EFFECTIVENESS OF INFLIXIMAB IN PATIENTS WITH RESISTANT BEHET UVEITIS

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EFFECTIVENESS OF INFLIXIMAB IN PATIENTS WITH
RESISTANT BEHÇET UVEITIS

• Loredana Latanza, MD, Emanuela Interlandi, MD,
  Franco Del Prete, MD, Francesco Calabrò, MD,
  Valentina Di Iorio, MD.
• Section of Ocular Immunopathology, Department
  Ophtalmology, Cardarelli Hospital, Naples, Italy.

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• Loredana Latanza, MD, Emanuela Interlandi, MD,
  Franco Del Prete, MD, Francesco Calabrò, MD,
  Valentina Di Iorio, MD
• declare no financial interest.

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INTRODUCTION 1/2

• Behçets disease (BD) is a chronic multisystem
  inflammatory disorder with relapsing course.
  Patients with ocular involvement typically have
  bilateral non-granulomatous panuveitis and
  retinal vasculitis.
• The main goals in the management of patients
  with Behçet uveitis are rapid resolution of
  intraocular inflammation, prevention of recurrent
  attacks and preservation of vision. The treatment
  of choice for this type of uveitis has been
  systemic immunosuppressive agents such as
  cyclosporine A, azathioprine, cyclophosphamide,
  chlorambucil in addition to corticosteroid.
  However in some patients the disease is
  unresponsive to any combination of
  munosuppressive drugs and relapses occur despite
  aggressive treatment leading to a significant
  loss of vision.

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INTRODUCTION 2/2

• Tumor Necrosis Factor a (TNFa) is an
  inflammatory cytokine that plays a key role in
  the pathogenesis of inflammation in BD.
  Infliximab is a chimeric monoclonal anti-TNF a
  antibody currently used in the treatment of
  rheumatoid arthritis and Crohn' s disease.
• Anti-TNF a agents have also begun to be used as
  a new therapeutic approach in other inflammatory
  disorders including BD. Therefore we conducted a
  retrospective chart review to evaluate the
  efficacy of Infliximab in patients with BD in
  whom uveitis was resistant to combination therapy
  with cyclosporine (CyA),
• azathioprine (AZA) and corticosteroids (CS).

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PATIENTS AND METHODS 1/2

• The study population consisted in 10 Behçet
  patients with severe relapsing posterior uveitis
  resistant to traditional immunosuppressive
  therapy. Patients enrolled in this study had
  undergone recurrence of the disease despite
  maximal tolerated immunosuppressant doses
  (including repeated intravenous pulse steroid) or
  had shown signs of systemic toxicity in response
  to therapy. Informed written consent to
  participate in our study was obtained from each
  patient.

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PATIENTS AND METHODS 2/2

• The intravenous infusions of Infliximab, 5mg/kg
  body weight, were administered at weeks 0, 2, 4,
  6, and than every 8 weeks until the end of the
  study (follow up 3-23 months, mean 11,1 6,86).
• All patients were followed up with complete
  ocular examination including best corrected
  visual acuity, slit-lamp biomicroscopy,
  tonometry, indirect ophthalmoscopy and
  fluorescein angiography.
• Incidence of ocular attacks was the primary
  efficacy goal for the study. Other outcome
  measures were changes in corticosteroid daily
  dose and increasing in visual acuity. Adverse
  events were recorded throughout the study period.

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RESULTS 1/3

• Table 1 shows the general characteristics of
  patients and previous immunosuppressive therapy.
• 10 patients (7 male, 3 female) with BD were
  enrolled in the study between April 2004 and
  December 2005. The mean age of the patients at
  the time of the enrollment was 32.2 (range 15-50
  ) and the mean disease duration was 7.4 years.
• 5 patients presented panuveitis and 5 retinal
  vasculitis. In 7 cases intravenous pulse steroid
  therapy was given in addition to
  immunosuppressive therapy during the six months
  before treatment.

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Table 1
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Table 1 abbreviations
G. Gastrointestinal lesions A. Arthralgia/
arthritis O.A. Oral aphthous lesions G.U.
Genital ulcerations E. Epididimitis NB.
Neuro-Behçet T.F. Trombofhlebitis S.L. Skin
lesions
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RESULTS 2/3

• The mean duration of treatment-period was 11.1
  months (range 3-23 months). During treatment the
  number of ocular attacks ( table 2 ) decreased in
  6 patients and 4 of them remained attack-free to
  the end of the study.
• The number of relapses increased in patients 1
  and 4 while kept stable in patient 6 and 9. In
  all patients no relapses were observed during the
  first 6 months of treatment. In 6 patients
  relapses were observed between the 6th and 12th
  month of treatment. In 3 cases the time span
  between infusions was reduced to 7 weeks
• (patient 1, 2, 5 ) and to 6 weeks in patient 4.
  Once the interval between infusions was reduced,
  no more attacks were observed. Visual acuity is
  given in table 3 administration of Infliximab
  improved the visual acuity of either or both eyes
  in 5 out of 10 cases. Visual acuity improved in
  most of the subjects that didnt show further
  ocular attacks.

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Table 2
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Table 3
HM hand motion LP light perception
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RESULTS 3/3

• In 7 patients, during the infusion period, the
  mean daily corticosteroid dose was significantly
  reduced with respect to the pre-treatment period.
  Two of them could discontinue corticosteroid
  treatment (table 4).
• Mild adverse events occurred during the study
  period. Such as headache and upper respiratory
  tract infection. A mild infusion reaction was
  observed in one patient.

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Table 4
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Caso clinico

• S.F.
• M, 27 aa
• Malattia di Behçet dal 2004
• EMC in OO (lt 6 mesi )
• Visus OO pre-terapia OD 6/10 OS 2/10
• post-terapia OD 10/10 OS 10/10
• Terapia Infliximab 5mg/Kg
• Azatioprina 150 mg/die
• Prednisone 50 mg 5 mg/die

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2004
S.F.
2006
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S.F.
OD
OS
2004
OD
OS
2006
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DISCUSSION 1/2

• In this study we investigated the efficacy of
  Infliximab for the treatment of uveitis resistant
  to the combination of cyclosporine, azathioprine
  and corticosteroids in 10 patients with BD. The
  frequency of uveitis attacks and the mean daily
  corticosteroid requirements were significantly
  reduced during treatment period. We observed that
  all patients remained attack-free during the
  first 6 months of treatment when interval
  between infusions is less than 8 weeks. Most of
  the attacks were observed at the end of the
  8-week-period after the last Infliximab infusion.
  Our results suggest that in at last some patients
  infusion should be administered at interval
  shorter than 8 weeks in order to achieve
  remission. Our study also showed a significant
  reduction in the mean daily corticosteroid dose
  in 70 of patients.

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DISCUSSION 2/2

• In conclusion, the results of this study suggest
  that Infliximab is effective in suppressing the
  occurrence of uveitis attacks and has a
  corticosteroid-sparing effect.
• These results have favorable implications for
  the visual prognosis of patients with BD.

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REFERENCES

• Tugal-Tutkun I, Abdulbaki M, Urgancioglu M et al.
  Efficacy of Infliximab in the treatment of
  Uveitis that is resistant to treatment with
  combination of Azathioprine, Cyclosporine and
  Corticosteroids in Behçets Disease. Arthritis
  Rheum 2005 522478-84.
• Shigeaki Ohno, Satoshi Nakamura, Sadao Hori.
  Efficacy, Safety and Pharmacokinetics of multiple
  administration of Infliximab in Behçets disease
  with refractory uveoretinitis. The Journal of
  Rheumatology 2004 317 1362-8.
• JM Benitez del Castillo, JM Martinez de la Casa,
  E Patocour et al. Long-term treatment of
  refractory posterior uveitis with anti TNFa
  (Infliximab). Eye 2005 19841-845.