BackgroundTumor necrosis factor inhibitors are highly effective and safe in treatment of juvenile idiopathic arthritis (JIA). Nonetheless, to select the optimal therapy and to achieve maximum therapeutic effect it is necessary to consider the individual characteristics of the patient. Adalimumab (ADA) is widespread use for mild and severe polyarticular JIA especially in the presence of uveitis, but there is lack of data about clinical and laboratory predictors of response to ADA in different JIA categories.ObjectivesTo identify clinical and laboratory parameters associated with response to adalimumab treatment in 12 months in patients with different JIA category.MethodsAnalysis include patients with enthesitis-related arthritis (ERA, n=56), RF-negative polyarthritis (polyRF-, n=50), extended oligoarthritis (extOligo, n=30), and persistent oligoarthritis (persOligo, n=62) with median age 10.5 (IQR 7–14) and median JADAS-71 19.5 (IQR 15–28). Patients were divided to response groups after 12 month treatment with ADA according to ACRPedi criteria, achieving inactive disease by Wallace criteria and JADAS-71 cut-off point as excellent, intermediate and poor responders. For each of JIA category univariate and multivariate logistic regression analysis was conducted to identify potential baseline factors associated with treatment response. Baseline factors included clinical, laboratory and anamnestic data.ResultsADA was shown to be effective in all groups with 90%/89%/82%/63% children with ACR30/50/70/90 during one year therapy. The most significant factors (p<0.05) associated with response to ADA treatment are presented in summarized table.Table 1FactorsExcellent response to ADAPoor response to ADA CHAQ scorelower at start of ADA (ExtOligo)–VAS disease activity by patient/parenthigher at start of ADA (ERA)lower at start of ADA (ERA)VAS disease activity by physician–lower at start of ADA (PersOligo)Need for corticosteroid eye drops (for uveitis patients)Absence in anamnesis (PersOligo)–Morning stiffnessShorter at start of ADA (ERA), longer at start of ADA (PersOligo)–Joints with active arthritis–higher at start of ADA (PolyRF-)erythrocyte sedimentation rate (ESR)–lower at start of ADA (PolyRF-)Our findings demonstrated that different predictors corresponded with different JIA categories. Interestingly subjective scales of disease activity was shown to be strongly associated with response to therapy. At the same time VAS severity at baseline were inversely correlated with achievement of good response. Duration of morning stiffness correlated with excellent response in children with 2 different categories. However, for ERA patients shorter duration was associated with better response to treatment while vice versa for PersOligo patients.ConclusionsPredictors of response to ADA treatment differ in JIA categories. Low disease activity parameters (clinical and laboratory) at baseline not always predict good response to therapy.Disclosure of InterestE. Kashchenko Grant/research support from: Novartis, E. Alexeeva Grant/research ...
BackgroundChildren with chronic rheumatic diseases, including juvenile idiopathic artritis, are at high risk of bacterial and viral infections. The risk of complications and severity of infectious diseases are increased in immunosuppressive therapy due to given the long-term use.ObjectivesTo evaluate the safety and tolerability of vaccination against pneumococcus in children with juvenile idiopathic arthritis.MethodsThe analysis included 39 patients with juvenile idiopathic arthritis who were in remission. Patients were divided into two groups, depending on the type of immunosuppressive therapy. Group 1 (n=24) consisted of patients receiving etanercept, mean age 5,4±2,5, observed 48 patient-years; Group 2 (n=15), patients who received methotrexate mean age 6,8±3,2, observed 30 patient-years. All patients had been vaccinated by 13-valent pneumococcal polysaccharide conjugate vaccine (13PPV). Recorded the incidence of infection diseases (such as pneumonia, tonsillitis, otitis media, etc.) in the 12 months prior to vaccination and 12 months after vaccination. All patients monitored the development of adverse events against the background of vaccination.ResultsThe study showed a decrease in the incidence ofinfection diseases after vaccination in the first group from 5,4±1,66 to 1,7±0,77, in second group from 4,4±1,05 to 1,6±0 73, (p<0.05). Adverse events related to vaccination are presented in the table. Results of the study showed no relapse of the underlying disease following immunization. Adverse events related to vaccination are presented in the table.Adverse eventsGroup I: MethotrexateGroup II: Etanercept Total, n63Hyperemia and soreness at the injection site32Swelling at the site of vaccine injection11Fever1–Headache1–ConclusionsThe results showed a good tolerability of the vaccine, no relapse of the underlying disease following immunization, as well as a statistically significant (p<0.05) reduction in the incidence following immunization.Disclosure of InterestM. Soloshenko: None declared, E. Alexeeva Grant/research support from: Roche, Abbott, Pfizer, Bristol-Myers Squibb, Centocor, Novartis., Speakers bureau: Roche, Merck Sharp & Dohme, Abbott, Bristol-Myers Squibb, Medac, Novartis, Pfizer, T. Bzarova Grant/research support from: Roche, Pfizer, Speakers bureau: Roche, Merck Sharp & Dohme, Abbott, Pfizer, S. Valieva Grant/research support from: Roche, Bristol-Myers Squibb, Speakers bureau: Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, Medac, Novartis, R. Denisova Grant/research support from: Roche, Centocor, Novartis, Speakers bureau: Roche, Merck Sharp & Dohme, Abbott, Medac, O. Lomakina: None declared, K. Isaeva: None declared, E. Kashchenko Grant/research support from: Novartis, A. Karaseva: None declared
BackgroundAnti-TNF biologics are highly effective and widely used in clinical practice for the treatment of JIA. However, some children lack of response with few reliable predictors of a good or poor response to treatment found [1–3]. As clinical picture patterns are significantly differ for 7 JIA subclasses, we propose to found predictors of response to therapy for each of JIA category.ObjectivesTo identify clinical and laboratory parameters associated with response to etanercept treatment in 12 months in patients with different JIA category.MethodsPatients from four JIA categories (n=195) were divided to groups with excellent, intermediate and poor response after 12 month treatment with etanercept according to ACRPedi criteria, achieving inactive disease by Wallace criteria and JADAS-71 cut-off point. For each of JIA category univariate and multivariate logistic regression analysis was conducted to identify potential baseline factors associated with treatment response. Baseline factors included clinical, laboratory and anamnestic data.ResultsFrom total cohort 91/90/85/68.5 percent of patients achieved ACR30/50/70/90 in one year etanercept treatment; 45.5% patients were considered excellent responders, 30% - intermediate responders, and 24.5% - poor responders. Highest efficacy of therapy was shown in persistent oligoarthritis patient, lowest – in enthesitis-related arthritis and polyarthritis patients. Potential baseline predictors of excellent and poor response which were significant are described in the table.JIA categoryPredictors of excellent responsePredictors of poor response Persistent oligoarthritissmaller amount of DMARD–Extended oligoarthritisshorter disease duration (DD)–Enthesitis-related arthritis–– longer DDRF-negative polyarthritis– smaller number of joints with limited range of motion (LOM)– longer DD– lower CRP level at the baseline– older ADO– younger age at disease onset (ADO)Analysis showed that poor response in all JIA categories was mainly associated with demographic data (longer DD and older ADO). However, factors associated with excellent response significantly differed depending on JIA category (anamnestic factors, number of involved joints, laboratory factors, and demographic factors).ConclusionsResponse to etanercept therapy is strongly associated with JIA category. Shorter disease duration and lower number of DMARDs used before start of etanercept, lower number of joints with LOM, and lower C-reactive protein at baseline are predictors of better response to etanercept.References Otten MH, et al. JAMA 2011;306:2340–7.Kearsley-Fleet L, et al. Rheumatology (Oxford) 2016;55:840–7.Solari N, et al. J Rheumatol 2013;40:192–200. Disclosure of InterestE. Kashchenko Grant/research support from: Novartis, E. Alexeeva Grant/research support from: Roche, Abbott, Pfizer, Bristol-Myers Squibb, Centocor, Novartis, Speakers bureau: Roche, Merck Sharp & Dohme, Abbott, Bristol-Myers Squibb, Medac, Novartis, Pfizer, T. Bzarova Grant/research support from: Roche, Pfizer, Novartis, Speakers bureau: Roche,...
BackgroundJuvenile idiopathic arthritis (JIA) is a chronic arthritis of unknown cause with an onset before 16 years of patient age.Patients with polyarticular-course JIA (pcJIA) have risk for profound disability. Although these patients may respond to methotrexate (MTX) or biological agents approved for pcJIA, up to 30% continue to have active disease.Interleukin-6 (IL-6) is increased in the serum and synovial fluid of patients with pcJIA; IL-6 concentrations are positively correlated with the severity of joint involvement and with C-reactive protein (CRP) levels. Tocilizumab is effective drug for the treatment of rheumatoid arthritis and systemic JIA refractory to immunosuppressive drugs.ObjectivesTo evaluate safety and efficacy of tocilizumab treatment in children with pcJIA.MethodsAnalysis of efficacy and safety tocilizumab therapy was performed in 22 patients (3 - RF+, 3-enthesitis related arthritis), whom follow up period was 6 months (n=21, tocilizumab treatment was discontinued in in 1 patient at week 3). Median age was 9,9 years (range; 2,9 to 17,2 years) and median disease duration was 3,9 years (range; 0.4 to 11,3 years). Tocilizumab was administrated intravenously at a dose of 8 or 10 mg/kg every 4 weeks. 11 patients were treated by biologics previously. The majority of patients received concomitant DMARDs, 18 patients received methotrexate, 1-leflunomid, 1-sulfasalazin, 4- prednisolone at dose 0.5 (0.5; 1) mg/kg/day. 3 patients had uveitis: 2-not active and 1-active. Efficacy end points included the American College of Rheumatology (ACR) Pediatric criteria for improvement 30 (ACR30), ACR50, ACR70, ACR90 and criteria of inactive disease and index JADAS10. During the follow-up period, significant side-effects were sought.ResultsThe ACR Pedi 30, 50, 70, 90 and 100 improvement were achieved by 100% (n=21), 85% (n=18), 52% (n=11), 24% (n=5), and 14% (n=3) of patients at Week 24 (n=21), respectively. Inactive disease was achieved by 7/21 (33%) of patients at week 24. The JADAS10 decreased from 26,5 (19,8; 28,8) to 6,2 (1,4; 18,9) at week 24 (p<0.001). The number of platelets decreased from 432x109/l (348; 505) to 253 (214; 281) at week 24 (p<0.001), number of leucocytes – from 9,0 x109/l (7,8; 9,0) to 6,3 (4,7; 7,1) at week 24 (p<0.01); level of hemoglobin increased from 105 (97; 120) g/l to 127 (120; 132) at week 24 (p<0.01).The frequently observed non-severe adverse events were nasopharyngitis, upper respiratory tract infections and gastroenteritis. No cases of opportunistic infections, malignancies or death were reported. 2 patients had incidences of neutropenia, 1 – trombocytopenia. Tocilizumab treatment was discontinued in 4 patients during the follow-up 24 weeks period. The causes for cancellation were lack of efficacy (n=3) at week 24, infusion reaction (n=1) at week 12. 3 patients were switched to antiTNF blockers and 1 – to abatacept.ConclusionsTocilizumab treatment provided clinically meaningful improvement for patients with pcJIA. Tocilizumab induced remission of arthritis and normalized laborator...
BackgroundProlonged therapy with biological agents (BAs) may cause adverse events, which leads to the necessity of discontinuation of BAs in patients with juvenile idiopathic arthritis (JIA), once complete disease quiescence has been achieved.ObjectivesTo estimate the length of time in clinical remission and time to disease flare after discontinuation of treatment with BAs.Methods83 patients with JIA (33 – with systemic onset, 50 – with oligo- or polyarticular arthritis) were included in the survey. The cohort was 34,9% (29 patients) male and 65,1% (54 patients) female with a mean age of 11±3,69 years (range 5–17 years). All patients with systemic JIA (sJIA) were treated with tocilizumab, 35 (70%) patients with other types of JIA received etanercept, 15 (30%) – adalimumab. 14 (42,4%) patients with sJIA additionally got methotrexate, 5 (15,1%) – cyclosporine, 5 (15,1%) – glucocorticoids, 1 (3,0%) – leflunomide; 9 (25,7%) and 7 (46,6%) patients took combination therapy of etanercept or adalimumab and methotrexate. Patients were randomized into 2 main groups using envelope method: in a first group a BA was discontinued abruptly, while in the second it was tapered gradually by increasing injection/infusion interval.ResultsDuration of inactive disease/clinical remission during tocilizumab treatment was 43±12,16/37±12,16 months, etanercept – 40±13,13/34±13,17 months, adalimumab – 48±11,9/40±12,06 months. Tocilizumab, etanercept, adalimumab were discontinued in 22 (66,6%), 28 (80,0%), 11 (73,3%) patients and were tapered by increasing injection/infusion interval in 11 (33,4%), 7 (20,0%), 4 (26,7%) cases, respectively. After withdrawal of tocilizumab, etanercept and adalimumab 29 (87,9%), 24 (68,6%), 6 (40,0%) patients remained in remission of JIA for 6±10,23 (1–48) months, 6±5,07 (1–20) months and 6±13,33 (4–38) months, respectively. 4 (12,1%), 11 (31,4%), 9 (60,0%) patients flared within 8±5,65 (6–18) months, 5,5±3,49 (1,5–12) months and 4±4,64 (1–13) months after discontinuation of tocilizumab, etanercept and adalimumab, respectively.ConclusionsWithdrawal of BAs after clinical remission for more than 1,5 years was not associated with a disease exacerbation in more than 70% of patients with JIA. A mean duration of clinical remission after withdrawal of BAs was 6 months.Disclosure of InterestE. Kashchenko Grant/research support from: Novartis, E. Alexeeva Grant/research support from: Roche, Abbott, Pfizer, Bristol-Myers Squibb, Centocor, Novartis, Speakers bureau: Roche, Merck Sharp & Dohme, Abbott, Bristol-Myers Squibb, Medac, Novartis, Pfizer, T. Bzarova Grant/research support from: Roche, Pfizer, Novartis, Speakers bureau: Roche, Merck Sharp & Dohme, Abbott, Pfizer, S. Valieva Grant/research support from: Roche, Bristol-Myers Squibb, Speakers bureau: Roche, Merck Sharp & Dohme, Bristol-Myers Squibb, Medac, Novartis, K. Isaeva Grant/research support from: Roche, Novartis, R. Denisova Grant/research support from: Roche, Centocor, Novartis, Speakers bureau: Roche, Merck Sharp & Dohme, Abbott, Medac, O. Lomakina: None dec...
BackgroundTNFα is one of the most important cytokine in the pathogeneses of poly-JIA. There are several TNF inhibitors for the treatment poly-JIA. Switching TNF-blockers is often strategy in the treatment of poly-JIA.MethodsAn open observational study in patients with poly-JIA taking the second TNFinhibitor. A total of 119 patients (46 boys and 73 girls) were included in this study. The mean age was 11 (7;14), disease duration was 5 (3;8) years. By the switching time 54/119 had active polyarthritis, 58/119 – olygoarthritis, 7/119 – active uveitis without arthritis. Infliximab was the first TNF inhibitor in 105/119, adalimumab – in 3/119, etanercept – 11/119. 81/119 were switched to adalimumab, 38/119 – to etanercept. Analysis of survival the second TNF blocker treatment was performed in all patients by Kaplan–Meier curve.ResultsThe causes for cancellation of the first and second TNF blockers were second inefficacy (3,7% and 8%), adverse events (5,6% and 2,5%) and administration causes (7% and 8%). Infliximab was cancelled because of primary inefficacy (7/105, 6.7%), second inefficacy (57/105, 54.3%), adverse events (12/105, 11.4%), relapse of uveitis (7/105, 6.7%), disease remission (19/105, 18.1%), administration causes (3/105, 2.8%). Etanercept was discontinued because of primary inefficacy (1/11, 9%), second inefficacy (2/11, 18%), adverse events (2/11, 18%), relapse of uveitis (6/11, 55%). Adalimumab was cancelled because of primary inefficacy (1/3), adverse events (1/3), administration causes (1/3). The second TNF inhibitor treatment survival in patients with the primary inefficacy of the first TNF inhibitor at 1,2 year was 73%, at 1,8 year was 73%, at 2,4 year was 53%. The second TNF inhibitor treatment survival in patients with the second inefficacy of the first TNF inhibitor at 1,2 year was 82%, at 1,8 year was 82%, at 2,4 year was 69%. The second TNF inhibitor treatment survival in patients with the remission of the first TNF inhibitor and relapse of disease at 1,2 year was 82%, at 1,8 year was 82%, at 2,4 year was 72%. The number of AE was 32.2 and 24.5 per 100 p.y. on the 1st and 2nd TNF blocker treatment, accordingly (p<0,0001).ConclusionsThe highest percent of survival of the second TNF inhibitor treatment was registered in patients with poly-JIA whom the first TNF inhibitor was cancelled because of disease remission and the lowest percent – in patients with poly-JIA whom the first TNF inhibitor was cancelled because of the primary inefficacy of the first TNF inhibitor.Disclosure of InterestT. Bzarova Grant/research support from: Pfizer, E. Alexeeva Grant/research support from: Roche, Novartis, UCB, S. Valieva Grant/research support from: Roche, R. Denisova Grant/research support from: Roche, Novartis, UCB, K. Isayeva Grant/research support from: Roche, Novartis, T. Sleptsova Grant/research support from: Novartis, UCB, E. Chistyakova: None declared, A. Chomahidze: None declared, O. Lomakina: None declared, M. Soloshenko: None declared, A. Fetisova: None declared, E. Kashchenko: None declared
BackgroundPatients with polyarticular-course Juvenile idiopathic arthritis (pcJIA) have risk for profound disability.Although these patients may respond to methotrexate (MTX) or biological agents approved for pcJIA, up to 30% continue to have active disease.Interleukin-6 (IL-6) is concentrations are positively correlated with the severity of joint involvement and with C-reactive protein (CRP) levels. Tocilizumab is effective drug for the treatment of JIA refractory to immunosuppressive drugs.ObjectivesTo evaluate safety and efficacy of tocilizumab treatment in children with pcJIAMethodsAnalysis of efficacy and safety tocilizumab therapy was performed in 46 patients (4 - RF+, 3-enthesitis related arthritis, 1-psoriatic JIA) and in 24 patients, whom follow up period was 6 and 12 m. Median age was 9,8 y (range; 1,9 to 17,2 y) and median disease duration was 5,1y (range; 0.4 to 13,7 y). Tocilizumab was administrated intravenously at a dose of 8or 10 mg/kg every 4 weeks. 29 patients were treated by biologics previously. The majority of patients received concomitantDMARDs, 31 patients received methotrexate, 1-leflunomid, 1-sulfasalazin,5-cyclosporin and 8- prednisolone at dose 0.4 (0.2; 1) mg/kg/day. 14 patients had uveitis: 6-not active,1-subactive and 7-active. Efficacy end points included the American College of Rheumatology (ACR)for improvement 30 (ACR30), ACR50, ACR70, ACR90 and criteria of inactive disease andindex JADAS10. During the follow-up period, significant side-effects were sought.ResultsThe ACR Pedi 30, 50, 70, 90 and 100 improvement were achieved by 92% (n=36), 82% (n=32), 56% (n=22), 23% (n=9),and 12% (n=5) of patients at Week 24 (n=39), by 100% (n=24), 87% (n=21), 83% (n=20), 54% (n=13), and 20% (n=5) of patients at Week 48 (n=24)respectively. Inactive disease was achieved by 14/39 (36%) of patients at week 24 and by 12/24 (50%) of patients at week 48. The JADAS10 decreased from 23,4 (14,8; 27,8) to 6,2 (1,6; 11,8) at week 24 (p<0.001) and to 2,0 (0,5; 4,9) at week 48 (p<0.001). The number of platelets decreased from 383 x109/l (302; 488) to 250 (220; 282) at week 24 (p<0.001) and to 258 (216; 284) at week 48 (p<0.001), number of leucocytes – from 8,8 x109/l (7,6; 9,9) to 6,5 (5,3; 7,3) at week 24 (p<0.001) and to 6,4 (4,7; 6,8)) at week 48 (p<0.001); level of hemoglobin increased from 112 (100; 123) g/l to 126 (118; 132) at week 24 (p<0.01) and to 129 (122; 136)) at week 48 (p<0.001).The frequently observed non-severe adverse events were nasopharyngitis, upper respiratory tract infections and gastroenteritis. No cases of opportunistic infections, malignancies or death were reported. 12 patients had incidences of neutropenia, 2 – thrombocytopenia,7-increased level of ALT and AST. Tocilizumab treatment was discontinued in 7 patients during the follow-up 48 weeks period. The causes for cancellation were lack of efficacy (n=6), infusion reaction (n=1), flare (n=1). 5patients were switched to antiTNF blockers and 2 – to abatacept.ConclusionsTocilizumab treatment provided clinically meaningful improvement f...
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