The article contains some suggestions on the formation of sets of local criteria for the selection of optimal building technologies. Tables of priority local criteria universal for all building ...technologies are provided. Interest of the construction participants in use of these criteria is proved. Application of priority local criteria will allow to exclude expenses of time for their analysis and to avoid mistakes at their choice and also to provide possibility of automation of the choice of optimum building technologies.
Even though the incidence of Multisystem Inflammatory Syndrome in children (MIS-C) is decreasing cases are still reported across the world. Studying the consequences of MIS-C enhances our ...understanding of the disease's prognosis. The objective of this study was to assess short- and medium-term clinical outcomes of MIS-C.
Prospective observational cohort study at Municipal Children's Hospital Morozovskaya, Moscow, Russia. All children meeting the Royal College of Paediatrics and Child Health (RCPCH), Centers for Disease Control and Prevention (CDC), or the World Health Organization (WHO) MIS-C case definition admitted to the hospital between 17 May and 26 October 2020 were included in the study. All survivors were invited to attend a clinic at 2 and 6 weeks after hospital discharge.
37 children median age 6 years (interquartile range IQR 3.3-9.4), 59.5% (22/37) boys were included in the study. 48.6% (18/37) of patients required ICU care. One child died. All children had increased levels of systemic inflammatory markers during the acute event. Echocardiographic investigations identified abnormal findings in 35.1% (13/37) of children. 5.6% (2/36) of children were presenting with any symptoms six weeks after discharge. By six weeks the inflammatory markers were within the reference norms in all children. The echocardiographic evaluation showed persistent coronary dilatation in one child.
Despite the severity of their acute MIS-C, the majority of children in our cohort fully recovered with none having elevated laboratory markers of inflammation at 6 weeks, few (< 10%) reporting persistent symptoms at 6 weeks, and only one with persistent echocardiographic abnormalities.
Remission is the primary objective of treating juvenile idiopathic arthritis (JIA). It is still debatable whether early intensive treatment is superior in terms of earlier achievement of remission. ...The aim of this study was to evaluate the effectiveness of early etanercept+methotrexate (ETA+MTX) combination therapy versus step-up MTX monotherapy with ETA added in refractory disease.
A multi-centre, double-blind, randomized study in active polyarticular JIA patients treated with either ETA+MTX (n = 35) or placebo+MTX (n = 33) for up to 24 weeks, followed by a 24-week open-label phase. The efficacy endpoints included pedACR30 criteria improvement at week 12, inactive disease at week 24, and remission at week 48. Patients who failed to achieve the endpoints at week 12 or at week 24 escaped to open-label ETA+MTX. Safety was assessed at each visit.
By intention-to-treat analysis, more patients in the ETA+MTX group reached the pedACR30 response at week 12 (33 (94.3%)) than in the placebo+MTX group (20 (60.6%); p = 0.001). At week 24, comparable percentages of patients reached inactive disease (11 (31.4%) vs 11 (33.3%)). At week 48, 11 (31.4%) and eight (24.2%) patients achieved remission. The median (+/-IQR) times to achieve an inactive disease state in the ETA+MTX and placebo+MTX groups were 24 (14-32) and 32 (24-40) weeks, respectively. Forty-four (74/100 patient-years) adverse events (AEs) were reported, leading to treatment discontinuation in 6 patients.
Early combination therapy with ETA+MTX proved to be highly effective compared to the standard step-up regimen. Compared to those treated with the standard regimen, more patients treated with a combination of ETA+MTX reached the pedACR30 response and achieved inactive disease and remission more rapidly.
Systemic juvenile idiopathic arthritis (SJIA) accounts for 10–15% of juvenile arthritis cases. The incidence of inflammatory bowel disease (IBD) is generally higher in SJIA patients than in the ...general pediatric population; however, the association of IBD with SJIA is rare. Among 65 patients with SJIA managed in two pediatric rheumatology centers, IBD was detected in 3 patients 3, 8, and 10 years from the SJIA onset. The clinical presentation of IBD in patients with SJIA is rather scanty; the diagnosis is mainly based on the colonoscopy and biopsy results. In 2 patients, Crohn's disease was diagnosed, and undifferentiated colitis in 1 patient.
An observational cohort study evaluated immunomodulatory therapy of multisystem inflammatory syndrome in children by comparing IVIG, IVIG plus glucocorticoids, or glucocorticoids alone. The ...investigators found no evidence of the superiority of any of the three therapies, although significant differences may emerge as more data accrue.
Objective To evaluate the interleukin-6 receptor inhibitor tocilizumab for the treatment of patients with polyarticular-course juvenile idiopathic arthritis (pcJIA). Methods This three-part, ...randomised, placebo-controlled, double-blind withdrawal study (NCT00988221) included patients who had active pcJIA for ≥6 months and inadequate responses to methotrexate. During part 1, patients received open-label tocilizumab every 4 weeks (8 or 10 mg/kg for body weight (BW) <30 kg; 8 mg/kg for BW ≥30 kg). At week 16, patients with ≥JIA-American College of Rheumatology (ACR) 30 improvement entered the 24-week, double-blind part 2 after randomisation 1:1 to placebo or tocilizumab (stratified by methotrexate and steroid background therapy) for evaluation of the primary end point: JIA flare, compared with week 16. Patients flaring or completing part 2 received open-label tocilizumab. Results In part 1, 188 patients received tocilizumab (<30 kg: 10 mg/kg (n=35) or 8 mg/kg (n=34); ≥30 kg: n=119). In part 2, 163 patients received tocilizumab (n=82) or placebo (n=81). JIA flare occurred in 48.1% of patients on placebo versus 25.6% continuing tocilizumab (difference in means adjusted for stratification: −0.21; 95% CI −0.35 to −0.08; p=0.0024). At the end of part 2, 64.6% and 45.1% of patients receiving tocilizumab had JIA-ACR70 and JIA-ACR90 responses, respectively. Rates/100 patient-years (PY) of adverse events (AEs) and serious AEs (SAEs) were 480 and 12.5, respectively; infections were the most common SAE (4.9/100 PY). Conclusions Tocilizumab treatment results in significant improvement, maintained over time, of pcJIA signs and symptoms and has a safety profile consistent with that for adults with rheumatoid arthritis. Trial registration number: NCT00988221.
Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA).
...This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434.
Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 29% of 72 patients) than with placebo (37 53% of 70 patients; hazard ratio 0·46, 95% CI 0·27–0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study.
The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections.
Pfizer.
BackgroundTreatment options in patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are currently limited. This trial aimed to demonstrate the efficacy and safety ...of secukinumab in patients with active ERA and JPsA with inadequate response to conventional therapy.MethodsIn this randomised, double-blind, placebo-controlled, treatment-withdrawal, phase 3 trial, biologic-naïve patients (aged 2 to <18 years) with active disease were treated with open-label subcutaneous secukinumab (75/150 mg in patients <50/≥50 kg) in treatment period (TP) 1 up to week 12, and juvenile idiopathic arthritis (JIA) American College of Rheumatology 30 responders at week 12 were randomised 1:1 to secukinumab or placebo up to 100 weeks. Patients who flared in TP2 immediately entered open-label secukinumab TP3 that lasted up to week 104. Primary endpoint was time to disease flare in TP2.ResultsA total of 86 patients (median age, 14 years) entered open-label secukinumab in TP1. In TP2, responders (ERA, 44/52; JPsA, 31/34) received secukinumab or placebo. The study met its primary end point and demonstrated a statistically significant longer time to disease flare in TP2 for ERA and JPsA with secukinumab versus placebo (27% vs 55%, HR, 0.28; 95% CI 0.13 to 0.63; p<0.001). Exposure-adjusted incidence rates (per 100 patient-years (PY), 95% CI) for total patients were 290.7/100 PY (230.2 to 362.3) for adverse events and 8.2/100 PY (4.1 to 14.6) for serious adverse events in the overall JIA population.ConclusionsSecukinumab demonstrated significantly longer time to disease flare than placebo in children with ERA and JPsA with a consistent safety profile with the adult indications of psoriatic arthritis and axial spondyloarthritis.Trial registration number NCT03031782.
Abstract
Background/Aims
Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are two conditions that represent paediatric correlates of axial spondyloarthritis (axSpA) and ...adult psoriatic arthritis (PsA), respectively. Secukinumab has demonstrated efficacy and safety in adult patients with PsA, ankylosing spondylitis, and non-radiographic axSpA. This study evaluated efficacy and safety of secukinumab using a randomized, double-blind, placebo-controlled flare prevention design in patients with active ERA and JPsA.
Methods
Patients (aged 2 to < 18 years) classified as ERA or JPsA according to ILAR criteria of ≥ 6 months’ duration with active disease were included. The 2-year study consisted open-label subcutaneous secukinumab (75/150 mg in patients <50/ ≥50 kg) treatment at baseline, and at Weeks 1, 2, 3, 4, 8, and 12 in treatment period (TP) 1. Responders who achieved at least JIA ACR 30 response at Week 12 were randomized into the double-blind TP2 to continue secukinumab or placebo every 4 weeks until disease flare, or up to Week 100. Primary endpoint was time to flare in TP2; key secondary endpoints included JIA ACR 30/50/70/90/100, inactive disease, juvenile arthritis disease activity score (JADAS), enthesitis and active joint counts, and safety. Analysis of time to flare in TP2 included proportion of patients with disease flare, Kaplan-Meier estimate of median days for time to flare, hazard ratio (HR) estimate, and stratified log-rank test P-value. Intent-to-treat (ITT) analysis using non-responder imputation (NRI) and as-observed analysis were performed for JIA ACR 30/50/70/90/100 responses and inactive disease.
Results
86/97 (88.7%) screened patients were enrolled in TP1 (mean age, 13.1 years; female, 33.7%; ERA, n = 52; JPsA, n = 34) with a mean JADAS-27 score of 15.1 and enthesitis count of 2.6 at baseline. At Week 12, 75/83 (90.4%) patients achieved JIA ACR 30 and entered TP2. There were 21 flares in placebo-treated and 10 flares in secukinumab-treated patients during TP2. Primary endpoint was met: secukinumab-treated patients had significantly longer time to flare versus placebo, resulting in a 72% reduced flare risk (HR: 0.28; 95% CI: 0.13-0.63; P<0.001). There were minor differences between the ITT and as-observed analysis in JIA ACR responses and inactive disease in TP1. Improvement in JADAS-27 score was observed in patients in both ERA and JPsA categories (mean JADAS-27 score of 4.6). Rates of adverse events (AEs; 91.7% vs 92.1%) and serious AEs (14.6% vs 10.5%) in secukinumab and placebo groups were comparable in entire TP. No new safety signals were observed in patients receiving secukinumab (injection-site reaction, n = 1; overall patient-years=141.5).
Conclusion
In children and adolescents with ERA and JPsA, efficacy of secukinumab was demonstrated with significantly longer time to flare versus placebo, with sustained improvement of signs and symptoms up to Week 104. Efficacy was observed in ERA and JPsA patients along with a favorable safety profile.
Disclosure
A.V. Ramanan: Consultancies; Novartis, Eli Lilly, UCB, Abbvie, Sobi, Roche. Honoraria; Novartis, Eli Lilly, UCB, Abbvie, Sobi, Roche. H.I. Brunner: Consultancies; Aurina, AbbVie, Astra Zeneca-Medimmune, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, F. Hoffmann-La Roche, Merck, Novartis, R-Pharm, Sanofi, Pfizer. Member of speakers’ bureau; Pfizer, Roche, GlaxoSmithKline. Grants/research support; Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, F. Hoffmann-La Roche, Janssen, Novartis, Pfizer. I. Foeldvari: Consultancies; Novartis, Eli Lilly, Pfizer. E. Alexeeva: Member of speakers’ bureau; Novartis, Pfizer, Sanofi, MSD, Amgen, Eli Lilly, Roche. Grants/research support; Novartis, Pfizer, Sanofi, MSD, Amgen, Eli Lilly, Roche. N.A. Ayaz: None. I. Calvo: Consultancies; Sobi, Novartis, Abbvie, GlaxoSmithKline, Pfizer, Amgen, Clementia. Member of speakers’ bureau; Sobi, Novartis, Novartis, GlaxoSmithKline, Pfizer, Amgen, Clementia. O. Kasapcopur: None. V.G. Chasnyk: None. M. Hufnagel: Grants/research support; Astellas, F. Hoffmann-La Roche, Novartis. Z. Zuber: None. G. Schulert: Consultancies; Sobi, Novartis. S. Ozen: None. A. Popov: None. C. Scott: None. B. Sözeri: None. E. Zholobova: Member of speakers’ bureau; Abbvie, Pfizer, Roche, Novartis. Grants/research support; Pfizer, Novartis. X. Zhu: Other; Employee of Novartis. S. Whelan: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. L. Pricop: Shareholder/stock ownership; Novartis. Other; Employee of Novartis. A. Ravelli: Consultancies; AbbVie, Pfizer. Honoraria; AbbVie, Pfizer, Novartis, Reckitt-Benkiser, Angelini. Member of speakers’ bureau; Novartis. Grants/research support; Novartis, Pfizer. A. Martini: Consultancies; Aurinia, Bristol Myers Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche. Honoraria; Aurinia, Bristol Myers Squibb, Eli-Lilly, EMD Serono, Janssen, Pfizer, Roche. D.J. Lovell: Consultancies; AstraZeneca, Wyeth, Amgen, Abbott, Pfizer, Hoffmann-La Roche, Novartis, UBC, Janssen, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Bristol Myers Squibb, AbbVie. Member of speakers’ bureau; Abbott, Novartis, DSMB member: Forest Research, NIH-NIAMS, Canadian Arthritis Society. N. Ruperto: Honoraria; Ablynx, Amgen, Astrazeneca-Medimmune, Aurinia, Bayer, Bristol Myers and Squibb, Cambridge Healthcare Research (CHR), Celgene, Domain therapeutic, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Idorsia, Janssen, Novartis, Pfizer, Sobi, UCB.
PDF
