Radiological Disease Activity Research Articles

Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis.

Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083). In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions. Log-linear trend in sNfL levels were modeled longitudinally using generalized estimating equations with robust variance estimator from baseline to week 28. Of 175 patients enrolled in RESTORE, 166 had serum samples for analysis. Participants with Gd+ lesions were younger (37.7 vs 43.1, p = 0.001) and had lower Expanded Disability Status Scale scores at baseline (2.7 vs 3.4, p = 0.017) than participants without Gd+ lesions. sNfL levels increased in participants with Gd+ lesions (n = 65) compared with those without (n = 101, mean change from baseline to maximum sNfL value, 12.1 vs 3.2 pg/mL, respectively; p = 0.003). As the number of Gd+ lesions increased, peak median sNfL change also increased by 1.4, 3.0, 4.3, and 19.6 pg/mL in the Gd+ lesion groups of 1 (n = 12), 2-3 (n = 18), 4-9 (n = 21), and ≥10 (n = 14) lesions, respectively. However, 46 of 65 (71%) participants with Gd+ lesions did not increase above the 95th percentile threshold of the group without Gd+ lesions. The initial increase of sNfL typically trailed the first observation of Gd+ lesions, and the peak increase in sNfL was a median [interquartile range] of 8 [0, 12] weeks after the first appearance of the Gd+ lesion. Although sNfL correlated with the presence of Gd+ lesions, most participants with Gd+ lesions did not have elevations in sNfL levels. These observations have implications for the use and interpretation of sNfL as a biomarker for monitoring MS disease activity in controlled trials and clinical practice.

Long-term follow up of alemtuzumab-treated patients: a retrospective study in a Belgian tertiary care center.

Pivotal studies have reported a significant proportion of patients achieving no evidence of disease activity (NEDA) after 2 cycles of treatment with alemtuzumab (ATZ), that can be maintained for several years. Long-term real-world evidence regarding ATZ as well as subsequent treatment trajectories is still scarce. To analyze the effectiveness and safety of ATZ-treated patients in a tertiary care Belgian center. A retrospective cohort study including 32 patients treated with ATZ between 2015 and 2021 was performed. 32 patients received 2 ATZ courses with a mean follow-up (FU) duration of 5.6years (range: 2.25-8.2). 21.75% patients were treatment naïve. 40.5% were previously treated with natalizumab or fingolimod. NEDA-3 was achieved in 61.3-85% of patients, with failure mostly attributed to recurrence of radiological disease activity. During FU, annualized relapse rates remained very low (0.06-0.14), disability improvement occurred in up to 40.5%, whereas disability worsening occurred in up to 13.5%. Retreatment risk was associated with younger age (< 45years old, Odds Ratio 8.0, p = 0.02) and a higher number of previous DMTs (Hazard ratio 2.7, 95%CI 1.3-7.4, p = 0.02). Safety in our cohort was consistent with the known profile of ATZ. At the end of FU, 65.6% patients remained untreated after 2 or 3 courses of ATZ, while the remaining switched to anti-CD20 therapy or cladribine. ATZ is a high efficacy therapy for active MS, providing long-term remission in a significant proportion of patients. Retreatment was more frequent in younger patients or patients having failed a higher number of previous DMTs.

Ublituximab Significantly Reduces Radiological Disease Activity at 12 Weeks: Post-hoc analysis of Participants with Highly Active Disease in the ULTIMATE I &amp; II Phase 3 Studies (P9-6.017)

Ublituximab Significantly Reduces Radiological Disease Activity at 12 Weeks: Post-hoc analysis of Participants with Highly Active Disease in the ULTIMATE I &amp; II Phase 3 Studies (P9-6.017)

CXCL10/IgG1 Axis in Multiple Sclerosis as a Potential Predictive Biomarker of Disease Activity.

Multiple sclerosis (MS) is a heterogeneous disease, and its course is difficult to predict. Prediction models can be established by measuring intrathecally synthesized proteins involved in inflammation, glial activation, and CNS injury. To determine how these intrathecal proteins relate to the short-term, i.e., 12 months, disease activity in relapsing-remitting MS (RRMS), we measured the intrathecal synthesis of 46 inflammatory mediators and 14 CNS injury or glial activation markers in matched serum and CSF samples from 47 patients with MS (pwMS), i.e., 23 RRMS and 24 clinically isolated syndrome (CIS), undergoing diagnostic lumbar puncture. Subsequently, all pwMS were followed for ≥12 months in a retrospective follow-up study and ultimately classified into "active", i.e., developing clinical and/or radiologic disease activity, n = 18) or "nonactive", i.e., not having disease activity, n = 29. Disease activity in patients with CIS corresponded to conversion to RRMS. Thus, patients with CIS were subclassified as "converters" or "nonconverters" based on their conversion status at the end of a 12-month follow-up. Twenty-seven patients with noninflammatory neurologic diseases were included as negative controls. Data were subjected to differential expression analysis and modeling techniques to define the connectivity arrangement (network) between neuroinflammation and CNS injury relevant to short-term disease activity in RRMS. Lower age and/or higher CXCL13 levels positively distinguished active/converting vs nonactive/nonconverting patients. Network analysis significantly improved the prediction of short-term disease activity because active/converting patients featured a stronger positive connection between IgG1 and CXCL10. Accordingly, analysis of disease activity-free survival demonstrated that pwMS, both RRMS and CIS, with a lower or negative IgG1-CXCL10 correlation, have a higher probability of activity-free survival than the patients with a significant correlation (p < 0.0001, HR ≥ 2.87). Findings indicate that a significant IgG1-CXCL10 positive correlation predicts the risk of short-term disease activity in patients with RRMS and CIS. Thus, the present results can be used to develop a predictive model for MS activity and conversion to RRMS.

P547 Improved clinical and radiologic healing of Crohn’s perianal fistulas using a novel coordinated care model optimising medical and surgical treatments: A prospective real-world observational study

Abstract Background Despite best standard care, sustained healing rates of Crohn’s perianal fistulas remain low. A novel coordinated multi-disciplinary care model optimising medical and surgical treatment was established with the aim to improve fistula healing rates. Methods A prospective real-world observational study evaluated the efficacy of this new care model in adults with Crohn’s perianal fistulas. Patients seen through the new care model were sequentially invited to participate, between March 2021 to April 2022, and included irrespective of disease activity, duration, or prior treatments. Three dynamic stages of care were directed towards patients’ clinical disease activity: stage A, active disease, focused on medical and surgical treatment optimisation; stage B, optimised treatments with a seton in situ, focused on definitive surgical management; and stage C, healed disease, focused on treatment maintenance. Endpoints included: [1] clinical fistula healing after a minimum of 12 months follow-up; [2] changes in radiologic disease activity and fibrosis on serial magnetic resonance imaging; and [3] proportion of patients requiring treatment optimisation. Results Sixty patients were included. At baseline, 47% were in stage A, 5% stage B, and 48% stage C. Median age was 40 years (IQR: 32-49), 52% were male, median perianal disease duration was 9 years (IQR: 2-16), and median attendance through the preexisting service was 6 years (IQR: 3-9). After a median of 22 months follow-up (IQR: 16-25), 83% had clinical healing which was significantly higher than baseline rates at study inclusion (83 vs 48%, p&amp;lt;0.001). For patients in stage A at baseline, 68% achieved clinical healing with estimated clinical healing rates of 39% (95%CI: 24-60) and 85% (95%CI: 64-97) at 1 and 2 years, respectively. This paralleled a significant reduction in radiologic disease activity and increase in radiologic fibrosis, with radiologic remission observed in 51% and radiologic response in 47% overall (Table 1). Patients who achieved clinical healing had significantly less radiologic disease activity and greater fibrosis compared to patients with non-healing fistulas. Overall, 53% had biologic dose escalation and 10% switched to an alternative biologic agent with the new care model. Thirty-seven percent underwent a median of two perianal surgical interventions (IQR: 1-3), 15% had closure or ablative techniques performed, and 15% had seton removal only. Conclusion A novel coordinated multi-disciplinary care model optimising medical and surgical treatments resulted in high rates of clinical healing and improved radiologic disease activity and fibrosis of Crohn’s perianal fistulas. Controlled-matched studies evaluating treatment optimisation are needed.

P457 Small bowel involvement proximal to the terminal ileum is a major risk factor for intestinal resection in patients with small bowel Crohn’s disease

Abstract Background The current Montreal classification categorizes Crohn's disease (CD) with small bowel involvement into two groups: L1 and L3. The study aimed to investigate the significance of small bowel involvement proximal to the terminal ileum as a significant risk factor for intestinal resection. Methods We conducted a retrospective review of the medical records of Crohn's disease patients diagnosed between January 2001 and December 2020 at Seoul St. Mary's Hospital, St. Vincent Hospital, and Eunpyeong St. Mary's Hospital. The extent of small bowel involvement was independently assessed by two experienced gastrointestinal radiologists using conventional CT, CT enterography, or MR enterography at the time of diagnosis. The terminal ileum was defined as the distal ileal segment within 10 cm from the ileocecal valve and the jejunum was defined as the proximal 1/2 of the small intestine beyond the ligament of Treitz. Radiologic disease activity and fibrostenosis at the time of diagnosis were also scored as 0, 1, and 2 using Maglinte classification, respectively. Results Out of 617 CD patients, 346 were included in the study, while 271 were excluded due to radiologic noninvolvement of the small bowel, inadequate or missing radiologic data, initial diagnosis made at another institution, or diagnosis through surgery. Median age at diagnosis was 24 years (range 10-76) and 250 (72.3%) were male. The median follow-up duration was 53 months (4-201). During the follow-up period, 43 patients (12.4%) underwent intestinal resection. Small bowel involvement proximal to the terminal ileum was significantly associated with a higher cumulative risk of intestinal resection (15.4% vs. 3.5%, P=0.006). Neither jejunal involvement or colonic involvement (L3 vs. L1) showed a significant association with cumulative risk of intestinal resection (16.0% vs. 11.1%, P=0.222; 12.4% vs. 12.4%, P=0.773). Radiologic disease activity and fibrostenotic score at the time of diagnosis were significantly associated with the cumulative risk of intestinal resection, respectively (0% vs. 4.4% vs. 19.7%, P&amp;lt;0.001; 8.5% vs. 16.7% vs. 28.2%, P&amp;lt;0.001). Conclusion Small bowel involvement proximal to the terminal ileum was a major risk factor for requiring intestinal resection in patients with small bowel CD, while jejunal involvement was not. These findings suggest a need for subclassifying small bowel CD.

Infliximab serum concentrations in luminal Crohn's Disease and its relationship with disease activity: a multicentric cross-sectional study

Objectives: In Latin America, experience with monitoring serum Infliximab (IFX) concentrations is scarce. Our study aimed to compare IFX serum concentrations between patients with active disease or in remission.Patients and methods: A cross-sectional study was performed in patients with luminal Crohn's disease (CD) during maintenance treatment with IFX. Patients were classified as in remission or disease activity according to clinical scores and endoscopic, radiological, and laboratory markers. A comparison of IFX trough levels between the two groups was performed.Results: 80 CD patients were included [41 (51%) in remission and 39 (49%) with active disease]. In the analysis of general disease activity, the median serum levels of IFX in patients with remission and with active CD were 5.63 [0.03 - 14.40] vs. 3.84 [0.03 - 14.40] (p = 0.287). Furthermore, there was no difference in serum IFX concentrations in endoscopic, radiological, and laboratory activities. Only in the clinical evaluation was there a significant difference between the IFX median serum levels between patients in remission and disease activity, 5.63 [0.03 - 14.40] vs. 2.14 [0.32 - 10.54] (p = 0.042).Conclusions: IFX serum concentrations during maintenance treatment were similar in patients with luminal CD in remission and general, endoscopic, radiological, and laboratory disease activity. Patients with clinically active disease had lower IFX concentrations than patients in remission.

Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS)

BackgroundExtended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals.MethodsThe...

MicroRNAs are dysregulated in peripheral blood mononuclear cells in multiple sclerosis and correlate with T cell mediators

T cell mediators and microRNAs are involved in the pathogenesis of multiple sclerosis (MS), but their interaction largely remains undetermined. We investigated by RT-qPCR the dysregulation of microRNAs in peripheral blood mononuclear cells of MS patients versus healthy controls, according to radiological disease activity or treatment. Several microRNAs correlated positively/negatively with IL21/FOXP3 mRNA expression, but not with serum neurofilament light chain levels. Cytokine expression is conceivably balanced by several regulators, whereas microRNAs possibly target upstream transcription factors rather than directly cytokine mRNAs. Functional studies are needed to investigate their interaction, notably for the predicted targeting of FOXP3 by miR-34c-5p.

Assessing the utility of magnetic resonance imaging-based "SuStaIn" disease subtyping for precision medicine in relapsing-remitting and secondary progressive multiple sclerosis.

Patient stratification and individualized treatment decisions based on multiple sclerosis (MS) clinical phenotypes are arbitrary. Subtype and Staging Inference (SuStaIn), a published machine learning algorithm, was developed to identify data-driven disease subtypes with distinct temporal progression patterns using brain magnetic resonance imaging; its clinical utility has not been assessed. The objective of this study was to explore the prognostic capability of SuStaIn subtyping and whether it is a useful personalized predictor of treatment effects of natalizumab and dimethyl fumarate. Subtypes were available from the trained SuStaIn model for 3 phase 3 clinical trials in relapsing-remitting and secondary progressive MS. Regression models were used to determine whether baseline SuStaIn subtypes could predict on-study clinical and radiological disease activity and progression. Differences in treatment responses relative to placebo between subtypes were determined using interaction terms between treatment and subtype. Natalizumab and dimethyl fumarate reduced inflammatory disease activity in all SuStaIn subtypes (all p < 0.001). SuStaIn MS subtyping alone did not discriminate responder heterogeneity based on new lesion formation and disease progression (p > 0.05 across subtypes). SuStaIn subtypes correlated with disease severity and functional impairment at baseline but were not predictive of disability progression and could not discriminate treatment response heterogeneity.

Discontinuation of first-line disease-modifying therapy in relapse onset multiple sclerosis.

It is not known if and when first-line disease modifying therapy (DMT) can safely be discontinued in relapse onset multiple sclerosis (MS) patients. To investigate the characteristics of patients who discontinued first-line DMT, and the occurrence of clinical and radiological inflammatory disease activity after discontinuation. We collected clinical and MRI parameters from patients with relapse onset MS in the MS Center Amsterdam and Rijnstate Hospital Arnhem who discontinued first-line DMT with no intention of restarting or switching treatment. In total, 130 patients were included in the analyses. After discontinuation, 78 patients (60%) experienced disease activity. Sixty-three patients (48.5%) showed MRI activity after DMT discontinuation, 40 patients (30.8%) experienced relapse(s), and 29 patients (22.3%) restarted DMT. Higher age at DMT discontinuation was associated with a lower risk of MRI activity (45 -55vs. <45 years: OR 0.301, p=0.007, >55vs. <45 years, OR: 0.296, p=0.044), and with a lower risk of relapse(s) after discontinuation (45-55vs. <45 years: OR=0.495, p=0.106, >55vs. <45 years: OR=0.081, p=0.020). Higher age at first-line DMT discontinuation is associated with lower risk and severity of radiological disease activity in MS, and a lower risk of relapse(s) after discontinuation.

Association between age and inflammatory disease activity on magnetic resonance imaging in relapse onset multiple sclerosis during long-term follow-up.

Inflammatory disease activity in multiple sclerosis (MS) decreases with advancing age. Previous work found a decrease in contrast-enhancing lesions (CELs) with age. Here, we describe the relation of age and magnetic resonance imaging (MRI) measures of inflammatory disease activity during long-term follow-up in a large real-world cohort of people with relapse onset MS. We investigated MRI data from the long-term observational Amsterdam MS cohort. We used logistic regression models and negative binomial generalized estimating equations to investigate the associations between age and radiological disease activity after a first clinical event. We included 1063 participants and 10,651 cranial MRIs. Median follow-up time was 6.1 years (interquartile range = 2.4-10.9 years). Older participants had a significantly lower risk of CELs on baseline MRI (40-50 years vs. <40 years: odds ratio [OR] = 0.640, 95% confidence interval [CI] = 0.45-0.90; >50 years vs. <40 years: OR = 0.601, 95% CI = 0.33-1.08) and a lower risk of new T2 lesions or CELs during follow-up (40-50 years vs. <40 years: OR = 0.563, 95% CI = 0.47-0.67; >50 years vs. <40 years: OR = 0.486, 95% CI = 0.35-0.68). Greater age is associated with a lower risk of inflammatory MRI activity at baseline and during long-term follow-up. In patients aged >50 years, a less aggressive treatment strategy might be appropriate compared to younger patients.

Association of age and inflammatory disease activity in the pivotal natalizumab clinical trials in relapsing-remitting multiple sclerosis

BackgroundFocal inflammatory disease activity in relapsing-remitting multiple sclerosis (RRMS) diminishes with increasing age. Here we use patient-level data from randomised controlled trials (RCTs) of natalizumab treatment in RRMS to investigate...

P538 Suboptimal disease control is common in patients with Crohn’s perianal fistulas with capacity to optimise medical and surgical treatment in real-world experience: A cross-sectional analysis of baseline disease characteristics in the FINESS study

Abstract Background Crohn’s perianal fistula treatment is often challenging, requiring combined medical and surgical treatment with heterogeneity in real-world practice. We herein evaluate disease activity and management history of patients with Crohn’s perianal fistulas, identifying those with active disease amenable for treatment optimisation. Methods We present the results of a cross-sectional study of disease characteristics among patients with Crohn’s perianal fistulas at a single specialist Inflammatory Bowel Disease service. Patients with Crohn’s perianal fistulas seen in clinic from February 2021 to June 2022 (new and review appointments) were sequentially enrolled. Patients were excluded based on rectovaginal or rectovesical fistulas, proctectomy, pregnancy or breastfeeding. Baseline disease activity was defined as active (stage A/B: sepsis, actively draining), optimised with a chronic seton in situ (stage C), or remission (stage D: no discharge from fistula tract external opening). Radiologic disease activity was assessed with magnetic resonance imaging using the Van Assche Index (VAI), VAI-inflammatory sub-score (VAIinfl; derived from T2-hyperintesnity, collections &amp;gt;3mm diameter, and rectal wall involvement), and Magnetic Resonance Novel Index for Fistula Imaging in Crohn’s Disease (MAGNIFI-CD) score. Results Sixty patients were included with a median age of 39 years (IQR 17.7), 52% male, median clinic attendance of 6 years (IQR 7.9), median Crohn’s and perianal disease duration of 13 (IQR 16.8) and 8 (IQR 13.5) years, respectively. Majority were on anti-tumour necrosis factor-α therapy (28% infliximab, 40% adalimumab) and an immunomodulator (55% thiopurine, 5% methotrexate). Forty-two percent had undergone perianal surgical intervention within the preceding 12 months, see Table 1. Forty-eight percent (n=29), 7% (n=4), and 45% (n=27) had stage A/B, C, and D disease activity, respectively. Radiologic disease activity scoring indices were lower between stage D and A/B (VAI 4 vs 12; VAIinfl 0 vs 8; MAGNIFI-CD 2 vs 6, respectively), see Table 2. Of those with stage A/B disease activity, 31% were not on a biologic (63% new diagnosis, 25% prior remission, 13% comorbidities precluding), 52% were infliximab naïve (71% new diagnosis, 14% prior remission, 14% contraindications), 85% who were on a biologic had potential for initial or further dose escalation, and 31% did not undergo perianal surgical intervention in the preceding 12 months. Conclusion In a single specialist centre, almost half the patients with Crohn’s perianal fistulas have clinically active disease, with capacity to optimise medical and/or surgical treatment in the majority. Prospective assessment of a model of care directed towards optimising treatment in these patients is needed.

Atypical clinical and novel radiological findings in Susac syndrome: Experience from a large monocentric cohort

Susac syndrome (SuS) is a rare immune-mediated endotheliopathy that affects the brain, retina and inner ear and is characterised by the variable clinical triad of encephalopathy, visual and vestibulocochlear dysfunction. Here, we present clinical and paraclinical data of 19 SuS patients followed at Ghent University Hospital and highlight some atypical clinical and novel radiological findings. Our findings suggest that spinal involvement expands the clinical phenotype of SuS. We further introduce dark blood sequences as a more sensitive technique to detect radiological disease activity in SuS. Our data add to the current understanding of the diagnosis, monitoring and treatment of SuS.

Radiological Disease Activity in Secondary Progressive Multiple Sclerosis

Introduction: MRI activity is less frequent among secondary progressive multiple sclerosis (SPMS) patients. In the current study, we aimed to identify SPMS patients with higher radiological disease activity (RDA) and determine their clinical characteristics. Methods: We evaluated the occurrence of RDA in SPMS patients followed at the Sheba Multiple Sclerosis Center between January 1, 2015, and December 31, 2020. All patients underwent brain and spinal cord MRI examinations as a routine follow-up unrelated to clinical disease activity. Patients were subdivided into RDA and non-RDA MRI groups based on the presence of active gadolinium-enhancing T1 lesions and/or new/enlarging T2 lesions. Demographic variables and disease-related data were compared. Results: One hundred consecutive SPMS patients, 74 females, median age of 50 years, disease duration of 19.5 years, and neurological disability by the Expanded Disability Status Scale (EDSS) score of 6.0, were included in the study. The RDA group comprised 35 patients (35%), of them 65.7% (n = 23) exhibited only brain MRI activity, 22.8% (n = 8) only spinal cord MRI activity, and 11.4% (n = 4) had both. Patients in the RDA group were diagnosed at a younger mean (SD) age of 28.2 (8.9) versus 33.7 (10.1) years and were younger with a mean (SD) age of 47.8 (9.9) versus 53.4 (10.1) years, as compared with the non-RDA group. No significant differences were found in relation to disease duration, EDSS, exposure to immunomodulatory treatments, and duration of immunomodulatory treatments. Conclusions: RDA unrelated to clinical symptomatology was more frequent in a subgroup of young SPMS patients.

Serum Neurofilament Light Trajectories and Their Relation to Subclinical Radiological Disease Activity in Relapsing Multiple Sclerosis Patients in the APLIOS Trial.

Several studies have described prognostic value of serum neurofilament light chain (sNfL) at the group level in relapsing multiple sclerosis (RMS) patients. Here, we aimed to explore the temporal association between sNfL and development of subclinical disease activity as assessed by magnetic resonance imaging (MRI) at the group level and evaluate the potential of sNfL as a biomarker for capturing subclinical disease activity in individual RMS patients. In the 12-week APLIOS study, patients (N = 284) received subcutaneous ofatumumab 20mg. Frequent sNfL sampling (14 time points over 12weeks) and monthly MRI scans enabled key analyses including assessment of the group-level temporal relationship of sNfL levels with on-study subclinical development of gadolinium-enhancing (Gd +)T1 lesions. Prognostic value of baseline sNfL ("high" vs. "low") level for subsequent on-study clinical relapse or Gd + T1 activity was assessed. Individual patient-level development of on-study Gd + T1 lesions was compared across three predictors: baseline Gd + T1 lesion number, baseline sNfL ("high" vs. "low"), and time-matched sNfL. In patients developing Gd + T1 lesions at week 4 (absent at baseline), sNfL levels increased during the month preceding the week-4 MRI scan and then gradually decreased back to baseline. High versus low baseline sNfL conferred increased risk of subsequent on-study clinical relapse or Gd + T1 activity (HR, 2.81; p < 0.0001) in the overall population and, notably, also in the patients without baseline Gd + T1 lesions (HR, 2.48; p = 0.0213). Individual patient trajectories revealed a marked difference in Gd + T1 lesions between patients with the ten highest vs. lowest baseline sNfL levels (119 vs. 19 lesions). Prognostic value of baseline or time-matched sNfL for on-study Gd + T1 lesions was comparable to that of the number of baseline MRI Gd + T1 lesions. sNfL measurement may have utility in capturing and monitoring subclinical disease activity in RMS patients. sNfL assessments could complement regular MRI scans and may provide an alternative when MRI assessment is not feasible. GOV: NCT03560739. This study provides class I evidence that serum neurofilament light may be used as a biomarker for monitoring subclinical disease activity in relapsing multiple sclerosis patients, as shown by its elevation in the weeks preceding the development of new gadolinium-enhancing T1 lesion activity.

Serum Collagen Triple Helix Repeat Containing-1 Levels are Related to Radiological Affection and Disease Activity in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a common systemic inflammatory disease. Collagen triple helix repeat containing-1 (CTHRC1) is a unique gene product able to reduce collagen deposition. The present study aimed to assess CTHRC1 level in RA patients and to uncover its relation to clinical, laboratory and radiological findings. The study included 60 adult RA patients. In addition, there were 60 control subjects who included patients with osteoarthritis (n = 20) and reactive arthritis (n = 20) and healthy controls (n = 20). Serum CTHRC1 levels were assessed by Enzyme-Linked Immunosorbent Assay (ELISA). Disease activity was calculated using the Disease Activity Score (DAS28-CRP). Radiological damage was evaluated using the Simple Erosion Narrowing Score (SENS). There was significantly higher serum CTHRC1 levels in RA patients when compared to OA, ReA and control groups [median (IQR): 4.66 (1.68-11.7) versus 1.88 (1.14-2.94), 1.55 (0.98-3.15) and 1.14 (0.85-1.3) mg/dL, respectively, p < 0.001]. There was significantly higher CTHRC1 levels in patients with higher disease activity [median (IQR): 2.23 (1.4-4.73) versus 6.55 (4.66-12.0) mg/dL, p = 0.004]. Patients with higher SENS had significantly higher CTHRC1 [median (IQR): 1.99 (1.4-4.66) versus 9.75 (4.39-12.63) mg/dL, p < 0.001] and DAS28 [median (IQR): 4.25 (2.9-5.2) versus 5.4 (4.65-5.8), p = 0.01]. Serum CTHRC1 levels are related to disease severity and radiological affection in RA patients.

Real-world evidence on siponimod treatment in patients with secondary progressive multiple sclerosis

BackgroundTherapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing–remitting MS, whereas few therapies are available for progressive forms of MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape.MethodsWe conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients. According to the retrospective study framework, data was acquired at prespecified time points. Clinical readouts were assessed every three months. Disease progression was determined as increase in expanded disability status scale (EDSS), radiological progression, or the occurrence of new relapses under treatment. For safety analyses, adverse events (AE) and reasons for discontinuation were documented. The collected data points were analyzed at baseline and after 6, 12 and 18 months. However, data were predominately collected at the 6- and 12-month time points as many patients were lost to follow-up. In a group consisting of 41 patients, a more detailed investigation regarding disease progression was conducted, including data from measurement of cognitive and motoric functions.ResultsUnder siponimod therapy, 64.8% of patients experienced sustained clinical disease stability at 12 months. Out of the stable patients 21.4% of patients improved. Of the remaining patients, 31.5% experienced EDSS progression, 3.7% worsened without meeting the threshold for progression. Relapses occurred in 7.4%. Radiological disease activity was detected in 24.1% of patients after six months of treatment and in 29.6% of patients at 12 months follow-up. The in-depth cohort consisting of 41 patients demonstrated no substantial changes in cognitive abilities measured by Paced Auditory Serial Addition Test and Symbol Digit Modalities Test or motoric functions measured with Timed 25-Foot Walk, 100-m timed test, and 9-Hole Peg Test throughout the 12-month study period. Radiological assessment showed a stable volume of white and grey matter, as well as a stable lesion count at 12 months follow-up. AE were observed in nearly half of the included patients, with lymphopenia being the most common. Due to disease progression or AE, 31.2% of patients discontinued therapy.ConclusionTreatment with siponimod had an overall stabilizing effect regarding clinical and radiological outcome measures. However, there is a need for more intensive treatment management and monitoring to identify disease progression and AE.

Serum salusin-α and salusin-β levels in patients with psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by skin lesions and joint involvement. Salusin-α and salusin-β are two new bioactive molecules. It is reported that salusins may have role in regulation of the immune system and inflammation. The aim of our study was to evaluate the serum salusin-α and salusin-β levels in PsA patients and to establish the possible relationship with the disease features. Our study included 40 PsA patients who fulfilled the CASPAR criteria and 40 healthy volunteers. Demographic, clinical, laboratory and radiological data and disease activity indices (PASI, BASDAI, BASFI, HAQ) were recorded in all patients. The enzyme-linked immunosorbent assay (ELISA) method was used to measure serum salusin-α and salusin-β levels. The demographic data were as follows: 13 patients (32.5%) were males and 27 (67.5%) were female, mean age was 48.5 years and mean disease duration was 2.4 years. Patients' history was taken and clinical assessment was performed; 20 (50%) patients had a family history, 18 (45%) patients were smoker, 19 (47.5%) patients had HLA-B27 positivity, 33 (82.5%) had sacroiliitis, 36 (90%) had enthesitis, 23 (57.5%) had distal interphalangeal (DIP) joint and nail involvement, 26 (65%) had wrist involvement, and 11 (27.5%) had ankle involvement. Laboratory data of the patients were recorded; 20 (50%) patients had elevated CRP level and 25 (62.5%) patients had an elevated ESR level. The study results showed that PsA patients had an elevated serum salusin-α level when compared with the control group (p = 0.004). The association between serum salusin-α level and ankle arthritis was found (p = 0.04). Serum levels of salusin-β were similar in PsA patients and controls both (p = 0.285). We found elevated serum salusin-α in PsA patients while the serum salusin-β levels were normal. Salusin-α may have a possible role in disease pathogenesis and it may be use as a reliable biomarker in PsA patients. Multicenter prospective studies are needed in this regard.