Table 3.
Hepatitis virus B reactivation in rheumatoid arthritis patients receiving tumor necrosis factor-α inhibitors: studies in patients with markers of chronic or remote hepatitis virus B infection
| Ref. | Study design | Target population | No. of patients | Treatment | Antiviral Prophylaxis | HBsAg+ | Anti-HBc+ and anti-HBs- | Anti-HBc+ and anti-HBs+ | HBV-DNA+ | Anti-HBs+/anti-HBc- | Reactivation |
| Carroll et al[69] | Case series | Rheumatic pts or pts with IBD with CHB | 13 | 11 treated with IFX, 2 treated with ETN | Lamivudine | 13 pts (100%) | - | - | - | - |
7 cases with IFX, 2 cases with ETN |
| Charpin et al[70] | Prospective | RA (12)/SpA (9) pts with resolved HBV infection | 21 | 4 treated with IFX, 14 with ETN, 3 with ADA | 0 pts | 0 pts | 0 pts 100% (with 3 pts < 100 UI/mL) | 0 pts | - |
Mean decrease in anti-HBs titre 8%; no cases of HBV reactivation |
|
| Chung et al[71] | Retrospective | RA (41), SpA (60), JIA (2) pts | 103 | TNFα inhibitors | 0 pts | 8 pts | - | - | 0 pts | - |
1/8 HBsAg+ (12.5%) after 6 wk of IFX |
| Caporali et al[72] | Prospective | RA (59), SpA (8) pts with resolved HBV infection | 67 | 25 treated with IFX, 23 with ETN, 19 with ADA | 0 pts | 0 pts | 46 pts | 28 pts | 0 pts | - |
No cases of HBV reactivation |
| Vassillopoulos et al[73] | Prospective | RA (66), SpA (64), other (1) patients with actual/remote HBV infection or vaccinated for HBV | 131 | 43 treated with IFX, 64 with ETN, 62 with ADA | 14 pts (100% of CHB group): 11 with lamivudine, 2 with entecavir, 1 with telbivudine | 14 pts | 19 pts | 0 pts among CHB group | 19 pts (vaccinated) |
No cases of HBV reactivation in pts with resolved HBV infection. In vaccinated pts, slight decrease in anti-HBs titres (median 163 > 105 IU/mL,
P
= 0.01). Among CHB pts, 1 (7%) treated with
Lamivudine + ETN developed HBV reactivation due to a resistant mutant strain |
|
| Mori et al[74] | Prospective | RA pts with actual/remote HBV infection | 239 | 9 treated with IFX, 18 with ETN, 2 with ADA, 5 with TCZ, 28 with csDMARDs | 2 (100% of HBsAg+ pts) with entecavir | 2 pts | 60 pts | 0 pts | - |
2 cases of HBV reactivation in anti-HBc+ pts (3.3%), 1 with csDMARDs and 1 with ADA |
|
| Tamori et al[75] | Prospective | RA pts with positive anti-HBc | 50 | 22 treated with IFX, 20 with ETN, 2 with ADA | Entecavir | 5 pts | 45 pts | - | - |
2/5 (40%) cases of HBV reactivation among HBsAg+ pts; 1/45 (2%) cases of HBV reactivation among HBcAb+/HBsAg- pts, not under TNFI |
|
| Pérez-Alvarez et al[76] | Systematic review | TNFI-treated pts | 257 | Anti-TNF (not specified) | Not specified | 89 pts | 168 pts | - | - |
HBV reactivation in 35 (39%) pts among HBsAg+ group, fatal in 4 cases. Lower risk if pre-emptive NAs (23%
vs
62%,
P
= 0.003). Higher risk with IFX
vs
ETN. Nine cases (5%) of HBV reactivation in HBcAb+/HBsAg- pts, fatal in 1 pt |
|
| Lan et al[77] | Prospective | RA anti-HBc+ pts | 88 | 40 pts treated with ETN, 48 with ADA | 10 HBsAg+ pts treated with lamivudine | 18 pts | 12 pts | 58 pts | 0 pts | 22 pts (vaccinated) |
Among HBsAg+ pts, no cases of HBV reactivation if pre-emptive NAs; mean decrease in HBV-DNA = 153 IU/mL (P < 0.001); 5/8 cases of reactivation without antivirals. 1 case of HBV reactivation in the HBsAg-/anti-HBs- group |
| Lee et al[78] | Systematic review | HBsAg+ rheumatic disease-positive pts | 122 | 14 pts treated with IFX, 56 with ETN and 25 with ADA | 48 pts (drug not specified) | 122 pts | - | - | Not specified | - |
15 cases (12.3%) of HBV reactivation, including 1 SpA patient treated with pre-emptive lamivudine |
| Lee et al[79] | Systematic Review | HBsAg-/anti-HBc+ rheumatic disease-positive (RA 327, SpA 121) pts | 468 | 100 pts treated with IFX, 269 with ETN and 95 with ADA | Not specified | 0 pts | Not specified | Not specified | Not specified | - |
8 cases (1.7%) of HBV reactivation, 7 with ETN and 1 with ADA; satisfactory clinical outcomes with antiviral therapy |
| Droz et al[38] | Retrospective | Pts with immune-mediated inflammatory diseases (RA 14, CTD 7, vasculitis 5, other 9) developing HBV reactivation | 35 | 7 pts treated with TNF-α inhibitors (not specified), 4 with RTX, 1 with ABA, 1 with TCZ, the others with steroids and/or other immunosuppressants | 5 pts (drug not specified) | 23 pts | 12 pts | Not specified | - |
Reactivation occurred a median of 35 wk after therapy start. 88.6% were asymptomatic; 25.7% had severe hepatitis. Management were NAs in 91.4% cases and decrease/withdrawal of immunosuppressants in 45.7%. Pooling these data with literature, earlier reactivation for RTX and HBsAg/HBV-DNA+ pts |
|
| Ye et al[80] | Prospective | Inflammatory arthritis pts (50 RA, 37 SpA) | 87 | TNFα inhibitors: 56 treated with IFX, 31 with ETN) | 4 pts among CHB group , 9 pts among inactive carriers (not specified) | 37 (6 HBV-DNA+, 31 HBV-DNA-) pts | 50 pts | Not specified | - |
2 cases of HBV reactivation among CHB pts not receiving pre-emptive NAs, none in those receiving it. Among inactive HBsAg carriers, 6 cases of reactivation in pts who didn’t receive NAs, none in those who did. No cases in HBsAg- pts |
|
| Nakamura et al[81] | Retrospective | RA | 57 | 48 treated with TNFα inhibitors (including 9 receiving also TCZ); 7 with TCZ alone and 2 with TCZ and ABA | 0 pts | 0 pts | 11 pts | 38 pts | 0 pts | 8 pts (not vaccinated) | HBV-DNA detected in 3 pts (5.3%), 2 receiving TCZ and 1 receiving ETN, with serum HBV-DNA < 2,1 log copies/mL, and subsequent undetectable HBV-DNA within months |
Pts: Patients; CHB: Chronic hepatitis B; IFX: Infliximab; ETN: Etanercept; IBD: Inflammatory bowel disease; SpA: Spondyloenthesoarthropaties (psoriatic arthritis included); csDMARDs: Conventiona Synthetic disease-modifying antirheumatic drugs; JIA: Juvenile idiopathic arthritis; TCZ: Tocilizumab; NAs: Nuclet(s)ide analogues; CTD: Connettive tissue disease; RTX: Rituximab; ABA: Abatacept. Adapted from Lunel-Fabiani et al[82] Joint Bone Spine 2014.