Absence Of Disease Activity Research Articles

Treat-to-target and shared decision-making in systemic lupus erythematosus from the patients' perspective: results from an international patient survey.

Treat-to-target (T2T) is being recognised as a promising concept to significantly improve the outcomes of patients with systemic lupus erythematosus (SLE). Despite its success being closely tied to patients' involvement, the patients' perspective regarding T2T has not been evaluated. We aimed to investigate patients' attitude towards T2T and their involvement in treatment decisions. We designed a 13-question online survey on T2T, examining acceptance, willingness to participate in T2T trials, and potential obstacles. This was distributed amongst Dutch, Austrian, German, and Bulgarian patient organisations. In total, 863 patients participated of whom 48.4% reported being in remission, while 13% were uncertain about their remission status. Regarding shared decision-making, 62.1% reported being somewhat fully involved in treatment decisions, while 20.7% felt uninvolved. Shared decision-making was associated with disease duration, Dutch origin and satisfaction with treatment and remission. As for satisfaction with their health status, 56.2% were somewhat fully satisfied, while 29.3% were unsatisfied. 65.5% were satisfied with their treatment, 14.8% were not. Leading treatment goals were quality of life (QoL) normalisation (37.4%), organ damage prevention (24.6%) and absence of disease activity (22.6%). T2T was mainly seen positive with additional doctors' visits and initiation of new immunosuppressive drugs as potential disadvantages. T2T was perceived as beneficial with improvement of QoL as the most important treatment goal and the possibility of additional doctors' visits and initiation of new immunosuppressive agents as potential drawbacks. Patients unsatisfied with their health status and treatment may benefit from greater involvement in treatment decisions.

Clinical predictors of NEDA-3 one year after diagnosis of pediatric multiple sclerosis: an exploratory single-center study.

Multiple sclerosis (MS) is an inflammatory and demyelinating disorder of central nervous system that can be diagnosed in pediatric age (<18 years) in 3-5% of the cases. This early onset is associated with higher relapse rates and earlier progression to neurological disability. By using NEDA-3 (No Evidence of Disease Activity-3) criteria, we aimed to identify clinical predictors associated with absence of disease activity and control of disease progression 12 months after the diagnosis, in a cohort of pediatric-onset MS (POMS) patients regularly followed-up in our center. We analyzed demographic, clinical, laboratorial and imaging variables of patients with POMS identified in our center, between 2010 and 2021, in two moments: at the diagnosis and 12 months after it. Statistical tests were applied to compare the distribution of those variables between groups defined by NEDA-3 status and by each one of its three variable components. We included 27 patients in the study (18 female), with a mean age of 14.8 years (± 2.8), being all diagnosed with relapsing-remitting MS and with a median score of 1.5 at the Expanded Disability Status Scale (EDSS). The use of natalizumab (p = 0.017) and the negativity for anti-EBV IgG antibodies (p = 0.018) at diagnosis were associated with a higher achievement of NEDA-3 status 12 months after, in our cohort. Prescribed treatment was also associated with statistically significant differences in the "absence of MRI activity" component of NEDA-3 (p = 0.006): patients under treatment with natalizumab had a higher probability of achieving this status, and the opposite was observed in glatiramer acetate-treated children. Our exploratory results underline the pivotal importance that an early and more effective therapeutical approach may have in the control of disease activity, in POMS. Additionally, they also seem to suggest that the presence of anti-EBV antibodies is not innocent, as it can be related to a less favorable evolution of the disease, even at a very early stage. Further studies are needed to confirm the applicability of these variables as prognostic and personalized tools in this clinical setting.

Use of individual measure and Z-scores to monitor disease course in Relapsing Multiple Sclerosis: A 1-year Prospective Study in a Single Center (P5-3.012)

<h3>Objective:</h3> To assess the performance of individual serum neurofilament (sNFL) values vs. Z-score to monitor inflammation in persons with relapsing forms of MS (pwRMS) <h3>Background:</h3> Population-based standards of sNFL levels have been recently proposed to detect activity in pwRMS. However, sNFL levels are variable, and the exact algorithm to diagnose individual-based disease activity is not defined yet. <h3>Design/Methods:</h3> A prospective cohort of 114 pwRMS were followed for 1 year. Clinical examination and sNFL assessment were performed and registered every three months. MRIs were performed annually. Baseline sNFL was the sNFL level measured at study inclusion in the absence of disease activity. Reference sNFL level was the lowest individual sNFL measure obtained during follow-up in the absence of disease activity. BMI-adjusted Z-score was registered for baseline, reference, and activity points. Non-parametric tests were used because data did not follow a normal distribution. <h3>Results:</h3> Median baseline sNFL levels were 6.85 (5.15 – 9.09); Z score 0.64 (−0.33 – 1.49). Median reference sNFL levels were 4.71 (4 – 5.87); Z score −0.36 (−1.13 – 0.42). Twenty-four patients (21.1%) had disease activity during follow-up. Median sNFL in these patients was 8.67 pg/ml (6.91 – 13) with an increase of 14.7% over the baseline level: 1.01 (−0.71 – 2.67; P = 0.66) and of 77% over the reference level: 3.63 (2.09 – 6.25; P = 0.001). Z-score during disease activity was 1.13 (0.45 – 2.27), overlapping with control levels in the population-based normogram. In our cohort, none of the individual sNFL measures or baseline Z-score predicted disease activity during the first year of follow-up, but patients with relapse at inclusion were more prone to have disease activity. <h3>Conclusions:</h3> Establishment of an individual sNFL reference value in the first year of follow-up might help to better diagnose ongoing inflammation. Baseline sNFL was not as good comparator for this outcome. <b>Disclosure:</b> Mr. Solís-Tarazona has received personal compensation for serving as an employee of Novo Nordisk A/S. Salma Reddam has nothing to disclose. Dr. Gil-Perotin has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck.

Long-term management of multiple sclerosis patients treated with cladribine tablets beyond year 4

ABSTRACT Introduction Oral cladribine is a highly effective pulsed selective immune reconstitution therapy licensed for relapsing multiple sclerosis (RMS) since 2017. A full treatment course comprises two treatment cycles given 1 year apart, followed by two treatment-free years. The management of cladribine-treated patients beyond year 4 needs to be addressed as patients have now passed the initial 4 years since European Medical Agency approval. Areas covered A panel of neurologists and a neuroradiologist experienced in MS treatment/monitoring evaluated clinical trial data and real-world evidence and proposed recommendations for the management of cladribine-treated patients beyond year 4. Expert opinion Continuous monitoring of disease activity during the treatment-free period is important. Subsequent management depends on the presence or absence of inflammatory disease activity, determined in the absence of consistent guidelines via practice-driven neurological decision criteria. Persisting or newly occurring inflammatory disease activity is an indication for further treatment, i.e. either re-initiation of cladribine or switching to another highly effective disease-modifying therapy. The decision to retreat or switch should be based on clinical and radiological evaluation considering disease course, treatment history, and safety aspects. In the absence of disease activity, either retreatment can be offered, or the treatment-free period can be extended under structured monitoring.

The Safety and Efficacy of Tofacitinib in 24 Cases of Pediatric Rheumatic Diseases: Single Centre Experience.

JAK-inhibitors are small molecules blocking the JAK-STAT pathway that have proven effective in the treatment of different immune-mediated diseases in adults and juvenile idiopathic arthritis (JIA).Aim of StudyTo evaluate the safety and efficacy of tofacitinib in children with different rheumatic diseases.Material and MethodsWe extracted information from 24 children with the following diagnosis: JIA (n = 15), undifferentiated systemic autoinflammatory diseases (SAIDs) (n = 7), and juvenile dermatomyositis (JDM) (n = 2) who have been treated with tofacitinib for a period of longer than 6 months. The treatment outcomes were classified according to the opinion of the attending physicians as having a complete response (CR), i.e., the absence of disease activity, or a partial response (PR)—a significant improvement of symptoms and disease activity, or no response (NR)—no changes in disease activity.ResultsCR was achieved in 10/24 patients; 7/15 among JIA patients, 1/2 among JDM patients, 4/7 among SAID patients, and PR in 5/15 of JIA, 1/2 of JDM, and 3/7 of SAID patients. Three non-responders with JIA discontinued tofacitinib. Corticosteroids were successfully tapered off in 11/14 patients and discontinued in 2/14 patients. Four patients had side effects not requiring treatment discontinuation: liver enzyme elevation (n = 2), hypercholesterolemia (n = 1), lymphadenitis (n = 1).ConclusionJAK-inhibitors are effective new therapies for the treatment of multiple immune-mediated diseases. Our experience has shown the best results in patients with JIA and JIA-associated alopecia, and type I interferonopathies. More data from randomized controlled clinical trials are needed to use JAK-inhibitors safely in pediatric rheumatic diseases.

P366 Exclusive enteral nutrition drives protective microbiome modulation in paediatric Crohn’s Disease

Abstract Background Exclusive enteral nutrition (EEN) is a first-line induction therapy for paediatric Crohn’s disease (CD). Although the protective mechanisms remain unclear, previous studies showed substantial changes in microbiome composition in response to EEN. We aim to assess the protective function of EEN and its impact on gut microbiome signatures in paediatric CD. Methods We prospectively followed, 15 newly diagnosed paediatric CD patients aged, 3–18 years between, 01/2019 –, 08/2021. Patients were treated according to international guidelines including EEN therapy for, 6–8 weeks, followed by a gradual re-introduction of solid food and concomitant start of maintenance treatment. Disease activity and inflammatory biomarkers were monitored during, 12-months follow-up. 16S rRNA gene sequencing and targeted/untargeted metabolomics was performed from stool samples collected weekly during EEN and monthly thereafter (n = 261). Dietary modulation and clinical activity of patient-derived stool microbiota were studied by ex-vivo faecal fermentation and after faecal microbiota transplantation (FMT) into germ free (GF) IL10-/- mice. Results All patients achieved remission with EEN therapy but, 6/15 had resuming CD activity within, 6 months. Longitudinal microbial and metabolite profiling of stool samples showed highly individualized responses to EEN without coherent signatures. Integrated multi-omics data analysis showed an enrichment of long-chain fatty acids in patients under EEN, which correlated with a reduced abundance of Lachnospiraceae, compared to patients under regular diet. Faecal microbiota from CD patients with active disease (baseline or relapse) or inactive disease (EEN-induced remission) were exposed to EEN-like or dietary control formulations in continuous ex-vivo cultures. EEN-like formulation induced protective changes in the patient-derived baseline microbiota confirmed by the absence of disease activity after FMT in GF IL10-/- mice. Mice colonized with baseline microbiota after ex-vivo EEN exposure showed a decreased abundance of Bacteroides, Akkermansia, Blautia and an increase of Lachnoclostridium and Parabacteroides in comparison to those colonized directly with patient’s baseline microbiota. In contrast, EEN-like diet failed to mitigate the aggressive behaviour of relapse microbiota when transferred into GF IL10-/- mice which was in line with an inability to cause significant compositional changes. Conclusion Our data show that clinical efficacy of EEN in paediatric CD is accompanied by temporal and individual gut microbial and metabolite changes. The combined findings of continuous culture and gnotobiotic mouse models point towards a direct protective role of EEN-modulated patient microbiomes in regulating intestinal inflammation.

CSF TNF and osteopontin levels correlate with the response to dimethyl fumarate in early multiple sclerosis.

Background:Disease activity in the first years after a diagnosis of relapsing-remitting multiple sclerosis (RRMS) is a negative prognostic factor for long-term disability. Markers of both clinical and radiological responses to disease-modifying therapies (DMTs) are advocated.Objective:The objective of this study is to estimate the value of cerebrospinal fluid (CSF) inflammatory markers at the time of diagnosis in predicting the disease activity in treatment-naïve multiple sclerosis (MS) patients exposed to dimethyl fumarate (DMF).Methods:In total, 48 RRMS patients (31 females/17 males) treated with DMF after the diagnosis were included in this 2-year longitudinal study. All patients underwent a CSF examination, regular clinical and 3T magnetic resonance imaging (MRI) scans that included the assessment of white matter (WM) lesions, cortical lesions (CLs) and global cortical thickness. CSF levels of 10 pro-inflammatory markers – CXCL13 [chemokine (C-X-C motif) ligand 13 or B lymphocyte chemoattractant], CXCL12 (stromal cell-derived factor or C-X-C motif chemokine 12), tumour necrosis factor (TNF), APRIL (a proliferation-inducing ligand, or tumour necrosis factor ligand superfamily member 13), LIGHT (tumour necrosis factor ligand superfamily member 14 or tumour necrosis factor superfamily member 14), interferon (IFN) gamma, interleukin 12 (IL-12), osteopontin, sCD163 [soluble-CD163 (cluster of differentiation 163)] and Chitinase3-like1 – were assessed using immune-assay multiplex techniques. The combined three-domain status of ‘no evidence of disease activity’ (NEDA-3) was defined by no relapses, no disability worsening and no MRI activity, including CLs.Results:Twenty patients (42%) reached the NEDA-3 status; patients with disease activity showed higher CSF TNF (p = 0.009), osteopontin (p = 0.005), CXCL12 (p = 0.037), CXCL13 (p = 0.040) and IFN gamma levels (p = 0.019) compared with NEDA-3 patients. After applying a random forest approach, TNF and osteopontin revealed the most important variables associated with the NEDA-3 status. Six molecules that emerged at the random forest approach were added in a multivariate regression model with demographic, clinical and MRI measures of WM and grey matter damage as independent variables. TNF levels confirmed to be associated with the absence of disease activity: odds ratio (OR) = 0.25, CI% = 0.04–0.77.Conclusion:CSF inflammatory markers may provide prognostic information in predicting disease activity in the first years after DMF initiation. CSF TNF levels are a possible candidate in predicting treatment response, in addition to clinical, demographic and MRI variables.

Применение нутрицевтика «Ресвега Форте» в комплексном лечении неоваскулярной возрастной макулярной дегенерации на фоне анти-VEGF терапии

Purpose. To evaluate clinical efficacy of using nutraceutical "Resvega Forte" in complex treatment neovascular age-related macular degeneration (nAMD) against the background anti-VEGF therapy using ranibizumab (LUCENTIS®). Material and methods. The object of the study was 30 patients (30 eyes) with nAMD, who received 3 "loading" intravitreal injections (IVI) of 0,5 mg (0,05 ml) ranibizumab at intervals of 1 time per month, then within a year – by the protocol "Tread-and-Extend" with increase interval between injections by 2 weeks in the absence of disease activity and its reduction in case of resumption of activity. Patients of the 1st group (16 people) were supplemented with 3 "loading" IVI of ranibizumab with appointment of "Resvega Forte" complex for 3 months and then after 6 months. Patients of the 2nd group (14 people) did not receive "Resvega Forte" complex. To assess the effectiveness of treatment, in addition to standard methods, optical coherence tomography was performed with assessment of the central retinal thickness (CRT), the presence of detachment of the retinal pigment epithelium (RPE), retinal neuroepithelium (RNE), sub- and intraretinal fluid under PE. Results. By the 12th month of observation, none of the patients of the 1st group against the background of using two complexes "Resvega Forte" was found to have resumption of disease activity: the BCVA increased 3 times and amounted to 0,78±0,04, the average indexes of CRT corresponded to the norm (249,5±12,1 µm). The interval between injections increased to 12 weeks, and their total number was 7. In the 2nd group, the resumption of disease activity was noted twice, which was accompanied by decrease in the functional and morphological parameters of retina and required decrease in the intervals between injections to 10 weeks, which accordingly led to an increase in their number to 9-10. Conclusion. The inclusion of nutraceutical "Resvega Forte" in the treatment regimen of nAMD against the background of the therapy using angiogenesis inhibitor LUCENTIS® in the protocol "Tread-and-Extend" mode allows to reduce the risk of progression of nAMD, as well as to improve the functional and morphological parameters of retina. An integrated approach makes it possible to increase the interval between injections and reduce additional monitoring, which reduces the burden on both the patient and the doctor. Key words: neovascular age-related macular degeneration, aflibercept, nutraceuticals, "Resvega forte".

AB0566 CONSENSUS-BASED RECOMMENDATIONS FOR THE MANAGEMENT OF PSORIATIC ARTHRITIS IN THE KINGDOM OF SAUDI ARABIA

Background:Psoriatic arthritis (PsA) is a chronic inflammatory condition associated with psoriasis. The common clinical features of PsA include peripheral arthritis, dactylitis, enthesitis, spondylitis, skin and nail disease1. Considering the heterogeneous course of disease and the different patient characteristics, there is a need to standardize management of PsA patients. At present, no established guidelines are available on PsA care pathway in Saudi Arabia.Objectives:To provide consensus-based guidance to all Saudi health care providers (HCPs) on the management of PsA patients including referral pathway, definition of remission and treat-to-target approach.Methods:A Delphi technique was used to understand PsA patient care pathway. In first step, a targeted literature review was conducted and a survey questionnaire including 16 questions was developed to explore PsA patient journey. In second step, this questionnaire was submitted to 127 HCPs and 33 of them provided their response. In third step, a panel of 12 experts including 10 rheumatologists, 1 dermatologist and 1 general physician reviewed the available evidence along with survey results to align on final recommendations.Results:The most common management guidelines recommended for PsA were European League against Rheumatism (EULAR, 100% agreed) and American College of Rheumatology (ACR, 100% agreed). Psoriasis Epidemiology Screening Tool (PEST) was recommended by 67% of experts as validated screening tool for PsA in dermatology clinic. The laboratory investigations included were C-reactive protein (CRP, 100%), erythrocyte sedimentation rate (ESR, 100%), complete blood count (92%), urea and creatinine (92%), liver function (92%), rheumatoid factor (56%) and X-ray of affected joints (75%). For patients with additional symptoms of back pain, X-ray of sacroiliac joints and human leukocyte antigen B27 (HLA-B27) test to be included. Only rheumatologists should recommend a magnetic resonance imaging based on the individual clinical picture. The agreement criteria for HCPs for referring patient to a rheumatologist were presence of psoriasis (100%) and one of the following features: dactylitis [100%], joint pain [100%], arthritis [100%], nail dystrophy [91%]. Patient with active arthritis should be referred to rheumatologist within 4 weeks. The referral pathway agreed by the experts for PsA patients is presented in Figure 1. Majority of experts (57%) defined clinical remission as absence of disease activity in all facets of disease assessed using the disease activity in psoriatic arthritis (DAPSA) or minimal disease activity (MDA) index. For treat-to-target, 71% of experts agreed on EULAR recommendations2. For remission and treat-to-target, experts identified a need for more clear definition.Conclusion:This expert consensus aimed to provide guidance to Saudi HCPs on standardizing diagnosis and care of PsA patients. Most experts recommended PEST as validated screening tool for PsA along with laboratory investigations such as CRP, ESR, X-ray, etc. Referral to a rheumatologist should be considered for patient with presence of psoriasis and one of the other defining features for PsA. There is a need for more clear definition of remission and treat-to-target.

THU0116 IS THE ROLE OF MEDICAL CONSULTATION IN RHEUMATOID ARTHRITIS A TIMELY TOPIC?

Background: Despite the treat-to-target recommendations and the efforts in dissecting factors that contribute to achieving disease control, the goal of remission in rheumatoid arthritis (RA) is accomplished in less than half of patients. Disease activity is assessed using composite indexes which are reliant on patient-reported outcomes, mainly the patient global assessment of disease activity (PGA). The debate on variables that can influence PGA is still open, and different internal and external factors had been taken into account: the origin of pain symptoms, psychosocial and lifestyle factors. Objectives: To canvass the opinion of RA Italian patients concerning patient-perceived topics that matter most for future research. Methods: A cross-sectional no-profit on-line anonymous survey was devised to evaluate opinions of the rheumatic diseases patients. In this sub-study we focused only on the data about RA patients. Patients were asked to rate the following topics: food/nutrition, air pollution, smoking, type of work, social participation, physical activity, emotional well-being/stress, alternative medicine, patient-physician relationship. Moreover, patients were inquired about why the topic was considered important (disease prevention, stop disease progression, control symptoms, cure the disease). The survey was disseminated between June and October 2019. Descriptive statistics were used to summarize the patient demographic, clinical data and survey results. Results: 94% (82/87) of RA patients (81 female, median age 50 yrs) rated the patient-physician relationship as the main topic for future research (figure below). Likewise, intriguing results came from the reasons of previous patient rating: the patient-physician relationship was considered important for a better control of RA symptoms (48.8%), to cure the disease (30.5%), to stop disease progression (19.5%), and to prevent the disease (1.2%). These results were similar in all age groups. Conclusion: These results highlight that the importance of medical consultation to patients and its impact on disease control should not be under-estimated. Administrative duties, time and economic constraints undermine the patient-physician relationship that is central to clinical care. The limited time spent for medical consultation is directly related to patient dissatisfaction, which in turn, may influence the patient’s perception about the absence of disease activity and could be one of motives behind the worse evaluation of PGA. Acknowledgments: We wish to thank the Lombard Association of Rheumatic Diseases (ALOMAR), Maria Vittoria Ausilio and Patrizia Angiolillo from the IT service of the University of Milan. Disclosure of Interests: Francesca Ingegnoli: None declared, Tania Ubiali: None declared, Tommaso Schioppo: None declared, Silvia Ostuzzi: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB

P381 Use of ustekinumab in Crohn’s disease: Singapore largest single-centre experience

Abstract Background Ustekinumab is the latest therapeutic option for Crohn’s disease (CD). Efficacy and safety outcomes of its use in the Asia CD population, however, have not been reported. Methods Patients with CD who received minimum 14 weeks of UST were included. The primary outcome was the percentage of patients who achieved remission by global physician assessment, GPA [defined by Steroid Free Remission (Harvey Bradshaw Index ≤4 and absence of systemic corticosteroid), stool calprotectin &amp;lt;250 μg/g and CR p &amp;lt; 5mg/l] at baseline, weeks 14, 24 and 54. Secondary outcomes included steroid-free remission, normalisation of CRP (&amp;lt;5mg/l), mucosal healing (absence of mucosal ulceration), transmural healing (absence of disease activity on CT/MR enterography); and adverse events including infection, infusion reaction, malignancy and surgery. Results Twenty-two patients were included in this study (Table 1). 22.7%, 50% and 55.6% of patients achieved remission by GPA at weeks 14, 24 and 54 respectively (Table 2). Two (2/5.40%) patients achieved mucosal healing with the median time to scope of 12 (IQR 4.5–15) months. Three (3/7, 42.9%) patients achieved transmural healing with the median time to scan of 8 (IQR 5–11) months. Reported on-treatment infection included pharyngitis, adenovirus, norovirus diarrhoea, dental abscess, shingles and cutaneous Mycobacterium abscessus. Four had surgery during the follow-up. No cases of an infusion reaction or malignancy were reported. Conclusion Efficacy and safety profile of ustekinumab in local patients with CD is comparable to their western counterpart in this first real-world Asia cohort.

Sonographic Findings of Hands and Wrists in Systemic Lupus Erythematosus Patients With Jaccoud Arthropathy.

Jaccoud arthropathy (JA) is a deforming nonerosive arthropathy, characterized by the presence of "reversible" joint deformity. The study aims at describing the main musculoskeletal ultrasound (US) findings of a series of systemic lupus erythematosus (SLE) patients with JA. Consecutive patients diagnosed as having JA and SLE were included in the study. All patients underwent a whole clinical evaluation and US of the hands and wrists. The US scan evaluated the presence of synovial hypertrophy, tenosynovitis, and bone erosions. Thirty-nine of 40 patients were female. The US examination was performed on 560 joints of the hands and wrists. At least 1 change was observed in the US examination of 20 patients (50.0%), but there was not a statistically significant association with disease activity (P = 0.33). Nineteen patients (47.5%) had synovial hypertrophy, 9 (22.5%) had tenosynovitis, and 7 (17.5%) had both. Isolated small bone erosions were identified in 2 patients (5.0%). Ultrasound examination is a reliable and noninvasive imaging method for the evaluation of joint involvement in SLE. Half of the patients with JA have ultrasonographic signs of joint inflammation, and these abnormalities may be found even in the absence of disease activity.

The patient perspective on absence of disease activity in rheumatoid arthritis: a survey to identify key domains of patient-perceived remission

BackgroundGuidelines suggest treatment in rheumatoid arthritis (RA) to target remission, in close consultation with the patient. Our recent qualitative study of the patients' perspective on remission in RA identified 26...

Activation of Tryptophan and Phenylalanine Catabolism in the Remission Phase of Allergic Contact Dermatitis: A Pilot Study

Background: Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by repeated skin exposure to contact allergens. The severity and duration of this disease are associated with many different factors. Some of these factors may represent markers for monitoring disease activity and the individual response to an intervention. Methods: We used a targeted metabolomics approach to find such factors in the serum of individuals with ACD. Metabolomics profiles were examined and compared in the acute phase of the disease and also in the absence of disease activity. Results: Our study identified a significant remission phase of ACD-associated systemic biochemical shifts in 2 metabolic pathways: tryptophan-kynurenine and phenylalanine-tyrosine. Conclusions: Although the responsible mechanisms are unclear, these results suggest that the remission phase of ACD is linked to tryptophan metabolism via kynurenine and phenylalanine-tyrosine pathways. However, further replication studies with a larger number of subjects and their subgroups are necessary to validate our results. These studies may provide a new perspective with which to understand the mechanism of and find potential biomarkers of ACD, as well as a new reference for personalized treatment.

Facial lipoatrophy secondary to Lupus Panniculitis corrected with hyaluronic acid – a case report

The present paper describes the case of a 47 year-old patient with facial Lupus Panniculitis, with absence of disease activity in excess of one year. The large malar and temporomandibular atrophy caused by the pathology has become a great problem for the patient, with impacts on her quality of life. A cutaneous filling procedure was carried out with hyaluronic acid using microcannulas, compensating the defect and with aesthetically appropriate results.

Single-dose rituximab for remission induction and maintenance therapy in ANCA-associated vasculitis: a retrospective analysis of 17 patients

Objectives: The aim of this study was to evaluate the efficacy of a repeated single-dose rituximab (RTX) regimen for remission induction and maintenance in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Method: We performed a retrospective analysis of all patients with an established diagnosis of AAV who were treated with single-dose RTX infusions at our institution. Clinical outcome data were assessed over a period of 24 months.Results: Sixteen patients were treated for remission induction and maintenance and one patient was treated for only maintenance therapy. Remission (absence of disease activity during the past 3 months and a prednisolone dose of ≤ 7.5 mg) was achieved in 11 patients (68%) with a mean time to remission of 9.4 (range 3–24) months. At 6 months, six patients (37.5%) were in remission and the mean prednisolone dose of all responding patients was 8.2 mg. Five patients had treatment failure due to early relapsing (n = 4) or persistently active (n = 1) disease. At 24 months, nine of the 11 responding patients (82%) were in remission. All patients still had concomitant steroid and/or disease-modifying anti-rheumatic drug (DMARD) therapy at 24 months. Overall, 11 relapses were seen in nine patients (five non-responders and four responders) with a mean time to relapse of 5.3 (range 4–24) months. No major relapses were observed in the responding patients. Severe infections were only seen in patients who had been previously treated with cyclophosphamide (CYC).Conclusions: The combination of single-dose RTX with other immunosuppressants seems less effective than the standard RTX regimen for the induction of remission of AAV.

Secukinumab treatment in rheumatoid arthritis is associated with incremental benefit in the clinical outcomes and HRQoL improvements that exceed minimally important thresholds

BackgroundThe primary aim of rheumatoid arthritis (RA) treatment is to induce remission, the absence of disease activity. The objective of this study was to explore the association between clinical endpoints used to gauge RA treatment efficacy and patient-reported outcomes of health-related quality of life, fatigue, and physical function in RA patients treated with secukinumab in a phase 2 randomized controlled trial (RCT).MethodAdult RA patients (n = 237) with incomplete responses to methotrexate were randomized equally to receive monthly s.c. injections of secukinumab 25 mg, 75 mg, 150 mg, 300 mg or placebo. Clinical endpoints used in this study included the ACR response criteria and its components and simplified disease activity score. Patient-reported outcomes (PRO) included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study Short Form-36 [SF-36] Survey, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue). Patients were categorized into mutually exclusive groups according to the magnitude and direction of change from baseline to week 16 in each clinical endpoint. Definitions of minimal important differences [MID] in each clinical endpoint were used to categorize patients, as well as thresholds beyond MID. Mean changes from baseline to week 16 were computed for each PRO and analyses of variance to test the differences in PRO changes observed across groups of patients that differed in each clinical endpoint. Analyses were limited to patients randomized to secukinumab treatment. All dose groups were combined (n = 187).ResultsMean changes from baseline in each PRO differed significantly across groups of patients in the expected direction. With few exceptions, there was considerable agreement between clinical endpoints and PROs concerning the magnitude of change defined as clinically meaningful. More importantly, results demonstrated that greater improvements in clinical endpoints were associated with incrementally better improvements in HRQoL, fatigue, and physical function.ConclusionResults of this study show considerable agreement between minimal thresholds of improvement established for PROs and clinical outcome measures used in RA treatment studies and provide thresholds to be considered in gauging the importance of a treatment effect that goes beyond what is considered as minimally important for PRO measures.

A101: The Impact of Sleep and Cytokine Levels on Pain Perception in JIA

Background/Purpose:Children with JIA experience more pain and disordered sleep than healthy children. JIA and poor sleep are associated with particular cytokine abnormalities, and the correlation between the two and how they relate to a patient's pain perception have not been studied. Elevation in TNF‐a, IL‐6, IL‐17, and IFN‐g have been found in the serum of children with JIA during active disease. Levels of proinflammatory cytokines are also increased during sleep loss. Indeed, blocking TNF‐a has been shown in adults with RA to improve sleep the night after the first dose. We hypothesize that dysfunctional sleep enhances pain in our patients and may be associated with abnormal cytokine profiles. In this pilot study, we hope to identify a subgroup of children with JIA that could benefit from intervention in improving sleep patterns.Methods:We plan to enroll 60 patients with JIA. Sleep is assessed by the sleep self‐report (SSR), the children's sleep habits questionnaire (CSHQ), and actigraphy. Good concordance in measurements of sleep duration has been established between PSG and actigraphy. Patients wear an actigraphy watch and keep a daily sleep and pain diary for 14 days. Disease activity is assessed using ESR, sum of active joints, patient/parent and physician global assessment of disease activity. Serum cytokine testing will be performed by flow cytometry.Results:31 patients are enrolled. We identified 7 children with disordered sleep using CSHQ/ SSR. These patients report having pain on most days, and they trend toward having elevated disease activity (increased physician and patient global assessments as well as number of active joints, ESR was non‐contributory). To date, 9 of the 31 patients underwent actigraphy. Preliminary data does not indicate an association between disease activity and objective sleep dysfunction. There is not yet enough data to comment on the association of pain and disordered sleep in the absence of disease activity. Serum from 22 patients has been collected for cytokine studies.Conclusion:There is a trend toward an association of perceived poor sleep (as reported subjectively by SSR/CSHQ) with increased pain and disease activity in our patient population. Increased disease activity does not appear to be objectively related to disordered sleep using actigraphy, however. So far, actigraphy has been conducted on patients without subjective complaints of sleep dysfunction. We plan to collect more objective data (via actigraphy) on patients with subjective sleep complaints (with and without active disease) to better characterize the relationship of pain and sleep. When this has been accomplished, we plan to investigate cytokine profiles in these groups.

Natalizumab saturation: biomarker for individual treatment holiday after natalizumab withdrawal?

More and more patients with multiple sclerosis (MS) switch from natalizumab to fingolimod because of the risk of progressive multifocal leukoencephalopathy. The duration of the treatment holiday is still under debate referring to a possible recurrence of disease activity. The aim of this study was to evaluate the prognostic value of natalizumab saturation on T cells for the recurrence of clinical and radiological disease activity. Cell surface-bound natalizumab saturation (in%) of CD8+ and CD4+ T cells from five patients with MS was determined before initiation of fingolimod by flow cytometry and related to clinical and MRI outcome during a 6-month follow-up. In two patients with either clinical or radiological disease activity, the natalizumab saturation on CD8+ and CD4+ T cells was <30%. In contrast, the remaining three patients with absence of disease activity had a median natalizumab saturation of 70% (range 59-79%) on CD4+ and 66% (range 52-68%) on CD8+ T cells. The data of this pilot study indicate that clinical and radiological disease activity is closely linked to natalizumab saturation at the time point of switch. The determination of natalizumab saturation may be an essential tool to monitor cessation of natalizumab treatment.

SAT0172 Psychiatric Disorders in Behcet’S Disease: is It a Primary or Secondary Feature of the Disease?

BackgroundFrequency of psychiatric disorders in BD is a debated issue: while some experts attribute their presence to the chronicity of the illness, others think that they may be imputable to...