Patrice Cacoub1, Si Nafa Si Ahmed2, Yasmina Ferfar3, Stanislas Pol4, Dominique Thabut5, Christophe Hezode6, Laurent Alric7, Cloe Comarmond3, Gafaar Ragab8, Luca Quartuccio9, Mohamed Hegazy8, Thierry Poynard5, Matthieu Resche Rigon10, David Saadoun3. 1. Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, Inflammation-Immunopathology-Biotherapy Department, Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France. Electronic address: patrice.cacoub@aphp.fr. 2. Department of Hepatology, Hôpital Orléans, Orléans, France. 3. Sorbonne Universités, UPMC Univ Paris 06, UMR 7211, Inflammation-Immunopathology-Biotherapy Department, Paris, France; INSERM, UMR_S 959, Paris, France; CNRS, FRE3632, Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Department of Internal Medicine and Clinical Immunology, Paris, France. 4. Université Paris Descartes, AP-HP, Unité d'Hépatologie, Hôpital Cochin, Paris, France. 5. Department of Hepatology, AP-HP, Groupe Hospitalier Pitié-Salpétrière, Paris, France. 6. Department of Hepatology, AP-HP, Hôpital Henri Mondor, Créteil, France. 7. Department of Internal Medicine and Digestive Diseases, CHU Purpan, UMR 152 Pharma Dev, IRD Toulouse 3 University, Toulouse, France. 8. Internal Medicine Department, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Cairo, Egypt. 9. University Hospital "Santa Maria della Misericordia," Udine, Italy. 10. Department of Biostatistics and Medical Data Processing, INSERM U717, Hôpital Saint-Louis, Paris, France.
Abstract
BACKGROUND & AIMS: In small-size and short-term studies of hepatitis C virus-associated cryoglobulinemia vasculitis (HCV-CryoVas), patients had a higher rate of response and tolerance to direct-acting antiviral (DAA) agents than interferon-containing regimens. We collected follow-up data from a clinical trial to determine the long-term effectiveness and tolerance of all-oral, interferon-free DAA regimens in patients with CryoVas. METHODS: We collected follow-up data from a prospective international multicenter cohort study of 148 patients with symptomatic HCV-CryoVas (53.7% with cirrhosis and 49.3% naive to treatment with DAAs). All patients received DAA (sofosbuvir plus daclatasvir, n = 53; sofosbuvir plus ribavirin, n = 51; sofosbuvir plus ledipasvir, n = 23; or sofosbuvir plus simeprevir, n = 18), for 12 or 24 weeks, from 2014 through 2017; the median follow-up time was 15.3 months. A complete clinical response was defined as improvement of all organs involved at baseline and the absence of clinical relapse; a partial response was defined as improvement in some but not all organs involved at baseline. The primary end point was clinical response of CryoVas symptoms at week 12 after stopping DAA therapy. RESULTS: A complete response was reported for 106 patients (72.6%), a partial response for 33 patients (22.6%), and no response for 7 patients (4.8%). Cryoglobulins were no longer detected in blood samples from 53.1% of patients, and 97.2% of the patients had a sustained virologic response to therapy. Premature DAA withdrawal was reported for 4.1% of patients. Factors associated with no or partial response to therapy included a severe form of CryoVas (odds ratio, 0.33; 95% CI, 0.12-0.91; P = .03) and peripheral neuropathy (odds ratio, 0.31; 95% CI, 0.11-0.84; P = .02). After a median follow-up time of 15.3 months, 4 patients (2.8%) died. The CryoVas manifestation of purpura was cleared from 97.2% of patients, renal involvement from 91.5% of patients, arthralgia from 85.7% of patients, neuropathy from 77.1% of patients, and cryoglobulinemia from 52.2%. CONCLUSIONS: In a long-term follow-up analysis of data from a clinical trial, we found that more than 95% of patients with HCV-CryoVas have a full or partial response of symptoms to different DAA treatment regimens. Fewer than 5% of patients stop therapy prematurely and less than 3% die. A severe form of CryoVas and peripheral neuropathy were associated with a lack of response of HCV-CryoVas to DAA therapy.
BACKGROUND & AIMS: In small-size and short-term studies of hepatitis C virus-associated cryoglobulinemia vasculitis (HCV-CryoVas), patients had a higher rate of response and tolerance to direct-acting antiviral (DAA) agents than interferon-containing regimens. We collected follow-up data from a clinical trial to determine the long-term effectiveness and tolerance of all-oral, interferon-free DAA regimens in patients with CryoVas. METHODS: We collected follow-up data from a prospective international multicenter cohort study of 148 patients with symptomatic HCV-CryoVas (53.7% with cirrhosis and 49.3% naive to treatment with DAAs). All patients received DAA (sofosbuvir plus daclatasvir, n = 53; sofosbuvir plus ribavirin, n = 51; sofosbuvir plus ledipasvir, n = 23; or sofosbuvir plus simeprevir, n = 18), for 12 or 24 weeks, from 2014 through 2017; the median follow-up time was 15.3 months. A complete clinical response was defined as improvement of all organs involved at baseline and the absence of clinical relapse; a partial response was defined as improvement in some but not all organs involved at baseline. The primary end point was clinical response of CryoVas symptoms at week 12 after stopping DAA therapy. RESULTS: A complete response was reported for 106 patients (72.6%), a partial response for 33 patients (22.6%), and no response for 7 patients (4.8%). Cryoglobulins were no longer detected in blood samples from 53.1% of patients, and 97.2% of the patients had a sustained virologic response to therapy. Premature DAA withdrawal was reported for 4.1% of patients. Factors associated with no or partial response to therapy included a severe form of CryoVas (odds ratio, 0.33; 95% CI, 0.12-0.91; P = .03) and peripheral neuropathy (odds ratio, 0.31; 95% CI, 0.11-0.84; P = .02). After a median follow-up time of 15.3 months, 4 patients (2.8%) died. The CryoVas manifestation of purpura was cleared from 97.2% of patients, renal involvement from 91.5% of patients, arthralgia from 85.7% of patients, neuropathy from 77.1% of patients, and cryoglobulinemia from 52.2%. CONCLUSIONS: In a long-term follow-up analysis of data from a clinical trial, we found that more than 95% of patients with HCV-CryoVas have a full or partial response of symptoms to different DAA treatment regimens. Fewer than 5% of patients stop therapy prematurely and less than 3% die. A severe form of CryoVas and peripheral neuropathy were associated with a lack of response of HCV-CryoVas to DAA therapy.
Authors: Hashem B El-Serag; Israel C Christie; Amy Puenpatom; Diana Castillo; Fasiha Kanwal; Jennifer R Kramer Journal: Aliment Pharmacol Ther Date: 2019-04-01 Impact factor: 8.171