D Lovell

Use of the JADAS criteria to assess efficacy of canakinumab in patients with SJIA – an analysis of 12-week pooled data

The composite score JADAS1, 2 27-CRP (J27), 10-CRP (J10), and cut-off values for inactive (ID), low (LDA), moderate (MDA) and high disease activity (HDA) were designed to monitor the level of disease activity in all JIA subtypes1. The efficacy of canakinumab (CAN), a selective, human, anti-IL-1β monoclonal antibody, was previously demonstrated in SJIA in phase III trials using aACR-JIA response criteria3.

FRI0528 Canakinumab in Systemic Juvenile Idiopathic Arthritis: Impact on the Rate and Clinical Presentation of Macrophage Activation Syndrome

Background Canakinumab is a fully human, selective, anti-IL-1β monoclonal antibody approved for the treatment of patients with systemic juvenile idiopathic arthritis (SJIA). In the phase III trials, macrophage activation syndrome (MAS), a potentially fatal complication of SJIA, was reported as an adverse event (AE) in both canakinumab and placebo group patients. This prompted Novartis to form an independent expert MAS Adjudication Committee (MASAC) to develop methodology to identify and review potential MAS events. Objectives To assess the impact of canakinumab on incidence of MAS in SJIA patients. Methods A periodic search of the canakinumab SJIA clinical study databases and the separate serious AE safety database was performed using MASAC-specified screening AE terms (cut-off date 31 May 2012). MASAC-specified laboratory criteria were also used to search clinical study databases. MAS events were then adjudicated blinded to treatment by the MASAC as either probable, possible, or unlikely MAS, or insufficient information loosely based on the diagnostic criteria by Ravelli et al.2 and personal experience. MAS rates were expressed as numbers of probable or possible MAS events per 100 patient-years (pt-yr). Results Forty-three potential MAS events were identified for adjudication (12 reported as MAS AEs and 31 by screening database searches). Nine events were adjudicated as probable, 5 as possible and 29 as unlikely MAS. Of the 9 probable MAS events, 7 occurred in the canakinumab and 2 in the placebo group, and all were also reported as a MAS AE by the treating physician. SJIA was well controlled in all 7 canakinumab patients and all developed classic clinical features of MAS. Of the 7 canakinumab patients, 6 reported MAS in the setting of an active infection. The MAS events were not associated with a change in concomitant therapy. The time period between the first injection of canakinumab and the onset of MAS ranged between 13 days to 1.7 years (median, 83 days). The rate for MASAC adjudicated probable MAS was 2.5/100 pt-yr and 7.7/100 pt-yr for the canakinumab and placebo groups, respectively with no statistically significant difference between groups (diff=-5.2, 95% CI, -16.0, 5.7). When events adjudicated as either probable or possible MAS were combined, the rate for the canakinumab group was 4.3/100 pt-yr and 7.7/100 pt-yr for the placebo group with no between-group difference (diff=-3.4, 95% CI, -14.3, 7.6). Five of the 7 patients adjudicated as probable MAS recovered completely and 2 (1 canakinumab and 1 placebo) died from complications of MAS and/or infection. Conclusions Canakinumab does not appear to have an effect on the incidence of MAS or its clinical presentation. MAS occurred even in those patients in whom underlying SJIA was well controlled with canakinumab treatment. As often seen in MAS, active infection was the most common associated trigger in this group. References Ruperto N, et al.N Engl J Med 2012;367(25):2396-406. Ravelli A, et al.J Pediatr.2005;146(5):598-604. Disclosure of Interest A. Grom Consultant for: Novartis, Roche, NovImmune, H. Brunner Consultant for: Novartis, Roche, Janssen, Astrazenca, UCB, Celegene, Pfizer, GSK, Speakers bureau: Novartis, N. Ruperto Grant/research support: To Gaslini hospital from Abbott, Astrazeneca, BMS, Centocor Research and developement, Eli Lilly and company, “ranscesco Angelini”, GSK, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences GmBH, Xoma, Wyeth, Speakers bureau: Astrazeneca, Bristol Myers and Squibb, Janssen Biologics B.V., Roche, Wyeth, Pfizer, A. Martini Grant/research support: From Bristol Myers and Squibb, Centocor Research & Development, Glaxo Smith & Kline, Novartis, Pfizer Inc, Roche, Sanofi Aventis, Schwarz Biosciences GmbH to Gaslini hospital to support PRINTO research activities, Consultant for: From Bristol Myers and Squibb, Centocor Research & Development, Glaxo Smith and Kline, Novartis, Pfizer Inc, Roche, Sanofi Aventis, Schwarz Biosciences GmbH to Gaslini hospital to support PRINTO research activities, Employee of: Gaslini hospital, Speakers bureau: Abbott, Bristol Myers Squibb, Astellas, Boehringer, Italfarmaco, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier, D. Lovell Grant/research support: National Institutes of Health- NIAMS, Consultant for: Astra-Zeneca, Centocor, Amgen, Bristol Meyers Squibb, Abbott, Pfizer, Regeneron, Roche, Novartis, UCB, Forest Research Institute, Horizon, Johnson & Johnson, Speakers bureau: Novartis, Roche, V. Pascual Consultant for: Served on the MAS adjudication committee for Novartis and is an author on the following patent: # 8221748; Compositions and methods for the treatment of systemic onset juvenile idiopathic arthritis with IL1 antagonists (issued on 7/17/2012), Speakers bureau: Served on the MAS adjudication committee for Novartis and is an author on the following patent: # 8221748; Compositions and methods for the treatment of systemic onset juvenile idiopathic arthritis with IL1 antagonists (issued on 7/17/2012), K. Lheritier Shareholder of: Novartis, Employee of: Novartis Pharma AG, K. Abrams Shareholder of: Novartis, Employee of: Novartis Pharmaceutical Corporation, N. Ilowite Consultant for: Novartis, Janssen DOI 10.1136/annrheumdis-2014-eular.3070

PReS-FINAL-2140: Neutropenia with Tocilizumab (TCZ) treatment is not associated with increased infection risk in patients with systemic juvenile idiopathic arthritis (SJIA)

In the phase 3 TENDER trial of TCZ in patients with sJIA, decreases in neutrophil count were commonly observed.

PReS-FINAL-2188: Insulin sensitivity is improved in sjia children with insulin resistance after tocilizumab treatment: results from the tender study.

In adults with inflammatory arthritis, insulin resistance (IR) is associated with diabetes and cardiovascular disease. Interleukin-6 (IL-6) is postulated to play a mechanistic role in IR.

Maintenance of efficacy of canakinumab in SJIA at the individual patient level in a 12-week pooled dataset

Recent advances in the management of SJIA considered the induction or maintenance of inactive disease according to the JADAS 10-CRP (J10) or 27-CRP (J27) scoring system [1,2]. The maintenance of efficacy of canakinumab (CAN), a selective, human, anti-IL-1β monoclonal antibody, was demonstrated in the withdrawal phase of 2 phase III trials [3], but was not evaluated at the individual level.

PReS-FINAL-2180: Efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA): 2-year data from CHERISH.

Efficacy and safety of TCZ, an IL-6 receptor inhibitor, were previously demonstrated at wk 40 of CHERISH, a phase 3 trial in patients (pts) with pcJIA [1].

THU0579 Treating To Target with Canakinumab in Patients with Active Systemic Juvenile Idiopathic Arthritis: Results from The Long-Term Extension The Phase III Pivotal Trial

Background The main therapeutic goals that can determine success of biologic treatment in systemic juvenile idiopathic arthritis (SJIA) include achieving and maintaining clinical remission, controlling disease activity and tapering corticosteroids (CS). Canakinumab (CAN) has been shown to improve several of these parameters in previous studies1. However, little is known about SJIA patients (pts) using CAN long-term. Objectives To evaluate the efficacy, safety and long-term treatment response of CAN treatment-naïve pts with active SJIA. Methods This was an open-label, non-comparative study (NCT00891046) of CAN-naïve SJIA pts (age ≥2 - <20 yrs) receiving CAN 4 mg/kg by s.c. q4w. Efficacy was assessed by the adapted pediatric ACR (aACR 30/50/70/90/100) responses compared to baseline (BL); inactive disease (ID) or clinical remission (ID for >6 Mo) and changes in JADAS-CRP (Juvenile Arthritis Disease Activity Score- C-reactive protein) scores over time. Safety was assessed by adverse events (AEs) and serious AEs (SAEs) reports. Results A total of 123 pts with active SJIA were enrolled of whom 70 (57%) pts had fever and 71 (57.7%) pts used CS at BL. Mean CRP was 117.8 mg/L (normal: 0–10mg/L) and, on average, pts had, 9.9 active joints and 8.9 joints with limited motion. A rapid response was observed at Day 15, 59 (51%) with aACR ≥70 responses and 27 (26%) having aACR 100 responses. These responses increased and were maintained at subsequent time points (Table). Overall, 73.0% of pts had ID on at least 1 visit. At 6th month, clinical remission was achieved in 52 (42.3%) pts and 33 (26.8%) pts had clinical remission for at least 12 consecutive months. At BL, the median JADAS10-CRP score was 22.3 (indicating high disease activity), with median changes from BL of -12.0 at Day 15 and -16.8 at last assessment indicating moderate and low disease activity, respectively. At the last assessment, 59 (48.4%) pts were rated as ID (JADAS <1); 14 (11.5%) with low active disease activity (JADAS >1 and <3.8); while 14 (11.5%) had moderate and 35 (28.7%) with high disease activity. 24 (33.8%) pts were steroid-free at last assessment. A total of 53 (43.4%) pts had at least 1 AE. Overall rate of AEs was 2.25 events/ 100 patient-days and SAEs was 0.15/ 100 patient-days. 40 (32.5%) pts had SAEs and the most commonly reported were disease flares or worsening of SJIA in 13 (10.6%) pts, macrophage activation syndrome in 6 (4.9%) pts, and pyrexia in 4 (3.3%) pts. No deaths were reported in this study. Conclusions In this long-term study, CAN treatment was associated with rapid response and sustained therapeutic effect over the long-term in the naïve pts with active SJIA. The safety profile is consistent with other CAN studies. References Ruperto et al. N Engl J Med. 2012;367:2396–406. Disclosure of Interest N. Ruperto Grant/research support from: BMS, GlaxoSmithKline (GSK), Hoffman-La Roche, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi and Merck Serono funded The Gaslini Hospital for the research activities of the hospital in a fully independent manner besides any commitment with third parties, Consultant for: AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda, UCB Biosciences GmbH, Speakers bureau: AbbVie, Amgen, Biogenidec, Alter, AstraZeneca, Baxalta Biosimilars, Boehringer, BMS, Celgene, CrescendoBio, EMD Serono, Hoffman-La Roche, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda, UCB Biosciences GmbH, H. Brunner Consultant for: Novartis, Genentech/Roche, BMS, Pfizer, Astrazeneca, Jannsen, Tekada, Biogen, BAXALTA, Speakers bureau: Novartis, Genentech/Roche, P. Quartier Grant/research support from: Abbvie, Novartis, Pfizer, Roche, Consultant for: Abbvie, Novartis, Sobi, Speakers bureau: Abbvie, BMS, Novartis, Pfizer, Roche, Sobi, T. Constantin Consultant for: Pfizer, Abbvie, Roche, Novartis, Bristol-Myers Squibb, Speakers bureau: Pfizer, Abbvie, Roche, Novartis, Bristol-Myers Squibb, E. Alexeeva Grant/research support from: Roche, Abbott, Pfizer, Centocor, Novartis, Speakers bureau: Roche, Pfizer, I. Kone-Paut Grant/research support from: Grant/research support to my institution: SOBI, Roche, Novartis, Consultant for: Novartis, SOBI, Pfizer, CHUGAI, Abbvie, K. Marzan Grant/research support from: Novartis and Abbvie, N. Wulffraat Grant/research support from: Sobi, AbbVie, Consultant for: Novartis, Pfizer, R. Schneider Consultant for: Novartis, Roche, Sobi, S. Padeh: None declared, V. Chasnyk: None declared, C. Wouters Grant/research support from: Unrestricted grant support GSK, Novartis, Roche, J. Kuemmerle-Deschner Grant/research support from: Novartis, Consultant for: Novartis, SOBI, Baxalta, T. Kallinich Speakers bureau: Novartis, B. Lauwerys: None declared, E. Haddad Grant/research support from: Unrestricted Institutional Educational Fund, E. Nasonov: None declared, M. Trachana Grant/research support from: Pfizer, O. Vougiouka Grant/research support from: Novartis, K. Leon Employee of: Novartis, A. Speziale Employee of: Novartis, K. Lheritier Employee of: Novartis, A. Martini Grant/research support from: Abbott, Bristol Myers and Squibb, Francesco Angelini S.P.A., Glaxo Smith & Kline, Janssen Biotech Inc Novartis,Pfizer Inc,Roche,Sanofi Aventis and Schwarz Biosciences GmbH funded Gaslini Institute for the PRINTO research activities, Consultant for: Bristol Myers and Squibb, Janssen Biotech Inc,Glaxo Smith & Kline, Novartis, Pfizer Inc, Roche, Sanofi Aventis and Schwarz Biosciences GmbH Biosciences GmbH funded Gaslini Institute for the PRINTO research activities, D. Lovell Grant/research support from: National Institutes of Health, NIAMS, Consultant for: Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene, Jannsen, Speakers bureau: Genentech

THU0215 Long-Term Efficacy and Safety of Canakinumab in Patients with Systemic Juvenile Idiopathic Arthritis (SJIA): 5-Year Follow-up of An Open-Label Trial

Background SJIA is a distinct and debilitating form of arthritis associated with elevated cytokine (interleukin [IL]-1 and IL-6) levels.1 Studies have shown that biologics (IL-1 and IL-6 inhibitors), including canakinumab (CAN), a selective, human anti-IL-1β monoclonal antibody, are more effective than conventional medications (NSAIDs, corticosteroids, methotrexate) in the treatment of SJIA patients (pts).1,2 However, little is known about long-term efficacy and safety of biologics in SJIA. Objectives To assess long-term efficacy and safety of CAN treatment in a 5-year (yr) follow-up of SJIA pts. Methods This was an open-label extension study of SJIA patients participating in the clinical trials of CAN, with details reported earlier.3 Pts (age, 2–20 yrs) received subcutaneous (sc) CAN (4 mg/kg) every 4 wks. Baseline is defined as the starting point of the extension trial. Efficacy measurements were done every 3 months including adapted paediatric response criteria (aACR), clinical inactive disease, clinical remission on medication (12 months of continuous clinical inactive disease) and juvenile arthritis disease activity score (JADAS). Safety was assessed monthly. Results Overall, 147 pts had a median treatment duration of 3.2 yrs, and 82 (56%) were exposed to CAN for >3 yrs (total treatment exposure of ∼365 pt-yrs). At 3 month of CAN therapy, 50% of pts had inactive disease, increasing to 49% at last assessment. Of the 107 pts with an aACR 30 at entry to the extension, 61.7% had aACR 100, with 86.0%, 87.9% and 91.6% having aACR 70/50/30 responses, respectively at last assessment. Clinical remission on medication was achieved in 43.0% of pts. Median JADAS10-CRP at baseline was 8.2 (indicating moderate disease activity), and at last assessment, median change from baseline was −0.2, with a median score of 1.8, indicating low disease activity, with similar results noted for JADAS27-CRP. Most common adverse event (AE) was infection (2.0 infections/100 pyr) typically involving the upper respiratory tract. Overall, 47 (32.0%) pts had >1 serious AE (SAE; mostly infections, macrophage activation syndrome [MAS] or SJIA flare), 10 cases of MAS (43.8 events/100 pyr) were reported, and 18 (12.2%) pts discontinued due to an AE. No deaths were reported. Conclusions In patients previously treated with CAN in pivotal trials, response to treatment was sustained or improved during long-term treatment in the extension study. Safety profile of CAN was consistent with safety findings from previous studies. References Ruperto N, et al. N Engl J Med. 2012;367:2396–406. Ringold S, et al. Arthhritis & Rheum. 2013;65(10):2499–512. Ruperto N, et al. Ann Rheum Dis. 2015;74(2):608. Disclosure of Interest N. Ruperto Grant/research support from: Abbott, BMS, “Francesco Angelini”, GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, Speakers bureau: Abbott, AbbVie, Amgen, Biogenidec, Astellas, Alter, AstraZeneca, Boehringer, BMS, CD-Pharma,Celgene, CrescendoBio, EMD Serono,Hoffman-La Roche, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo Nordisk, Pfizer, Sanofi Aventis, Servier, Takeda, Vertex, H. Brunner Consultant for: Novartis, Roche, Pfizer, UCB, Celgene, Regeneron, Amgen, Astrazeneca, GSK, BMS, Speakers bureau: Novartis, Roche, P. Quartier Grant/research support from: Abbvie, BMS, Chugai-Roche, Novartis, Pfizer, SOBI, Consultant for: Abbvie, Novartis, Servier, SOBI, Speakers bureau: Abbvie, BMS, Chugai-Roche, Medimmune, Novartis, Pfizer, SOBI, T. Constantin: None declared, E. Alexeeva Grant/research support from: Roche, Abbott, Novartis, Pfizer, Bristol-Myers Squibb, Centocor, Speakers bureau: Roche, Novartis, Merck Sharp Dohme, Bristol-Myers Squibb, Medac, Pfizer, R. Schneider Consultant for: Novartis, Novimmune, Sobi, Innomar Strategies, I. Kone-Paut Grant/research support from: SOBI, Novartis, Roche, Consultant for: Novartis, SOBI, Pfizer, Abbvie, Roche/Chugai, K. Schikler Consultant for: Novartis, Novimmune, Sobi, Innomar Strategies, K. Marzan Grant/research support from: Novartis, Abbvie, N. Wulffraat Grant/research support from: Novartis, S. Padeh: None declared, V. Chasnyk: None declared, C. Wouters Grant/research support from: GSK, Novartis, Roche, J. Kuemmerle-Deschner Grant/research support from: Novartis, Consultant for: Novartis, SOBI, Baxalta, T. Kallinich: None declared, B. Lauwerys: None declared, E. Haddad: None declared, E. Nasonov: None declared, M. Trachana Grant/research support from: Novartis, Abbvie, Bristol Meyers, Consultant for: Novartis, Roche, Pfizer, O. Vougiouka: None declared, K. Leon Employee of: Novartis, A. Speziale Employee of: Novartis, K. Lheritier Shareholder of: Novartis, Employee of: Novartis, A. Martini Grant/research support from: Abbott, BMS, “Francesco Angelini”, GlaxoSmithKline (GSK), Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, Speakers bureau: Abbott, Abbvie, Amgen, Biogenidecm Bristol MyersSquibb, Astellas, Behringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, Pfizer, Sanofi, Roche, Servier, Takeda, D. Lovell Grant/research support from: National Institutes of Health, Consultant for: Astra-Zeneca, Bristol Meyers Squibb, AbbVee, Pfizer, Roche, Novartis, UCB, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, Glaxo Smith Kline, Boehringer Ingelheim, Celgene, Jannsen, Speakers bureau: Genentech, Roche, Novartis

FRI0502 Long-Term Safety of Adalimumab Treatment in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis and Enthesitis-Related Arthritis

Background The long-term safety of anti-tumor necrosis factor (TNF) drugs is particularly important in pediatric patients (pts) who may require prolonged treatment of their inflammatory disease. Objectives To evaluate long-term rates of serious adverse events (AE) and anti-TNF AEs of special interest in adalimumab (ADA) clinical trials in pediatric pts with polyarticular or polyarticular course juvenile idiopathic arthritis (pJIA) or enthesitis-related arthritis (ERA). Methods Safety data from pts treated with ADA, either dosed 24 mg/m2 BSA every other week (eow) or 20 mg eow (<30 kg) to 40 mg eow (≥30 kg), in 4 clinical trials in pJIA and ERA were analyzed. Three studies in pJIA enrolled pts aged 2–17 years (yrs) treated with ADA for up to 8.5 yrs. One study enrolled pts with ERA aged 6–17 yrs who were treated with ADA for up to 52 wks in this analysis. AEs of special interest included malignancy, serious infections, tuberculosis (TB) and other opportunistic infections, and death. Events per 100 patient-years (PY) were calculated using AEs reported after first ADA dose through 70 days after last dose. Results ADA was administered to 274 pts, representing 769.0 PY of exposure. Infections, the most common AE, occurred in ≥10% of pts. Serious infection was the most frequently reported SAE (table). One case of latent TB was reported. No malignancies, opportunistic infections, or deaths were reported. 8.4% of pts (23/274) discontinued study due to AE (range, 5.1% in age <5 yr to 9.6% in ages 5 - <12 yrs). Other than uveitis, liver events, and injection site-related AEs, no differences in AE rates were observed between age groups.(table) Rates (E, E/100 PY) Age <5 yr Age 5–<12 yr Age 12–<18 yr Total N=39 N=104 N=131 N=274 Adalimumab exposure, PY 65.4 308.4 395.2 769.0 Serious AE* 8 (12.2) 31 (10.1) 64 (16.2) 103 (13.4) Infectious AE 106 (162.1) 499 (161.8) 560 (141.7) 1165 (151.5) Serious infectious AE 2 (3.1) 7 (2.3) 11 (2.8) 20 (2.6) Tuberculosis (latent) 0 0 1 (0.3) 1 (0.1) New onset/worsening psoriasis 0 5 (1.6) 1 (0.3) 6 (0.8) Allergic reactions 4 (6.1) 28 (9.1) 29 (7.3) 61 (7.9) Liver events 1 (2.6) 1 (1.0) 3 (2.3) 5 (1.8) Uveitis 2 (3.1) 3 (1.0) 1 (0.3) 6 (0.8) Injection site-related AE 14 (21.4) 451 (146.2) 379 (95.9) 844 (109.8)* Death, life-threatening, hospitalization or prolongation of hospitalization, persistent or significant disability, or important medical event. AEs coded by Medical Dictionary for Regulatory Activities version 16.1. Conclusions These data provide support for the long-term safety of ADA in pediatric pts aged 2–17 yrs with pJIA or ERA and demonstrate a safety profile consistent with ADA in adult pts and known information about the anti-TNF class. Acknowledgements AbbVie funded the studies (NCT00048542, NCT00690573, NCT00775437, and NCT01166282), contributed to their design and was involved in the collection, analysis, and interpretation of the data, and in the writing, review, and approval of the publication. Medical writing support was provided by Kathleen V. Kastenholz, PharmD, MS, of AbbVie. Disclosure of Interest N. Ruperto Grant/research support from: AbbVie, AstraZeneca, BMS, Janssen, “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences, Sobi, Xoma, and Wyeth for the PRINTO network paid to GASLINI Hospital, Consultant for: AbbVie, Amgen, Astellas, Alter, AstraZeneca, Biogen Idec, Boehringer, BMS, CD-Pharma, Celgene, Crescendo Bioscience, EMD Serono, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo-Nordisk, Pfizer, Roche, Sanofi Aventis, Servier, Sinergie, Takeda, and Vertex, Speakers bureau: AbbVie, Amgen, Astellas, Alter, AstraZeneca, Biogen Idec, Boehringer, BMS, CD-Pharma, Celgene, Crescendo Bioscience, EMD Serono, Italfarmaco, Janssen, MedImmune, Medac, Novartis, Novo-Nordisk, Pfizer, Roche, Sanofi Aventis, Servier, Sinergie, Takeda, and Vertex, D. Lovell Consultant for: AbbVie, AstraZeneca, Boehringer Ingelheim, Celgene, Centocor, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Horizon Pharma, Janssen Biologics B.V., Novartis, Pfizer, Regeneron, Hoffman La-Roche, and UBC and served on data and safety monitoring boards for Forest Research, Speakers bureau: Genentech and Wyeth Pharmaceuticals, D. Kingsbury Grant/research support from: AbbVie, R. Burgos-Vargas Grant/research support from: AbbVie, Consultant for: AbbVie, BMS, Janssen, Pfizer, and Roche, Speakers bureau: AbbVie, BMS, Janssen, Pfizer, and Roche, T. Imagawa Grant/research support from: AbbVie/Eisai and Novartis, Consultant for: AbbVie/Eisai, Speakers bureau: AbbVie/Eisai, Chugai, and Mitsubishi Pharma, G. Horneff Grant/research support from: AbbVie, Pfizer, and Roche, Speakers bureau: AbbVie, Novartis, Pfizer, and Roche, P. Quartier Grant/research support from: AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, and Swedish Orphan Biovitrum, Consultant for: AbbVie, Novartis, Pfizer, BMS, Chugai-Roche, Medimmune, Servier, and Swedish Orphan Biovitrum, S. Goodman Consultant for: Amgen, A. Reiff Consultant for: AbbVie and Amgen, Speakers bureau: AbbVie and Amgen, E. Giannini Consultant for: AbbVie, A. Cardoso Shareholder of: AbbVie, Employee of: AbbVie, J. Anderson Shareholder of: AbbVie, Employee of: AbbVie, N. Varothai Shareholder of: AbbVie, Employee of: AbbVie, J. Kalabic Shareholder of: AbbVie, Employee of: AbbVie, A. Martini Grant/research support from: AbbVie, AstraZeneca, BMS, Janssen, “Francesco Angelini”, GlaxoSmithKline, Italfarmaco, Novartis, Pfizer, Roche, Sanofi Aventis, Schwarz Biosciences, Xoma, and Wyeth for the PRINTO network paid to GASLINI Hospital, Consultant for: AbbVie, Amgen, Biogen Idec, Boehringer, BMS, Celgene, EMD Serono, Janssen, MedImmune, Medac, Novartis, Novo- Nordisk, Pfizer, Roche, Sanofi Aventis, Servier, Takeda, and Vertex, Speakers bureau: AbbVie, Amgen, Biogen Idec, Boehringer, BMS, Celgene, EMD Serono, Janssen, MedImmune, Medac, Novartis, Novo- Nordisk, Pfizer, Roche, Sanofi Aventis, Servier, Takeda, and Vertex

Tapering and withdrawal of tocilizumab in patients with systemic juvenile idiopathic arthritis in inactive disease: results from an alternative dosing regimen in the TENDER study

The TENDER clinical trial is a 3-part, 5-year, phase 3 study of tocilizumab (TCZ) in patients with active systemic juvenile idiopathic arthritis (sJIA). After 2 years of treatment, sJIA patients who have maintained clinically inactive disease (CID) for 3 months are given the option to participate in an alternative TCZ dosing regimen aimed at spacing the infusions and eventually withdrawing TCZ.