VALORACIÓN DE LA ACTIVIDAD EN VASCULITIS ASOCIADAS A ANCA · VALORACIÓN DE LA ACTIVIDAD EN...

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VALORACIÓN DE LA ACTIVIDAD EN VASCULITIS ASOCIADAS A ANCA Xavier Solanich Moreno Medicina Interna Hospital Universitari de Bellvitge

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  • VALORACIN DE LA ACTIVIDAD EN VASCULITIS ASOCIADAS A ANCA

    Xavier Solanich Moreno

    Medicina Interna

    Hospital Universitari de Bellvitge

  • Fauci AS. Effects of cyclophosphamide upon the immune response in Wegener's granulomatosis. EJM 1971; 285:1494-1496Fauci AS. Wegener's granulomatosis: prospective clinical and therapeutic experience with 85 patients for 21 years. Ann Intern Med. 1983 Jan;98(1):76-85Gayraud M. Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome:. Arthritis Rheum. 2001 Mar;44(3):666-75

    Mortalidad

    CrnicasRecidivantes

  • Ensayos clnicos

    randomizados

    valoracin de aspectos de las vasculitis relacionados con la morbilidad

    Merkel PA. Current Status of Outcome Measure Development in Vasculitis. J Rheumatol 2014;41;593-598

    DiseoUso

    Validacin

    ControlTratamiento

    Prctica clnica

    HERRAMIENTAS

  • CMO SE MIDE LAACTIVIDAD?

  • Van der Woude. Autoantibodies against neutrophils and monocytes. Lancet. 1985 Feb 23;1(8426):425-9Nlle B. Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis. Ann Intern Med. 1989 Jul 1;111(1):28-40

    Tomasson G. Value of ANCA measurements during remission to predict a relapse of ANCA-associated vasculitis-a meta-analysis. Rheumatology 2012 51:100-9Monach PA. Serum proteins reflecting inflammation, injury and repair as biomarkers of disease activity in ANCA-associated vasculitis. Ann Rheum Dis. 2013

    CMO MEDIR LA ACTIVIDAD?

    BIOMARCADORES

    Aumento

    Persistencia

    AN

    CA

  • Qu significa ACTIVIDAD?

    Manifestaciones secundarias a la vasculitisactivas (en el diagnstico se recogen todas)

    y de intensidad suficiente (intencin de tratar y/o mayor monitorizacin)

    y DAO?

    Manifestacin de cualquier causa (vasculitis, tratamiento) a partir de debut de la vasculitis (acumulativo)

    han estado o estn activas durante > 12 semanas (aunque sea curable)

    NUEVA/PEORdurante las ltimas 4 semanas

    PERSISTENTESque empezaron/empeoraron hace > 4 y < 12 semanaslas ltimas 4 semanas estn activas pero igual o mejor

  • 412

    visita

    semanas

    nueva / peor

    persistente

    dao

  • Groningen

    VAI

    BVASoriginal

    BVAS v2

    BVAS / WG

    BVAS v3

  • Kallenberg CG. Criteria for disease activity in Wegeners granulomatosis: a requirement for longitudinal clinical studies. APMIS Suppl 1990;19:379

    Exacerbacin mayor Prednisona 1mg/kg/d + CYC vo 2mg/kg/dexpertos

    Exacerbacin minor Prednisona 0.5mg/kg/d + CYC vo 75mg/dScore >5

    Score mximo 137

    GRONINGEN INDEX

    Manifestaciones secundarias a GPA, nuevas y de menos de 12 semanas

  • Kallenberg CG. Criteria for disease activity in Wegeners granulomatosis: a requirement for longitudinal clinical studies. APMIS Suppl 1990;19:379Whiting-OKeefe. Validity of a vasculitis activity index for systemic necrotizing vasculitis. Arthritis Rheum 1999;42:2365-71

    Luqmani RA.. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 1994;87:6718Luqmani RA,. Disease assessment and management of the vasculitides. Baillieres Clin Rheumatol 1997;11:42346

    Stone JH. A disease-specific activity index for Wegeners granulomatosis: modification of the Birmingham Vasculitis Activity Score. Arthritis Rheum 2001;44:91220Mukhtyar C. Modification and validation of the Birmingham vasculitis activity score (version 3). Ann Rheum Dis 2009;68:1827-32

    Suppiah R. A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis. Rheumatology (Oxford). 2011 May;50(5):899-905

    Caractersticas Groningen Kallenberg

    1990

    VAI Olsen 1992

    Whiting-OKeefe 1999

    BVAS BVAS v2Luqmani

    1994 / 1997

    BVAS/WGStone 2001

    BVAS v3Mukhtyar Suppiah

    2009 2011

    Tipo vasculitis GPA Mltiples Mltiples GPA Mltiples (no Horton)

    Mltiples

    N pacientes ? 74 213 117 313 238

    Face validity Si Si Si Si Si Si

    Feasybility Biopsias Si Si Si Si Si

    Reliability- Inter (reproducible)- Intra (repetible)

    ?ICC=0.45 Si

    -ICC = 0.97ICC = 0.62

    ICC = 0.96ICC = 0.96

    ICC=0.99

    Construct validity- PGA- VAI- Otros indices- PCR- Decisin tto

    ?-----

    R=0.92----

    T=0.35T=0.56

    T=0.29 (Gron.)?-

    R=0.92----

    R=0.91R=0.88

    R=0.94(s1) 0.6 (s2)R=0.43R=0.66

    R=0.85R=0.82

    VDI= -0.1R=0.18R=0.54

    Sensibilidad al cambio de estadio

    - Si Si Si Si -

  • Olsen TL. Validity and precision of a vasculitis activityindex (VAI). Arthritis and Rheumatism 1992;35: S164.

    Whiting-OKeefe. Validity of a vasculitis activity index forsystemic necrotizing vasculitis. Arthritis Rheum1999;42:2365-71.

    VASCULITIS ACTIVITY INDEX

    ltimas 4 semanas

    8 rganosPonderacin subjetiva

    39

    secundarias a vasculitis nuevas / peor

  • Kallenberg CG. Criteria for disease activity in Wegeners granulomatosis: a requirement for longitudinal clinical studies. APMIS Suppl 1990;19:379Whiting-OKeefe. Validity of a vasculitis activity index for systemic necrotizing vasculitis. Arthritis Rheum 1999;42:2365-71

    Luqmani RA.. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 1994;87:6718Luqmani RA,. Disease assessment and management of the vasculitides. Baillieres Clin Rheumatol 1997;11:42346

    Stone JH. A disease-specific activity index for Wegeners granulomatosis: modification of the Birmingham Vasculitis Activity Score. Arthritis Rheum 2001;44:91220Mukhtyar C. Modification and validation of the Birmingham vasculitis activity score (version 3). Ann Rheum Dis 2009;68:1827-32

    Suppiah R. A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis. Rheumatology (Oxford). 2011 May;50(5):899-905

    Caractersticas Groningen Kallenberg

    1990

    VAI Olsen 1992

    Whiting-OKeefe 1999

    BVAS BVAS v2Luqmani

    1994 / 1997

    BVAS/WGStone 2001

    BVAS v3Mukhtyar Suppiah

    2009 2011

    Tipo vasculitis GPA Mltiples Mltiples GPA Mltiples (no Horton)

    Mltiples

    N pacientes ? 74 213 117 313 238

    Face validity Si Si Si Si Si Si

    Feasybility Biopsias Si Si Si Si Si

    Reliability- Inter (reproducible)- Intra (repetible)

    ?ICC=0.45 Si

    -ICC = 0.97ICC = 0.62

    ICC = 0.96ICC = 0.96

    ICC=0.99

    Construct validity- PGA- VAI- Otros indices- PCR- Decisin tto

    -----

    R=0.92----

    T=0.35T=0.56

    T=0.29 (Gron.)?-

    R=0.92----

    R=0.91R=0.88

    R=0.94(s1) 0.6 (s2)R=0.43R=0.66

    R=0.85R=0.82

    VDI= -0.1R=0.18R=0.54

    Sensibilidad al cambio de estadio

    - Si Si Si Si -

  • Luqmani RA.. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 1994;87:6718

    secundarias a vasculitisnuevas / peor

    ltimas 4 semanas

    59 tems(9 rganos)

    Todos ponderadossegn expertos

    63

    BVAS original

  • Kallenberg CG. Criteria for disease activity in Wegeners granulomatosis: a requirement for longitudinal clinical studies. APMIS Suppl 1990;19:379Whiting-OKeefe. Validity of a vasculitis activity index for systemic necrotizing vasculitis. Arthritis Rheum 1999;42:2365-71

    Luqmani RA.. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 1994;87:6718Luqmani RA,. Disease assessment and management of the vasculitides. Baillieres Clin Rheumatol 1997;11:42346

    Stone JH. A disease-specific activity index for Wegeners granulomatosis: modification of the Birmingham Vasculitis Activity Score. Arthritis Rheum 2001;44:91220Mukhtyar C. Modification and validation of the Birmingham vasculitis activity score (version 3). Ann Rheum Dis 2009;68:1827-32

    Suppiah R. A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis. Rheumatology (Oxford). 2011 May;50(5):899-905

    Caractersticas Groningen Kallenberg

    1990

    VAI Olsen 1992

    Whiting-OKeefe 1999

    BVAS BVAS v2Luqmani

    1994 / 1997

    BVAS/WGStone 2001

    BVAS v3Mukhtyar Suppiah

    2009 2011

    Tipo vasculitis GPA Mltiples Mltiples GPA Mltiples (no Horton)

    Mltiples

    N pacientes ? 74 213 117 313 238

    Face validity Si Si Si Si Si Si

    Feasybility Biopsias Si Si Si Si Si

    Reliability- Inter (reproducible)- Intra (repetible)

    ?ICC=0.45 Si

    -ICC = 0.97ICC = 0.62

    ICC = 0.96ICC = 0.96

    ICC=0.99

    Construct validity- PGA- VAI- Otros indices- PCR- Decisin tto

    -----

    R=0.92----

    T=0.35T=0.56

    T=0.29 (Gron.)?-

    R=0.92----

    R=0.91R=0.88

    R=0.94(s1) 0.6 (s2)R=0.43R=0.66

    R=0.85R=0.82

    VDI= -0.1R=0.18R=0.54

    Sensibilidad al cambio de estadio

    - Si Si Si Si -

  • Luqmani RA,. Disease assessment and management of the vasculitides. Baillieres Clin Rheumatol 1997;11:42346

    BVAS versin 2

    6332

    Inicio (66 tems)

    BVASs1BVASs2

    .. Seguimiento (62 tems)

  • Groningen(1990)

    VAI(1992)

    BVAS(1994)

    BVAS v2(1997)

    BVAS v3(2003)

    BVAS / WG(2001)

    Persistente

    Simplificar (actividad persistente)

  • BVAS v3 (2003)

    Mukhtyar C. Modification and validation of the Birmingham vasculitis activity score (version 3). Ann Rheum Dis 2009;68:1827-32Suppiah R. A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis. Rheumatology. 2011 May;50(5):899-905

    secundario a vasculitis (56 tems)

    Simplifica recogida informacin:

    Inicio / SeguimientoActivas = nuevas o persistentesCasilla (solo todo persistente)

  • ponderadas expertos

    Nu

    evas

    / p

    eore

    s

    Per

    sist

    ente

    s

  • Caractersticas Groningen Kallenberg

    1990

    VAI Olsen 1992

    Whiting-OKeefe 1999

    BVAS BVAS v2Luqmani

    1994 / 1997

    BVAS v3Mukhtyar Suppiah

    2009 2011

    BVAS/WGStone 2001

    Tipo vasculitis GPA Mltiples Mltiples Mltiples (no Horton)

    Mltiples GPA

    N pacientes ? 74 213 313 238 117

    Face validity Si Si Si Si Si Si

    Feasybility Biopsias Si Si Si Si Si

    Reliability- Inter (reproducible)- Intra (repetible)

    ?--

    ICC=0.45-

    Si-

    ICC = 0.96ICC = 0.96

    ICC=0.99 ICC = 0.97ICC = 0.62

    Construct validity- PGA- VAI- Otros indices- PCR- Decisin tto

    -----

    R=0.92----

    T=0.35T=0.56

    T=0.29 (Gron.)?-

    R=0.91R=0.88

    R=0.94(s1) 0.6 (s2)R=0.43R=0.66

    R=0.85R=0.82

    VDI= -0.1R=0.18R=0.54

    R=0.92----

    Sensibilidad al cambio de estadio

    - Si Si Si - Si

    Kallenberg CG. Criteria for disease activity in Wegeners granulomatosis: a requirement for longitudinal clinical studies. APMIS Suppl 1990;19:379Whiting-OKeefe. Validity of a vasculitis activity index for systemic necrotizing vasculitis. Arthritis Rheum 1999;42:2365-71

    Luqmani RA.. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 1994;87:6718Luqmani RA,. Disease assessment and management of the vasculitides. Baillieres Clin Rheumatol 1997;11:42346

    Stone JH. A disease-specific activity index for Wegeners granulomatosis: modification of the Birmingham Vasculitis Activity Score. Arthritis Rheum 2001;44:91220Mukhtyar C. Modification and validation of the Birmingham vasculitis activity score (version 3). Ann Rheum Dis 2009;68:1827-32

    Suppiah R. A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis. Rheumatology (Oxford). 2011 May;50(5):899-905

  • BVAS / WG(GPA)

    Stone JH. A disease-specific activity index forWegeners granulomatosis: modification of theBirmingham Vasculitis Activity Score. Arthritis Rheum2001;44:91220.

    secundario a GPA (34 tems)nuevas o persistentes

    mayores* (x3) y menores (x1)

    Mximo 68- 64 predeterminados- 1 otro mayor (x3)- 1 otro menor (x1)

    Decisiones teraputicas

    x3x3 x1 x1

  • Kallenberg CG. Criteria for disease activity in Wegeners granulomatosis: a requirement for longitudinal clinical studies. APMIS Suppl 1990;19:379Whiting-OKeefe. Validity of a vasculitis activity index for systemic necrotizing vasculitis. Arthritis Rheum 1999;42:2365-71

    Luqmani RA.. Birmingham Vasculitis Activity Score (BVAS) in systemic necrotizing vasculitis. QJM 1994;87:6718Luqmani RA,. Disease assessment and management of the vasculitides. Baillieres Clin Rheumatol 1997;11:42346

    Stone JH. A disease-specific activity index for Wegeners granulomatosis: modification of the Birmingham Vasculitis Activity Score. Arthritis Rheum 2001;44:91220Mukhtyar C. Modification and validation of the Birmingham vasculitis activity score (version 3). Ann Rheum Dis 2009;68:1827-32

    Suppiah R. A cross-sectional study of the Birmingham Vasculitis Activity Score version 3 in systemic vasculitis. Rheumatology (Oxford). 2011 May;50(5):899-905

    Caractersticas Groningen Kallenberg

    1990

    VAI Olsen 1992

    Whiting-OKeefe 1999

    BVAS BVAS v2Luqmani

    1994 / 1997

    BVAS v3Mukhtyar Suppiah

    2009 2011

    BVAS/WGStone 2001

    Tipo vasculitis GPA Mltiples Mltiples Mltiples (no Horton)

    Mltiples GPA

    N pacientes ? 74 213 313 238 117

    Face validity Si Si Si Si Si Si

    Feasybility Biopsias Si Si Si Si Si

    Reliability- Inter (reproducible)- Intra (repetible)

    ?--

    ICC=0.45-

    Si-

    ICC = 0.96ICC = 0.96

    ICC=0.99 ICC = 0.97ICC = 0.62

    Construct validity- PGA- VAI- Otros indices- PCR- Decisin tto

    -----

    R=0.92----

    T=0.35T=0.56

    T=0.29 (Gron.)?-

    R=0.91R=0.88

    R=0.94(s1) 0.6 (s2)R=0.43R=0.66

    R=0.85R=0.82

    VDI= -0.1R=0.18R=0.54

    R=0.92----

    Sensibilidad al cambio de estadio

    - Si Si Si - Si

  • UTILIDAD del BVAS

    Merkel PA. Current status of outcome measures in vasculitis: focus on Wegener's granulomatosis and microscopic polyangiitis. JRheumatol. 2005 32:2488-95Hellmich B, EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. Ann Rheum Dis. 2007 May;66(5):605-17

    Gayraud M. Long-term followup of polyarteritis nodosa, microscopic polyangiitis, and Churg-Strauss syndrome:. Arthritis Rheum. 2001 Mar;44(3):666-75Flossmann O. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011 Mar;70(3):488-94

    Informacin pronstica (al igual que el FFS)

    Estandarizar en los ensayos / prctica clnica

  • UTILIDAD del BVAS

    Ntatsaki E. BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis. Rheumatology (Oxford). 2014 Apr 11.

    Decisin teraputica inicial / recidiva

    Early systemicLimitada

    BVAS = menoresFFS = 0

    GeneralizadaSevera

    BVAS = mayores (o 3)FFS 1

  • UTILIDAD del BVAS

    Definir estadios evolutivos de la vasculitis

    Determinar la eficacia del tratamiento durante evolucin

    Merkel PA. Current status of outcome measures in vasculitis: focus on Wegener's granulomatosis and microscopic polyangiitis. JRheumatol. 2005 32:2488-95Hellmich B, EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. Ann Rheum Dis. 2007 May;66(5):605-17

    Remisin: ausencia completa de actividad = BVAS 0

    Respuesta: descenso del BVAS >50% y ausencia de nuevas manifestaciones

    Refractario: BVAS igual o mayor tras 4 semanas de tratamiento estndar, o

    falta respuesta, descenso del BVAS

  • Gracias