NPLATE - NPLATE - CT 6579 - English version

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Introduction NPLATE 250 MICROGRAMMES, powder for solution for injection B/1 (CIP code: 392 581-0) B/4 (CIP code: 394 409-0) NPLATE 500 MICROGRAMMES, powder for solution for injection B/1 (CIP code: 392 582-7) B/4 (CIP code: 394 410-9) Posted on Jun 04 2012 Active substance (DCI) romiplostim HEMATOLOGIE – NOUVEAU MEDICAMENT Progrès thérapeutique important dans le traitement de recours du purpura thrombopénique idiopathique chronique NPLATE est un médicament orphelin indiqué dans le traitement du purpura thrombopénique idiopathique (PTI) chronique de l’adulte en échec aux traitements habituels (corticoïdes, immunoglobulines) chez les patients réfractaires à la splénectomie et chez les patients non splénectomisés mais auxquels la splénectomie ne peut être proposée.NPLATE représente un progrès thérapeutique important comme traitement de recours chez ces patients.Pour en savoir plus, téléchargez la synthèse ou l'avis complet ci-dessous ATC Code B02BX04 Laboratory / Manufacturer AMGEN S.A.S. NPLATE 250 MICROGRAMMES, powder for solution for injection B/1 (CIP code: 392 581-0) B/4 (CIP code: 394 409-0) NPLATE 500 MICROGRAMMES, powder for solution for injection B/1 (CIP code: 392 582-7) B/4 (CIP code: 394 410-9) Posted on Jun 04 2012

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• Publié par: haute-autorite-sante-maladies-sang-et-lymphe
• Publié le: 10 juin 2009
• Nombre de lectures: 12
• Licence : En savoir +
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• Langue: English

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  The legally binding text is the original French version   TRANSPARENCY COMMITTEE

  OPINION   10 June 2009       NPLATE 250 MICROGRAMMES, powder for solution for injection B/1 (CIP code: 392 581-0) B/4 (CIP code: 394 409-0)   NPLATE 500 MICROGRAMMES, powder for solution for injection B/1 (CIP code: 392 582-7) B/4 (CIP code: 394 410-9)     Applicant: AMGEN S.A.S.   Romiplostim  ATC code: B02BX04   List I Medicine for hospital prescription only. For prescription only by haematology or internal medicine specialists. Medicinal product requiring special supervision during treatment.   Orphan medicinal product   Date of marketing authorisation (centralised procedure): 4 February 2009       Reason for request: Inclusion on the list of medicines reimbursed by National Health Insurance and approved for hospital use.                     Medical, Economic and Public Health Assessment Division

 

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CHARACTERISTICS OF THE MEDICINAL PRODUCT

1.1. Active ingredient Romiplostim 

1.2. Background NPLATE is the first synthetic platelet growth factor that is an agonist of endogenous thrombopoietin receptors, indicated for use in chronic idiopathic thrombocytopenic purpura.

1.3. Indications “NPLATE is indicated for adult chronic immune (idiopathic) thrombocytopenic purpura (ITP) splenectomised patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins).  NPLATE may be considered as second-line treatment for adult non-splenectomised patients were surgery is contra-indicated.”

1.4. Dosage “Treatment should remain under the supervision of a physician who is experienced in the treatment of haematological diseases. NPLATE should be administered once weekly as a subcutaneous injection.   Initial dose The initial dose of romiplostim is 1 µg/kg based on actual body weight.   Dose calculation Initial or subsequent once Weight* in kg x dose ing/kg = individual patient dose ing   weekly dose:   Volume to administer:   1ml Dose in µg x 500 = amount to inject in ml   µ g Example:   75 kg patient is initiated at 1g/kg of romiplostim The individual patient dose = 75 kg x 1g/kg = 75g   The corresponding amount of Nplate solution to inject =   1ml 75 µg x = 0.15 ml   500µ g

*Actual body weight at initiation of treatment should always be used when calculating the dose of romiplostim. Dose adjustments are based on changes in platelet counts only and made in 1 µg/kg increments (see table below).     Dose adjustment A subject’s actual body weight at initiation of therapy should be used to calculate dose adjustments. The once weekly dose of romiplostim should be increased by increments of 1 µg/kg until the patient achieves a platelet count≥50 x 10 9 /l. Platelet counts should be assessed weekly until a stable platelet count (≥50 x 10 9 /l for at least 4 weeks without dose adjustment) has been achieved. Platelet counts should be assessed monthly thereafter. Do not exceed a maximum once weekly dose of 10 µg/kg.          

 

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Adjust the dose as follows: Platelet count (x 10 9 /l)   Action   < 50 Increase once weekly dose by 1 µg/kg     > 200 for two consecutive weeks   Decrease once weekly dose by 1 µg/kg   Do not administer, continue to assess the platelet count weekly. > 400 After the platelet count has fallen to < 200 x 10 9 /l, resume dosing with once weekly dose reduced by 1 µg/kg.     A loss of response or failure to maintain a platelet response with romiplostim within the recommended dosing range should prompt a search for causative factors without delay (see section 4.4 1 , loss of response to romiplostim).   Method of administration   NPLATE solution for injection is administered subcutaneously once it has been reconstituted. The amount to be injected may be very small. A syringe with 0.01 ml markings must be used.     Treatment discontinuation Treatment with romiplostim should be discontinued if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after four weeks of romiplostim therapy at the highest weekly dose of 10 µg/kg.   Patients should be clinically evaluated periodically and continuation of treatment should be decided on an individual basis by the treating physician. The reoccurrence of thrombocytopenia is likely upon discontinuation of treatment (see section 4.4 1 ). Elderly patients (≥65) No overall difference in safety or efficacy has been observed in patients < 65 and≥65 (see section 5.1 1 ). Although no dose adjustment is necessary for elderly patients, they should be closely monitored in view of the small number of elderly patients included in clinical trials so far.     Paediatric population (< 18)   NPLATE is not recommended for use in children below 18 due to insufficient data on safety or efficacy. No recommendation on a posology can be made in this population.     Hepatic and renal impairment No formal clinical studies have been conducted in these patient populations. NPLATE should be used with caution in these populations.”      

 

2 SIMILAR MEDICINAL PRODUCTS

2.1. ATC Classification (2009) B : Blood and blood forming organs   B02 : Antihaemorrhagics   B02B : Vitamin K and other haemostatics   B02BX : Other systemic haemostatics   B02BX04 : Romiplostim  

                                             1 of the SPC

 

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2.2. Medicines in the same therapeutic category NPLATE is the only medicinal product in its pharmacotherapeutic class indicated for the treatment of chronic ITP.

2.3. Medicines with a similar therapeutic aim The other medicinal products used in the treatment of chronic ITP are: corticosteroids, immunoglobulins, vinca alkaloids and immunosuppressants.   Rituximab is used to treat ITP in the context of a short-term treatment protocol.    

3 ANALYSIS OF AVAILABLE DATA

  The file submitted in support of the application includes:   - 2 phase III studies versus placebo lasting six months (study 105 on refractory splenectomised patients and study 212 on non-splenectomised patients),   - an interim analysis (carried out after three years) of a five-year non-comparative extension study of all studies conducted in the context of the clinical development of romiplostim, with the primary objective of investigating safety (study 213).  

3.1. Efficacy  

Patients with chronic refractory ITP despite splenectomy (study 105)

Randomised, double-blind study carried out over six months assessing the efficacy and safety of romiplostim versus placebo.   Inclusion criteria: - age≥18 - diagnosed with ITP according to the criteria of the American Society of Hematology 2 (ASH ) - myelogram confirming the diagnosis of chronic ITP in subjects over 60 - splenectomised patients (procedure performed at least four weeks before the start of the study) - patients who were refractory despite undergoing splenectomy: patients were regarded as refractory if the mean of the three platelet counts taken on inclusion was≤30x10 9 /l and no individual reading was above 35x10 9 /l - normal hepatic and renal function - haemoglobin level > 9.0 g/dl.     Exclusion criteria: - history of bone marrow disease   - patients who have previously taken the following treatments for ITP:   or Ig anti-D in the two weeks prior to the inclusion visitIg IV   rituximab in the 14 weeks prior to the inclusion visit   haematopoietic growth factors in the four weeks prior to the inclusion visit   vinca alkaloids in the 8 weeks prior to the inclusion visit.  

                                             2 George JN, Woolf SH, Raskob GE, et al. Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 1996;88:3-40

 

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Treatments and study design: Patients were randomised in a 2:1 ratio to receive either romiplostim or placebo, with stratification according to whether or not they were taking concomitant medication on inclusion. NPLATE was administered at a dose of 1 µg/kg in subcutaneous injections once a week with the aim of maintaining platelet levels between 20 and 200x10 9 /l. The treatment was suspended after 24 weeks and the patients’ platelet levels were monitored up to week 36.   One of the following emergency treatments could be administered in the event of haemorrhage, mucous membrane bleeding or if the investigator considered that the patient was exposed to serious risk: Ig IV, platelet transfusion and corticosteroids.     The following concomitant anti-ITP treatments were authorised: azathioprine, corticosteroids and/or danazole, administered at a fixed dose. Dose reductions were permitted in the first 12 weeks of treatment once the platelet count was above 100x10 9 /l.     Primary efficacy endpoint: percentage of patients with a sustained platelet response (weekly platelet count equal to or greater than 50x10 9 /l for at least six of the last eight weeks of the study and no administration of emergency treatment).   N.B.: this definition is stricter than those used in the guidelines of the ASH and the British Committee for Standards in Haematology 3 , which have set a minimum threshold of 30x10 9 /l to avoid the clinical consequences of the condition.   Other endpoints: - percentage of patients with an overall response defined as a sustained or temporary platelet response (weekly platelet count≥50 x 10 9 /l for at least four weeks that cannot however be regarded as sustained) - length of the overall response - percentage of patients requiring emergency treatment.   Results: A total of 63 patients took part in this study: 21 in the placebo group and 42 in the romiplostim group.   More than half the patients in the placebo group (12 patients) and two patients in the romiplostim group discontinued their treatment but did not stop taking part in the study. 19 patients in the placebo group and 40 in the romiplostim group completed the study.     The average patient age was slightly over 50 (53.9 in the placebo group and 51.1 in the romiplostim group). They had been suffering from chronic ITP for a little over 10 years on average and had undergone splenectomy on average 10 years previously. Almost all of the patients had failed third-line treatment: 20/21 in the placebo group and 39/42 in the romiplostim group.   The median baseline platelet counts were 14.1 and 15x10 9 /l in the placebo and romiplostim groups respectively.    Results for the primary efficacy endpoint (ITT): After six months treatment, romiplostim was superior to placebo in terms of the percentage of patients achieving a sustained platelet response (see table 1). The difference was statistically significant and clinically relevant.                                                3 British Committee for Standards in Haematology General Haematology Task Force. Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol 2003;120(4):574-96.

 

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Table 1: Sustained platelet response (primary efficacy endpoint) - Study 105 on refractory splenectomised patients

   

Placebo (N=21)  

Romiplostim (N=42)  

p  

Number of patients achieving a response (%)   0 (0.0) (38.1) 16  < 0.0013 r 9 e 5 s % po C n I  s o e f the proportion of patients achieving a  [0.0 ; 16.1]   [23.6 ; 54.4]          Results for the secondary endpoints (ITT): During the six months of treatment, the percentage of patients achieving an overall response was statistically higher in the romiplostim group than in the placebo group (see table 2). The average length of the overall response was around three months in the romiplostim group compared to less than a week in the placebo group (see table 2).   More patients in the placebo group required emergency treatment than in the romiplostim group (see table 2). The two emergency treatments most often used were corticosteroids and immunoglobulins: 8/21 patients on placebo and 7/42 patients on romiplostim were given corticosteroids and 11/21 patients on placebo and 7/42 patients on romiplostim were given immunoglobulins.      Table 2: Secondary endpoints - Study 105 on refractory splenectomised patients

    Overall response Patients achieving a response (%) 95%CI (%)   Length of the overall response    Number of weeks (average)   Patients requiring   emergency treatment (%)          

Placebo (N=21)  

0 (0.0) [0.0 ; 16.1]   0.2 ± 0.5  

12 (57.1)

Romiplostim (N=42)  

33 (78.6) [63.2 ; 89.7]   12.3 ± 7.9  

11 (26.2)

Non-splenectomised patients with chronic ITP (study 212)

p     < 0.0001   

0.0001 <

0.0175

Randomised, double-blind study carried out over six months assessing the efficacy and safety of romiplostim versus placebo.   Inclusion criteria: - age≥18   - diagnosed with ITP according to the criteria of the American Society of Hematology (ASH) - myelogram confirming the diagnosis of chronic ITP in subjects over 60 - patients who had had at least one anti-ITP treatment - non-splenectomised patients - average of the three platelet counts taken on inclusion≤ 30x10 9 /l and no individual count above 35x10 9 /l - normal hepatic and renal function - haemoglobin level > 9.0 g/dl.   Exclusion criteria: - history of bone marrow disease - cancer - patients who have taken the following treatments for ITP:  IV or  IgIg anti-D in the two weeks prior to the inclusion visit  rituximab in the 14 weeks prior to the inclusion visit

 

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  haematopoietic growth factors in the four weeks prior to the inclusion visit     vinca alkaloids in the 8 weeks prior to the inclusion visit.   The study design, treatments, primary efficacy endpoint and secondary endpoints are the same as those of study 105.  Resu ts: l A total of 62 patients took part in this study: 21 in the placebo group and 41 in the romiplostim group.   Eight patients in the placebo group and three patients in the romiplostim group discontinued treatment during the study. 13 patients in the placebo group and 38 in the romiplostim group completed the study.   The average age of the patients was 55.0 in the placebo group and 53.3 in the romiplostim group. They had been suffering from chronic ITP for four years on average. Five of the 21 patients in the placebo group and 15 of the 41 patients in the romiplostim group had failed third-line treatment.   The median baseline platelet counts were 19.1 and 17.9x10 9 /l in the placebo and romiplostim groups respectively.    Results for the primary efficacy endpoint (ITT): After six months treatment, romiplostim was superior to placebo in terms of the percentage of patients achieving a sustained platelet response (see table 3). The difference was statistically significant and clinically relevant.   Table 3: Sustained platelet response (primary efficacy endpoint) - Study 212 on non- splenectomised patients

   

Patients achieving a response (%)  

Placebo (N=21)  

1 (4.8)

romiplostim (N=41)  

25 (61.0)

p  

< 0.0001

95%CI (%)    ; 75.8] [44.5[0.01; 23.8]       Results for the secondary endpoints (ITT): During the six months of treatment, the percentage of patients achieving an overall response was statistically higher in the romiplostim group than in the placebo group (see table 4). The average length of the overall response was 15.2 weeks in the romiplostim group and 1.3 weeks in the placebo group (see table 4).   More patients in the placebo group required emergency treatment than in the romiplostim group (see table 4). The two emergency treatments most often used were corticosteroids and immunoglobulins: 6/21 patients on placebo and 7/41 patients on romiplostim were given corticosteroids and 7/21 patients on placebo and 4/41 patients on romiplostim were given immunoglobulins. Anti-D Igs were also given as emergency treatment, to 4/21 patients in the placebo group and 2/41 patients in the romiplostim group.     Table 4: Secondary endpoints - Study 212 on non-splenectomised patients

    Overall response Patients achieving a response (%) 95%CI (%)   Length of the overall response    Number of weeks (average)   Patients requiring emerg treatment (%)        

 

ency

Placebo (N=21)  

21 (14.3) [3.0 ; 36.3]   1.3 ± 3.5   1 3 (61.9)  

romiplostim (N=41)  

41 (87.8) [73.8 ; 95.9]   15.2 ± 7.5  

7(17.1)

p     < 0.0001

< 0.0001

0.0004

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  Non-comparative long-term study (study 213)

Five-year non-comparative extension phase of all studies conducted in the context of the clinical development of romiplostim. The aim of this study was to assess the long-term safety of romiplostim. One hundred and forty three patients were included, of whom 142 actually received romiplostim. The patients had previously been assigned to a placebo group (25%) or to a romiplostim group (75%).   The results of the interim analysis carried out after three years of the study showed that long- term efficacy was maintained. However, this result needs to be interpreted with caution since the study was a non-comparative study with a small cohort who were followed up for at least 18 months because of the way that inclusions were spread over time (62 patients were monitored for 18 months, 27 for two years and 11 for three years).    

3.2. Adverse effects

Adverse effects in studies 105 and 212 (six months): 83 patients were treated with romiplostim and 42 with placebo (figures for both studies). 40.5% of patients suffered adverse events regarded as treatment-related, and the corresponding figure for patients on placebo was 26.8%. The most common adverse events regarded as being related to romiplostim treatment (> 5%) were: headache (19.0% vs. 7.3% for placebo), myalgia (8.3% vs. 0.0%), fatigue (6.0% vs. 2.4%) and arthralgia (6.0% vs. 0.0%).   Serious adverse events (see SPC): Bleeding:  An inverse relationship between haemorrhagic events and platelet counts was observed during the clinical progression of ITP. All clinically significant haemorrhagic events (≥ grade 3) occurred in patients with platelet counts of < 30x10 9 /l. All haemorrhagic events of grade 2 and above (at least moderate) occurred in patients with platelet counts of < 50x10 9 /l.   Taking the findings for studies 105 and 212 together, the incidence of bleeding of any degree of severity was similar for romiplostim (57%) and placebo (61%). Bleeding of grade 2 and above was observed in 15.5% of patients on romiplostim and 34.1% of patients on placebo (OR = 0.35; 95%CI   = [0.14; 0.85]).   Bleeding of grade 3 and above was observed in 7.1% of patients on romiplostim and 12.2% of patients on placebo (OR = 0.55; 95%CI   = [0.16; 1.96]). Bleeding regarded as severe was observed in 5 patients in the romiplostim group (6.0%) and 4 patients in the placebo group (9.8%) (OR = 0.59; 95%CI   = [0.15; 2.31]).  Bone marrow abnormalities: Bone marrow abnormalities (reticulin deposit) were observed in at least 9 out of 219 patients (4.1%), including one case of medullary aplasia, but no abnormalities were observed in the placebo group (bone marrow biopsies were systematically performed in one study during the clinical development of romiplostim).   Thromboembolic events: Thromboses affecting various organs (including the lungs, heart, liver, intestines and brain) were observed in 13 out of 219 patients treated with romiplostim. Ten thromboembolic events observed in seven of these patients were regarded as treatment-related.   Thrombocytopenia:  Thrombocytopenia increasing the risk of bleeding was observed in four out of 271 patients when romiplostim treatment was withdrawn. Malignant tumours: Malignant tumours were observed in 15 out of 219 patients (6.8%) treated with romiplostim, including three cases of lung cancer, one multiple myeloma, one B-cell lymphoma, 1 case of Bowen’s disease, one breast cancer, one colon cancer, one hepatic haemangioma, one liver

 

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cancer, one cancer of the larynx, one melanoma, one melanocytic naevus, one myelofibrosis and one seborrhoeic keratosis. No indication as to their possible connection with administration of romiplostim was given.   In view of the theoretical risk of progression of malignant haemopathy due to activation of the thrombopoietin receptor, including myelodysplasia symptoms, the SPC specifies that romiplostim must not be used to treat thrombocytopenias that are not related to ITP. Immunogenicity:  Only one patient treated with romiplostim in the context of studies developed neutralising antibodies with no cross-reaction with the thrombopoietin receptor. These neutralising antibodies were not found four months later.     Death during the clinical development of romiplostim: Fourteen deaths were observed during development (11 in the ITP indication and three in another indication). In the ITP studies, eight patients in a romiplostim group and three patients in a placebo group died. One death following medullary aplasia was regarded as being linked to romiplostim.     Long-term safety: study 213 (three years): The safety profile after treatment for up to three years was similar to that seen after six months of treatment. The findings suggest that bleeding becomes less common over time (subject to the methodological reservations set out above): in the first six months (n = 127) 43% of patients experienced bleeding, a figure which fell to 23% in the following six months (n = 92) and 20% between month 12 and month 18 (n = 62). Severe bleeding was observed in 8.5% of patients. None of these haemorrhagic events was life-threatening. The platelet count at the time when bleeding occurred was below 30x10 9 /l in all but one cases (the exception was a case of sub- conjunctival haemorrhage).     Pharmacovigilance data: PSURs for the period from 31 July 2008 to 31 December 2009. The data for this first PSUR is in line with the current SPC. No new cases of medullary aplasia were reported during this period.    

3.3. Conclusion

The efficacy of romiplostim has been assessed versus placebo in two randomised double- blind studies conducted over six months in adult patients suffering from idiopathic thrombocytopenic purpura. One was performed on refractory splenectomised patients and the other on patients not eligible for splenectomy. The primary efficacy endpoint was the percentage of patients with a sustained platelet response (weekly platelet count equal to or greater than 50x10 9 /l for at least six of the last eight weeks of the study and no administration of emergency treatment).   The percentage of patients who were refractory despite undergoing splenectomy achieving a sustained response was higher in the romiplostim group (38.1%) than in the placebo group (0.0%, p<0.0013). Romiplostim was also found to be superior to placebo in patients who had not undergone splenectomy: 61.0% of patients in the romiplostim group and 4.8% in the placebo group achieved a sustained response (p<0.001).         There was no difference between romiplostim and placebo in respect of the incidence of bleeding (safety criterion in the studies). A difference in favour of romiplostim was observed in respect of cases of bleeding of grade 2 and above (at least moderate), but not in cases of bleeding of grade 3 and above (clinically significant) or of cases of bleeding regarded as serious. These observations were made in a context of concomitant treatments and

 

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emergency treatments being used less often in the romiplostim group than in the placebo group. A long-term non-comparative follow-up study carried out over three years observed a decline in the overall incidence of bleeding compared to baseline. These results do not allow any conclusions to be drawn as to the efficacy of romiplostim in reducing bleeding, especially clinically significant or serious bleeding that could put patients’ lives at risk.     The most common adverse events related to romiplostim treatment (> 5%) were: headache (19.0% vs. 7.3% for placebo), myalgia (8.3% vs. 0.0%), fatigue (6.0% vs. 2.4%) and arthralgia (6.0% vs. 0.0%). The main risks of serious adverse events identified as being related to romiplostim’s mechanism of action were thromboembolic events and bone marrow abnormalities caused by reticulin deposit. The risk management plan provides for these risks to be monitored and assessed.   The adverse events observed during the interim analysis conducted after three years of a long-term non-comparative follow-up were similar to those observed after six months of treatment.     

4 TRANSPARENCY COMMITTEE CONCLUSIONS

4.1. Actual benefit   Idiopathic thrombocytopenic purpura is an auto-immune disease leading to peripheral destruction and central inhibition of platelet formation. Chronic forms mainly affect adults.   The disease is characterised by thrombocytopenia (platelet count <150x10 9 /l), usually associated with a haemorrhagic syndrome, generally limited to purpura, ecchymosis, petechia and/or mucous membrane bleeding (epistaxis, bleeding buccal bullae, menometrorrhagia). A visceral haemorrhagic syndrome can develop in rare cases when the platelet count is extremely low (10x10 9 /l).   Idiopathic thrombocytopenic purpura has a severe impact on the quality of life of patients who are always at risk of bleeding, which forces them to limit their activities.   This product is intended as curative therapy.   Public health benefit:   Idiopathic thrombocytopenic purpura is a serious condition but is a minor public health burden because it is so rare. The burden represented by the smaller population covered by the therapeutic indication of NPLATE (chronic thrombocytopenic purpura in adults who are refractory despite splenectomy or for whom splenectomy is contraindicated) is small.   The improved management of idiopathic thrombocytopenic purpura is a public health need coming within the scope of identified priorities (GTNDO, National rare diseases plan). NPLATE is expected to have a minor impact on morbidity in view of the clinical data available and current therapeutic strategies. Transposability into practice of trial results cannot be ensured because of the comparator chosen (placebo) and the limited duration of the studies carried out (six months). Consequently, NPLATE is likely to provide only a partial response to the identified public health requirement.

                                             4 GTNDO: National Technical Objective Definitions Group (DGS) 2003

 

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Finally, it may be that NPLATE might ease the burden on the healthcare system as a result of fewer patients needing emergency immunoglobulin treatment. However, it is difficult to quantify at this stage how far the need for immunoglobulins among patients treated with NPLATE might be reduced.   Consequently, NPLATE is expected to benefit public health in this indication. This

benefit is minor at best.     The efficacy/adverse effects ratio is high.   This product is a fallback treatment in cases of chronic ITP among adults who have undergone splenectomy but are still refractory or who are unsuitable for splenectomy for which the usual treatments have failed.   There is no validated therapeutic alternative in these clinical situations.   The actual benefit of NPLATE 250 µg and 500 µg is substantial.  

4.2. Improvement in actual benefit (IAB)   NPLATE 250 µg and 500 µg, powder for solution for injection, provides an important improvement in actual benefit (IAB II) in the context of fallback treatment in cases of chronic ITP among adults who have undergone splenectomy but are still refractory or who are unsuitable for splenectomy for which the usual treatments have failed.    

4.3. Therapeutic use 5, 6, 7, 8  

  4.3.1. Treatment strategy The treatment strategy for ITP depends on three main factors: - the severity of the haemorrhagic syndrome   - the extent of the thrombocytopenia   - the patient’s characteristics (age, gender, other diseases, etc.) Normally, patients with ITP are regarded as not requiring treatment if their platelet level is over 30x10 9 /l and they have no haemorrhagic syndrome. This means that only patients whose platelet levels are below 30x10 9 treated. The aim of treatment is to increase the/l are platelet count as quickly as possible in order to protect the patient from haemorrhagic complications, hoping that the condition will be cured within the next six months.    In the acute phase, the first line of treatment involves administering corticosteroids and/or - intravenous immunoglobulins. The indications for these substances are based on the severity of the haemorrhagic syndrome and whether the patient has previously responded to either of these treatments. Platelet transfusion is indicated only in exceptional circumstances where the patient’s life is at risk.   - In cases of chronic ITP (defined as persisting for more than six months), the aim of treatment is to raise the platelet count to more than 30 to 50x10 9 /l and to maintain it above this threshold. Splenectomy is the reference treatment despite the risks associated with

                                             5 Godeau B, Provan D, Bussel J. Immune thrombocytopenic purpura in adults. Current Opinion Hematol 2007;14:535-56 6 Orphanet [homepage on the Internet]. Paris : Purpura Thrombopénique Auto-immun. [updated Jul 2006 ; cited 7 2008 Dec 10]. Available from :http://www.orpha.net/conso i r c /   c P gi u - r b p in u / r O a: C R _ e E c x o p. m ph m p e ? n l d n a g t = io F n R s & o E f x t p h e e r   t A =3 m 0 e 0 ri 2 can Society Diagnosis and Treatment of Idiopathic Thrombocytopen  n Intern Med 8 dutE’d epuorG esnipétoCys dee  ynA9-266:317;12 199 mmI lonunépoeuqiI)PTmo [iqog (ueumen.sL A tu-omIa Thrombe Purpuraph nogr foH metalogo on the Internet]. Créteil; 2007 Nov [cited 2009 Feb 09]. Available from: http://www.lesmedecins.org/gecai/files/Purpura_Thrombopenique.pdf 

 

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