Contributions
Abstract: P1243
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Daily high-dose biotin has been suggested to improve disability in patients with progressive multiple sclerosis (P-MS) in a small-size controlled trial conducted in France. This led to the possibility to give high-dose biotin to P-MS patients while a phase 3 trial is ongoing. As high-dose biotin therapy may lead to analytical interference in immunoassays that use streptavidin-biotin system, we addressed whether HBV serology, which is needed in the pre-therapeutic screening for some MS second line treatments, might be impacted.
Methods: The risk of false positive or negative HBV serology was analyzed during pre-therapeutic screening for anti-CD20 monoclonal antibody therapy in P-MS patients. Surface antigen (HBsAg) anti-HBs and anti-HBc antibodies assays were performed using routine screening system Architect® (Abbott) by chemiluminescent microparticulate immunoassays. Samples were also tested by electrochemiluminescence on Cobas® system (Roche Diagnostics) using biotin-streptavidin system, with sandwich tests (HBsAg, anti-HBs) or competitive test (anti-HBc).
Results: We tested for HBV 17 consecutive P-MS patients receiving biotin (300 mg/d). Female was predominant (72%), and mean age was 55 years (range: 30,6-77,5). Seven patients were followed for primary P-MS and 10 for secondary P-MS. The mean duration of progressive disease was 11.2 years (range: 1.8-28) and median EDSS was 6.0 (range: 3.5-8). Median duration of treatment by high-dose biotin was 20 months (range: 5-70). None had a past history of viral hepatitis. For all of them, anti-HBc antibodies were positive on Cobas® but negative on Architect® systems. Four patients were vaccinated for HBV with anti-HBs detected by Architect® system. By Cobas® system, anti-HBs were not detected in two samples, and lowered for the remaining two.
Conclusions: Our study is the first to evaluate the risk of misdiagnosis in HBV infection for MS patients treated by high-dose of biotin. Serology profile refers to a previous contact with hepatitis B using a biotin-streptavidin-based immunoassay, hence a need to initiate a pre-emptive HBV therapy to prevent reactivation in case of immunosuppression. To avoid inadequate anti-HBV therapy, neurologists and virologists should be aware of this risk of biotin-induced false HBV status. The use of a biotin-free immunoassay to assess HBV infection is necessary in patients treated with high-dose biotin.
Disclosure: V. Pourcher has received consulting and lecturing fees from Merck Serono.
E. Todesco and C. Dubois : nothing to disclose
C.. Lubetzki received research grants from Merck Serono and Biogen, and consultation fees for advisory board participation from Roche.
C. Louapre has received compensation for travel grants, consulting services or speaker honoraria from Biogen, Sanofi Genzyme, Merck Serono, Novartis and Teva.
C. Papeix has received consulting and lecturing fees from Merck Serono, Roche, Novartis, Biogen, Medday.
E.Maillart has received consulting and lecturing fees, travel grants, from Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi, and Teva Pharma, and research support from Novartis and Roche.
Abstract: P1243
Type: Poster Sessions
Abstract Category: Therapy - Risk management for disease modifying treatments
Introduction: Daily high-dose biotin has been suggested to improve disability in patients with progressive multiple sclerosis (P-MS) in a small-size controlled trial conducted in France. This led to the possibility to give high-dose biotin to P-MS patients while a phase 3 trial is ongoing. As high-dose biotin therapy may lead to analytical interference in immunoassays that use streptavidin-biotin system, we addressed whether HBV serology, which is needed in the pre-therapeutic screening for some MS second line treatments, might be impacted.
Methods: The risk of false positive or negative HBV serology was analyzed during pre-therapeutic screening for anti-CD20 monoclonal antibody therapy in P-MS patients. Surface antigen (HBsAg) anti-HBs and anti-HBc antibodies assays were performed using routine screening system Architect® (Abbott) by chemiluminescent microparticulate immunoassays. Samples were also tested by electrochemiluminescence on Cobas® system (Roche Diagnostics) using biotin-streptavidin system, with sandwich tests (HBsAg, anti-HBs) or competitive test (anti-HBc).
Results: We tested for HBV 17 consecutive P-MS patients receiving biotin (300 mg/d). Female was predominant (72%), and mean age was 55 years (range: 30,6-77,5). Seven patients were followed for primary P-MS and 10 for secondary P-MS. The mean duration of progressive disease was 11.2 years (range: 1.8-28) and median EDSS was 6.0 (range: 3.5-8). Median duration of treatment by high-dose biotin was 20 months (range: 5-70). None had a past history of viral hepatitis. For all of them, anti-HBc antibodies were positive on Cobas® but negative on Architect® systems. Four patients were vaccinated for HBV with anti-HBs detected by Architect® system. By Cobas® system, anti-HBs were not detected in two samples, and lowered for the remaining two.
Conclusions: Our study is the first to evaluate the risk of misdiagnosis in HBV infection for MS patients treated by high-dose of biotin. Serology profile refers to a previous contact with hepatitis B using a biotin-streptavidin-based immunoassay, hence a need to initiate a pre-emptive HBV therapy to prevent reactivation in case of immunosuppression. To avoid inadequate anti-HBV therapy, neurologists and virologists should be aware of this risk of biotin-induced false HBV status. The use of a biotin-free immunoassay to assess HBV infection is necessary in patients treated with high-dose biotin.
Disclosure: V. Pourcher has received consulting and lecturing fees from Merck Serono.
E. Todesco and C. Dubois : nothing to disclose
C.. Lubetzki received research grants from Merck Serono and Biogen, and consultation fees for advisory board participation from Roche.
C. Louapre has received compensation for travel grants, consulting services or speaker honoraria from Biogen, Sanofi Genzyme, Merck Serono, Novartis and Teva.
C. Papeix has received consulting and lecturing fees from Merck Serono, Roche, Novartis, Biogen, Medday.
E.Maillart has received consulting and lecturing fees, travel grants, from Biogen Idec, Genzyme, Novartis, Merck Serono, Roche, Sanofi, and Teva Pharma, and research support from Novartis and Roche.