Objective To assess the long-term efficacy and safety of infliximab plus methotrexate in juvenile rheumatoid arthritis (JRA). Methods Patients eligible for the open-label extension (OLE, weeks ...52–204) received infliximab 3–6 mg/kg every 8 weeks plus methotrexate. Results Of the 78/122 (64%) children entering the OLE, 42 discontinued infliximab, most commonly due to consent withdrawal (11 patients), lack of efficacy (eight patients) or patient/physician/sponsor requirement (eight patients). Infliximab (mean dose 4.4 mg/kg per infusion) was generally well tolerated. Infusion reactions occurred in 32% (25/78) of patients, with a higher incidence in patients positive for antibodies to infliximab (58%, 15/26). At week 204, the proportions of patients achieving ACR-Pedi-30/50/70/90 response criteria and inactive disease status were 44%, 40%, 33%, 24% and 13%, respectively. Conclusions In the limited population of JRA patients remaining in the study at 4 years, infliximab was safe and effective but associated with a high patient discontinuation rate. Clinical trials registration number NCT00036374.
Objective. Juvenile localized scleroderma (JLS) includes a number of conditions often grouped together. With the long-term goal of developing uniform classification criteria, we studied the ...epidemiological, clinical and immunological features of children with JLS followed by paediatric rheumatology and dermatology centres. Methods. A large, multicentre, multinational study was conducted by collecting information on the demographics, family history, triggering environmental factors, clinical and laboratory features, and treatment of patients with JLS. Results. Seven hundred and fifty patients with JLS from 70 centres were enrolled into the study. The disease duration at diagnosis was 18 months. Linear scleroderma (LS) was the most frequent subtype (65%), followed by plaque morphea (PM) (26%), generalized morphea (GM) (7%) and deep morphea (DM) (2%). As many as 15% of patients had a mixed subtype. Ninety-one patients (12%) had a positive family history for rheumatic or autoimmune diseases; 100 (13.3%) reported environmental events as possible trigger. ANA was positive in 42.3% of the patients, with a higher prevalence in the LS-DM subtype than in the PM-GM subtype. Scl70 was detected in the sera of 3% of the patients, anticentromere antibody in 2%, anti-double-stranded DNA in 4%, anti-cardiolipin antibody in 13% and rheumatoid factor in 16%. Methotrexate was the drug most frequently used, especially during the last 5 yr. Conclusion. This study represents the largest collection of patients with JLS ever reported. The insidious onset of the disease, the delay in diagnosis, the recognition of mixed subtype and the better definition of the other subtypes should influence our efforts in educating trainees and practitioners and help in developing a comprehensive classification system for this syndrome.
BackgroundIntravenous (IV) tocilizumab (TCZ) was approved in the, US (2011), EU (2013) and other countries for the treatment of systemic juvenile idiopathic arthritis (sJIA) patients (pts)≥2 years of ...age, based on a phase 3 study WA18221.1 US Food and Drug Administration approval resulted in postmarketing requirement to investigate TCZ in pts with sJIA <2 years of age (study NP25737; ClinicalTrials.gov, NCT01455701). Results from the 12 week main evaluation period (MEP) have been reported.2 ObjectivesReport safety results after completion of the optional extension period (OEP) of NP25737 (until 52 weeks from baseline or 2 years of age, whichever was longer).MethodsNP25737 was a multicenter, open-label, single-arm study to evaluate the pharmacokinetics and safety of IV TCZ, 12 mg/kg every 2 weeks, for 12 weeks in pts aged <2 years with active sJIA for ≥1 month who failed corticosteroid and nonsteroidal anti-inflammatory drug treatment and received stable background therapy during the MEP. After the 12 week MEP, pts could participate in the OEP and continue TCZ treatment (without requirement for stable background therapy). Cumulative adverse events (AEs) over the entire study period are reported.ResultsSeven of 11 pts enrolled in the MEP continued to the OEP and received ≥1 dose of TCZ. Over the entire study period (n=11), the median number of TCZ doses was 11 (range, 2–26) and the median duration of TCZ exposure was 22 weeks (range, 4–58). Most pts (10/11; 91%) had ≥1 AE; most were mild or moderate in intensity and unrelated to study drug. The most common AEs were upper respiratory tract infection (6/11 pts, 55%), hypersensitivity, neutropenia, rash, viral upper respiratory tract infection, and vomiting (each in 3/11 pts; 27%). Seven serious AEs occurred in 5 of 11 pts (46%): 2 in the OEP (transaminases increased and histiocytosis hematophagic), 3 in the MEP (3 hypersensitivity events), and 2 in the safety follow-up of the MEP (sJIA flare and hand-foot-and-mouth disease). AEs leading to dose modification occurred in 5 of 11 pts (1 in the MEP, 4 in the OEP) mostly because of infections, neutropenia, and elevated liver enzymes, all mild or moderate in intensity. AEs leading to withdrawal occurred in 5 of 11 pts (46%): 1 in the OEP because of serious increased transaminases, 3 in the MEP because of serious hypersensitivity reactions to TCZ, and 1 in the MEP because of thrombocytopenia. No deaths were reported during the study. AE rates per 100 pt-years of exposure are reported in the table 1.Abstract THU0598 – Table 1Rates of AEsConclusionsDuring the OEP of the study, long-term treatment with TCZ was well tolerated in sJIA pts aged <2 years, and no additional safety signals were reported in the OEP beyond those reported in the MEP or observed previously for pts with sJIA aged ≥2 years.References1 De Benedetti F, et al. N Engl J Med2012;367:2385–2395.2 Mallalieu NL, et al. Arthritis Rheumatol2017;69(suppl 10):abstract 2856.AcknowledgementsThis study was sponsored by F. Hoffmann-La Roche Ltd.Disclosure of InterestS. Wimalasundera Employee of: Roche, I. Calvo Penades: None declared, R. Cuttica Consultant for: Roche, Novartis, Lilly, GlaxoSmithKline, BMS, Janssen, Speakers bureau: Roche, Novartis, Lilly, GlaxoSmithKline, BMS, Janssen, H.-I. Huppertz: None declared, R. Joos: None declared, D. Milojevic: None declared, M. Rosenkranz: None declared, K. Schikler: None declared, T. Constantin: None declared, W. Douglass Employee of: Roche, C. Wells Shareholder of: Roche, Employee of: Roche, Y. Kimura Grant/research support from: Novartis, SOBI, Consultant for: Novartis, SOBI, C. Wouters: None declared
BackgroundIV abatacept (ABA) 10 mg/kg every 4 weeks is safe and effective in reducing signs and symptoms of polyarticular forms of juvenile idiopathic arthritis (pJIA) in children and adolescents.1 ...SC ABA 125 mg weekly has therapeutically equivalent efficacy and comparable safety to IV ABA in adult RA, but similar data in pJIA are lacking.ObjectivesTo assess the PK, efficacy and safety of SC ABA in children and adolescents with active pJIA.MethodsThis single-arm, open-label (OL), Phase III study (NCT01844518) enrolled patients (pts) aged 2–17 years (yrs) with pJIA and an inadequate response/intolerance to ≥1 DMARD. Pts received SC ABA weekly OL for 4 months (M), based on body weight tier (10–<25 50 mg ABA, 25–50 87.5 mg ABA and >50 kg 125 mg ABA). JIAACR criteria 30 (JIAACR30) responders at 4M could enter a 20M OL extension; JIAACR30 non-responders could continue SC ABA for 3M more and discontinued if JIAACR30 was not achieved by M7. The primary endpoint was steady-state blood trough concentration (Cminss) of ABA at 4M in the 6–17-yr-old pJIA pts (n=173); we report PK, efficacy and safety from the initial 4M OL phase for these pts.ResultsBaseline characteristics of the 173 pJIA pts were: mean age (SD) =12.3 (3.1) yrs; mean number of active joints (SD) =12.4 (8.3); 78.6% of patients used MTX (mean dose: 12 mg/m2/week) and 26.6% failed prior biologic treatment. The target therapeutic Cminss of 10 μg/mL was achieved (Figure); at 4M, mean (SD) Cminss was 42.1 (14.7) μg/mL and was consistent across all three weight groups. Robust JIAACR responses were seen at 4M (Figure): JIAACR30, 80.9%; inactive disease, 29.5%. Biologic-naïve pts had a numerically higher JIAACR30 response than biologic-experienced pts at 4M. The number of pts with serious AEs and those who discontinued study drug due to AEs during the initial 4M were low (n=5 and n=3 fatigue, exanthematous rash and ovarian germ cell teratoma pts, respectively). AEs of interest reported included infections (31.8%) with 1 case of sepsis, injection-site reactions (5.2%) and malignancy (0.6%). No laboratory abnormalities or unexpected safety concerns were reported.ConclusionsThe target therapeutic exposure for SC abatacept was achieved in pts aged 6–17 yrs with pJIA irrespective of weight group. The exposures for SC abatacept were within the range for IV abatacept in pJIA and comparable with SC abatacept in adult RA. Robust efficacy was observed with SC abatacept with no new safety concerns after 4M of treatment.ReferencesRuperto N, et al. Lancet 2008;372:383–91.Disclosure of InterestN. Ruperto Grant/research support from: Gaslini Hospital, Bristol-Myers Squibb, Hoffman-La Roche, Janssen, Novartis, Pfizer, sanofi aventis, Schwarz Biosciences, Sobi, Consultant for: AbbVie, Amgen, Biogen Idec, Baxalta, Boehringer, Bristol-Myers Squibb, Celgene, EMD Serono, Hoffman-La Roche, Janssen, Novartis, Pfizer, Servier, Sinergie,Takeda, Speakers bureau: AbbVie, Amgen, Biogen Idec, Baxalta, Boehringer, Bristol-Myers Squibb, Celgene, EMD Serono, Hoffman-La Roche, Janssen, Novartis, Pfizer, Servier, Sinergie,Takeda, D. J. Lovell Grant/research support from: NIH, Consultant for: AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Janssen, N. Tzaribachev Grant/research support from: UCB, Pfizer, Janssen, Roche, G. Vega-Cornejo: None declared, I. Louw: None declared, A. Berman: None declared, I. Calvo Grant/research support from: Novartis, Speakers bureau: AbbVie, Roche, Novartis, Sobi, R. Cuttica: None declared, G. Horneff Grant/research support from: Pfizer, AbbVie, Roche, F. Avila-Zapata: None declared, J. Anton Grant/research support from: Pfizer, Novartis, Speakers bureau: Pfizer, AbbVie, Novartis, Sobi, Roche, D. Viola: None declared, I. Foeldvari: None declared, V. Keltsev: None declared, D. Kingsbury: None declared, X. Li Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, M. Nys Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, R. Wong Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, S. Banerjee Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, A. Martini Grant/research support from: The Gaslini Hospital, which is the public Hospital where I work as full time public employee, has received contributions from the following industries: Abbott, Bristol-Myers Squibb, “Francesco Angelini”, GlaxoSmithKline, Hoffman-La Roche, Italfarmaco, Janssen, Novartis, Pfizer, sanofi aventis, Schwarz Biosciences, Sobi, Xoma, Wyeth, Consultant for: Abbott, AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Astellas, Boehringer, Italfarmaco, Janssen, MedImmune, Novartis, NovoNordisk, H. I. Brunner Consultant for: Pfizer, Bristol-Myers Squibb, UCB, Janssen, Amgen, Celgene, AstraZeneca, Novartis, Genentech, Speakers bureau: Novartis, Genentech
BackgroundTwo-year results from the 3-part, 5-year, phase 3 TENDER study demonstrated that tocilizumab (TCZ), an anti–interleukin-6 receptor antibody, was effective in the treatment of patients with ...severe, persistent systemic juvenile idiopathic arthritis (sJIA).1ObjectivesTo report the long-term safety and efficacy of TCZ in patients with sJIA treated for up to 5 years in the TENDER trial.MethodsIn part 1, patients (2-17 years) with active sJIA for ≥6 months were randomly assigned 2:1 to receive TCZ (body weight BW ≥30 kg, TCZ 8 mg/kg; BW <30 kg, TCZ 12 mg/kg) or placebo every 2 weeks (q2w) for 12 weeks. Patients received open-label TCZ q2w based on BW in part 2 (weeks 12-104) and part 3 (weeks 104-260). In part 3, an alternative dosing regimen in which TCZ and concomitant medications were tapered and discontinued in patients with clinically inactive disease (CID) was optional. Efficacy was assessed in those who entered part 3 (ITT3 population) and up to the point of entry into the alternative dosing schedule; safety was assessed in all patients who entered part 1 (safety population). The primary end point in part 3 was long-term safety.ResultsOf the 112 patients enrolled in part 1, 89 entered part 3 and were included in the ITT3 population; 66 patients (59%) completed the full 260-week study. Patients in the ITT3 population had a mean (SD) age of 9.5 (4.4) years, and 53% were male. The high proportion of patients achieving JIA ACR 30/50/70/90 responses on entry into part 3 was maintained through week 260 (Table 1). Among the 30 patients who did not enter the alternative dosing regimen and completed the study, 8 (26.7%) met the criteria for CID at week 260. During the study, an additional 39 patients reached and maintained CID for at least 3 months and entered the alternative dosing regimen. Of patients remaining in the study at week 260, 31 received oral glucocorticoids (GCs) and 34 received methotrexate (MTX) at baseline. By the end of the study, 17/31 and 6/34 patients stopped oral GCs and MTX, respectively. The 5-year safety profile for patients on q2w dosing was similar to the 2-year safety profile, with no new safety findings observed (Table 2). Rates/100 patient-years (PY) of adverse events (AEs) and of serious AEs (SAEs) did not increase between year 2 and year 5 (Table 2). Most SAEs were unrelated to study treatment, and infections accounted for nearly half of all SAEs. Four deaths occurred over the 5 years at a rate of 1.1/100 PY; 1 death (sepsis) was possibly related to study treatment.ConclusionsThese results demonstrate the continued maintenance of efficacy and no change in the safety profile over 5 years of TCZ treatment in patients with sJIA.ReferencesDe Benedetti F et al. Ann Rheum Dis. 2012;71(suppl 3):425.Disclosure of InterestF. De Benedetti Grant/research support from: Roche, Novartis, Pfizer, Novimmune, Sobi, Consultant for: Roche, Novartis, N. Ruperto Grant/research support from: Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Consultant for: Roche, Speakers bureau: Abbott, AbbVie, Amgen, Astellas, Bristol Myers-Squibb, Boehringer, Celgene, CrescendoBio, EMDSerono, Italfarmaco, Janssen, Medimmune, Novartis, Novonordisk, Pfizer, Sanofi, Reumatic.com, Servier, Sinergie, Takeda, H. Brunner: None declared, C. Keane Employee of: Roche, C. Wells Employee of: Roche, J. Wang Employee of: Roche, I. Calvo: None declared, R. Cuttica: None declared, A. Ravelli Grant/research support from: Pfizer, Consultant for: Novartis, Roche, AbbVie, Bristol-Myers Squibb, Johnson & Johnson, Pfizer, R. Schneider Consultant for: Roche, Novartis, D. Eleftheriou: None declared, C. Wouters: None declared, R. Xavier Consultant for: Roche, Janssen, Pfizer, AstraZeneca, AbbVie, L. Zemel: None declared, E. Baildam Grant/research support from: Roche, Chugai, Speakers bureau: Roche, R. Burgos-Vargas: None declared, P. Dolezalova Grant/research support from: Novartis, Consultant for: Roche, Novartis, Pfizer, S. Garay: None declared, R. Joos: None declared, A. Grom Consultant for: Novartis, Genentech, N. Wulffraat Grant/research support from: European Union (EAHC), Z. Zuber: None declared, F. Zulian: None declared, A. Martini Grant/research support from: Roche, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences GmbH, Consultant for: Roche, Speakers bureau: Roche, Abbott, AbbVie, Amgen, Astellas, Bristol-Myers Squibb, Boehringer, Celgene, CrescendoBio, EMDSerono, Italfarmaco, Janssen, Medimmune, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Takeda, D. Lovell Grant/research support from: NIH, Consultant for: AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Janssen, Speakers bureau: Genentech, Roche, Novartis
Background The IL-6 receptor inhibitor TCZ was investigated for the treatment of sJIA patients (pts) in the ongoing 3-part, 5-y, phase 3 TENDER study. Objectives Long-term efficacy and safety are ...presented. Methods 112 pts 2-17 y with active sJIA for ≥6 mo were randomised 2:1 to TCZ (8 mg/kg if body weight ≥30 kg; 12 mg/kg if <30 kg, n=75) or placebo (n=37) every 2 wks for 12 wks in part 1; all pts received open-label TCZ in part 2 (to 104 wks). Oral corticosteroid (CS) tapering was permitted according to pre-defined criteria. Data were cut for each ongoing pt 104 wks from randomisation, with first dose of TCZ as baseline (BL) in the extension. At the data cut, 61 pts received ≥104 wks of TCZ, 32 pts were ongoing and 20 withdrew, including 1 at wk 104 (safety, 9; insufficient therapeutic response, 5; other non-safety, 6). Results BL characteristics included mean disease duration of 5.2 y, mean active joint count of 19.8 and presence of fever in 43% of pts. At 2 y, 88% and 71% of pts on TCZ achieved JIA ACR70 and 90 responses (Table 1). In pts on oral CS at BL, 60% stopped by wk 104, and mean dose decreased from 0.30 mg/kg/d at BL to 0.04 at wk 104. 47 serious adverse events (SAEs), 15 considered TCZ-related, occurred in 35 pts (Table 2). Of 22 serious infections (8 considered TCZ-related) in 20 pts, all but 1 resolved (pt death). 3 pts died (1, suspected tension pneumothorax; 1 traffic accident both unrelated; 1 suspected streptococcal sepsis; possibly related). 3 additional pts died 6, 12 and 13 mos after leaving the study. Table 1. Efficacy Endpoints (ITT Population) Wk 12aWk 52bWk 104b Placebo (N=37)TCZ (N=75)TCZ (N=106)TCZ (N=65) JIA ACR70/90, n (%)3 (8)/2 (5)c53 (71)/28 (37)c92 (87)/67 (63)e57 (88)/46 (71)e Active joints, mean (SD)9.5 (9.0)d7.3 (11.9)d2.8 (6.4)f1.9 (3.6)f Absence of active joints, n (%)2 (5)12 (16)50 (47)e36 (55)e aBL was date of randomisation. bBL was first dose of TCZ. c% is based on all pts; those who withdrew or escaped were assumed non-responders. dPts who withdrew or escaped were excluded. e% is based on number of pts who reached time point + pts who withdrew because of insufficient therapeutic response and are assumed to have been non-responders. fPts who withdrew have been excluded at post-withdrawal visits. Table 2. Cumulative Safety (Safety Population, N=112) Prior Safety UpdateaWk 104b Exposure to TCZ, y157.46202.03 SAEs/100PY (n)24.8 (39)23.3 (47) Serious infection AEs/100PY (n)11.4 (18)10.9 (22) SAEs related (remotely, possibly, probably) to TCZ/100PY (n)8.3 (13)7.4 (15) AEs leading to withdrawal/100PY (n)3.8 (6)c3.0 (6)c Deaths/100PY (n)0.6 (1)1.5 (3) PY, pt-years. aIncludes all safety data up to 10 Aug 2010. bAll safety data up to wk 104 infusion for each pt. Last date for this was 31 May 2011. cIncludes 2 withdrawals (protocol mandated) for transaminase increases. Conclusions TENDER 2-y results demonstrated continued maintenance of efficacy and no change in the safety profile with long-term TCZ treatment. Disclosure of Interest F. De Benedetti Grant/Research support from: Abbott, BMS, Pfizer, SOBI, Novimmune, Roche, Novartis, Consultant for: BMS, Pfizer, Roche, H. Brunner Consultant for: Genentech, Novartis, UCB, Jansen, Medimmune, GSK, BMS, PFizer, Employee of: Cincinnati Children’s Hospital Medical Center, N. Ruperto Grant/Research support from: Abbott, Astrazeneca, BMS, Centocor Research and Development, Eli Lilly and Company, “Francesco Angelini” s.p.a., GSK, Italfarmaco, Merk Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc., Speakers Bureau: Astrazeneca, BMS, Jansen Biologics BV, Novartis, Roche, A. Kenwright Employee of: Roche, C. Devlin Shareholder of: Roche, Employee of: Roche, I. Calvo: None Declared, R. Cuttica Grant/Research support from: Novartis, Hoffmann-La Roche, Consultant for: Hoffmann-La Roche, Speakers Bureau: Hoffmann-La Roche, A. Ravelli: None Declared, R. Schneider: None Declared, D. Eleftheriou: None Declared, C. Wouters: None Declared, R. Xavier Consultant for: Pfizer, Roche, Speakers Bureau: Pfizer, Roche, Abbott, L. Zemel: None Declared, E. Baildam: None Declared, R. Burgos-Vargas Grant/Research support from: Abbott, Consultant for: Abbott, BMS, Jannsen, Pfizer, Roche, Speakers Bureau: Abbott, BMS, Jannsen, Pfizer, Roche, P. Dolezalova Grant/Research support from: Novatis, Speakers Bureau: BMS, Novartis, S. M. Garay: None Declared, R. Joos: None Declared, A. Grom Consultant for: Novartis, Merck, N. Wulffraat: None Declared, Z. Zuber: None Declared, F. Zulian: None Declared, D. Lovell Grant/Research support from: BMS, Abbott, Consultant for: Astrazeneca, Wyeth, Amgen, Pfizer, Regeneron, Roche, Novartis, UMC, Xoma, A. Martini Grant/Research support from: Abbott, Astrazeneca, BMS, Centocor Research and Development, Eli Lilly and Company, “Francesco Angelini” s.p.a., GSK, Italfarmaco, Merk Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Xoma, Wyeth Pharmaceuticals Inc., Speakers Bureau: Astrazeneca, Novartis, BMS, GSK
Background Data regarding the safety and efficacy of treatment regimens for juvenile dermatomyositis (JDM) tends to be from anecdotal, small, uncontrolled, non-randomized case series. Objectives This ...randomized trial was aimed to find out the treatment regimen associated with the lowest occurrence of flare and the lowest drug related toxicity. Methods Children with newly diagnosed JDM were randomized in an open fashion to receive one of 3 different therapeutic approaches: prednisone (PDN) versus PDN plus methotrexate (MTX) versus PDN plus Cyclosporine A. The overall hypothesis to be tested in this trial was that the early introduction of combination therapy of corticosteroids and either MTX or CsA will prove more effective and safe than corticosteroids alone in the treatment of JDM. Primary outcome measures after 6 months of treatment: response rate according to the Paediatric Rheumatology International Trials Organisation (PRINTO) provisional definition of improvement in the 3 arms (20% improvement in at least 3 core set variables with no more than 1 of the remaining variables, (muscle strength excluded), worsened by > 30%). The PRINTO JDM core set variables are: 1) muscle strength by the mean of the Childhood Myositis Assessment Scale (CMAS); 2) physician’s global assessment of disease activity on a 10 cm VAS ; 3) global disease activity assessment by the mean of the Disease Activity Index (DAS); 4) parent’s/patient’s global assessment of overall well-being on a 10 cm VAS; 5) functional ability assessment by the mean of the Childhood Health Assessment Questionnaire (CHAQ); 6) health-related quality of life assessment. Primary outcome measures after 24 months of treatment: a) time to inactive disease; b) time to major therapeutic changes because of inefficacy/flare/adverse events. Results 138/139 randomized patients were included in the efficacy dataset. There were 81/138 females (59%) with a median age at onset of 7.4 years (1st-3rd quartiles 1.1-15.4) and a median disease duration of 2.8 months (1.4-5.3). Frequency of response at 6 months was for 24/46 (52.2%) for PDN, 31/46 (67.4%) for PDN+CSA and 34/46 (73.9%) for PDN+MTX (p 0.082). Time to inactive disease in the combination group (PDN+CSA or PDN+MTX) was significantly shorter than that of PDN alone (p 0.031). Time to major therapeutic changes in the combination group (PDN+CSA or PDN+MTX) was significantly longer than that of PDN alone (p 0.009). Total number of adverse events were 57/276 (20.7%) in the PDN group, 141/276 (51.1%) in PDN+CSA and 78/276 (28.3%) in PDN+MTX (p < 0.0001). Skin and subcutaneous tissue disorders, and nervous system disorders were statistically more frequent in PDN+CSA (p 0.0015, p 0.039 respectively). Conclusions Combined therapy with PDN and either CSA or MTX was more effective than with PDN alone. However the safety profile favour the combination with MTX toward that with CSA. Disclosure of Interest None Declared
Background Polyarteritis nodosa (PAN) is a predominantly medium size vasculitis characterized by non granulomatous necrotizing vasculitis. In children (c-) the disease may be confined to the skin ...only (cutaneous involvement-PAN) or may present with systemic involvement (systemic c-PAN) as in adult polyarteritis nodosa. Objectives We aimed to evaluate clinical, laboratory and imaging features of cutaneous c-PAN and the systemic c-PAN form in a large international pediatric vasculitis registry available on the PRINTO database. Methods We extracted from the PRINTO database all the patients who fulfilled the Ankara 2008-EULAR/PRES/PRINTO criteria for systemic c-PAN. The cutaneous c-PAN patients as per the treating physician diagnosis were also extracted. To define clinical and laboratory characteristics who could help to differentiate cutaneous PAN from cPAN and univariate logistic regression analysis was performed. Results There were 109 and 45 patients classified as systemic c-PAN, and cutaneous c-PAN respectively with a mean age at diagnosis of 9.47±3.59 years; and 9.12±3.83 years; respectively. The female/male ratio and ethnicity did not differ in the 2 subtypes. The cutaneous group had significantly less constitutional features and less acute phase reactant levels, as expected. The median values (IQR 25-75%) for the ESR and CRP for cPAN were 78 (48-108) mm/h and 7.36 (2.76-15.03) mg/dL. Musculoskeletal features such as myalgia was present in 82 (75.2%) patients with c-PAN and 18 (40.9%) patients with cutaneous PAN (p<0.001) both groups. As differentiating features skin infarcts were observed in c-PAN only and constitutional features, angiographic abnormalities, and organ involvement was not seen in any of the cutaneous PAN patients. Malaise, fever, severe headache, motor mononeuritis multiplex, sensory peripheral neuropathy, abdominal pain, and hematuria were the most statistically significant clinical characteristics able to differentiate these two entities. Conclusions This is the first study comparing the features of childhood PAN and cutaneous PAN in a large group of pediatric patients. Further biological studies are needed to effectively differentiate the two entities. References Ozen S, Pistorio A, Iusan SM et al.: EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria. Ann Rheum Dis 2010; 69(5):798-806. Disclosure of Interest None Declared
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