Hepatitis B virus reactivation associated with antirheumatic therapy: Risk and prophylaxis recommendations

Table 3 Studies evaluating reactivation rates in rheumatic disease patients with resolved hepatitis B virus infection¹

Study2	Patient number	Age (yr)	Biological DMARDs (number)	Non-biological DMARDs and PSL (%)	Follow-up (mo)	Prophylaxis (number)	Reactivation number (%)	Ref.
1	21	58 (mean)	ETN (14), ADM (3), IFX (4)	MTX (48)	27 (mean)	No	0	[46]
2	19	52 (mean)5	ETN, ADM, IFX	ND	24	No	0	[47]
3	67	57 (mean)	ETN (23), IFX (25), ADM (19)	MTX (76), PSL (64)	43 (mean)	No	0	[48]
4	153	49 (mean)5	ETN, IFX	MTX(42)5, PSL(60)5	24	No	0	[55]
5	20	63 (mean)	ETN (10), ADM (7), IFX (2), GOL (1)	MTX (80), others (35), PSL (65)	45 (mean)	No	0	[57]
6	25	63 (mean)5	ETN (15), ADM (10)	DMARDs (72)5	27 (mean)5	2	0	[58]
7	179	57 (mean)	ETN (74), IFX (43), ADM (29), RTX (14), TCZ (7), ABT (9), ANK (3)	DMARDs (75), PSL (46), High-dose PSL (4)	55, 32, 17 (median)	No	010	[60]
8	88	51 (mean)	ETN (60), IFX (12), ADM (16)	ND	25 (mean)	No	144	[29]
9	523	ND	ETN (38), IFX (15), ADM (7), TCZ (4), RTX (1)8	MTX (48)6, others (59)6, PSL (39)6	12	No	6 (11.5)	[49]
9	833	ND	Not used	MTX (48)6, others (59)6, PSL (39)6	12	No	1 (1.2)	[49]
10	42	59 (mean)6	ETN (19), IFX (21), ADM (2)	DMARDs (93)6,	23 (mean)6	No	0	[50]
				PSL (76)6
10	3	59 (mean)6	Not used	DMARDs (93)6,	23 (mean)6	No	1 (33)	[50]
				PSL (76)6
11	36	73 (median)6	ETN (18), IFX (19), ADM (2), TCZ (5)8	MTX (90)6, others (50)6, PSL (63)6	ND	No	1 (2.8)	[51]
11	24	73 (median)6	Not used	MTX (90)6, others (50)6, PSL (63)6	ND	No	1 (4.2)	[51]
12	6	62 (mean)6	ETN (1), IFX (1), TCZ (1), RTX (3)	DMARDs (60)6,	6	No	1 (16.7)	[52]
				PSL pulse (60)6
12	29	62 (mean)6	Not used	DMARDs (60)6,	6	No	5 (17.2)	[52]
				PSL pulse (60)6
13	57	64 (median)	ETN (22), IFX (20), ADM (22), TCZ (18), ABT (2)8	MTX (74), others (18), PSL (74)	18 (median)	No	3 (5.3)	[59]
14	70	51 (mean)	ETN (31), ADM (39)	MTX (91), PSL (100)	ND	No	1 (1.4)	[53]
15	188	ND	Not used	DMARDs (123), PSL (65)	20 (mean)	No	2 (1.1)	[54]
16	50	46 (mean)	ETN (9), IFX (41)	MTX (780), others (16)	12 (mean)	No	0	[56]
177	7	51 (mean)	ADM (7)	ND	ND	No	0	[114]
187	34	54 (mean)9	ETN (20), ADM (10), IFX (4)	ND	19, 28, 29 (mean)	No	0	[113]
19	12	60 (mean)5	RTX (12)	DMARDs (80)5,	19 (mean)5	No	0	[115]
				MTX (41)5, PSL (85)5

¹Resolved HBV infection was defined as HBsAg-negative/anti-HBc-positive serology;

²Study numbers 1-16 correspond to those used in Table 2;

³In these studies, HBsAg-negative/anti-HBs-positive/anti-HBc-negative serology was also considered to indicate resolved infection if patients had no history of HBV vaccination;

⁴In this study, 14 patients showed an abnormality in a liver function test (a twofold or greater increase of aminotransferases on two consecutive tests), but HBV reactivation could not be confirmed (no data on viral load);

⁵Data reported for all patients included in this study, not just for those with resolved infection;

⁶Data reported for all patients included in this study, not separately reported according to the use or nonuse of biological DMARDs;

⁷This study was performed on psoriatic arthritis patients in Italy;

⁸Some patients in these studies received two or three different biological DMARDs;

⁹Data reported for all psoriasis patients included in this study, not just for those with psoriatic arthritis;

¹⁰In this study, seven patients showed an abnormality in a liver function test (among those, three had a twofold or greater increase of aminotransferases), but no HBV DNA was detected. DMARDs: Disease-modifying antirheumatic drugs; PSL: Prednisolone; MTX: Methotrexate; RTX: Rituximab; TCZ: Tocilizumab; ANK: Anakinra; ABT: Abatacept; ADM: Adalimumab; IFX: Infliximab; ETN: Etanercept; GOL: Golimumab; ND: Not described.