Risk of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing biologic treatment: Extending perspective from old to newer drugs

Table 4 Case reports and studies of hepatitis B virus reactivation in rheumatoid arthritis patients undergoing rituximab

Ref.	Study design	Patients charachteristics	Therapy	Baseline virological status	Timing of HBV reactivation	Antiviral Therapy	Results	Comments
Pyrpasopoulou et al[88]	Case Report	56-year-old female RA pt starting RTX after 3 anti-TNF (ETN, IFX, ADA) and ABA. Previous diagnosis of CHB	RTX Antiviral prophylaxis with lamivudine	HBsAg+, anti-HBe+	1 mo after first RTX administration	Tenofovir + lamivudine RTX withdrawal	Good clinical, serological and virological response	-
Ghrénassia et al[89]	Case Report	78-year-old with RA test+ and erosive RA starting RTX after IFX because of a concomitant diagnosis of lymphoma	RTX monotherapy	HBsAg-/anti-HBc+	9 mo after RTX starts	Entecavir RTX withdrawal	Good clinical, serological and virological response	-
Gigi et al[90]	Case Report	64-year-old female RA pt starting RTX as a first-line bDMARD	RTX + methotrexate	HBsAg-/anti-HBc+	2 yr after RTX start	Entecavir RTX withdrawal	Good clinical, serological and virological response	-
Mitroulis et al[91]	Prospective study	41 rheumatic pts (34 RA; 7 others) who had received ≥ 1 cicle of RTX and had ≥ 6 mo of follow-up	17 pts treated with concomitant methotrexate, 35 with concomitant steroids. 2 pts treated with NAs without HBV reactivation	23 pts not HBV exposed; 4 vaccinated pts; 12 HBsAg-/anti-HBc+ (9 anti-HBs+); 2 pts HBsAg+ anti-HBc+. HBV-DNA undetectable in all pts	No cases of viral reactivation observed	-	-	Slight decrease in anti-HBs titres in vaccinated pts (P = 0.29), never under protective levels
Droz et al[38]	Retrospective (subgroup analysis)	4 pts affected with immune-mediated inflammatory disease treated with RTX	Not specified	Not specified	4 cases of HBV reactivation a median of 35 wk after therapy start (global data)	Not specified	No cases of fulminant hepatitis	Early reactivation with RTX and in HBsAg+/HBV-DNA+ pts (global data)

Pts: Patients; ETN: Etanercept; IFX: Infliximab; ADA: Adalimumab; ABA: Abatacept; CHB: Chronic hepatitis B; bDMARD: Biological disease-modifying antirheumatic drug; NAs: Nucleot(s)ide analogues; RTX: Rituximab; HBsAg: Hepatitis B surface antigen.