BackgroundCAPS (Cryopyrin-associated periodic fever syndromes) are monogenic autoinflammatory diseases causing great burden to patients due to severe systemic and organ inflammation caused by increased production of interleukin-1β (IL-1β). In clinical trials as well as in real-life, the monoclonal antibody canakinumab (CAN) effectively inhibits IL-1β and results in rapid suppression of CAPS symptoms.ObjectivesThe RELIANCE registry explores long-term safety and effectiveness of CAN under routine clinical practice conditions in pediatric (≥2 years) and adult patients with CAPS, including Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS) and neonatal onset multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular syndrome (CINCA).MethodsThis prospective, non-interventional, observational study enrolls patients with clinically confirmed diagnoses of CAPS routinely receiving CAN. Clinical data, physician assessments and patient-reported outcomes are evaluated in 6-monthly intervals.Results107 CAPS patients (53% female; 16% NOMID/CINCA subtypes) were enrolled by December 2022. At baseline, median age was 23 years and median duration of prior CAN treatment was 6 years. 92% of patients received greater than standard dose CAN.75% of the patients were in disease remission at month 48 by physician assessment. Patients report stable low level disease activity (median 2.0 at baseline and 1.5 at month 48) and fatigue (median 3.0 at baseline and 1.0 at month 48). No relevant differences regarding subtype severity were observed (Table 1). At baseline vs. month 48, 46% vs. 50% of patients experienced impairment of social life and 32% vs. 25% reported days off from school or work due to the disease.Severe adverse events (SAE) suspected to be drug-related were reported for N=9 (8.4%) CAPS patients. The incidence rate (IR) per 100 patient-years kept stable over time.ConclusionThe 48-month interim analysis of the RELIANCE registry demonstrates that long-term CAN treatment is safe and effective in patients with CAPS, independent of subtype severity.Table 1.Assessment of clinical CAPS disease activity and laboratory markers over time.Baseline24 months48 monthsNOMID/CINCAMWS, FCASNOMID/ CINCAMWS, FCASNOMID/ CINCAMWS, FCASNumber* of patients, N17801054313Number (%**) of patients with days absent from work/school during last 6 months6 (35)25 (32)2 (20)20 (37)0 (0)4 (31)Number (%**) of patients in disease remission (physician assessment)13 (77)53 (68)8 (80)33 (61)2 (67)10 (77)Patient’s assessment of current disease activity; 0–10, median (min; max)1.0 (0; 7)2.0 (0; 7)2.0 (0; 4)1.0 (0; 8)0.0 (0; 0)2.0 (0; 5)Patient’s assessment of current fatigue; 0–10, median (min; max)3.0 (0; 9)3.0 (0; 9)2.0 (0; 7)2.0 (0; 9)0.0 (0; 0)1.0 (0; 7)Number (%**) of patientswithoutimpairment of social life by the disease5 (56)29 (57)3 (50)25 (63)0 (0)2 (67)Current influence of the disease on mood; % of patients** with negative | positive | no influence30 | 10 | 6023 | 19 | 5917 | 33 | 5024 | 37 | 400 | 0 | 025 | 25 | 50CRP, median (mg/dl)0.20.10.30.20.90.1SAA, median (mg/dl)0.40.40.90.40.60.2ESR, median (mm/h)6.05.08.05.05.02.5SAENumber of eventsIR‡per 100 patient-yearsAll types of SAE6522.85SADR28#9.84NOMID/CINCA00MWS/FACS2611.55#Abdominal pain, Alport’s syndrome, appendicitis, arthralgia, blister, cardiovascular disorder, chest pain, circulatory collapse, dehydration, diplopia, dyspnoea, erythema, febrile convulsion, gastroenteritis, glomerulonephritis, haemophilus test positive, myalgia, oedema, pneumonia, premature delivery, skin discolouration, tonsillectomy, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (all N=1 event), pyrexia (N=3 events)*subtype not reported for all patients.**not reported for all patients.‡IR = number of events * 36525/ sum of observation days (=103905)CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; SAA, serum amyloid A; SADR, serious adverse drug reactionREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsJ. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Birgit Kortus-Goetze Consultant of: Novartis, Catharina Schuetz Grant/research support from: Novartis, Prasad Oommen Grant/research support from: Novartis, Ales Janda: None declared, Jürgen Rech Speakers bureau: AbbVie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: AbbVie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Frank Weller-Heinemann: None declared, Tilmann Kallinich Speakers bureau: Roche, Anne Pankow: None declared, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Ivan Foeldvari Consultant of: Novartis, Peter Wasiliew Grant/research support from: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Michael Fiene: None declared, Florian Meier Speakers bureau: Novartis, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Ioana Andreica Speakers bureau: Abbvie, Chugai, Novartis, UCB, MSD, Lilly, Sobi, Astrazeneca, Amgen, Pfizer, Gilead, Paid instructor for: Astrazeneca, UCB; Consultant Abbvie, Chugai, Novartis, UCB, Galapagos, Takeda, Astrazeneca, Lilly, Boehringer Ingelheim, Amgen, Sobi, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi.

Background Granulomatosis with polyangiitis is a granulomatous, necrotizing small-vessel vasculitis affecting both children and adults. However, subglottic tracheal stenosis appears more frequently in the pediatric cohort. To date, granulomatosis with polyangiitis is often treated with steroids, cyclophosphamide, azathioprine, or rituximab, but tumor-necrosis-factor-α-antagonistic drugs are increasingly gaining significance in treatment of refractory cases. Case presentation We report the case of a 15-year-old Caucasian male diagnosed with proteinase-3-positive granulomatosis with polyangiitis with acute shortness of breath. X-ray and magnet resonance imaging showed extensive subglottic narrowing. Forced expiratory volume in 1 s was reduced to 50% of age norm, with massively increased effective airway resistance. The patient initially responded very well to high-dose steroids and maintenance therapy with azathioprine. He was subsequently treated with four doses of rituximab, and levels of proteinase 3 antibodies normalized. After 6 months of clinical remission, the patient presented again with acute respiratory symptoms. Again, he was treated with high-dose steroids, but showed poor clinical response this time. Therefore, we decided to commence a tumor-necrosis-factor-α-antagonistic treatment with infliximab, under which our patient achieved clinical remission and normalization of lung function parameters. Conclusions The use of tumor-necrosis-factor-α-antagonistic agents might be a promising alternative for the treatment of refractory tracheal stenosis in pediatric patients with granulomatosis with polyangiitis.

Zusammenfassung Hintergrund Alternativ zu ambulanten 24h-Blutdruckmessgeräten wurde die kontinuierliche, nicht-invasive Blutdruckaufzeichnung mittels Pulswellenlaufzeit bzw. Puls -Transit-Zeit (PTZ) sowohl mit oszillometrischen als auch intraarteriellen Messmethoden verglichen. Methoden An 144 pädiatrischen Patienten (9,4±5,2 Jahre) wurde der akute Blutdruck mithilfe von 3 verschiedenen Messmethoden ermittelt. An 57 Patienten (11,4±4,9 Jahre) der pädiatrischen Normalstation wurde simultan der Blutdruck kontinuierlich mittels PTZ im Vergleich zur intermittierenden oszillometrischen Langzeitmessung bestimmt. Bei 9 Patienten (9,8±6,8 Jahre) der pädiatrischen Intensivstation mit kontinuierlicher intraarterieller Blutdruckmessung wurde der Blutdruck parallel mittels PTZ gemessen. Ergebnisse Verglichen mit dem Goldstandard der Sphygmomanometrie, waren die mittleren systolischen Blutdruckwerte mit 2 verschiedenen oszillometrischen Messgeräten vergleichbar, aber bei der diastolischen Druckmessung waren die Druckwerte signifikant niedriger bzw. höher als mit der Sphygmomanometrie und Auskultation. Die Ergebnisse der nicht-invasiven vergleichenden Langzeitmessungen zeigten insgesamt bessere Korrelationen für den systolischen als für den diastolischen Druck. Ähnliche Ergebnisse ergab der Vergleich der direkten intraarteriellen Blutdruckmessung mit dem SOMNOtouch™ NIBP -Messgerät, das den Blutdruck mittels PTZ misst. Schlussfolgerung Die kontinuierliche, indirekte Blutdruckaufzeichnung mittels PTZ liefert im Vergleich zur Langzeitmessung des Blutdrucks bei Kindern und Jugendlichen gute Korrelationen zu den Referenzmessungen und scheint eine brauchbare Methode, v. a. in Ruhe den Blutdruck bei Kindern zu messen.