ESR score was 3.35 ± 1.24 (SD). The mean BDI-II was 10.97 ± 9.15 (SD). The mean HADS-A score was 5.57 ± 3.77 (SD). The mean PSQI score was 7.55 ± 4.16 (SD). The BDI-II score was statistically correlated with the DAS28-ESR and PSQI scores. Multiple regression analysis revealed that the association of BDI-II with DAS28-ESR and PSQI was confounded by the HAQ. The association of DAS28-ESR with BDI-II but not with PSQI is in accordance with the results of previous studies. The association between the HAQ and BDI-II has also been demonstrated in previous studies. Clinicians should be aware of mood and sleep problems in patients with RA and adopt a multidisciplinary approach to their management. Future studies should provide information on causality in a more representative sample of patients with RA.

How Did COVID-19 Affect Mental Health and Access to Care in Persons With Inflammatory Bowel Disease.

The coronavirus disease pandemic globally affected public health and the world economy, leading to an increase in mental health symptoms, thought to be due in part to periods of quarantining, restrictions, and other interventions used to curb ongoing transmission of the virus. It is well established that persons with inflammatory bowel disease (IBD) have significantly higher rates of depression and anxiety than the general population and that mental health symptoms can exacerbate disease severity. For persons with IBD, psychological distress was correlated with challenges in accessing medical care. In the early stages of the pandemic, endoscopy suites were closed, leading to fewer colonoscopies, although this rebounded the following year. This likely led to fewer diagnoses of IBD initially as people avoided the health care system, and also a reduction in IBD-related dysplasia being detected during colonoscopy. Many hospitals and health care clinics adjusted by delivering telemedicine for ambulatory care. Persons with IBD had increased stress about accessing both their health care provider and gastroenterologist during the pandemic, although many had increased satisfaction with the level of care they received virtually. Telemedicine is now being used in most clinics in conjunction with in-person care, to help deliver care, and can be cost-effective. Additional research is needed to assess whether heightened levels of mental health symptoms have led to worsening disease activity, and further, if a delay in health care access including colonoscopies and surgeries, or the perceived decreased access to health care professionals for some will have detrimentally affected the disease course for persons with IBD.

Comprehensive Genomic Characterization of Staphylococcus aureus Isolated from Atopic Dermatitis Patients in Japan: Correlations with Disease Severity, Eruption Type, and Anatomical Site.

Atopic dermatitis (AD) shows frequent recurrence. Staphylococcus aureus is the primary microbial component in AD and is associated with disease activity. However, traditional typing methods have failed to characterize virulent AD isolates at the clone level. We conducted a comprehensive genomic characterization of S. aureus strains isolated from the skin of AD patients and healthy donors, comparing the whole-genome sequences of the 261 isolates with anatomical and lesional (AD-A)/nonlesional (AD-NL)/healthy sites, eruption types, clinical scores, virulence, and antimicrobial resistance gene repertoires in Japan. Sequence type (ST) diversity was lost with worsening disease activity; ST188 was the most frequently detected ST in AD-A and had the strongest correlation with AD according to the culture rate and proportion with worsening disease activity. ST188 and ST20 isolates inhabited all skin conditions, with significantly higher proportions in AD skin than in healthy skin. ST8, ST15, and ST5 proportions were equivalent for all skin conditions; ST30 was detected only in healthy skin; and ST12 was detected only in AD skin. ST97 detected in AD-A and healthy skin was clearly branched into two subclades, designated ST97A and ST97H. A comparison of two genomes led to the discovery that only ST97A possessed the complete trp operon, enabling bacterial survival without exogenous tryptophan (Trp) on AD skin, where the Trp level was significantly reduced. Primary STs showing an AD skin inhabitation trend (ST188, ST97A, ST20, and ST12) were all trp operon positive. The predominant clones (ST188 and ST97) possessed almost no enterotoxin genes, no mecA gene, and few other antimicrobial resistance genes, different from the trend observed in Europe/North America. IMPORTANCE While Staphylococcus aureus is a member of the normal human skin flora, its strong association with the onset of atopic dermatitis (AD) has been suggested. However, previous studies failed to assign specific clones relevant to disease activities. Enterotoxins produced by S. aureus have been suggested to aggravate and exacerbate the inflammation of AD skin, but their role remains ambiguous. We conducted a nuanced comprehensive characterization of isolates from AD patients and healthy donors, comparing the whole-genome sequences of the isolates with anatomical and lesional/nonlesional/healthy sites, eruption types, clinical scores, virulence, and antimicrobial resistance gene repertoires in Japan. We demonstrate that specific clones are associated with disease severity and clinical manifestations, and the dominant clones are devoid of enterotoxin genes and antimicrobial resistance genes. These findings undermine the established notion of the pathophysiological function of S. aureus associated with AD and introduce a new concept of S. aureus colonization in AD.

Safety of Measles-Mumps-Rubella booster vaccination in patients with juvenile idiopathic arthritis: A long-term follow-up study.

To study short and long-term disease activity and vaccine-related adverse events in a cohort of JIA patients who received the live attenuated measles-mumps-rubella (MMR) booster vaccine while being treated with immunosuppressive and immunomodulatory therapies. A retrospective study was performed in the UMC Utrecht, clinical and therapeutic data were collected from electronic medical records for two visits before and two visits after the MMR booster vaccine of JIA patients. Drug therapy was collected and adverse events related to the vaccine were requested from the patients during clinical visits or by short phone interviews. Associations between MMR booster vaccination and the active joint count, physician global assessment of disease activity, patient-reported visual analogue scale (VAS) for well-being and clinical Juvenile Arthritis Disease Activity Score (cJADAS) were analyzed using multivariable linear mixed effects analyses. A total of 186 JIA patients were included in the study. At the time of vaccination, 51% of the patients used csDMARD and 28% used bDMARD therapy. Overall, adjusted disease activity scores after MMR booster vaccination were not significantly different compared to pre-vaccination. Mild adverse events related to the MMR booster were reported for 7% of the patients. No serious adverse events were reported. MMR booster vaccination was safe and did not worsen disease activity during long-term follow-up in a large cohort of JIA patients being treated with both csDMARDs and biological DMARDs.

Pregnancy course and outcomes of patients with polymyositis and dermatomyositis (PM/DM) managed in a single center

We aimed to determine the association between disease activity during pregnancy and pregnancy outcomes of women with polymyositis and dermatomyositis (PM/DM). Patients with PM/DM who were managed from pregnancy to delivery at Kagawa University Hospital from March 2006 to May 2021 were enrolled. Clinical data were retrospectively analyzed to evaluate the association between disease activity during pregnancy and pregnancy outcomes. Eight pregnancies in 5 women with PM/DM were analyzed. The mean age at conception was 28.3 ± 3.8 years, and mean disease duration was 6.3 ± 3.2 years. Four patients required an increased glucocorticoid dosage because of worsening disease activity (sustained elevation of creatine phosphokinase [CPK] concentration). Two patients who continuously received immunosuppressive drugs from conception to delivery showed no increase in disease activity and did not need increased glucocorticoid dosages. The pregnancy outcomes were 1 spontaneous abortion and 7 live births. The mean gestation length was 35.3 ± 5.2 weeks, and mean birthweight was 2297.7 ± 1041.4 g. Five adverse pregnancy outcomes (APOs) occurred (2 preterm births and 4 low birthweights); most of these cases had sustained elevation of CPK concentration and increased glucocorticoid dosages. No APOs occurred in the 2 patients who received continuous immunosuppressive medication. Continued use of pregnancy-compatible medications and control of disease activity with lower glucocorticoid dosages in pregnancies with PM/DM may be important to achieve good pregnancy outcomes.

Improvement or Worsening of Disease Activity After Switch to Sarilumab in Patients With Rheumatoid Arthritis With a Partial Response to Adalimumab.

The aim of this study was to assess the effect of switching from adalimumab to sarilumab monotherapy in partial responders with rheumatoid arthritis from the MONARCH randomized trial and its open-label extension (OLE). Partial response was defined as improvement in Clinical Disease Activity Index (CDAI) of 12 or 6 units (baseline score: >22 or >10 and ≤22, respectively). Proportions of adalimumab partial responders with meaningful worsening or improvement at OLE weeks 12 and 24 were evaluated using 2 CDAI thresholds (≥6 and ≥12 points), 28-joint Disease Activity Score using erythrocyte sedimentation rate (≥0.6 and ≥1.2 points), Health Assessment Questionnaire Disability Index (≥0.22 and ≥0.30 points), Simple Disease Activity Index (≥7 and ≥13 points), physician and patient global assessments (≥10 and ≥20), and 28-joint swollen and tender joint counts (≥1 and ≥2 joints). Outcomes were analyzed using mixed-effect models with repeated measures for observed cases. The p values were produced using Wilcoxon tests. Of 369 enrolled patients, 320 (87%) entered the OLE and 155 switched from adalimumab to sarilumab; 59% (91/155) were partial responders. At week 24, 4%-17% and 2%-12% of partial responders experienced a worsening using the lower and higher thresholds, respectively, whereas 47%-78% and 27%-66% experienced improvement. Partial responders to adalimumab who switched to sarilumab had a low likelihood of experiencing meaningful worsening, with most patients showing meaningful improvement or no change in disease activity. This may help alleviate patients' fears of worsening when considering switching to a treatment with a different mechanism of action.

Non-pustular annular psoriasis with signs of high disease activity

Background: Non-pustular annular psoriasis is a rare condition in which a type of plaque psoriasis appears with ring-like lesions and a clearer central appearance. The disease activities in psoriasis may be evaluated clinically. It is essential to provide a more meaningful approach to treatment management. Case illustration: A 33-year-old woman complained of a one-year history of multiple erythematous, scaly, and annular plaques with central clearing. Some lesions were surrounded by discrete pinpoint papules on several parts of her body. The lesions worsened during seven weeks of topical and systemic therapy. Discussion: Psoriasis is a chronic, multisystem inflammatory disease with predominantly skin and joint involvement. High disease activity or unstable psoriasis was defined as recent exacerbations showing pinpoint papules developing around established and erythematous borders of the lesions. The active severe disease may present with systemic involvement due to the production of pro-inflammatory chemokines and cytokines in the skin lesions and circulation. Conclusion: A complete clinical history and physical examination can help the clinician diagnose non- pustular annular psoriasis. Several factors may cause worsening disease activity in a patient with psoriasis. Distinguishing between stable and unstable plaque psoriasis is essential to obtain information on psoriasis pathomechanism related to systemic involvement and managing therapeutic strategies. A multidisciplinary approach must be conducted in the management of a patient with high disease activity.

COVID-19 was not associated or trigger disease activity in spondylarthritis patients: ReumaCoV-Brasil cross-sectional data

ObjectivesTo evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA).MethodsReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria.Results353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62–8.47, p = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02–5.08, p = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33–24.9, p = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02–0.50, p = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41–53.64; p = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03–0.71; p = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02–0.76; p = 0.02) remained at final model as protective factor.ConclusionsOur results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments.

Inflammatory Bowel Disease and Pregnancy

Inflammatory Bowel Disease and Pregnancy

POS0288 A CANADIAN RETROSPECTIVE CHART REVIEW EVALUATING CONCOMITANT METHOTREXATE DE-ESCALATION PATTERNS IN RA PATIENTS TREATED WITH BIOLOGIC OR TARGETED SYNTHETIC DMARDS

POS0288 A CANADIAN RETROSPECTIVE CHART REVIEW EVALUATING CONCOMITANT METHOTREXATE DE-ESCALATION PATTERNS IN RA PATIENTS TREATED WITH BIOLOGIC OR TARGETED SYNTHETIC DMARDS

Overweight and Obese Status Is Not Associated With Disease Activity for Children and Adolescents With Newly Diagnosed Inflammatory Bowel Disease.

Despite the high prevalence of pediatric obesity, its impact on Crohn's disease (CD) and ulcerative colitis (UC) activity remains poorly characterized. The aim of this study was to evaluate disease-related outcomes in overweight and obese children with CD and UC. We conducted a retrospective cohort study using the ImproveCareNow Network, a multicenter registry of children with inflammatory bowel disease. We included children with newly diagnosed CD and UC enrolled in ImproveCareNow Network from September 2006 to December 2018 who had at least 1 follow-up visit 12-18 months after diagnosis. Patients were stratified into normal weight, overweight, or obese categories. Primary outcome was remission at 1 year based on physician's global assessment (PGA); key secondary outcomes included short pediatric CD activity index and pediatric UC activity index. There were 4,972 children included (70% CD). Compared with normal weight, obese and overweight children with CD did not have worse disease activity at 1 year based on PGA. However, obese children did have modestly worse disease activity based on short pediatric CD activity index (inactive 43% vs 58%, mild 48% vs 36%, and moderate-severe 9% vs 7% for obese vs normal weight, P < 0.01). For children with UC, there were no differences in disease activity at 1 year based on PGA or pediatric UC activity index. Logistic regression mirrored these findings. Obese and overweight children with newly diagnosed inflammatory bowel disease do not seem to have worsened disease activity at 1 year after diagnosis compared with normal weight children.

Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study

Serum neurofilament light chain (sNfL) is a biomarker of neuronal damage that is used not only to monitor disease activity and response to drugs and to prognosticate disease course in people with multiple sclerosis on the group level. The absence of representative reference values to correct for physiological age-dependent increases in sNfL has limited the diagnostic use of this biomarker at an individual level. We aimed to assess the applicability of sNfL for identification of people at risk for future disease activity by establishing a reference database to derive reference values corrected for age and body-mass index (BMI). Furthermore, we used the reference database to test the suitability of sNfL as an endpoint for group-level comparison of effectiveness across disease-modifying therapies. For derivation of a reference database of sNfL values, a control group was created, comprising participants with no evidence of CNS disease taking part in four cohort studies in Europe and North America. We modelled the distribution of sNfL concentrations in function of physiological age-related increase and BMI-dependent modulation, to derive percentile and Z score values from this reference database, via a generalised additive model for location, scale, and shape. We tested the reference database in participants with multiple sclerosis in the Swiss Multiple Sclerosis Cohort (SMSC). We compared the association of sNfL Z scores with clinical and MRI characteristics recorded longitudinally to ascertain their respective disease prognostic capacity. We validated these findings in an independent sample of individuals with multiple sclerosis who were followed up in the Swedish Multiple Sclerosis registry. We obtained 10 133 blood samples from 5390 people (median samples per patient 1 [IQR 1-2] in the control group). In the control group, sNfL concentrations rose exponentially with age and at a steeper increased rate after approximately 50 years of age. We obtained 7769 samples from 1313 people (median samples per person 6·0 [IQR 3·0-8·0]). In people with multiple sclerosis from the SMSC, sNfL percentiles and Z scores indicated a gradually increased risk for future acute (eg, relapse and lesion formation) and chronic (disability worsening) disease activity. A sNfL Z score above 1·5 was associated with an increased risk of future clinical or MRI disease activity in all people with multiple sclerosis (odds ratio 3·15, 95% CI 2·35-4·23; p<0·0001) and in people considered stable with no evidence of disease activity (2·66, 1·08-6·55; p=0·034). Increased Z scores outperformed absolute raw sNfL cutoff values for diagnostic accuracy. At the group level, the longitudinal course of sNfL Z score values in people with multiple sclerosis from the SMSC decreased to those seen in the control group with use of monoclonal antibodies (ie, alemtuzumab, natalizumab, ocrelizumab, and rituximab) and, to a lesser extent, oral therapies (ie, dimethyl fumarate, fingolimod, siponimod, and teriflunomide). However, longitudinal sNfL Z scores remained elevated with platform compounds (interferons and glatiramer acetate; p<0·0001 for the interaction term between treatment category and treatment duration). Results were fully supported in the validation cohort (n=4341) from the Swedish Multiple Sclerosis registry. The use of sNfL percentiles and Z scores allows for identification of individual people with multiple sclerosis at risk for a detrimental disease course and suboptimal therapy response beyond clinical and MRI measures, specifically in people with disease activity-free status. Additionally, sNfL might be used as an endpoint for comparing effectiveness across drug classes in pragmatic trials. Swiss National Science Foundation, Progressive Multiple Sclerosis Alliance, Biogen, Celgene, Novartis, Roche.