Effects of prophylactic and therapeutic paracetamol treatment during vaccination on hepatitis B antibody levels in adults: two open-label, randomized controlled trials

Abstract

Worldwide, paracetamol is administered as a remedy for complaints that occur after vaccination. Recently published results indicate that paracetamol inhibits the vaccination response in infants when given prior to vaccination. The goal of this study was to establish whether paracetamol exerts similar effects in young adults. In addition, the effect of timing of paracetamol intake was investigated. In two randomized, controlled, open-label studies 496 healthy young adults were randomly assigned to three groups. The study groups received paracetamol for 24 hours starting at the time of (prophylactic use) - or 6 hours after (therapeutic use) the primary (0 month) and first booster (1 month) hepatitis B vaccination. The control group received no paracetamol. None of the participants used paracetamol around the second booster (6 months) vaccination. Anti-HBs levels were measured prior to and one month after the second booster vaccination on ADVIA Centaur XP. One month after the second booster vaccination, the anti-HBs level in the prophylactic paracetamol group was significantly lower (p = 0.048) than the level in the control group (4257 mIU/mL vs. 5768 mIU/mL). The anti-HBs level in the therapeutic paracetamol group (4958 mIU/mL) was not different (p = 0.34) from the level in the control group. Only prophylactic paracetamol treatment, and not therapeutic treatment, during vaccination has a negative influence on the antibody concentration after hepatitis B vaccination in adults. These findings prompt to consider therapeutic instead of prophylactic treatment to ensure maximal vaccination efficacy and retain the possibility to treat pain and fever after vaccination.

Trial registration: Controlled-Trials.com ISRCTN03576945.

Figure 1. Consort 2010 Flow Diagram.

The participation flow during the vaccination, intervention and blood collection.

Figure 2. Timeline of the vaccination, intervention and blood collection.

The study was composed of two phases. In phase 1, one prophylactic and one control group were investigated. In phase 2, one prophylactic paracetamol, one therapeutic paracetamol and one control group were investigated. The paracetamol groups received paracetamol after the primary and first booster hepatitis B vaccine doses, at 0 and 1 month. Participants received no paracetamol after the second booster vaccine dose at 6 months. The control group received no paracetamol or placebo during the hepatitis B vaccination procedure. Blood (14–21 mL) was taken of all participants prior to and one month after the second booster vaccination.

Figure 3. Timeline of the paracetamol treatment after the primary and first booster vaccination.

The prophylactic paracetamol group received three doses of paracetamol (1000 mg/dose) starting immediately after vaccination, 8 hours and 16 hours after the vaccination. The therapeutic paracetamol group received three doses of paracetamol (1000 mg/dose) starting 6 hours after vaccination, 14 hours and 22 hours after vaccination. The control group received no paracetamol or placebo during the hepatitis B vaccination procedure.

Figure 4. Anti-HBs levels prior (A) to and one month after (B) the second booster vaccination.

Line at GMC. A) The anti-HBs levels in the groups were not significantly different. B) The anti-HBs level in the prophylactic paracetamol group (4257 mIU/mL) is significantly lower (p = 0.048) from the anti-HBs level in the control group (5768 mIU/mL). The anti-HBs level in the therapeutic paracetamol group (4958 mIU/mL) was not significantly different from the control group. Significant differences in anti-HBs levels were tested by using the Mann-Whitney U test. * = p<0.05.

Figure 5. Ratio between the anti-HBs levels prior to and one month after the second booster vaccination.

The increase in antibody concentration after the second booster vaccination is expressed in ratio. The ratio in the prophylactic paracetamol group (20.3) is significantly lower from the ratio in the control group (34.9). The ratio in the therapeutic paracetamol group (27.4) was not significantly different from the control group. * = p<0.01.