The Efficacy of Baricitinib in Real-World Patients with Refractory or Severe Juvenile Dermatomyositis:A Monocentric Retrospective Study

Objective To evaluate the efficacy and safety of low dose baricitinib in children with refractory or severe juvenile dermatomyositis (JDM) in a real-world setting. Methods A monocentric retrospective real-world study was conducted, in which fourteen refractory and one severe newly diagnosed JDM patients were included. These patients were all treated by low dose baricitinib (below the recommended dose) combined with corticosteroids and or immunosuppressive agents. Clinical data were collected at the baseline and 4, 12, 24 weeks after baricitinib implication. Treatment response (complete response (CR), Partial response (PR) and non-response (NR)) was evaluated using both the Paediatric Rheumatology International Trials Organization (PRINTO) remission criteria and skin Disease Activity Score (DAS). All the adverse events (AEs) were recorded. Results After baricitinib treatment, all 15 patients showed improvement of skin involvement, including 14 patients with recurrent skin rashes and one newly diagnosed JDM. Calcinosis stabilized in two patients (2/3) and partially regressed in one. Four patients (4/15) had interstitial lung disease (ILD), which normalized in one, improved in two and stabilized in one. One patient complicated with macrophage activation syndrome (MAS) achieved clinical remission. CR was achieved in 3/15 patients, ranging from 4 to 12 weeks after baricitinib initiation. Five patients (5/15) got PR 4 to 24 weeks after baricitinib use. Daily steroid dosage was decreased from 0.632 mg/kg to 0.357 mg/kg (P = 0.043) at 24 weeks in all responders. However, there was no statistically difference in muscle improvement. One patient was stopped using baricitinib because of varicella zoster virus infection, while no other serious side effect was observed in this study. Conclusion Low dose baricitinib had efficacy and was safe to applied in refractory or severe JDM patients, especially for recurrent skin rashes. Baricitinib may also be helpful for JDM complicated with ILD and MAS.

Establishing clinical remission criteria and the framework of a treat-to-target algorithm for Takayasu arteritis: Results of a Delphi exercise carried out by an expert panel of the Japan Research Committee of the Ministry of Health, Labour and Welfare for intractable vasculitis

ABSTRACT Objectives To develop a proposal for remission criteria and a framework for a treat-to-target (T2T) algorithm for Takayasu arteritis (TAK). Methods A study group of the large-vessel vasculitis group of the Japanese Research Committee of the Ministry of Health, Labour and Welfare for Intractable Vasculitis consists of 10 rheumatologists, 5 cardiologists, 1 nephrologist, 1 vascular surgeon, 1 cardiac surgeon, and 2 paediatric rheumatologists. A Delphi survey of remission criteria items was circulated among the study group over four reiterations. To develop the T2T algorithm, the study group conducted four face-to-face meetings and two rounds of Delphi together with three patients. Results Initial literature review resulted in a list of 117 candidate items for remission criteria, of which 56 items with a mean score of ≥4 (0–5) were extracted including disease activity domains and treatment/comorbidity domains. The study group provided six overarching principles for the T2T algorithm, two recommendations on treatment goals, five on evaluation of disease activity and imaging findings including positron emission tomography–computed tomography, and two on treatment intensification. Conclusions We developed a T2T algorithm and proposals for standardised remission criteria by means of a Delphi exercise. These will guide future evaluation of different TAK treatment regimens.

Validity of Remission Criteria in Rheumatoid Arthritis Compared to Ultrasound-Defined Remission

Objectives: Remission is the ultimate purpose of treatment in Rheumatoid Arthritis (RA). However, even when the most stringent composite scores were used, structural damages can occur. For that purpose ultrasonography (US) appears to be the best way to assess real remission. Our principal aim was to investigate the validity of different RA remission scores using the US as the reference. Methods: An analytic diagnostic study of 30 RA patients in remission according to DAS28 and a control group with active RA was conducted between January and October of 2018. Among them, we identified patients in remission according to the SDAI, the CDAI, and the ACR/EULAR remission score. The validity of each activity score for remission was calculated using as a gold standard the absence of PD signal. Results: All patients were in remission according to DAS28 with an average score of 2.03 [1.13-2.6]. US examination showed PD signals in 57% of all patients. Twenty-six patients were in remission according to CDAI, a Doppler signal was detected in 58% of those cases. SDAI remission was accomplished in 19 patients with PD activity in 53% of cases. For the 14 patients in remission according to ACR/EULAR criteria, synovial hyper-vascularization was found in 64%. Considering true remission as the absence of PD signals, the most sensitive and specific score was DAS28 (93% and 68% respectively). Conclusion: Considering remission in RA as the absence of vascularized synovitis, the DAS28 was the most sensitive and the most specific score. Keywords: Rheumatoid Arthritis, remission, ultrasonography, validity

The efficacy of bariticinib in real-world patients with refractory or severe juvenile dermatomyositis:a monocentric retrospective study

Objective To evaluate the efficacy and safety of low dose baricitinib in children with refractory or severe juvenile dermatomyositis(JDM) in a real-world setting. Methods A monocentric retrospective real-world study was conducted, in which fourteen refractory and one severe newly diagnosed JDM patients were included. These patients were all treated by low dose baricitinib (below the recommended dose) combined with corticosteroids and or immunosuppressive agents. Clinical data were collected at the baseline and 4, 12, 24 weeks after baricitinib implication. Treatment response (complete response, CR, Partial response, PR and non-response,NR) was evaluated using both the Paediatric Rheumatology International Trials Organization (PRINTO) remission criteria and skin Disease Activity Score (DAS). All the adverse events (AEs) were recorded. Results After baricitinib treatment, all 15 patients showed improvement of skin involvement, including 14 patients with recurrent skin rashes and one newly diagnosed JDM. Calcinosis stabilized in two patients (2/3) and partially regressed in one. Four patients (4/15) had interstitial lung disease (ILD), which normalized in one, improved in two and stabilized in one. One patient complicated with macrophage activation syndrome (MAS) achieved clinical remission. CR was achieved in 3/15 patients, ranging from 4 to 12 weeks after baricitinib initiation. Five patients (5/15) got PR 4 to 24 weeks after baricitinib use. Daily steroid dosage was decreased from 0.632 mg/kg to 0.357 mg/kg (P = 0.043) at 24 weeks in all responders. However, there was no statistically difference in muscle improvement. One patient was stopped using baricitinib because of varicella zoster virus infection, while no other serious side effect was observed in this study. Conclusion Low dose baricitinib had efficacy and was safe to applied in refractory or severe JDM patients, especially for recurrent skin rashes. Baricitinib may also be helpful for JDM complicated with ILD and MAS.

Early Improvements in Disease Activity Indices Predict Long-Term Clinical Remission Suggested by the Treat-to-Target Strategy in Patients with Ankylosing Spondylitis Receiving TNF-α Inhibitor Treatment

This study evaluated the possibility of clinical remission suggested by the treat-to-target strategy and identified predictors of clinical remission in 139 patients with ankylosing spondylitis (AS) receiving tumor necrosis factor-α inhibitors (TNFi). Clinical remission criteria selected were AS Disease Activity Score Inactive Disease (ASDAS-ID) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) < 2 with normal C-reactive protein (CRP) levels (BASDAI-CRP). The longitudinal relationship between clinical parameters and clinical remission was assessed using generalized estimating equations (GEEs). Responders to ASDAS-ID and BASDAI-CRP increased from 32.4% to 68.9% and from 39.9% to 75.2% at months 3 and 33, respectively. Responders to ASDAS-ID and BASDAI-CRP almost overlapped. In the univariable GEE model, age and 3-month improvement in BASDAI, ASDAS-CRP, physician and patient global assessments, and spinal pain predicted clinical remission achievement, while the presence of syndesmophytes predicted ASDAS-CRP achievement, and normalized CRP at 3 months was associated with BASDAI-CRP achievement. Multivariable GEE analysis revealed age (odds ratio (OR): 0.67; 95% confidence interval (CI), 0.49–0.93) and 3-month BASDAI improvement (OR: 1.70; CI, 1.19–2.41) as independent predictors of ASDAS-ID achievement and age (OR: 0.69; CI, 0.54–0.89), 3-month BASDAI improvement (OR: 2.00; CI, 1.45–2.76), and normalized CRP at 3 months (OR: 3.72; CI, 1.39–9.95) as independent predictors of BASDAI-CRP achievement.

Validity and Risk of Adopting PGA ≤ 2 As A Remission Criteria of Boolean in Clinical Practice in Patient With Rheumatoid Arthritis

Validity and risk of setting patient’s global assessment (PGA) ≤ 2 as a Boolean remission criteria substituting PGA ≤ 1 in treating rheumatoid arthritis (RA) was investigatedPatients were recruited from an area cohort, of whom attained Boolean remission (Boolean-1) or near remission with PGA ≤ 2 and the rest components were ≤ 1 (Boolean-2). Simplified disease activity index (SDAI) score was compared according to the criteria variations.A total of 517 patients were studied. Mean SDAI score of patients with Boolean-1 was significantly lower than that of patients with Boolean-2 at acquisition. The trend was evident in the patients who attained Boolean-1 remission. Mean SDAI score at acquisition, 6 months after, and 1 year after of patients who attained Boolean-2 first and then Boolean-1, was significantly inferior to that of patients who attained the remissions at the same time. The mean SDAI score at month 6 in the Boolean-2 was not SDAI remission at all.We concluded that setting PGA ≤ 2 as a remission criteria may not have statistical difference in disease activity from PGA ≤ 1, however, there was an determinant risk to misread that includes patient who losses clinical remission after acquisition.

Persistence and adherence to biologic therapies in juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease that often requires biological therapy to control its activity. Medication persistence and adherence are important aspects on which we have scarce information. We performed a longitudinal, retrospective, and observational study based on data from the daily clinical management of JIA patients. We recorded clinical remission at 6 and 12 months. Persistence of biological therapy was evaluated using Kaplan–Meier curves, and adherence was assessed using the medication possession ratio (MPR). We included 68 patients who received biological therapy. Of these, 11 (16.2%) and 5 (7.4%) required a second and third drug, respectively. The persistence rate for biological therapy at 5 years was 64%, with no differences between the first and second lines. Adherence was high during the first year of treatment (MPR80: 96.3%) and also in the second and third years (MPR80: 85.2% and 91.8%, respectively). Persistence and adherence to biological therapy were remarkably high in our JIA cohort. Adherence to biological treatments could be related to a higher probability of fulfilling the Wallace remission criteria at 6 months, although this was not confirmed at 12 months.

Sonographic estimation of monosodium urate burden predicts the fulfillment of the 2016 remission criteria for gout: a 12-month study

Objective To investigate whether baseline monosodium urate (MSU) burden estimated by ultrasound (US) predicts the achievement of the 2016 remission criteria for gout after 12 months. Methods In this 12-month prospective, observational and single-center study, patients with gout fulfilling all the domains of the 2016 preliminary remission criteria for gout at baseline and on urate-lowering therapy (ULT) for at least the preceding 6 months were consecutively enrolled. The US findings indicative of MSU deposits [aggregates, double contour (DC) sign, and/or tophi] were identified according to the Outcome Measure in Rheumatology US Working Group definitions. The US MSU burden was estimated by evaluating elbows, wrists, 2nd metacarpophalangeal joints, knees, ankles, and 1st metatarsophalangeal joints. Results Remission criteria were fulfilled in 21 (42.0%) out of 50 patients at 12 months. The baseline US MSU burden was significantly lower in patients who achieved remission than in those who did not fulfill the remission criteria at 12 months (1.9±1.8 vs 5.1±3.1, p<0.01). US scores and ongoing flare prophylaxis were the only significant predictors of remission with an odds ratio of 10.83 [(95%CI=1.14–102.59), p=0.04] for the absence of MSU deposits, 5.53 [(95%CI=1.34–22.76), p<0.01] for the absence of aggregates, 7.33 [(95%CI=1.71–31.44), p<0.01] for the absence of DC sign, 3.88 [(95%CI=1.08–13.92), p=0.04] for the absence of tophi, and 0.23 [(95%CI=0.07–0.75), p=0.02] for ongoing flare prophylaxis. Conclusion In gout, baseline US estimation of MSU burden is an independent predictor of the achievement of the remission criteria at 12 months.

Tocilizumab in management of refractory juvenile idiopathic arthritis, 10 years of experience at tertiary university hospital

Background Juvenile idiopathic arthritis (JIA) is the most prevalent pediatric rheumatic disorder. Progress in modalities of therapy improves the disease outcome. We aimed to determine the efficacy and safety of tocilizumab (TCZ) in the management of systemic (sJIA) and polyarticular (pJIA) in children who are resistant to conventional as well as other biological therapies. In this retrospective study, we selected JIA patients according to the International League of Association for Rheumatology (ILAR) criteria and were treated with TCZ. Response to TCZ was assessed using Juvenile Arthritis Disease Activity Score-10 (JADAS-10) and also outcomes were assessed according to the American College of Rheumatology (ACR) remission criteria. Safety of the drug was assessed by documenting possibly related adverse effects (AE). Statistical analysis using SPSS version 25 with statistical significance is considered if p ≤ 0.05. We included 16 JIA patients aged ≤ 18 years but 2 of them were excluded as they developed severe reaction during the TCZ 1st dose, so finally, 14 patients were included. Results The median age of our patients was 12 years. Of these 14 patients, 9 (64.3%) had sJIA and 5 (35.7%) had pJIA. TCZ use led to significant improvement in the JADAS-10 from mean 22.4 (± 7.9) when it was initially assessed and then 3, 6, 12, and 24 months after TCZ initiation with means 5.7 (± 3.9), 4.4 (± 3.7), 3.5 (± 3.1), and 2.7 (± 2.2), (P = 0.001, 0.001, 0.005, 0.012), respectively. Five patients exhibited TCZ possibly expected side effects. Neutropenia and infusion-related reactions were the most frequent AE. Conclusions Tocilizumab seems to be generally effective and safe drug in the management of sJIA and pJIA especially in cases refractory to conventional as well as other biologic agents.

Post-hospitalization Daycare Treatment for Adolescents With Eating Disorders

Background: There are several possible facilities for the treatment of eating disorders (EDs). Specifically, there is the issue of the use of specialized daycare and ambulatory services over inpatient settings and the place of daycare programs following inpatient treatment.Aim: We sought to examine the contribution of post-hospitalization daycare program to the treatment of adolescents hospitalized with an ED.Methods: We assessed 61 female adolescents hospitalized with an ED. All but three were diagnosed with clinical or subthreshold anorexia nervosa (AN). Three were diagnosed with bulimia nervosa. Thirty-seven patients continued with a post-hospitalization daycare program for at least 5 months, whereas 24 did not enter or were enrolled in the program for &lt;5 months. Patients completed on admission to, and discharge from, inpatient treatment self-rating questionnaires assessing ED-related symptoms, body-related attitudes and behaviors, and depression and anxiety. Social functioning was assessed 1 year from discharge using open-ended questions. One-year ED outcome was evaluated according to the patients' body mass index (BMI) and according to composite remission criteria, assessed with a standardized semistructured interview. To be remitted from an ED, patients were required to maintain a stable weight, to have regular menstrual cycles, and not to engage in binging, purging, and restricting behaviors for at least eight consecutive weeks before their assessment.Results: BMI was within normal range at follow-up, whether completing or not completing daycare treatment, and around 75% of the patients had menstrual cycles. By contrast, when using comprehensive composite remission criteria, less than a quarter of former inpatients not entering/not completing daycare program achieved remission vs. almost a half of the completers. In addition, a greater percentage of completers continued with psychotherapy following discharge. Fifty percent of both groups showed good post-discharge social functioning. No between-group differences were found in the BMI and the scores of the self-rating questionnaires at admission to, and discharge from, inpatient treatment.Conclusion: Adolescent females with EDs can maintain a normal-range BMI from discharge to 1-year follow-up, even if not completing daycare treatment. By contrast, completion of a post-hospitalization daycare program may improve the 1-year follow-up ED-related outcome of former ED inpatients.