Nuovi Farmaci Biotecnologici nelle      Patologie Reumatiche          e Autoimmuni     C. Salvarani, N Pipitone,MG Catanos...
Topics• TNF-blockers and Tocilizumab in Giant  Cell Arteritis and Takayasu Arteritis• TNF-blockers and Rituximab in ANCA- ...
TNF-BLOCKERS AND TOCILIZUMB IN GIANT CELL ARTERITIS AND     TAKAYASU ARTERITIS
Caso ClinicoB.G., Maschio, 63 aa, iperteso, BMI 35.6Cefalea di nuova insorgenza in sede fronto-temporale dxe occipitaleAst...
Caso Clinico: Diagnosi     BIOPSIA A. TEMPORALE DX           DIAGNOSI ISTOLOGICA   Sezioni di vaso arterioso con marcatafl...
Caso Clinico: Follow-up Clinico (2007-2010)Inizia terapia con prednisone 50 mg/dìRecidiva di malattia con prednisone < 15 ...
CT-PET Whole Body April 2010patologico accumulo del FDG a livello delle carotidi interne (prevalente a sx),           dell...
Caso clinico: inizio Tocilizumab 8 mg/Kg                          ogni 4 sett.                 Giugno   Luglio   Agosto   ...
Glucocorticoids are        the treatment of choice for GCA• Adequate GC doses quickly suppress clinical  manifestations of...
Glucocorticoids are      the treatment of choice for GCA• The needed duration of GC therapy is variable,  but in most pati...
Points to consider in the therapy of GCA•   vision loss or cerebrovascular accidents occur in    a minority of patients an...
Points to consider in the therapy of GCA •   The morbidity of GCA is related to the     impact of long-term therapy with  ...
Gucocorticoid-related side-effects in GCA•   In a population based study: adverse events    associated with GCs were recor...
Major adverse events that occurred in 103 of 120               patients with giant cell arteritis     Type of adverse even...
Therapy of GCAWe need effective treatments inGCA to reduce the exposureto glucocorticoids
Steroid-sparing agents in GCA:              evidence from RCTs•   Methotrexate: 3 RCTs with different results    and 1 met...
What is the evidence from randomized         controlled trials (RCTs)?• MTX may have a small steroid-sparing effect• MTX i...
What is the evidence from randomized          controlled trials (RCTs)?• Infliximab does not have a steroid-sparing  effec...
What is the evidence from randomized          controlled trials (RCTs)?• Before completely excluding a potential  therapeu...
Future directions in GCA therapy          Salvarani et al, Lancet 2008• RCTs are needed to assess new  therapeutic agents•...
IL-6 and Disease Activity in GCA• IL-6 concentrations, but not TNF alpha, are  increased in GCA patients• GCs rapidly supp...
IL-6 and Disease Activity in GCA• Plasma IL-6 is more sensitive than  ESR for indicating disease activity• Circulating IL-...
Points to consider in the therapy             of Takayasu Arteritis• 20% of patients have a self-limited, monophasic  infl...
Limitations of therapy and a guarded prognosis     in an American cohort of TA patients     Maksimowicz-McKinnon et al, Ar...
Role of Immunosuppressive Agents in TAThey are addded to GCs:• Halting disease progression• Reducing GC-related morbidity
Traditional immunosuppressive agents•   Only open-label pilot studies in GC-resistant cases:    - methotrexate    - micoph...
Anti-TNF therapy in patients with        refractory TA: long-term follow-up             Molloy et al, Ann Rheum Dis 2008• ...
IL-6R inhibition in refractory TA•   IL-6R inhibition with tocilizumab improved the    clinical manifestations and the abn...
IL-6 and Disease Activity in TA• IL-6 is strongly expressed in aortic tissue  of TA patients• IL-6 is probably locally pro...
IL-6 and Disease Activity in TA• Clinical improvement was associated with  a marked reduction in serum IL-6 levels• A posi...
Take-Home Messages• TNF-blockers as steroid-sparing agents  TNF-               steroid-  are not effective in GCA• TNF-blo...
Therapy of AAV: RCTs• Biologic agents  - TNF-blockers (etanercept)  - Rituximab
Wegener’s granulomatosis:                Early Outcomes• Natural History:  - Mean survival time: 5 months  - Mortality: 82...
The Fauci-Wolff Protocol:      NIH Longitudinal Series (began 1968)• Cyclophosphamide (CYC) 2 mg/Kg/day• Glucocorticoids: ...
CYC Therapy for AAV                    The Good/The Bad• 91% marked                      • 42% permanent morbidity  improv...
Conventional therapy for AAV• How can we minimize exposure to  CYC?• How can we avoid CYC?
Take-Home Points from RCTs• A short course of CYC for remission induction,  followed by a longer course of methotrexate or...
Biologic Agents
Wegener’s Granulomatosis              Etanercept Trial (WGET)• Etanercept in addition to standard therapy is not  effectiv...
Pathogenic immune mechanisms in AAV   Chen M & Kallenberg CGM, Nat Rev Rheumatol 2010
RTX versus CYC in ANCA-Associated Renal Vasculitis           (RITUXVAS) Jone RB et al, N Engl J Med 2010• Randomized (3:1)...
Main RITUXVAS ResultsNo difference between treatment arms of:• Mortality: 18% in each arm• Sustained remission at 12 month...
RTX versus CYC for ANCA-Associted Vasculitis (RAVE)                    Stone JH et al, N Engl J Med 2010• Randomized (1:1)...
Main RAVE ResultsNo difference between treatment arms of:• Remission without the use of prednisone at 6 months:  - RTX 64%...
Rituximab Dosage• RITUXIVAS and RAVE trials used rituximab at a dose  of 375 mg per square meter per week for 4  consecuti...
Take-Home Messages• Available data do no support the use of anti-TNF therapy  in AVV• Results from 2 RCTs comparing RTX to...
Rituximab in IgG4-related    Systemic Disease
IgG4-related systemic disease (IgG4-RSD)• IgG4-RSD is a recently recognized systemic  conditions characterized by unique p...
Organ involvement in IgG4-RSD         Khosroshahi and Stone, Curr Opin Rheumatol 2011•   Pancreas                       • ...
Conditions recognized to be explained at least partly             by the IgG4-RSD spectrum         Khosroshahi and Stone, ...
IgG4-associated sclerosing mesenteritis    Salvarani et al, Arthritis Rheum submitted
Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-RSD           Khosro...
Take-home message• Rituximab is a viable treatment option  for patients with IgG4-RSD that is  refractory to conventional ...
RingraziamentiReumatologiaDr GL Bajocchi, Dr PL Macchioni, Dr N Pipitone,Dr.ssa F Rossi, Dr G Germanò, Dr.ssa L Dardani,Dr...
Grazie per l’attenzione
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Salvarani carlo nuovi farmaci biologici torino gennaio 2011_14° convegno patologia immune e malattie ra

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Salvarani carlo nuovi farmaci biologici torino gennaio 2011_14° convegno patologia immune e malattie ra

  1. 1. Nuovi Farmaci Biotecnologici nelle Patologie Reumatiche e Autoimmuni C. Salvarani, N Pipitone,MG Catanoso, L Magnani, F Muratore, Unità di Reumatologia, Ospedale di Reggio Emilia
  2. 2. Topics• TNF-blockers and Tocilizumab in Giant Cell Arteritis and Takayasu Arteritis• TNF-blockers and Rituximab in ANCA- associated Vasculitis• Rituximab in IgG4-related Systemic Disease
  3. 3. TNF-BLOCKERS AND TOCILIZUMB IN GIANT CELL ARTERITIS AND TAKAYASU ARTERITIS
  4. 4. Caso ClinicoB.G., Maschio, 63 aa, iperteso, BMI 35.6Cefalea di nuova insorgenza in sede fronto-temporale dxe occipitaleAstenia e febbricola serale (37,5 °C – 38 °C )Tosse stizzosa e seccaIncremento indici di flogosi: VES 120 mm/h, PCR 4,25 mg/dl
  5. 5. Caso Clinico: Diagnosi BIOPSIA A. TEMPORALE DX DIAGNOSI ISTOLOGICA Sezioni di vaso arterioso con marcataflogosi linfomonocitaria transparietale con cellule giganti Reperto istologico diagnostico di Arterite a Cellule Giganti Inizia terapia steroidea con Prednisone 50 mg/die
  6. 6. Caso Clinico: Follow-up Clinico (2007-2010)Inizia terapia con prednisone 50 mg/dìRecidiva di malattia con prednisone < 15 mg/dìComparsa di diabete e frattura vertebrale dorsalePersistenza elevati indici di flogosi (VES: 80-120 mm/h)Associazione con MTX 15 mg/sett.Per inefficacia del MTX come risparmiatore di steroidedopo 1 anno si associa anti-TNFα (prima Infliximab 5 mg/kg,quindi dopo 12 mesi per inefficacia passa a Etanercept 50 mg/sett)Aprile 2010: CT-PET positiva e VES 110 mm/ora
  7. 7. CT-PET Whole Body April 2010patologico accumulo del FDG a livello delle carotidi interne (prevalente a sx), dell’arco dell’aorta e dell’aorta ascendente espressione di persistente flogosi vascolare in dette sedi
  8. 8. Caso clinico: inizio Tocilizumab 8 mg/Kg ogni 4 sett. Giugno Luglio Agosto Settembre OttobreVESmm/1h 120 25 18 20 8PCR(mg/dl) 4,70 0,28 0,16 0,36 0,30Prednisone(mg/dì) 12,5 12,5 12,5 10 7,5Segni/SintomiCostituzionali SI NO NO NO NO
  9. 9. Glucocorticoids are the treatment of choice for GCA• Adequate GC doses quickly suppress clinical manifestations of GCA and prevent ischemic complications• If visual loss has occurred before starting therapy, it is usually not reversed• An empiric initial dose of 40-60 mg daily of prednisone (or equivalent) as a single or divided dose is recommendedSalvarani et al, Lancet 2008
  10. 10. Glucocorticoids are the treatment of choice for GCA• The needed duration of GC therapy is variable, but in most patients it can be discontinued within 1-2 years• Some patients have a chronic relapsing course and may require low doses of GCs for several years or even indefinitelySalvarani et al, Lancet 2008
  11. 11. Points to consider in the therapy of GCA• vision loss or cerebrovascular accidents occur in a minority of patients and are very unusual once GC therapy has been initiated• The potentially catastrophic thoracic aneurysm and dissection occur only in 7.6% and 1% of patients, years after the onset of the diseaseSalvarani et al, Lancet 2008 and Arthritis Rheum 2005
  12. 12. Points to consider in the therapy of GCA • The morbidity of GCA is related to the impact of long-term therapy with glucocorticoids in elderly patients, who often have many comorbidities
  13. 13. Gucocorticoid-related side-effects in GCA• In a population based study: adverse events associated with GCs were recorded in 103 (86%) of 120 patients and 2 or more events occurred in 70 patients (58%)• Age and higher cumulative dose of GCs were associated with the development of adverse GC side effectsProven et al, Arthritis Rheum 2003
  14. 14. Major adverse events that occurred in 103 of 120 patients with giant cell arteritis Type of adverse event Patients with the event, number (%)Diabetes mellitus 11 (9)Total fractures 46 (38) Hip fracture 19 (16) Vertebral fracture 27 (23) Colles fracture 3 (2.5) Other fractures 11 (9)Gastrointestinal bleeding 5 (4)Hypertension 26 (22)Infection 37 (31)Posterior subcapsular 49 (41)cataract
  15. 15. Therapy of GCAWe need effective treatments inGCA to reduce the exposureto glucocorticoids
  16. 16. Steroid-sparing agents in GCA: evidence from RCTs• Methotrexate: 3 RCTs with different results and 1 meta-analysis• Azathioprine: 1 RCT• Infliximab: 1 RCT• Etanercept: 1 RCT• Alternate day GC treatment: 1 RCT• Pulse GC therapy: 2 RCTs
  17. 17. What is the evidence from randomized controlled trials (RCTs)?• MTX may have a small steroid-sparing effect• MTX is effective only after a latency period of 24-36 weeks• High MTX dosages (20-25 mg/week) have not been adequately studied• MTX does not decrease the incidence of steroid-related side effects• Azathioprine may have a small steroid-sparing effect and it may be tried if MTX is contro- indicated or not tolerated
  18. 18. What is the evidence from randomized controlled trials (RCTs)?• Infliximab does not have a steroid-sparing effect in newly diagnosed patients• Etanercept could have a steroid-sparing effect in patients with relapsing disease• Infliximab and etanercept do not reduce the incidence of steroid-related side effects in the short-term• A GC-sparing effect for infliximab may not be completely excluded: the study was too small to definitively identify small benefits
  19. 19. What is the evidence from randomized controlled trials (RCTs)?• Before completely excluding a potential therapeutic role for TNF-blockers, a large RCT should be performed enrolling only GCA patients with relapsing disease• Alternate-day GC regimen is not recommended• Additional investigations are needed on the use of pulse GC at the onset of treatment for GCA to confirm whether this regimen reduces GC toxicity
  20. 20. Future directions in GCA therapy Salvarani et al, Lancet 2008• RCTs are needed to assess new therapeutic agents• Strong evidence suggest that IL-6 has a major role in sustaining disease activity in GCA
  21. 21. IL-6 and Disease Activity in GCA• IL-6 concentrations, but not TNF alpha, are increased in GCA patients• GCs rapidly suppress IL-6 production• There is a close correlation of plasma IL-6 concentrations with clinical symptoms• Vasculitic lesions in GCA samples are characterized by in situ production of IL-6, IL-1 beta, and TGF-beta1 mRNA, indicative of macrophage activationRoche et al, Arthritis Rheum 1993;Weyand et al, Ann Intern Med 1994
  22. 22. IL-6 and Disease Activity in GCA• Plasma IL-6 is more sensitive than ESR for indicating disease activity• Circulating IL-6 may persist elevated in GCA patients after long- term followup and remain higher in patients with more relapsing diseaseWeyand et al, Arthritis Rheum 2000Garcia-Martinez et al, Arthritis Rheum 2010
  23. 23. Points to consider in the therapy of Takayasu Arteritis• 20% of patients have a self-limited, monophasic inflammatory episode• 80% have a progressive or relapsing/remitting course• Serial angiographic studies show that new lesions can be found in 61% of patients, even when the arteritis is thought to be in remission• Fixed vascular lesions are not reversed by drug therapy• GCs constitute the first line of treatment, with suggested initial dosages of 0.5 to 1 mg/Kg/dayKerr et al, Ann Intern Med 1994;Liang and Hoffman, Current Opin Rheumatol 2004
  24. 24. Limitations of therapy and a guarded prognosis in an American cohort of TA patients Maksimowicz-McKinnon et al, Arthritis Rheum 2007• Results: 93% of patients attained disease remission of any duration, but only 28% had sustained remission of at least 6 months duration after prednisone was tapered to <10 mg daily• Conclusion: although improvement of symptoms in TA usually follows GC therapy, relapses and anatomic progression usually occur with dosage reduction
  25. 25. Role of Immunosuppressive Agents in TAThey are addded to GCs:• Halting disease progression• Reducing GC-related morbidity
  26. 26. Traditional immunosuppressive agents• Only open-label pilot studies in GC-resistant cases: - methotrexate - micophenolate mofetil - azathioprine - oral cyclophosphamideHoffman et al, Arthritis Rheum 1994; Daina et al, Ann Intern Med 1999;Shinjo et al, Clin Rheumatol 2007; Valsakumar et al, J Rheumatol 2003;Shelhamer et al, Ann Intern Med 1985; Hoffman et al, Arthritis Rheum 2004;Molloy et al, Ann Rheum Dis 2008
  27. 27. Anti-TNF therapy in patients with refractory TA: long-term follow-up Molloy et al, Ann Rheum Dis 2008• Methods: Retrospective single-centre study of 25 patients with refractory TA treated with infliximab (21) or etanercept (9) for up to 7 years• Results: Following anti-TNF therapy remission was achieved and prednisone was discontinued in 15 patients (60%) and successfully tapered below 10 mg/day in an additional 7 patients (28%)• Conclusions: anti-TNF therapy may lead to durable remission and reduction in glucocorticoid requirements in most patients with refractory TA
  28. 28. IL-6R inhibition in refractory TA• IL-6R inhibition with tocilizumab improved the clinical manifestations and the abnormal laboratory findings in one patient who needed a daily prednisone dosage of 30 mg/day and was refractory to several immunosuppressive agentsNishimoto et al, Arthritis Rheum 2008
  29. 29. IL-6 and Disease Activity in TA• IL-6 is strongly expressed in aortic tissue of TA patients• IL-6 is probably locally produced at the site of aortic inflammation• All patients with active disease have elevated serum IL-6 levelsSeko et al, Circulation 1996Noris et al, Circulation 1999Salvarani et al, Clin Exp Rheumatol 2003Park et al, Rheumatology 2006
  30. 30. IL-6 and Disease Activity in TA• Clinical improvement was associated with a marked reduction in serum IL-6 levels• A positive correlation was found between IL-6 levels and the disease activity score (NIH criteria for disease activity)Noris et al, Circulation 1999Salvarani et al, Clin Exp Rheumatol 2003Park et al, Rheumatology 2006
  31. 31. Take-Home Messages• TNF-blockers as steroid-sparing agents TNF- steroid- are not effective in GCA• TNF-blockers are effective in refractory TNF- Takayasu arteritis• IL-6 inhibition with tocilizumab might be a IL- logical target for future RCTs in GCA and Takayasu arteritis
  32. 32. Therapy of AAV: RCTs• Biologic agents - TNF-blockers (etanercept) - Rituximab
  33. 33. Wegener’s granulomatosis: Early Outcomes• Natural History: - Mean survival time: 5 months - Mortality: 82% in 1 year• Glucocorticoid-treated generalized WG - Mean survival time: 12.5 monthsFauci S and Wolff SM, Medicine 1973
  34. 34. The Fauci-Wolff Protocol: NIH Longitudinal Series (began 1968)• Cyclophosphamide (CYC) 2 mg/Kg/day• Glucocorticoids: - Pulse methylprednisolone (1g/day X 3) - Prednisone 1 mg/Kg/day - Tapered to qod after 3 months• Typical duration of therapy: - Glucocorticoids: 12 months - CYC: Remission + 12 monthsHoffman GS et al, Ann Intern Med 1992
  35. 35. CYC Therapy for AAV The Good/The Bad• 91% marked • 42% permanent morbidity improvement - 46% serious infections - 43% hemorrhagic cystitis - 33-fold  risk of bladder CA• 75% complete - 11-fold  risk of lymphoma remission - 57% infertility Steroid-induced damage: Cushingoid features, weight gain, hypertension, cataracts, fractures Hoffman et al, Ann Intern Med 1992
  36. 36. Conventional therapy for AAV• How can we minimize exposure to CYC?• How can we avoid CYC?
  37. 37. Take-Home Points from RCTs• A short course of CYC for remission induction, followed by a longer course of methotrexate or azathioprine is an effective treatment strategy for AAV• The pulse CYC (15 mg/kg pulse q2wkX3, then q3wk) induces remission as well as the daily oral regimen at a reduced cumulative CYC dose and causes fewer cases of leukopeniaJayne D et al, N Engl J Med 2003 (CYCAZAREM);Pagnoux C et al, N Engl J Med 2008 (WEGENT);de Groot K et al, Ann Intern Med 2009 (CYCLOPS);
  38. 38. Biologic Agents
  39. 39. Wegener’s Granulomatosis Etanercept Trial (WGET)• Etanercept in addition to standard therapy is not effective for the maintenance of remission in pts with WG- No difference in time to remission- No difference in frequency of remission- No difference in duration of remission- No difference in severity or frequency of flares- Increased risk of cancer in patients treated with etanercept (6 vs 0, P = 0.01)WGET Research Group, N Engl J Med 2005
  40. 40. Pathogenic immune mechanisms in AAV Chen M & Kallenberg CGM, Nat Rev Rheumatol 2010
  41. 41. RTX versus CYC in ANCA-Associated Renal Vasculitis (RITUXVAS) Jone RB et al, N Engl J Med 2010• Randomized (3:1), controlled, open-label• 44 patients• All ANCA-positive, all new diagnosis• All had severe renal disease• Comparing: RTX plus 2 infusions of CYC (n=33) Intravenous CYC for 6 months, followed by oral AZA (n=11)• Everybody remained on ~ 10 mg/day of prednisone• Primary endpoints: sustained remission at 12 months and severe adverse events
  42. 42. Main RITUXVAS ResultsNo difference between treatment arms of:• Mortality: 18% in each arm• Sustained remission at 12 months: - RTX 76% vs CYC 82%• Time to remission: RTX 90 days vs CYC 94 days• Relapse rate• Time to relapse• Improvement of renal function• Adverse events rateConclusion: over 12 months one course of RTXachieves the same results as 6 months of CYCfollowed by AZAJone RB et al, N Engl J Med 2010
  43. 43. RTX versus CYC for ANCA-Associted Vasculitis (RAVE) Stone JH et al, N Engl J Med 2010• Randomized (1:1), double blind• 197 patients (newly diagnosed or relapsing disease)• All ANCA-positive• Limited disease (not requiring CYC) and too severe disease (mechanical ventilation because of alveolar hemorrhage or serum creatinine > 4 mg/dL) were excluded• Comparing: RTX plus daily placebo-CYC (n=99), then placebo-AZA for pts in remission between 3-6 months Daily CYC (2 mg/Kg) plus placebo-RTX infusions (n= 98), then daily AZA (2 mg/Kg) for pts in remission between 3-6 months• Primary endpoint: remission without the use of prednisone at 6 month
  44. 44. Main RAVE ResultsNo difference between treatment arms of:• Remission without the use of prednisone at 6 months: - RTX 64% vs CYC 53% - RTX 67% vs CYC 42% (p=0.01) for relapsing disease• Improvement of renal function• Adverse events rate• Loss of proteinase 3-ANCA production occurred more frequently with RTX than with CYCConclusion: RTX was not inferior to daily CYCfor induction of remission and may be superior inrelapsing diseaseStone JH et al, N Engl J Med 2010
  45. 45. Rituximab Dosage• RITUXIVAS and RAVE trials used rituximab at a dose of 375 mg per square meter per week for 4 consecutive weeks• However, in a retrospective evaluation of 65 sequential patients receiving RTX for refractory AAV there was no difference in efficacy between 4 infusions of 375 mg/m2 each given 1 week apart or 2 infusions of 1 gm each given 2 weeks apartJones RB et al, Arthritis Rheum 2009
  46. 46. Take-Home Messages• Available data do no support the use of anti-TNF therapy in AVV• Results from 2 RCTs comparing RTX to CYC complement each other: - RTX is effective as CYC for newly diagnosed pts with severe AAV - RTX seems to be superior for pts with severe relapses - RTX is preferable for young patients who want to preserve their fertility• More data on RTX for maintaining remission in AAV are needed
  47. 47. Rituximab in IgG4-related Systemic Disease
  48. 48. IgG4-related systemic disease (IgG4-RSD)• IgG4-RSD is a recently recognized systemic conditions characterized by unique pathological features:- extensive lymphoplasmacytic infiltration- abundant IgG4+ plasma cells- extensive fibrosis• Increased numbers of IgG4+ plasma cells (more than 10/hpf) strongly support the diagnosis of IgG4-RSDSmyrk TC et al, Curr Opin Rheumatol 2011
  49. 49. Organ involvement in IgG4-RSD Khosroshahi and Stone, Curr Opin Rheumatol 2011• Pancreas • Mesentery• Bile duct • Aorta• Liver • Thyroid• Gastrointestinal tract • Breast• Salivary and lacrimal glands • Lung• Orbit • Kidney• Retroperitoneum • Pituitary glands• Skin • Meninges• Lymphonodes • Prostate • Pericardium
  50. 50. Conditions recognized to be explained at least partly by the IgG4-RSD spectrum Khosroshahi and Stone, Curr Opin Rheumatol 2011Previous name Target organ(s)• Mikulicz’s disease • Salivary and lacrimal glands• Küttner’s tumor • Submandibular glands• Riedel’s tyroiditis • Thyroid• Chronic sclerosing aortitis • Aorta• Inflammatory abdominal aortitis • Abdominal aorta• Retroperitoneal fibrosis • Retroperitoneum• Autoimmune pancreatitis • Pancreas• Sclerosing cholangitis • Biliary tree• Orbital pseudotumor • Orbital adnexa• Eosinophilic angiocentric fibrosis • Sinuses and nasal cavities• Multifocal fibrosclerosis • Various organs
  51. 51. IgG4-associated sclerosing mesenteritis Salvarani et al, Arthritis Rheum submitted
  52. 52. Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-RSD Khosroshahi et al, Arthritis Rheum 2010• Glucocorticoids have become a standard therapy for AIP• AIP relapses in one third of patients treated with glucocorticoids• Experience with traditional DMARDs as steroid sparing agents is limited• Treatment with rituximab led to prompt clinical and serological improvement in 4 patients with refractory IgG4-RSD
  53. 53. Take-home message• Rituximab is a viable treatment option for patients with IgG4-RSD that is refractory to conventional immunosuppressive therapy
  54. 54. RingraziamentiReumatologiaDr GL Bajocchi, Dr PL Macchioni, Dr N Pipitone,Dr.ssa F Rossi, Dr G Germanò, Dr.ssa L Dardani,Dr.ssa MG Catanoso, Dr A Caruso,Dr.ssa I Chiarolanza, Dr.ssa G Restuccia,Dr.ssa A Ghinoi, Dr L Magnani, Dr F MuratoreAnatomia PatologicaDr A CavazzaOculisticaDr L CiminoMedicina NucleareDr A VersariRadiologiaDr G Zuccoli, Dr A Levrini
  55. 55. Grazie per l’attenzione

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