Treatment with simeprevir RECOMMENDATIONS ON TREATMENT

7.6 Treatment with simeprevir

Treatment regimens • Simprevir in combination with PEG-IFNRBV is given for 12 weeks followed by an additional 12 weeks of PEG-INFRBV for a total of 24 weeks treatment for all treatment-naive and prior relapsed patients including those with cirrhosis. • Prior non-responder patients including partial or null-responders should undergo an additional 36 weeks of PEG-INFRBV for a total of 48 weeks of treatment. • HCV RNA should be monitored and treatment discontinued if it is 25 IU mL at weeks 4, 12 or 24. Background The simeprevir is associated with high SVR rates when given in combination with PEG-IFNRBV for treatment-naive and -experienced patients with HCV genotype 1 infection. For the time being, the medicine is approved for use only in the US and Canada, according to its manufacturer Janssen Pharmaceuticals, the wholesale price in the US for a single 12-week regimen is US 66 000. Evidence Data were considered from four RCTs comparing simeprevirRBVPEG-IFN with PEG-IFNRBV in persons with chronic HCV infection. 86,179-181 The combined SVR rate for patients treated with simeprevirRBVPEG-IFN was 79.2, and for patients treated with PEG-IFNRBV it was 45.6 Appendix 4. This difference would result in 332 fewer SVR failures per 1 000 persons treated high quality of evidence and two more serious adverse events per 1 000 persons treated moderate quality of evidence due to imprecision. Persons with genotype 1a infection with the Q80K mutation approximately 30 of patients in the included studies were found to have SVR rates similar to those who received PEG-IFN Simeprevir, given in combination with pegylated interferon and ribavirin, is recommended for persons with HCV genotype 1b infection and for persons with HCV genotype 1a infection without the Q80K polymorphism rather than pegylated interferon and ribavirin alone. Strong recommendation, high quality of evidence. This recommendation was made without taking resource use into consideration, as pricing information was not available for any country other than the United States at the time this recommendation was formulated. and RBV only. And therefore simeprevir is not recommended for persons infected with genotype 1a infection in which the Q80K mutation has been detected. The analysis did not include persons infected with HIV but one single-arm study was available and showed an SVR rate of 74, similar to that reported in RCTs in HIV-negative individuals. 182 Rationale for the recommendation Balance of benefits and harms: The Guidelines Development Group concluded that the beneits of simeprevir were considerable in view of the shorter duration of therapy, the much higher SVR, and the low rate of side-effects. The Group considered that the total number of patients treated with this medicine is small, and that the trials were conducted primarily in Europe and North America. These trials did include persons of Asian and African origin who responded similarly to other persons. Taking into consideration all of these factors the high SVR rate, shorter duration of treatment and favourable safety proile, the Guidelines Development Group felt that the beneits clearly outweighed the risks. Values and preferences: It was felt that this medicine would be acceptable to patients because of the shorter duration of therapy and the expectation of a higher SVR. However, the acceptability may be lowered by the fact that it must be administered with RBV and PEG-IFN, thereby exposing patients to the inconvenience of IFN injections and the toxicity of these two medicines. Simeprevir sometimes causes photosensitivity, and the resulting rash may also reduce acceptability. Resource considerations: At the time of the meeting of the Guidelines Development Group, simeprevir was approved for use only in North America where the wholesale price for a single treatment costs approximately US 66 000. The anticipated high cost of simeprevir in other countries is likely to be a signiicant barrier to its use. Policy-makers might be reluctant to introduce simeprevir into national treatment programmes in view of its high price. Implementation Although simeprevir results in high SVR rates, the fact that it is administered with PEG-IFN and RBV means that frequent monitoring for side-effects is necessary. Also, since the Q80K mutation reduces the eficacy of simeprevir, patients must be tested for the presence of this mutation prior to treatment. The availability of this test may be limited in many countries. Research questions Combinations of different DAAs not requiring the use of PEG-IFN are being tested in clinical trials. The use of simeprevir in genotype 4 infection also requires further evaluation.

8. CLINICAL CONSIDERATIONS