The availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug ...registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden.
Descriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available.
Data from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1-6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor-negative polyarthritis (range of 24.6-29.9%). Methotrexate (61-84%) and etanercept (24%-61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7-42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4-30.1%) followed by gastrointestinal disorders (11.5-19.6%). The most frequent ESIs were infections (75.3-89%).
This article is the first attempt to present a very large sample of data on JIA patients from different national and international registries and represents the first proposal for data merging as the most powerful tool for future analysis of safety and effectiveness of immunosuppressive therapies in JIA.
The Pharmachild registry is registered at ClinicalTrials.gov ( NCT01399281 ) and at the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) ( http://www.encepp.eu/encepp/viewResource.htm?id=19362 ). The BiKeR registry is registered at ENCePP ( http://www.encepp.eu/encepp/viewResource.htm?id=20591 ).
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.
Background:
The efficacy of tocilizumab for treatment patients with systemic juvenile idiopathic arthritis (sJIA) was demonstrated before. We want to describe tocilizumab drug survival based on data ...from a single-center observation.
Objectives:
To analyze the drug survival of tocilizumab in patients with sJIA treated at the National Medical Research Center of Children`s health, Moscow, Russia.
Methods:
Medical records from sJIA patients treated with tocilizumab (TOC) were analyzed retrospectively from the National Medical Research Center of Children`s health, Moscow, Russia.
Results:
One hundred ninety-two patients presenting with sJIA were included in this observation, with a median age at treatment initiation of 7,2 (interquartile range, IQR 3,9-10,8) years and a median disease duration of 1,9 (IQR 0,4-5,9) years. All patients had been bio-naive. TOC therapy was highly effective in patients with sJIA. At 6 month of follow-up 148/172 (86%) patients achieved inactive disease according the criteria C. Wallace, disease activity persisted in 24/172 (14%) patients. At 1 year of medication 139/150 (92%) patients had inactive disease. We analyzed the reason of TOC withdrawal retrospectively. A total of 82/192 drug withdrawals were performed. TOC was discontinued due to primary ineffectiveness in 4 patients, due to secondary ineffectiveness in 39 patients. 33 patients achieved drug-free remission. Six patients developed side effects that required discontinuation of TOC therapy (4 patients had allergic reactions, 1 patient developed tuberculosis, 1 patient had severe neutropenia). 47/82 patients were switched on other biologic drug: on canakinumab (31), on TNF-inhibitors (11), on rituximab (5). In summary, TOC was canceled in 49/192 (25%) patients due to ineffectiveness or AEs in our cohort.
Conclusion:
These results demonstrated that TOC is highly effective as the first biologic drug in patients with sJIA. Our observations have shown a good tolerability and survival of the IL-6 inhibitor TOC in patients with sJIA treated in a real-world clinical setting.
Disclosure of Interests:
None declared
Background:
Juvenile idiopathic arthritis (JIA) is the most common and prevalent rheumatic disease in childhood which is based on a chronic autoimmune inflammation. Inactive disease and remission are ...now the primary treatment goal in JIA and biologics have been playing an important role to reach this objective.
The biologics of the first choice for the treatment of non-systemic JIA are the Tumor Necrosis Factor - alpha (TNFα) inhibitors; on this therapy patients can achieve clinically inactive disease and long-term remission.
Currently, little is known about when or how to stop TNFα inhibitors, when a good clinical response is achieved, and therefore no guidelines are available.
Objectives:
To estimate the length of clinical remission after discontinuation of treatment with TNFα inhibitors in patients with non-systemic juvenile idiopathic arthritis.
Methods:
A total of 393 patients with JIA who were treated with TNFα inhibitors at the Rheumatology Department of the National Medical Research Center of Children’s Health (Moscow, Russia) were screened for inclusion in this retrospective study.
Patients were treated with etanercept 1 times a week, 0.8 mg per kg of body weight per dose, with adalimumab 24 mg/m2 body surface area administered every other week until the end of therapy.Treatment was terminated abruptly. Inactive disease was defined according to the preliminary criteria of Wallace et al.1
Results:
77 patients (27—male, 50—female) with a mean age at diagnosis of 4 years (range 1–18 years) were included in the analysis. Of those, 69 of them discontinued TNFα inhibitors due to a long-term remission on treatment, 8 patients as a result of side effects, and there were excluded from our study.:
allergic reaction (n = 5), development of uveitis (n = 1), alopecia (n = 1), recurrent infection (n=11).The clinical subtypes of JIA were RF-negative polyarticular JIA -28 (40,58%) oligoarthritis—38 (55,07%), enthesitis-related arthritis—3 (4,35%).
TNFα inhibitors were started after a mean 46,43 (range 1–144) months of disease. The mean duration of therapy with TNFα inhibitors were 46,63 (range 10-113) months, with a mean duration of remission on medication 40,63 (range 6-107) months before withdrawal of TNFα inhibitors.
40/69 (57,97 %) patients did not develop a disease exacerbation and remained in long-term remission off medication—more than 24 months.
Early flares, that is less than 6 months after termination of TNFα inhibitors, were observed in 4/69 (5,8%) patients.
29 (42,03%) patients restarted TNFα inhibitors after exacerbation, due to lack of improvement after no biological DMARDs. All patients in whom TNFα inhibitors were reinitiated responded satisfactorily.
Conclusion:
Among patients with JIA in whom TNFα inhibitors were discontinued after inactive disease was achieved, 57,97 % had disease in clinical remission more than 24 months after stopping anti-TNFα therapy. No association was observed between the duration of inactive disease prior to TNFα inhibitors cessation and the time to disease relapse. In addition, we also ob- served no correlation between the risk of flare and the length of anti-TNF α therapy after inactive disease was achieved. In our population, TNFα antagonists were withdrawn a median of 38 (4-107) months after inactive disease was achieved. Data from our experience with anti-TNF α agents in the treatment of JIA suggest that 57,97 % of patients can be successfully withdrawn from TNF α antagonists for at least 24 months.
References:
1Wallace CA, Giannini EH, Huang B, Itert L, Ruperto N, for the Childhood Arthritis and Rheumatology Research Alliance (CARRA), the Pediatric Rheumatology Collaborative Study Group (PRCSG), and the Paediatric Rheumatology Interna- tional Trials Organisation (PRINTO). American College of Rheumatology provisional criteria for defining clinical in- active disease in select categories of juvenile idiopathic arthritis. Arthritis Care Res (Hoboken) 2011;63:929–36.
Disclosure of Interests:
None declared.
Background:
The safety of vaccination of children with rheumatic diseases is determined not only by the risk of adverse events but also by the risk of exacerbation of the disease. The simultaneous ...administration of several vaccines can increase the likelihood of these events.
Objectives:
To evaluate the clinical and laboratory signs of disease activity in children with juvenile idiopathic arthritis (JIA) after simultaneous vaccination against pneumococcal and Haemophilus influenzae type b (Hib) infections.
Methods:
We included hospitalized patients with JIA ages 2 through 18 without serious comorbidity, immunized with polysaccharide conjugate vaccines against pneumococcal (PCV13) and Hib infections. Vaccines were administered (0.5 ml each) concurrently subcutaneously into the deltoid area. In all children before and 3 weeks after vaccination, clinical (joints with active arthritis, uveitis activity) and laboratory signs (increased ESR, concentrations of highly sensitive C-reactive protein – hsCRP, and calprotectin) of JIA activity were assessed. Serum hsCRP and calprotectin were quantified by ELISA. The upper limit of the reference interval for hsCRP was considered (according to the manufacturer’s instructions) a value of 8.2 mg/L, for calprotectin – 2.9 μg/ml, and for ESR – > 10 mm/h.
Results:
The study included 430 patients with JIA (girls 60.9%), median (IQR) age – 11.1 years (7.3 to 14.4), onset of JIA – 4.7 years (2.4 to 8.6). Patients with persistent oligoarticular JIA numbered 149 (34.7%), polyarticular RF-negative – 148 (34.4%), systemic – 101 (23.4%), enthesitis-related – 20 (4.7%), and polyarticular RF-positive JIA – 12 (2.8%). Biologic disease-modifying antirheumatic drugs (DMARDs) were administered to 278 (64.7%), non-biologic DMARDs (mostly methotrexate) – 282 (65.6%), corticosteroids – 45 (10.5%), and NSAIDs – 18 (4.2%) patients. Three weeks after vaccination, out of 100 (23.3%) patients with initially active joints, signs of active arthritis remained in 96 patients, of which 16 patients had a decrease in the median (IQR) number of active joints by 4 (2 to 8). Among patients without active joints at baseline, signs of active arthritis were not subsequently detected. Before vaccination, 9 patients had uveitis in the exacerbation phase, 7 - in the subactive phase, and 41 - in the remission phase. After vaccination, exacerbation of uveitis persisted in 4 patients. There were no new cases of uveitis or its exacerbation. The dynamics of laboratory signs of JIA activity are presented in Table 1. Initially, the high concentration of calprotectin was found in 191 (44.4%) patients, and after vaccination – in 220 (51.2%) patients; the difference was 6.7% (95% CI 1.0 - 12.5); hsCRP - in 34 (7.9%) and 51 (11.9%) patients; the difference was 4.0% (95% CI 0.6 - 7.3); high ESR – in 76 (17.7%) and 41 (9.5%) patients; the difference was -8.1% (95% CI -11.6 to -4.7), respectively. An independent predictor of new cases of high concentration of hsCRP (n = 36), but not new cases of high concentration of calprotectin (n = 94), was the initial number of joints with active arthritis – odds ratio 2.37 (95% CI 1.14 - 4.93).
Table 1.
Laboratory signs of JIA activity after simultaneous administration of vaccines against pneumococcal (PCV13) and Hib-infections
Variables
Baseline
After 3 weeks
Ratio*
p**
Geometric mean (95% CI)
Calprotectin, μg/ml
2.93 (2.70 – 3.17)
3.15 (2.92 – 3.40)
1.08 (0.99 – 1.17)
0.087
hsCRP, mg/L
0.69 (0.60 – 0.78)
0.79 (0.69 – 0.90)
1.15 (0.99 – 1.33)
0.073
ESR, mm/h
4.4 (4.0 – 4.8)
3.7 (3.4 – 4.0)
0.84 (0.78 – 0.90)
0.001
Note. CI – confidence interval. * Ratios of paired observations (95% CI). ** P-value calculated in paired samples t-test.
Conclusion:
Simultaneous vaccination against pneumococcal (PCV13) and Hib-infections in children with JIA produced no negative dynamics of the traditional indicators of disease activity (joint activity, uveitis, high ESR). At the same time, 3 weeks after vaccination, an increase in the concentration of calprotectin and hsCRP was found in a small number of patients (<10%).
Disclosure of Interests:
None declared
Background:Anti-IL-17A biologic drug secukinumab (SEC) proved to be effective for treatment of psoriatic arthritis. However data about its efficacy in juvenile idiopathic arthritis (JIA) are ...restricted to off-label experience.Objectives:To evaluate the effectiveness and safety of SEC in JIA patients in the National Medical Research Center of Children`s health, Moscow, Russia.Methods:25 patients started SEC therapy from 12/2017 to 11/2019 in single-center prospective study. 3 patients withdrew treatment: two patients (8%) due to AE (1 - allergy followed by MAS after first injection and 1 – leukopenia) and one patient (4%) – after 10 months of treatment due to secondary inefficacy. Among others, 14 patients which were successfully treated for 6 months or longer were included into analysis. At the baseline, information was collected on the characteristics of the onset of the disease, previous therapy and its success. Patients were monitored at least 1 time per year. At each visit, clinical and laboratory characteristics of JIA severity were assessed. Response to therapy was assessed using the ACRPedi 30/50/70/90 criteria, the C.Wallace criteria for inactive disease (WID) and clinical remission. AEs were assessed at each visit.Results:Among 14 patients received SEC for at least 6 months, 7 (50%) have enthesitis-related arthritis, one (7.1%) – persistent oligoarthritis, 4 (28.6%) – RF-negative polyarthritis, 2 (14.3%) – psoriatic arthritis. 6 patients (42.9%) were HLA-B27 positive. Median age of JIA onset was 8.8 (IQR 5:11), age at SEC initiation – 14 (9.9:16.1), disease duration before SEC start – 3.3 (2.7:5.8). 7 (50%) were biologics-naïve, 2 (14.3%) were previously treated with anti-TNF drug, 5 (35.7%) have 2 or more different biologics in anamnesis.SEC demonstrated high efficacy after the first injection resulting in JADAS-71 decreasing in all patients by median 4.3 (1.6:7.1) points and 7/7/5/2 patients (50%/50%/35.7%/14.3%) achieved ACR Pedi 30/50/70/90 response.After 6 months of treatment, WID was achieved by 7 (50%) patients, JADAS-71 decreased from baseline level 15.2 (12.7:20.5) to 0.8 (0:4.2) points, and 14/13/11/9 patients (100%/92.9%/78.6%/64.3%) achieved ACR Pedi 30/50/70/90 response. One patients who had active uveitis at SEC initiation remained with subactive uveitis; one patient with uveitis remission had not flare episodes during follow-up period. One patient (7.1%) had successfully treated evaluation of transaminases after 4-th injection.Conclusion:Secukinumab showed high effectiveness and safety in children with JIA and can be further used both as a first-line drug in JIA associated with HLA-B27, and as an alternative drug for the ineffectiveness of the standard treatment regimen with biologics. No serious adverse events were registered during follow-up period.Disclosure of Interests:Ivan Kriulin: None declared, Ekaterina Alexeeva Grant/research support from: Roche, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Novartis, Pfizer., Tatyana Dvoryakovskaya: None declared, Ksenia Isaeva: None declared, Aleksandra Chomakhidze: None declared, Evgeniya Chistyakova: None declared, Olga Lomakina: None declared, Rina Denisova: None declared, Anna Mamutova: None declared, Anna Fetisova: None declared, Marina Gautier: None declared, Dariya Vankova: None declared, Elizaveta Krekhova: None declared, Meyri Shingarova: None declared, Alina Alshevskaya: None declared, Andrey Moskalev: None declared
Background:
Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are two ILAR categories of juvenile idiopathic arthritis (JIA) and represent paediatric correlates of axial ...spondyloarthritis (axSpA) and adult psoriatic arthritis (PsA), respectively.
1,2
Secukinumab (SEC) has demonstrated efficacy and safety in adult patients (pts) with PsA, ankylosing spondylitis and non-radiographic axSpA.
3-5
Objectives:
Evaluate efficacy and safety of SEC using a flare prevention design in pts with active ERA and JPsA.
Methods:
This 2-yr study consisted of an open-label (OL) s.c. SEC (75/150 mg in pts <50/ ≥50 kg) at baseline (BL), and at Weeks (Wk) 1, 2, 3, 4, 8 and 12 in treatment-period (TP) 1. Responder pts who achieved at least JIA ACR 30 response at Wk 12 were randomised into the double-blinded TP2 to continue SEC or placebo (PBO) q4w until a disease flare, or up to Wk 100. Pts (aged 2 to <18 yrs) classified as ERA or JPsA according to ILAR criteria of ≥6 months duration with active disease were included. Primary endpoint was time to flare in TP2 and key secondary endpoints were JIA ACR 30/50/70/90/100, inactive disease, JADAS, enthesitis count and safety. Analysis of time to flare in TP2 included proportion of disease flare, Kaplan-Meier (KM) estimate of median time to flare in days, hazard ratio (95% CI) from Cox model, and
P
-value for the Stratified log-rank test. KM estimates of the probability to disease flare by treatment groups in TP2 were plotted against days. Observed data were used in all analyses. Post-hoc analyses using non-responder imputation (NRI) were performed for JIA ACR 30/50/70/90/100 responses.
Results:
86/97 (89%) pts were enrolled in the OL period TP1 (mean age, 13.1 yrs; female, 33.7%; ERA, n=52; JPsA, n=34). At BL, mean JADAS-27 score was 15.1 and enthesitis count was 2.6. At the end of TP1, 90.4% (75/83) of pts achieved JIA ACR 30 and 69.9% (58/83) achieved JIA ACR 70. There were 21 and 10 flares in TP2, respectively in PBO and SEC treated pts with a significantly longer time to flare and 72% risk of flare reduction in SEC treatment vs PBO (HR: 0.28; 95% CI: 0.13–0.63;
P
<0.001) (Figure 1). JIA ACR responses, disease activity and enthesitis count are reported in Table 1. NRI analyses showed that 87.2%, 83.7%, 67.4%, 38.4% and 24.4% of pts achieved JIA ACR 30/50/70/90/100, respectively. Rates of adverse events (AEs; 91.7% vs 92.1%) and serious AEs (14.6% vs 10.5%) in SEC and PBO groups were comparable in the entire TP. No new safety signals were observed.
Table 1.
Efficacy of secukinumab in Treatment Periods 1 and 2 (Key secondary endpoints)
Efficacy Outcomes, %
TP1
TP2
¥
SEC (N=83
)
^
SEC (N=37
)
PBO (N=37
)
P
-value
JIA ACR 30
90.4
89.2
64.9
0.014
JIA ACR 50
86.7
78.4
62.2
0.152
JIA ACR 70
69.9
67.6
43.2
0.042
JIA ACR 90
39.8
51.4
40.5
0.431
JIA ACR 100
25.3
43.2
37.8
0.745
Inactive disease
#
36.1
47.2
37.8
0.500
JADAS-27, mean (SD)
15.1 (7.2)
14.6 (8.1)
13.3 (5.8)
NA
Enthesitis count, mean change from BL (SD)
−1.8 (2.3)
−2.1 (2.0)
−1.9 (1.2)
NA
P
-values: Cochran-Mantel-Haenszel test, adjusted for analysis factors: JIA category (ERA/ JPsA) and MTX use at BL
¥
The N numbers are values at the end of TP2
^
Efficacy outcomes (%) in TP1 calculated in patients with evaluable data at Wk 12 (N=83)
#
Inactive disease: Definition adapted from JIA ACR criteria of Wallace et al., 2011. N=36 for SEC at the end of TP2
JADAS, Juvenile Arthritis Disease Activity Score; N, total number of patients in the treatment group; NA, data not available
Figure 1.
Time to flare in Treatment Period 2 (Primary Endpoint)
Conclusion:
In children and adolescents with ERA and JPsA, efficacy of SEC was demonstrated with a significantly longer time to flare vs PBO with sustained improvement of signs and symptoms up to Wk 104 and a favourable safety profile.
References:
1Colbert RA.
Nat Rev Rheumatol
. 2010;6:477–85.
2Martini A, et al.
J Rheumatol
. 2019;46:190–7.
3McInnes IB, et al.
Lancet
. 2015;386:1137–46.
4Baeten D, et al.
N Engl J Med
. 2015;373:2534–48.
5Deodhar A, et al.
Arthritis Rheumatol
. 2021;73:110–20.
Disclosure of Interests:
Nicolino Ruperto Consultant of: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers and Squibb, Celgene, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Grant/research support from: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi, Speakers bureau: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers and Squibb, Celgene, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Ivan Foeldvari Consultant of: Novartis, Speakers bureau: Novartis, Ekaterina Alexeeva Grant/research support from: Novartis, Pfizer, Sanofi, MSD, AMGEN, Eli Lilly, Roche, Speakers bureau: Novartis, Pfizer, Sanofi, MSD, AMGEN, Eli Lilly, Roche, NURAY AKTAY AYAZ: None declared, Inmaculada Calvo Consultant of: Sobi, Novartis, Abbvie, GlaxoSmithKline, Pfizer, Amgen, Clementia, Speakers bureau: Sobi, Novartis, Abbvie, GlaxoSmithKline, Pfizer, Amgen, Clementia, Ozgur KASAPCOPUR: None declared, Vyacheslav Chasnyk: None declared, Markus Hufnagel Grant/research support from: Astellas, F. Hoffmann-La Roche, Novartis, Zbigniew Żuber: None declared, Grant Schulert Consultant of: Sobi, Novartis, Seza Ozen: None declared, Artem Popov: None declared, Athimalaipet Ramanan Speakers bureau: Roche, Sobi, Eli Lilly, UCB, Novartis, Christiaan Scott: None declared, Betül Sözeri: None declared, Elena Zholobova Grant/research support from: Pfizer, Novartis, Speakers bureau: Abbvie, Pfizer, Roche, Novartis, Xuan Zhu Employee of: Novartis, sarah whelan Employee of: Novartis, Shareholder of: Novartis, Luminita Pricop Employee of: Novartis, Shareholder of: Novartis, Angelo Ravelli Consultant of: Abbvie, Bristol-Myers Squibb, Pfizer, Hoffmann-LaRoche, Novartis, Centocor, Angelini Holding, Reckitt Benckiser, Speakers bureau: Abbvie, Bristol-Myers Squibb, Pfizer, Hoffmann-LaRoche, Novartis, Centocor, Angelini Holding, Reckitt Benckiser, Alberto Martini Consultant of: Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, Abbvie, Speakers bureau: Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, Abbvie, Daniel J Lovell Consultant of: AstraZeneca, Wyeth, Amgen, Abbott, Pfizer, Hoffmann-La Roche, Novartis, UBC, Takeda, Janssen, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Bristol Myers Squibb, AbbVie, Forest Research, Speakers bureau: AstraZeneca, Wyeth, Amgen, Abbott, Pfizer, Hoffmann-La Roche, Novartis, UBC, Takeda, Janssen, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Bristol Myers Squibb, AbbVie, Forest Research, Hermine Brunner Consultant of: Aurina, AbbVie, Astra Zeneca-Medimmune, Biogen, Boehringer, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, F. Hoffmann-La Roche, Merck, Novartis, R-Pharm, Sanofi, Pfizer, Grant/research support from: Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, F. Hoffmann-La Roche, Janssen, Novartis, and Pfizer, Speakers bureau: Pfizer, Roche and GlaxoSmithKline
BackgroundThe use of therapy with anti-cytokine biologicals in routine practice has significantly increased the percentage of children showing good response to therapy and reduced the time to achieve ...pharmacological remission. Nevertheless, the problem related to selecting the optimal drug for a certain patient still remains to be solved.ObjectivesThis study was aimed at identifying clinical and laboratory parameters associated with response to tocilizumab (TOC) treatment in patients with RF-negative polyarticular JIA.MethodsThe prospective study to assess TOC efficacy involved 55 patients with RF-negative polyarticular JIA aged 9.42 years (IQR 5.96–13.42), with females (85.5%) predominating was conducted at the National Medical Research Centre of Children’s Health (Moscow). Treatment efficacy was evaluated using the ACRPedi criteria; Wallace’s criteria were used to assess whether a patient had reached inactive disease or remission. The potential baseline characteristics associated with treatment response were identified using univariate and multivariate logistic regression analyses. Baseline factors included the clinical, laboratory, and anamnestic data.ResultsTOC therapy showed high efficacy in children with RF-negative polyarticular JIA: 81.8/67.3/47.3/23.6% of patients reached the ACR30/50/70/90 criteria for the end of follow-up, respectively. The median time of achieving at least 30% improvement from baseline (ACR30) was 1 months (IQR 1:3).Univariate analysis showed that earlier age at initiation of Tocilizumab therapy, higher physician’s global assessment score using the 100-point Visual Analogue Scale, and longer morning stiffness were the factors associated with reaching ACR90. Younger age at therapy initiation, greater number of swollen joints and joints with limited range of motion, and history of using fewer biologicals are the factors associated with reaching inactive disease and remission. However, multifactorial analysis showed that only earlier age at initiation of TOC therapy was a statistically significant factor associated with reaching the best response to therapy in all the models.ConclusionsEarlier initiation of TOC therapy is associated with higher chances for reaching ACR90 and pharmacological remission in patients with RF-negative polyarticular JIA. Further studies in larger cohorts are needed to identify the optimal age at therapy initiation.Disclosure of InterestE. Alexeeva: None declared, T. Dvoryakovskaya Grant/research support from: Roche, Pfizer, M. Soloshenko: None declared, R. Denisova: None declared, K. Isaeva: None declared, A. Mamutova: None declared, V. Gladkikh: None declared, A. Moskalev: None declared
BackgroundDevelopment of biologics gives rise to novel classes of drugs, offering more options for treating children with primary or secondary failure of anti-TNF therapy. However, the question of ...whether or not previous exposure to biologic therapy and the number of previously administered biologics influence the efficacy of current treatment still needs to be solved.ObjectivesTo compare tocilizumab efficacy in biologics-naïve and biologics-switched patients with JIA.MethodsComparative analysis involved patients who had initiated TOC treatment at the National Medical Research Centre of Children’s Health (Moscow) depending on previous history of biologics therapy. Treatment efficacy was evaluated according to the dynamics of clinical and laboratory signs using the ACRPedi criteria. The Wallace criteria were used to evaluate whether or not remission had been achieved.ResultsThirty-two patients were biologics-naïve and 43 patients switched to TOC were previously treated with ETA (n=10), ADA (n=34), certolizumab (n=2), and infliximab (n=1). Children in the biologics-naïve group differed from the switchers in a number of important baseline parameters: shorter disease duration (2.13 1.25:5.34 and 7.42 3:10.75 years, respectively; p<0.001) and lower arthritis severity indices (the number of joints affected, the CHAQ and JADAS scores). Therapy with TOC in children was found very effective. The CHAQ and JADAS disease activity scores, the CRP and ESR laboratory values, morning stiffness duration, and the VAS score (assessed by both patient and physician), and the number of affected joints (swollen or painful joints, joints with the limited range of motion and with active arthritis) significantly decreased after 4 week therapy in all patients (p<0.01). The percentages of biologics-naïve patients and switchers who achieved ACR90 after the first 12 months of therapy were 31.25% and 25.6%, respectively (p=0.613). A smaller percentage of children achieved stable remission: 4.65% of switchers and 6.25% of biologics-naïve patients (p>0.999).ConclusionsTocilizumab therapy is highly efficient both as the first and subsequent biologic agent. Children with history of therapy with at least one biologic agent have lower chances for achieving remission during the first 12 months of therapy. However, this difference is most likely caused by the longer and more severe arthritis course in children allocated to the group of biologics-switched patients compared to biologics-naïve ones. Further matched large-cohort study is needed to identify predictors of response to therapy.Disclosure of InterestE. Alexeeva: None declared, T. Dvoryakovskaya Grant/research support from: Roche, Pfizer, M. Soloshenko: None declared, R. Denisova: None declared, K. Isaeva: None declared, A. Mamutova: None declared, V. Gladkikh: None declared, A. Moskalev: None declared
BackgroundRemission is the major goal of treatment of juvenile idiopathic arthritis(JIA). Advances in treatment options allowed achievement of remission to come into reach. Timing for initiating ...intensive treatment in a treat to target approach to early reach remission is still a debate.ObjectivesMulti-centre, double-blind, randomised study in polyarticular JIA patients (pts) receiving either Etanercept+Methotrexate (cohort 1) or Placebo +Methotrexate (cohort 2) for 24 weeks followed by 24 week open label phase. Escape to open-label ETN and MTX for pts not achieving paedACR30 at week 12 or not achieving inactive disease at week 24.Results35 pts were randomised to cohort 1 and 33 to cohort 2. Baseline demographic and clinical characteristics were comparable between the groups except mean tender joint count, physician assessment of global disease activity and JADAS10 which all were higher in cohort 1. At week 12, 12 pts randomised to cohort 2 did not reach paedACR30. At week 24, further 10 pts of cohort 2 not reaching inactive disease escaped to ETA and MTX. 5 pts of cohort 1 and 4 pts of cohort 2 dropped out. At week 12, significantly more pts on ETA and MTX (33 (94%)/27 (79%)) than on PLC and MTX (17 (52%)/15 (47%) reached paedACR30/50 (p<0.001/0.01). At week 24, inactive disease was reached by 10 pts on ETA and MTX vs. 6 on PLC and MTX. Inactive disease at week 48 was achieved by 5 pts of cohort 2 on MTX alone while 22 patients (67%) escaped to open label ETA and MTX. 15 (43%) pts of cohort 1 and 16 (49%) of cohort 2 reached inactive disease at week 48. At week 48, paedACR30/50/70/90 was reached by 100%/97%/97%/77% in cohort 1 compared to (97%/93%/93%/73%) in cohort 2. The number of visits with inactive disease in cohort 1 (87 (24%)) was comparable to that of cohort 2 (79 (21%)) while the number of visits with no active joint was significantly higher in cohort 1 (178(48%) vs. 146 (39%); OR 1.45 (1.08–1.94); p=0.012). 44 (74/100 y) adverse events (AE) were noted leading to discontinuation in 6 patients. 3 serious AE occurred, two first uveitis events and one diagnosis of dermatomyositis, all in the placebo group. No new safety signal arised from our observation.ConclusionsEarly combination of ETA and MTX proved to be highly effective with a high rate of patients reaching high paediatric ACR response and 50% reaching inactive disease. Pre-defined targets to treat to, paediatric ACR30 at week12, defining minimal response or inactive disease at week 24/48 were more often reached upon ETA and MTX than with MTX alone. Compared to immediate intense antirheumatic combination treatment with ETA and MTX, a comparable rate of patients on targeted therapy reached the final endpoint of inactive disease at week 48 but numbers of visits with active arthritis were higher in patients receiving delayed combination therapy.Reference1 Wallace CA, et al. Arthritis Care Res2011;63:929–36.AcknowledgementsThe study was sponsored by an unrestricted grant by Pfizer, RussiaDisclosure of InterestNone declared
PDF
