Safety of TNF-blocking agents in rheumatic patients with serology suggesting past hepatitis B state: results from a cohort of 21 patients.
BACKGROUND
Reactivation of hepatitis B virus (HBV) infection in patients with past infection has been described in 5% to 10% of individuals undergoing immunosuppressive therapies. No data are available to date on the outcome of patients treated by tumour necrosis factor-alpha (TNFalpha) inhibitors for chronic arthritis with a serological pattern of past HBV infection. The aim of our study was to monitor HBV markers in HBV surface antigen (HBsAg)-negative/anti-HBcAb-positive patients treated with a TNFalpha inhibitor for inflammatory arthritides.


METHODS
Twenty-one HBsAg-negative/anti-HBcAb-positive patients were included. HBV serological patterns were compared with those determined before starting TNFalpha inhibitors. Serum HBV DNA testing by polymerase chain reaction was additionally performed. Spearman correlation analysis was used and P < 0.05 was chosen as the significance threshold.


RESULTS
Before starting therapy, mean anti-HBsAb titre was 725 IU/L, no patient had an anti-HBsAb titre <10 IU/L, and 18 patients had an anti-HBsAb >100 IU/L. At a mean time of 27.2 months following therapy introduction, mean anti-HBsAb titre was 675 IU/L and anti-HBsAb titre remained >100 IU/L in 17 patients. There was a strong correlation between the first and second anti-HBsAb titres (r = 0.98, P = 0.013). Moreover, no patient had an anti-HBsAb titre below 10 IU/L or HBV reactivation (HBsAg seroreversion or positive HBV DNA detection). However, the anti-HBsAb titre decreased by more than 30% in 6 patients. The mean anti-HBsAb titre at baseline was significantly lower (P = 0.006) and the mean duration of anti-TNFalpha therapy, although non-significant (P = 0.09), was longer in these six patients as compared to patients without a decrease in anti-HBsAb titre.


CONCLUSIONS
Anti-TNFalpha treatments are likely to be safe in patients with past hepatitis B serological pattern. However, the significant decrease of anti-HBsAb titre observed in a proportion of patients deserves HBV virological follow-up in these patients, especially in those with a low anti-HBsAb titre at baseline.
Charpin
Caroline
C
Service de Rhumatologie, Centre Hospitalier Universitaire Conception, 147 Boulevard Baille, 13385 Marseille, France. caroline.charpin@ap-hm.fr
Guis
Sandrine
S
Colson
Philippe
P
Borentain
Patrick
P
Mattéi
Jean-Pierre
JP
Alcaraz
Patrice
P
Balandraud
Nathalie
N
Thomachot
Benoit
B
Roudier
Jean
J
Gérolami
René
R
D000068879:Adalimumab; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D015331:Cohort Studies; D000068800:Etanercept; D005260:Female; D006509:Hepatitis B / Q000097:blood / Q000150:complications*; D006510:Hepatitis B Antibodies / Q000097:blood / Q000187:drug effects*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D014775:Virus Activation / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept