Lessons learned from CAPS: Genes, pathways and clinical care
|
|
|
- Adelia Andra Jenkins
- 6 years ago
- Views:
Transcription
1 Exon 3 NACHT - domain Q703K G755R G307V A439V F309S F443L S710C G755A PYR NACHT Y141Y D310D H458H R168Q E311K C461C I172T P315L H463H S196N G326E I480F V198M S331R R488K T219T P340P A495V A242A L344L F523C C259W T348M F523L(C>A) R260W V351M F523L(C>G) R260L V351L E525K R260P A352V L534L R260R L353P R554X V262A E354D T557A L264F H358R Y563N L264H A374D G569R L264R T405P Y570C L264V L411L Y570F G301D S343S F573S D303H T436P T587I D303N T436N E627G D303G T436I L632F L305P A439T M659K Q306L A439P M662T LRRs 133 Exon Lessons learned from CAPS: Genes, pathways and clinical care Susa Benseler Section of Rheumatology Alberta Children s Hospital
2 Objectives To review the pathophysiology of cryopyrin associated periodic syndromes CAPS. To discuss the clinical spectrum and distinct organ diseases To discuss CAPS treatment options, monitoring approaches and patient outcomes
3 a tired child
4 Patient 1, 07 year old boy HPI: 3 month history of joint pains, no swelling or warmth of any joints, quit soccer team Multiple episodes of low grade fevers, no pattern, associated with red eyes and rashes, possible viral illnesses in late fall and winter ``not as active as peers`` pmhx: healthy, chickenpox at age 4
5 Examination O/E Thriving well Vital signs: Temp 37.9 C, normal HR, BP General physical examination: Fatigued, hearing loss, otherwise normal MSK: arthralgia
6 Laboratory tests Inflammatory markers: ESR 22mm/hr CRP 56mg/l WBC 14.5, normal diff Remainder normal including TSH Urine normal
7 Sensorineural hearing loss Increase in hearing thresholds in high frequencies
8 Hearing thresholds
9 Symptoms Fever, fatigue Arthralgia Conjunctivitis Rash Non itchy Urticaria-like Cold-induced Sensorineural hearing loss
10 Family history Kuemmerle-Deschner, ART 2011
11 Suspected diagnosis: monogenic periodic fever syndrome Cryopyrin associated periodic syndrome CAPS
12
13 DD autoinflammatory diseases
14 DD autoinflammatory diseases
15 DD autoinflammatory diseases
16 DD autoinflammatory diseases
17 Cryopyrin Associated Periodic Syndrome (CAPS) mild Familial Cold-induced Autoinflammatory Syndrom (FCAS) Spectrum of disease Muckle Wells Syndrome (MWS) severe Neonatal-Onset Multisystem Inflammatory Disease (NOMID/CINCA) Courtesy Dr. Kuemmerle-Deschner
18 Gene: NLRP3 Location: 1q44 Name: NLR (nucleotide-binding domain and leucine rich repeat containing family). pyrin domain containing 3 (previously CIAS1) Encodes and therefore provides instructions for making a protein called cryopyrin Gatekeeper protein of the immune system
19 NLRP3 mutations Infevers database, 2013
20 Gatekeeper Jurg Tschopp & Kate Schroder Nature Reviews Immunology 2010
21 Loss of gatekeeper IL1β Jurg Tschopp & Kate Schroder Nature Reviews Immunology 2010
22 Cryopyrin Associated Periodic Syndrome (CAPS) mild Familial Cold-induced Autoinflammatory Syndrom (FCAS) Spectrum of disease Muckle Wells Syndrome (MWS) severe Neonatal-Onset Multisystem Inflammatory Disease (NOMID/CINCA) Courtesy Dr. Kuemmerle-Deschner
23 Diagnosis delay (years) A Time to diagnosis of CAPS B MKD CAPS TRAPS FMF <70' 70's 80's 90's >2000 Decade of birth Toplak, ARD, 2012
24 Familial Cold-induced Autoinflammatory Syndrome (FCAS) Cutaneous Manifestations of two affected siblings from Family B (A,B) and one affected child from Family A (C). A. 16 month old boy after a 5 minute exposure to 5 C atmosphere outdoor exposure followed by 5 minutes at room temperature. B. 34 month old boy at room temperature for 2 hours, crying. C. 4 year old girl bathing indoors at room temperature. Hoffman, J All Clin Immun 2009
25 Neutrophilic dermatitis Hoffman, J All Clin Immun 2009
26 Neutrophilic dermatitis Hashkes, The Rheumatologist 2014
27 Associated symptoms Fatigue Fevers Arthralgia/myalgia Conjunctivitis
28 Cryopyrin Associated Periodic Syndrome (CAPS) mild Familial Cold-induced Autoinflammatory Syndrom (FCAS) Spectrum of disease Muckle Wells Syndrome (MWS) severe Neonatal-Onset Multisystem Inflammatory Disease (NOMID/CINCA) Courtesy Dr. Kuemmerle-Deschner
29 Muckle Wells Syndrome (MWS) Triad of triad of urticaria, deafness, and amyloidosis (Muckle, Wells, 1962) Clinical presentation Kuemmerle-Deschner, AR 2013
30 Clinical symptoms and age Figure 3 Clinical phenotypes across the age spectrum in Muckle-Wells Syndrome: A proposed model for inherited autoinflammatory diseases Organ-disease phenotype phenotype Systemic inflammatory phenotype Childhood Adulthood Kuemmerle-Deschner, AR 2013
31 Dimension 2 (33%) Clinical symptoms and age Correspondence analysis years irritability 0.0 hearing loss headache eye symptoms skin rash musculoskeletal abdominal pain >20 years 10 years fatigue -0.5 relapsing fever Dimension 1 (67%) Kuemmerle-Deschner, AR 2013
32 Hearing loss in three generations Audiogramm Patient (6 einer years) 5 Jahre alten Patientin Father (37 years) Patient (6 years) Father (37 years) Audiogramm Grandmother einer (675 years) Jahre alten
33 Hearing loss in three generations Patient (6 years) Father (37 years) Grandmother (67 years) Audiogramm einer 5 Jahre alten Patientin Hearing thresholds
34 Inner ear inflammation on MRI Inflammation End-organ damage Cochlear inflammation Figures courtesy of Raphaela Goldbach-Mansky Hearing loss
35 Pure Tone Average (PTA) right ear [db] NLRP3 mutation and hearing loss Controls V198M A 439 V E311K T348M Age in years Kuemmerle-Deschner, AR 2012
36 Organ disease in MWS
37 Cryopyrin Associated Periodic Syndrome (CAPS) mild Familial Cold-induced Autoinflammatory Syndrom (FCAS) Spectrum of disease Muckle Wells Syndrome (MWS) severe Neonatal-Onset Multisystem Inflammatory Disease (NOMID/CINCA) Courtesy Dr. Kuemmerle-Deschner
38 Neonatal-Onset Multisystem Inflammatory Disease NOMID chronic infantile neurologic cutaneous and articular syndrome CINCA first described in 1981 by Prieur and Griscelli Early onset of severe organ disease and inflammation Skin MSK: bones CNS
39 Neonatal-Onset Multisystem Inflammatory Disease NOMID
40 Neonatal-Onset Multisystem Inflammatory Disease NOMID Pre-term birth (30%), SGA Fevers Skin: early onset urticaria like rash MSK: non directional growth due to Inflammation, destructive arthritis CNS: meningitis, hydrocephalus, seizures, developmental delay, hearing loss Eyes: conjunctivitis, uveitis, scleritis, papilledema
41
42 Treatment of CAPS: IL1 blockade
43 Loss of gatekeeper IL1β Jurg Tschopp & Kate Schroder Nature Reviews Immunology 2010
44 Treatment of CAPS: IL1 blockade Anakinra Rilonacept Canakinumab Half life 4 hours 67 hours days costs/year [USD]
45 Disease activity in CAPS Clinical instruments: MWS disease activity score MWS-DAS (physician derived) AIDAI questionnaire (patient diary) Laboratory markers: C-reactive protein CRP Serum amyloid A SAA Neutrophil markers: MRP S100A8 and A9 Kuemmerle-Deschner, AR 2010, Lotze/Tracey Nat Rev Immunol 2005 Foell et al. J Leukoc Biol 2007, Piram, ARD 2014
46 Myeloid-Related Protein (MRP) 8/14 MRP 8/14 calcium binding proteins (S100A8/S100A9) form heterocomplexes in cytosol of neutrophils and macrophages Ca 2+ Ca identified as ligands and 2+ activators of TLR-4 assigned to the Damage Associated Molecular Pattern (DAMPS) Ca 2+ Ca 2+ hmrp8/hmrp14
47 Pattern recognition of the innate immune system PAMP Pathogen Associated Molecular Pattern TLR Exogenous ligands NOD TLR Endogenous ligands alarmins Danger Signals RAGE DAMP Damage Associated Molecular Pattern Lotze/Tracey Nat Rev Immunol 2005 Foell et al. J Leukoc Biol 2007
48 Pattern recognition of the innate immune system PAMP Pathogen Associated Molecular Pattern TLR Exogenous ligands NOD TLR Endogenous ligands alarmins Danger Signals e.g. S100 proteins MRP8/14 RAGE DAMP Damage Associated Molecular Pattern Lotze/Tracey Nat Rev Immunol 2005 Foell et al. J Leukoc Biol 2007
49 MRP8/MRP14 expression in human diseases Rheumatoid arthritis Psoriasis arthritis Dermatomyositis Glomerulonephritis (SLE) Kane et al. Arthritis Rheum. 48, (2003) Seeliger et al. Am. J. Pathol. 163, (2003) Frosch et al. J. Leuko. Biol. 75, (2004) MRP8/MRP14 / ng/ml * MRP8/MRP14 serum concentrations reflect local disease activity 0 controls active remission
50 Monitoring treatment response Physician s global assessment (5 point scale) of disease activity and assessment of skin disease on a 5-point scale (1=absent, 2=minimal, 3=mild, 4=moderate, 5=severe). Remission: 2 Patient s global assessment (5 point scale) Inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA) Remission: normal serum values (below 10 mg/l) of CRP and SAA
51 Definitions of response Complete Response: Disease activity and assessment of skin disease on a 5-point scale 2 plus normal serum values of CRP and SAA on day 8 of therapy Partial response: Absence of complete response but reduction of CRP and/or SAA from baseline by > 30 % but not reaching normal values (<10mg/l) and physician s global assessment improvement from baseline by one step
52 Treatment efficacy Anakinra, Rilonacept (FCAS) and Canakinumab have excellent efficacy Improvement or resolution of clinical signs and symptoms of active inflammation Improvement or normalization of inflammatory markers
53 Clinical applications for IL1 blockade Dinarello, van der Meer Semin Immunol 2013
54 MWS disease activity at baseline and on anakinra
55 ESR mm/h CRP mg/dl ESR and CRP at baseline and on anakinra 6 60 p=0,013 4 p=0, before IL-1Ra during IL-1Ra IL-1Ra during IL-1Ra
56 MRP8/14 markers at baseline and on anakinra MRP 8/14 levels decreased significantly in successfully treated patients (p<0,001) p<0,001 but were still elevated in comparison to healthy controls (<450ng/ml) even without clinical signs of inflammation 2000 healthy controls 0 before IL-1Ra during IL-1Ra
57 Excellent response of inflammatory markers to IL1 blockade CRP levels ESR values Kuemmerle-Deschner, ART 2013
58 S100A12: response to anakinra and canakinumab Kuemmerle-Deschner, ART 2013
59 3,5 Patients assessment 3 2,5 2 1,5 1 0,5 0 BL-PatDia D8-PatDia Canakinumab induced a complete clinical response in all cases 6 Physician assessment Immediately pre first treatment 1 0 BL-DisAct D8-DisAct Day 8 post treatment
60 1000 SAA ,1 Baseline Day 8 Canakinumab induced a complete biochemical response in all cases CRP mean 1 Immediately pre first treatment 0,1 Baseline Day 8 Day 8 post treatment
61 Efficacy of anti IL1 therapy for organ disease: hearing
62 Early detection of hearing loss Standard 4 pure-tone-average (4PTA) and proposed high frequency pure-toneaverage (HF-PTA) 4PTA range includes 0.5, 1, 2, and 4 khz The proposed HF-PTA captures high frequency at 6 and 8 khz
63 Early detection of hearing loss: Standard 4 pure-tone-average (4PTA) and proposed high frequency pure-tone-average (HF-PTA)
64 PTA versus HF PTA for early detection of hearing loss Normal PTA Abnormal HF-PTA Abnormal PTA Abnormal HF-PTA
65 Early hearing loss is reversible
66 Efficacy of anti IL1 therapy for organ disease: hearing MWS patient follow-up assessments
67 Hearing loss and MRI Inflammation After treatment with anakinra Cochlear inflammation Resolving cochlear inflammation Figures courtesy of Raphaela Goldbach-Mansky
68 Objectives To review the pathophysiology of cryopyrin associated periodic syndromes CAPS. To discuss the clinical spectrum and distinct organ diseases To discuss CAPS treatment options, monitoring approaches and patient outcomes
Rilonacept for cryopyrin associated periodic syndromes
Rilonacept for cryopyrin associated periodic syndromes August 2009 This technology summary is based on information available at the time of research and a limited literature search. It is not intended
Cryopyrin Associated Periodic Syndromes (CAPS) (CINCA/Muckle Wells/FCAS)
https://www.printo.it/pediatric-rheumatology/gb/intro Cryopyrin Associated Periodic Syndromes (CAPS) (CINCA/Muckle Wells/FCAS) Version of 2016 1. WHAT IS CAPS 1.1 What is it? Cryopyrin-Associated Periodic
Supplementary Table S1 CAPS systematic literature review search strategy
Supplementary Table S1 CAPS systematic literature review search strategy CAPS Pubmed CAPS Embase cryopyrin associated periodic syndromes [MeSH Terms] OR Cryopyrin Associated Periodic Syndromes [tiab] OR
Supplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Goldbach-Mansky R, Dailey NJ, Canna SW, et al. Neonatal-onset
Familial Cold Autoinflammatory Syndrome
Familial Cold Autoinflammatory Syndrome The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases,
CAPS for Ophthalmologists. Prof. Michaël Hofer Unité d immuno-allergologie et rhumatologie Unité Romande de rhumatologie pédiatrique CHUV, Lausanne
CAPS for Ophthalmologists Prof. Michaël Hofer Unité d immuno-allergologie et rhumatologie Unité Romande de rhumatologie pédiatrique CHUV, Lausanne A newborn with a rash Premature birth 34 weeks, hydramnion
Cinzia Marchica 1, Faisal Zawawi 1, Dania Basodan 2, Rosie Scuccimarri 2 and Sam J. Daniel 1*
Marchica et al. Journal of Otolaryngology - Head and Neck Surgery (2018) 47:9 DOI 10.1186/s40463-018-0256-0 CASE REPORT Open Access Resolution of unilateral sensorineural hearing loss in a pediatric patient
MEDICAL POLICY I. POLICY POLICY TITLE POLICY NUMBER CANAKINUMAB (ILARIS ) MP-2.147
Original Issue Date (Created): May 1, 2010 Most Recent Review Date (Revised): March 25, 2014 Effective Date: June 1, 2014 I. POLICY Preauthorization is required for injectable Canakinumab (Ilaris ): Note:
Arcalyst (rilonacept)
Arcalyst (rilonacept) Policy Number: 5.02.510 Last Review: 4/2018 Origination: 06/2013 Next Review: 4/2019 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for Arcalyst
Umbrella study design in patients with Hereditary Periodic Fevers, an orphan autoimmune disease. Karine Lheritier 15 June 2016 PSI Immunology meeting
Umbrella study design in patients with Hereditary Periodic Fevers, an orphan autoimmune disease Karine Lheritier 15 June 2016 PSI Immunology meeting Outline Hereditary Periodic Fevers Canakinumab Study
hereditary periodic fever periodic fever syndrome recurrent fever familial Mediterranean FMF autoinflammatory syndrome T 1 Tsutomu Oh-ishi
Vol. 20 No. 3331 1 FMFTNF TRAPS IgD HIDSCAPS FMF recurrent fever autoinflammatory syndrome T 1,2 1 1 hereditary periodic fever periodic fever syndrome 3 familial Mediterranean fever FMF 4 1 Key wordsmefv
S. Yokota 1, T. Imagawa 1, R. Nishikomori 2, H. Takada 3, K. Abrams 4, K. Lheritier 5, T. Heike 2, T. Hara 6
Long-term safety and efficacy of canakinumab in cryopyrin-associated periodic syndrome: results from an open-label, phase III pivotal study in Japanese patients S. Yokota 1, T. Imagawa 1, R. Nishikomori
2017 Blue Cross and Blue Shield of Louisiana
Applies to all products administered or underwritten by Blue Cross and Blue Shield of Louisiana and its subsidiary, HMO Louisiana, Inc.(collectively referred to as the Company ), unless otherwise provided
Coverage Criteria: Express Scripts, Inc. monograph dated 12/15/ months or as otherwise noted by indication
BENEFIT DESCRIPTION AND LIMITATIONS OF COVERAGE ITEM: PRODUCT LINES: COVERED UNDER: DESCRIPTION: CPT/HCPCS Code: Company Supplying: Setting: Kineret (anakinra subcutaneous injection) Commercial HMO/PPO/CDHP
Clinical Policy: Canakinumab (Ilaris) Reference Number: ERX.SPA.04 Effective Date:
Clinical Policy: (Ilaris) Reference Number: ERX.SPA.04 Effective Date: 04.01.17 Last Review Date: 05.18 Revision Log See Important Reminder at the end of this policy for important regulatory and legal
Pedido de acesso a dados do Registo Nacional de Doentes Reumáticos (Reuma.pt) da Sociedade Portuguesa de Reumatologia
Pedido de acesso a dados do Registo Nacional de Doentes Reumáticos (Reuma.pt) da Sociedade Portuguesa de Reumatologia 1. Title Autoinflammatory Diseases: analysis based on The Rheumatic Diseases Portuguese
Long-term safety profile of anakinra in patients with severe cryopyrin-associated periodic syndromes
RHEUMATOLOGY Original article Rheumatology 2016;55:1499 1506 doi:10.1093/rheumatology/kew208 Advance Access publication 3 May 2016 Long-term safety profile of anakinra in patients with severe cryopyrin-associated
NIH Public Access Author Manuscript Nat Rev Rheumatol. Author manuscript; available in PMC 2012 July 11.
NIH Public Access Author Manuscript Published in final edited form as: Nat Rev Rheumatol. 2011 February ; 7(2): 82 84. doi:10.1038/nrrheum.2010.229. Expanding clinical spectrum and broadening therapeutic
Dental Treatment in a Patient with CINCA Syndrome under General Anesthesia
https://doi.org/10.5933/jkapd.2018.45.1.109 J Korean Acad Pediatr Dent 45(1) 2018 ISSN (print) 1226-8496 ISSN (online) 2288-3819 Dental Treatment in a Patient with CINCA Syndrome under General Anesthesia
Policy Number: PHA044 Effective Date: March 1, 2019
ILARIS (CANAKINUMAB) UnitedHealthcare Commercial Medical Benefit Drug Policy Policy Number: PHA044 Effective Date: March 1, 2019 Table of Contents Page COVERAGE RATIONALE... 1 U.S. FOOD AND DRUG ADMINISTRATION
TRANSPARENCY COMMITTEE
The legally binding text is the original French version TRANSPARENCY COMMITTEE Opinion 17 September 2014 KINERET 100 mg/0.67 ml, solution for injection in pre-filled syringe B/1 (CIP: 3400927731952) B/7
Early detection of sensorineural hearing loss in Muckle-Wells-syndrome
Kuemmerle-Deschner et al. Pediatric Rheumatology (2015) 13:43 DOI 10.1186/s12969-015-0041-9 RESEARCH ARTICLE Open Access Early detection of sensorineural hearing loss in Muckle-Wells-syndrome Jasmin B.
Autoimmunity and autoinflammation
Autoimmunity and autoinflammation Primary immunodeficiencies Autoimmunity and autoinflammation 1 Primary immunodeficiencies List of some common abbreviations APECED CAPS CGD CINCA CRMO CVID FCAS FMF HIDS
Ilaris (canakinumab) (Subcutaneous)
Ilaris (canakinumab) (Subcutaneous) Last Review Date: 08/02/2018 Date of Origin: 11/07/2013 Dates Reviewed: 08/2014, 07/2015, 07/2016, 10/2016, 10/2017, 08/2018 Document Number: IC-0177 I. Length of Authorization
Autoinflammatory Syndromes: An Overview
Autoinflammatory Syndromes: An Overview Dr. Elizabeth Stringer Pediatric Rheumatologist Presented at the Canadian CAPS Network Forum Fredericton, New Brunswick Sept 15, 2013 ObjecMves To have a broad understanding
Long term management of patients with cryopyrin-associated periodic syndromes (CAPS): focus on rilonacept (IL-1 Trap)
REVIEW Long term management of patients with cryopyrin-associated periodic syndromes (CAPS): focus on rilonacept (IL-1 Trap) Leigh D Church 1 Sinisa Savic 2 Michael F McDermott 2 1 Department of Rheumatology,
Policy Number: CS2019D0066C Effective Date: March 1, 2019
ILARIS (CANAKINUMAB) UnitedHealthcare Community Plan Medical Benefit Drug Policy Policy Number: CS2019D0066C Effective Date: March 1, 2019 Instructions for Use Table of Contents Page COVERAGE RATIONALE...
Ilaris (canakinumab for subcutaneous [SC] injection Novartis)
![Ilaris (canakinumab for subcutaneous [SC] injection Novartis)](/thumbs/80/81838043.jpg "Ilaris (canakinumab for subcutaneous [SC] injection Novartis)")
Ilaris (canakinumab for subcutaneous [SC] injection Novartis) Policy Number: 5.02.512 Last Review: 8/2017 Origination: 7/2013 Next Review: 8/2018 Policy Blue Cross and Blue Shield of Kansas City (Blue
Neurologic Manifestations of Systemic Disease (N Scolding, C Rice, A Wilkins, Section Editors)
Curr Treat Options Neurol (2018) 20: 43 DOI 10.1007/s11940-018-0526-1 Neurologic Manifestations of Systemic Disease (N Scolding, C Rice, A Wilkins, Section Editors) Cryopyrin-Associated Periodic Fever
Spectrum of Clinical Features in Muckle-Wells Syndrome and Response to Anakinra
ARTHRITIS & RHEUMATISM Vol. 50, No. 2, February 2004, pp 607 612 DOI 10.1002/art.20033 2004, American College of Rheumatology Spectrum of Clinical Features in Muckle-Wells Syndrome and Response to Anakinra
NALP12, a gene responsible for periodic fever syndromes. Isabelle Jéru INSERM U.654, Paris, FRANCE
NALP12, a gene responsible for periodic fever syndromes Isabelle Jéru INSERM U.654, Paris, FRANCE Hereditary periodic fever syndromes (HPFs) Phenotype 6 clinical entities Fever episodes Abdominal pain
Publique Hôpitaux de Paris, Hôpital Necker-Enfants-Malades, INSERM U768, and Université René Descartes Paris 5, IFR 94, Paris, France;
ARTHRITIS & RHEUMATISM Vol. 62, No. 1, January 2010, pp 258 267 DOI 10.1002/art.25057 2010, American College of Rheumatology Long-Term Efficacy of the Interleukin-1 Receptor Antagonist Anakinra in Ten
Opinion 5 February 2014
The legally binding text is the original French version TRANSPARENCY COMMITTEE Opinion 5 February 2014 ILARIS 150 mg, powder for solution for injection B/1 bottle (CIP: 34 009 397 457-6 3) ILARIS 150 mg,
Proceedings of the World Small Animal Veterinary Association Sydney, Australia 2007
Proceedings of the World Small Animal Sydney, Australia 2007 Hosted by: Next WSAVA Congress AUTO-INFLAMMATORY (HYPER-INFLAMMATORY) SYNDROMES AN UPDATE Dr. John M. Angles BVSc, BSc(Vet), MVS, PhD, MACVSc,
2. Innate immunity 2013
1 Innate Immune Responses 3 Innate immunity Abul K. Abbas University of California San Francisco The initial responses to: 1. Microbes: essential early mechanisms to prevent, control, or eliminate infection;
recurrent febrile syndromes what a rheumatologist needs to know
recurrent febrile syndromes what a rheumatologist needs to know Hal M. Hoffman and Anna Simon abstract rheumatologists are likely to be asked to evaluate patients with recurrent febrile syndromes, so it
Cigna Drug and Biologic Coverage Policy
Cigna Drug and Biologic Coverage Policy Subject Canakinumab Table of Contents Coverage Policy... 1 General Background... 3 Coding/Billing Information... 5 References... 5 Effective Date... 7/15/2017 Next
AMERICAN COLLEGE OF RHEUMATOLOGY/ ASSOCIATION OF RHEUMATOLOGY HEALTH PROFESSIONALS (ACR/ARHP) 2015 MEETING HIGHLIGHTS: NEW DATA ON CANAKINUMAB
AMERICAN COLLEGE OF RHEUMATOLOGY/ ASSOCIATION OF RHEUMATOLOGY HEALTH PROFESSIONALS (ACR/ARHP) 2015 MEETING HIGHLIGHTS: NEW DATA ON CANAKINUMAB *Caroline Charles Scilink Medical Writing, Biarritz, France
See Important Reminder at the end of this policy for important regulatory and legal information.
Clinical Policy: (Ilaris) Reference Number: CP.PHAR.246 Effective Date: 08.01.16 Last Review Date: 05.18 Line of Business: Commercial, Medicaid Revision Log See Important Reminder at the end of this policy
Clinical Policy Bulletin: Canakinumab (Ilaris)
Canakinumab (Ilaris) Page 1 of 13 Clinical Policy Bulletin: Canakinumab (Ilaris) Number: 0881 Policy I. Aetna considers canakinumab (Ilaris) medically necessary for the following indications: Canakinumab
Disclosures. Learning Objectives. Periodic Fever Syndromes. Innate Immune System. Our Immune System
39 th National Conference on Pediatric Health Care March 19-22, 2018 CHICAGO Disclosures Periodic Fevers in Children: Solving the puzzle leading toward treatment No disclosures to report Betsy Roth Wojcicki
Innate immunity. Abul K. Abbas University of California San Francisco. FOCiS
1 Innate immunity Abul K. Abbas University of California San Francisco FOCiS 2 Lecture outline Components of innate immunity Recognition of microbes and dead cells Toll Like Receptors NOD Like Receptors/Inflammasome
Neonatal-onset multisystem inflammatory disorder (NOMID) is a rare congenital disorder
OBSERVATION Neonatal-Onset Multisystem Inflammatory Disorder The Emerging Role of Pyrin Genes in Autoinflammatory Diseases Christine Kilcline, MD; Kanade Shinkai, MD, PhD; Alanna Bree, MD; Renee Modica,
TNF Receptor Associated Periodic Syndrome (TRAPS)
https://www.printo.it/pediatric-rheumatology/gb/intro TNF Receptor Associated Periodic Syndrome (TRAPS) Version of 2016 1. WHAT IS TRAPS 1.1 What is it? TRAPS is an inflammatory disease characterised by
Familial Mediterranean Fever
Familial Mediterranean Fever FMF most often occurs in individuals of Mediterranean and Middle Eastern descent, and the first episodes typically begin in childhood Fast Facts FMF causes episodic fevers
Gout and Nucleic Acid Metabolism Vol.33 No
Gout and Nucleic Acid Metabolism Vol.33 No.1 2009 1 1 2 3 in vitro 14 IgM 1 IgM IgM 1 PAMPs Pattern recognition receptors PRRs PRRs PRRs PAMPs Toll Toll-like receptor TLR PAMPs Nod Nod-like receptor NLR
Use of Canakinumab in the Cryopyrin- Associated Periodic Syndrome
The new england journal of medicine original article Use of in the Cryopyrin- Associated Periodic Syndrome Helen J. Lachmann, M.D., Isabelle Kone-Paut, M.D., Jasmin B. Kuemmerle-Deschner, M.D., Kieron
Innate Immunity: (I) Molecules & (II) Cells
Innate Immunity: (I) Molecules & (II) Cells Stephanie Eisenbarth, M.D., Ph.D. FOCIS Advanced Course 2/19/18 Department of Laboratory Medicine Yale School of Medicine Department of Immunobiology Yale School
Division of Pediatric Rheumatology, Department of Pediatrics, University Hospital Tuebingen, Germany
Title Diagnosing cryopyrin-associated periodic syndromes (CAPS) Authors Jasmin B Kuemmerle-Deschner 1, Seza Ozen 2, Pascal Tyrell 3, Isabelle Kone-Paut 4, Raphaela Goldbach-Mansky 5, Helen Lachmann 6,
ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS
ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Ilaris 150 mg powder for solution for injection 2. QUALITATIVE AND QUANTITATIVE COMPOSITION One vial contains 150 mg of canakinumab*.
ACCME/Disclosure Dr. Russo has nothing to disclose
USCAP 2016 EVENING SPECIALTY CONFERENCE Pierre Russo, MD ACCME/Disclosure Dr. Russo has nothing to disclose A 2 month old girl with fevers and intractable enterocolitis Clinical History The patient presented
MEDICAL COVERAGE GUIDELINES ORIGINAL EFFECTIVE DATE: 04/09/18 SECTION: DRUGS LAST REVIEW DATE: LAST CRITERIA REVISION DATE: 09/05/18 ARCHIVE DATE:
ILARIS (canakinumab) Non-Discrimination Statement and Multi-Language Interpreter Services information are located at the end of this document. Coverage for services, procedures, medical devices and drugs
Supplementary Figure 1
Count Count Supplementary Figure 1 Coverage per amplicon for error-corrected sequencing experiments. Errorcorrected consensus sequence (ECCS) coverage was calculated for each of the 568 amplicons in the
Canakinumab comprises two 447(or 448)-residue heavy chains and two 214-residue light chains.
1 ILARIS canakinumab NAME OF THE MEDICINE Active ingredient: Chemical name: CAS number: Molecular weight: Structure: Canakinumab Immunoglobulin G1, anti-(human interleukin-1beta (IL-1β)) human monoclonal
To test the possible source of the HBV infection outside the study family, we searched the Genbank
Supplementary Discussion The source of hepatitis B virus infection To test the possible source of the HBV infection outside the study family, we searched the Genbank and HBV Database (http://hbvdb.ibcp.fr),
A Comprehensive Study of TP53 Mutations in Chronic Lymphocytic Leukemia: Analysis of 1,287 Diagnostic CLL Samples
A Comprehensive Study of TP53 Mutations in Chronic Lymphocytic Leukemia: Analysis of 1,287 Diagnostic CLL Samples Sona Pekova, MD., PhD. Chambon Ltd., Laboratory for molecular diagnostics, Prague, Czech
Supplementary Figure 1. FACS analysis of cells infected with TY93/H5N1 GFP-627E,
Supplementary Figure 1. FACS analysis of cells infected with TY93/H5N1 GFP-627E, TY93/H5N1 GFP-627K, or the TY93/H5N1 PB2(588-759) virus library. To establish our GFP- FACS screening platform, we compared
Interleukin-1, inflammasomes, autoinflammation and the skin
Published 31 May 2012, doi:10.4414/smw.2012.13590 Cite this as: Interleukin-1, inflammasomes, autoinflammation and the skin Emmanuel Contassot*, Hans-Dietmar Beer*, Lars E. French Department of Dermatology,
Journal club. Lama Nazzal
Journal club Lama Nazzal Background Kidney stone disease affects about 12% of men and 5% of women during their lifetimes in the United States Intrarenal nephrocalcinosis is often asymptomatic, but can
Mevalonate Kinase Deficiency (MKD), or Hyper IGD Syndrome
www.printo.it/pediatric-rheumatology/gb/intro Mevalonate Kinase Deficiency (MKD), or Hyper IGD Syndrome Version of 2016 1. WHAT IS MKD 1.1 What is it? Mevalonate kinase deficiency is a genetic disease.
Initial Phase 3 Studies Results for Rilonacept in the Prevention of Gout Flares in Patients Initiating Uric Acid-lowering Therapy and the Treatment
Initial Phase 3 Studies Results for Rilonacept in the Prevention of Gout Flares in Patients Initiating Uric Acid-lowering Therapy and the Treatment of Patients in the Midst of an Acute Gout Attack Investor
modified dye uptake assay including formazan test EC 90 not tested plaque reduction assay
Sauerbrei A, Bohn-Wippert K, Kaspar M, Krumbholz A, Karrasch M, Zell R. 2015. Database on natural polymorphisms and resistance-related non-synonymous mutations in thymidine kinase and DNA polymerase genes
SUPPLEMENTARY INFORMATION. Rare independent mutations in renal salt handling genes contribute to blood pressure variation
SUPPLEMENTARY INFORMATION Rare independent mutations in renal salt handling genes contribute to blood pressure variation Weizhen Ji, Jia Nee Foo, Brian J. O Roak, Hongyu Zhao, Martin G. Larson, David B.
Inflammasoma e malattie
Inflammasoma e malattie Ferrara, Novembre 2017 The rediscovery of inflammation Body Defense Dummy arm Smart arm Inflammation Innate Immunity Adaptive Immunity tumor, calor, dolor, rubor Very smart Control
2/23/18. Disclosures. Rheumatic Diseases of Childhood. Making Room for Rheumatology. I have nothing to disclose. James J.
Making Room for Rheumatology James J. Nocton, MD Disclosures I have nothing to disclose Rheumatic Diseases of Childhood Juvenile Idiopathic Arthritis (JIA) Systemic Lupus Erythematosus (SLE) Juvenile Dermatomyositis
Familial Mediterranean Fever. By:Ismaeel Qattam
Familial Mediterranean Fever By:Ismaeel Qattam FMF : It s characterized by auto inflammatory condition that causes recurrent fevers and painful inflammation of the abdomen, lungs, joints, etc. It s an
ISSN: (Print) (Online) Journal homepage:
mabs ISSN: 1942-0862 (Print) 1942-0870 (Online) Journal homepage: https://www.tandfonline.com/loi/kmab20 Canakinumab Eugen Dhimolea To cite this article: Eugen Dhimolea (2010) Canakinumab, mabs, 2:1, 3-13,
Pediatrics Grand Rounds 29 April University of Texas Health Science Center at San Antonio. Ancestral Mutations in FMF
Horror Autoinflammaticus: The Expanding Spectrum of Systemic Autoinflammatory Disease The Systemic Autoinflammatory Diseases: What Are They and Why Should You Care? Recurring episodes of seemingly unprovoked
Kineret (anakinra) When Policy Topic is covered Kineret (anakinra) requires prior authorization through the pharmacy services area.
Kineret (anakinra) Policy Number: 5.01.622 Last Review: 3/2018 Origination: 3/2017 Next Review: 3/2019 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for Kineret (anakinra)
FROM BENCH TO BEDSIDE: TARGETING THE IL-1β PATHWAY IN AUTOINFLAMMATORY DISEASES
FROM BENCH TO BEDSIDE: TARGETING THE IL-1β PATHWAY IN AUTOINFLAMMATORY DISEASES This symposium took place on 1 st October 2015 as part of ISSAID 2015: the International Society of Systemic Auto-inflammatory
Infant girl with deafness and abnormal TFTs. August 8, 2013 Matt Wise, MD/Katie Stanley All ages
Infant girl with deafness and abnormal TFTs August 8, 2013 Matt Wise, MD/Katie Stanley All ages HPI 4 month old AA girl when initially evaluated in endocrine clinic Birth: full term, uncomplicated preg/delivery
The Organism as a system
The Organism as a system PATIENT 1: Seven-year old female with a history of normal development until age two. At this point she developed episodic vomiting, acidosis, epilepsy, general weakness, ataxia
Case # 1. RAIN- Difficult Diagnosis. History of Present Illness. Referring Information
RAIN- Difficult Diagnosis Case # 1 Audrey Foster-Barber, MD UCSF Child Neurology Referring Information 9 year old girl with a several year history of episodic headaches Previous normal MRI of the brain,
A Rare Case of Cryopyrin-associated Periodic Syndrome in an Elderly Woman with NLRP3 and MEFV Mutations
doi: 10.2169/internalmedicine.1401-18 Intern Med Advance Publication http://internmed.jp CASE REPORT A Rare Case of Cryopyrin-associated Periodic Syndrome in an Elderly Woman with NLRP3 and MEFV Mutations
Abstract. Kuemmerle-Deschner et al. Arthritis Research & Therapy 2011, 13:R34
RESEARCH ARTICLE Open Access Canakinumab (ACZ885, a fully human IgG1 anti-il-1b mab) induces sustained remission in pediatric patients with cryopyrin-associated periodic syndrome (CAPS) Jasmin B Kuemmerle-Deschner
777 Old Saw Mill River Road Tarrytown, NY Copyright 2008, Regeneron Pharmaceuticals, Inc. ARC-0007-PB-10.09
REG43214_Patient_Covers_FINAL:Layout 1 10/13/08 1:18 PM Page 1 References 1. ARCALYST (rilonacept) for Subcutaneous Injection full Prescribing Information. 2. Aksentijevich I, Putnam CD, Remmers EF, Mueller
Introduction. Keywords: AA amyloidosis; TNFRSF1A; MEFV; NALP3; periodic fever
(2004) 5, 289 293 & 2004 Nature Publishing Group All rights reserved 1466-4879/04 $30.00 www.nature.com/gene FULL PAPER Allelic variants in genes associated with hereditary periodic fever syndromes as
SUPPLEMENTAL MATERIAL
SUPPLEMENTAL MATERIAL SUPPLEMENTAL MATERIAL Supplemental Methods Phenotype Prediction Analyses In order to assess the phylogenetic properties of nssnvs, sequence conservation analysis was conducted using
https://www.printo.it/pediatric-rheumatology/gb/intro Majeed Syndrome Version of 2016 1. WHAT IS MAJEED 1.1 What is it? Majeed syndrome is a rare genetic disease. Affected children suffer from Chronic
Familial Mediterranean Fever
www.printo.it/pediatric-rheumatology/gb/intro Familial Mediterranean Fever Version of 2016 1. WHAT IS FMF 1.1 What is it? Familial Mediterranean Fever (FMF) is a genetically transmitted disease. Patients
Autoinflammatory Syndromes
Autoinflammatory Syndromes Philip J. Hashkes, MD, MSc a,b, *, Ori Toker, MD c KEYWORDS Autoinflammatory syndromes Periodic fever Interleukin-1 Autoinflammatory syndromes are defined as recurrent attacks
pediatric rheumatology european society
Autoinflammatory Diseases Working Party Chairman: Secretary: pediatric rheumatology european society The PRES European Network of Registries for Autoinflammatory Diseases in Childhood (EuroFever) STUDY
Pyrexia of unknown origin? Think still
Pyrexia of unknown origin? Think still Lawrence Owino Okong o, Mmed (UoN); Mphil. (UCT). Lecturer, Department of Paediatrics and Child Health, University of Nairobi. Paediatrician/ Rheumatologist. DISCLAIMER
Fever in Lupus. 21 st April 2014
Fever in Lupus 21 st April 2014 Fever in lupus Cause of fever N= 487 % SLE fever 206 42 Infection in SLE 265 54.5 Active SLE and infection 8 1.6 Tumor fever 4 0.8 Miscellaneous 4 0.8 Crucial Question Infection
Drug Class Prior Authorization Criteria Therapeutic Agents in Rheumatic and Inflammatory Diseases
Drug Class Prior Authorization Criteria Therapeutic Agents in Rheumatic and Inflammatory Diseases Line of Business: Medicaid P & T Approval Date: August 16, 2017 Effective Date: August 16, 2017 This policy
CHECK LIST FORM-MONTH 27 (Please note Month 27 is from enrolment not randomisation)
CHECK LIST FORM-MONTH 27 (Please note Month 27 is from enrolment not randomisation) Participant Initials: Date of Birth: Were the following forms completed for this visit? Follow Up Form Done t Done BVASWG
LECOM Health Ophthalmology
Patient Name: Date of Birth: New Patient Questionnaire Your answers will be used by your healthcare provider get an accurate history of your medical conditions and ocular concerns. If you are uncomfortable
Suitable Patient Populations and Study Designs for rapid PoC
Suitable Patient Populations and Study Designs for rapid PoC Dr. med. Anton Drollmann Translational Medicine Respiratory Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, CH 22th
Case Report A Case of Hyperimmunoglobulinemia D Syndrome Successfully Treated with Canakinumab
Case Reports in Rheumatology Volume 2013, Article ID 795027, 4 pages http://dx.doi.org/10.1155/2013/795027 Case Report A Case of Hyperimmunoglobulinemia D Syndrome Successfully Treated with Canakinumab
Autophagy, NLRP3 inflammasome and auto-inflammatory/immune diseases
Autophagy, NLRP3 inflammasome and auto-inflammatory/immune diseases Z. Zhong, E. Sanchez-Lopez, M. Karin Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology; and Pathology,
Inflammation: How to Cool the Fire Inside your Gut? REINVENTING DIAGNOSTICS
Inflammation: How to Cool the Fire Inside your Gut? REINVENTING DIAGNOSTICS Future of Healthcare REINVENTING DIAGNOSTICS Inflammation Gut Inflammation Basis of a Healthy
Blau's Disease / Juvenile Sarcoidosis
https://www.printo.it/pediatric-rheumatology/gb/intro Blau's Disease / Juvenile Sarcoidosis Version of 2016 1. WHAT IS BLAU S DISEASE/JUVENILE SARCOIDOSIS 1.1 What is it? Blau syndrome is a genetic disease.
Periodic Fever Syndromes
Article collagen vascular & other multisystem diseases Periodic Fever Syndromes Objectives After completing this article, readers should be able to: Donald P. Goldsmith, MD* Author Disclsure Dr Goldsmith
Neurological manifestations in autoinflammatory diseases
Neurological manifestations in autoinflammatory diseases A. Uccelli 1,2,3, M. Gattorno 4 1 Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health Unit, University
EuroTRAPS, a consortium for new therapeutic models in TNF receptor Associated Periodic Syndrome and hereditary recurrent fevers
EuroTRAPS, a consortium for new therapeutic models in TNF receptor Associated Periodic Syndrome and hereditary recurrent fevers Isabelle TOUITOU Medical Unit for Auto Inflammatory diseases Hôpital Arnaud