At least one mobile phone will ring during a meeting or concert Anything that can go wrong will go wrong

The Aim of This Presentation Is to present our experience with Exjade (Deferasirox or ICL670) in the context of 1.Effects on serum Ferritin in chronically transfused patients who had received Desferoxamine earlier. 2.Side effects and patients tolerance to the drug 3.Effects on Serum Creatinine and liver Transaminase 4.Other side observations

Inclusion Criteria 1.Transfusion-dependent Thalassemia patients with ≥ 100 ml/kg cumulative prior PRBC. 2.No contraindication to Exjade therapy 3.Prior DFO therapy at an average daily dose of = mg/kg/day 4.Started on Exjade in 2006.

Exjade 2 Years Experience 1.N=135 in 2007 reduced to N=134 in Follow up period: from date of initiation of therapy in 2006 to Dec.2008(24-28months) 3.Average pre-treatment serum ferritin was calculated as the average of 3 pretreatment serum ferritin readings at least 2 months a apart. 4.Other baseline investigations: Urea,electrolytes,s.creatinine,FBC,transaminases,EC G,Echocardiography,audiometry,and ophthalmic evaluation

95 Patients (71%) were ≤ 18 year The youngest patient Was 4-year old & the Oldest was 38- year old

Maximum Prescribed Dose of Exjade 37.5 mg/kg 32 mg/kg

P value is <

Serum Ferritin Serum Ferritin

Mean Ferritin Jan-07 Feb-07 Mar-07 Apr-07 May-07 Jun-07 Jul-07 Aug-07Sep-07 Oct-07 Nov-07 Dec-07 Jan-08 Feb-08 Mar-08 Apr-08 May-08 Jun-08 Jul-08 Aug-08Sep-08 Oct-08 Nov-08 Dec-08 Month 2008 N= N=135 P value is ,

S. Ferritin (<500ng/ml) BaselineEnd S. Ferritin <500ng/ml 0019(16%) BaselineEnd 2007End 2008 S. Ferritin <500ng/ml 0019(16%)

37 (27 6%) 44 (36%) 19 (16%) <500 ng/ml <1500 ng/ml

S. Ferritin (<500ng/ml) Factor# of cases Age :≤ 12 yr 7 Age :>12 yr 11 Males 6 Females 12 Min. age 5 Max. age 33 Mean age(yrs) 14.8 Max. Baseline S.ferritin 9326 Min Basline. s.ferritin 732 Mean Basline s.ferritin 2357

P value =0.1598,

P value is

Temporary Dose Interruption or Reduction REASONS low S. Ferritin (<500mg/dl) Drug Side effects Reporting error total # CASES (100%) 0 15 # CASES (70%) 7(26%) 1(4%) reactions seen in 15 patients * 17 reactions seen in 15 patients

70% 30% Side Effects that Necessitated Reduction or Interruption of Treatment Total=24

Total=24

TOTA L S.Creatinine rise >50% baseline 13 (54%) Allergic Skin Reactions 5 (21%) Transaminase Rise > 5x baseline 2 (8%) GI. Symptoms 3 (13%) Fever+/-abdominal pain 1 (4%) TOTAL (30%) (70%)

Side Effects that Necessitated Reduction or Interruption of Treatment

CONTINUED EXJADE DISCONTINUED EXJADE (90.3%) 13 (9.7%) (99.3%) 1 (0.7%)

(99.3%) (0.7%) (90%) (10%)

10 3

DISCONTINUED EXJADE 2008 CAUSES# CASES low MRIT2* 4 On patients' request 3 None Exjade related death 2 Heart failure ( MRIT2*=7 ) 1 Fever +/_Abd.pain 1 Renal impairment 1 Severe GI symptoms 1 TOTAL 13 (9.7%)

OTHER SCREENING TESTS During 2008Result OphthalmologySame as baseline AudiogramSame as baseline Echo/EFNo significant change

Other Observations 1.Our nursing staff observed that patients pre-transfusion HB. is rising after starting Exjade. To validate this observation: 2.Baseline pre-transfusion HB. was calculated as = average of 6 visits readings before starting Exjade in End of 2008 pre-transfusion HB. was calculated as = average of 6 last visits readings in Mean and average of the too groups was compared.

1-Possible Interference -> introduction of leukodepleted PRC In July A case- control using Desferal is needed. Mean pre-transfusion HB; baseline versus end 2008 P value is

CONCLUSION - Exjade appeared to be safe over the last 2 years with limited and usually reversible side effects. -Using serum S.Ferritin as a guide; Exjade appeared to be as effective as Desferal. -We hope to be able to correlate our result to MRIT2* at the end of We need to study in depth the characteristics of the responders to Exjade.

o Dr Ahmed M.A. Khadem o Miss Meitha M.Hassan o Mrs Maria A.J.Pinto o Miss Maryam Omar Ali AKNOWLEDGMENT

TWO NONE EXJADE RELATED DEATH -AGE :27 YEARS /male -Thalassemia Major -Heart failure 2002 on treatment -DM 2004 & hypogonadism -HC Treatment Failure -EF: % SYMPTOMS???? -EF: % -Cause of death:Nocturnal hypoglycemia -AVERAGE SERUM FERRITIN ??/ MRI not done -Last Exjade dose 30mg/dl -AGE :33 YEARS /female -Thalassemia Major - Hypogonadism - hypothyroidism - Impaired glucose tolerance -HC Treatment Failure -Hypersplenism -interrupted Exjade treatment -serum ferritin 10,000-15,000 - MRI not done -Last Exjade dose 29 mg/dl