Objectives To report the 5 year immunogenicity of a quadrivalent human papillomavirus (HPV) vaccine (GARDASIL) in patients with systemic lupus erythematosus (SLE).

Methods Female SLE patients and healthy controls, aged 18–35 years, who received GARDASIL in the year 2011 and sero-converted 12 months post-vaccination were followed for the persistence of immunogenicity at 5 years. Antibodies to HPV serotypes 6,11,16,18 were repeated at 5 years using an IgG immunoassay developed on a Luminex microsphere platform (total IgG LIA; Merck Research Laboratory). The rate of sero-reversion was compared between patients and controls. Factors associated with sero-reversion of the anti-HPV antibodies were studied by statistical analyses.

Results 50 SLE patients (age 25.8±3.9 years) and 50 controls (25.8±3.9 years) were vaccinated with Gardasil in 2011. The sero-conversion rates of anti-HPV serotypes 6,11,16 and 18 in patients and controls were 82%, 89%, 95%, 76%, and 98%, 98%, 98%, 80%, respectively, at month 12 post-vaccination. Among those subjects who sero-converted and were available for follow-up, persistence of the antibodies to HPV serotypes 6,11,16 and 18 at 5 years was present in 24/27 (89%), 26/31 (84%), 32/34 (94%), 24/25 (96%) of the SLE patients and 32/33 (97%), 32/33 (97%), 32/32 (100%) and 23/24 (96%) of the controls, respectively. Moreover, antibody titers to HPV serotypes 6 and 16 at 5 years were significantly lower in SLE patients than controls. Seven (21%) SLE patients had sero-reversion of any one of the four anti-HPV antibodies (6,11,16 or 18) at year 5 post-vaccination. Patients who sero-reverted had received a significantly higher cumulative dose of prednisolone (13.0±5.34 vs 4.63±4.59 grams; p=0.002), mycophenolate mofetil (1050±1180 vs 238±49.5 grams; p=0.007) and tacrolimus (375±580 vs 268±1180 mg; p=0.03) during the 5 year follow-up than those with persistence of immunogenicity. These sero-reverted patients had also received a non-significantly higher cumulative dose of cyclophosphamide (1.97±5.22 vs 0.43±2.24 grams; p=0.27). In addition, sero-reverted patients had more SLE flares in the 5 year follow-up period compared to those with persistence of immunogenicity (3.14±1.21 vs 1.89±1.28; p=0.03). Among 64 flares in patients with persistent anti-HPV antibodies and 26 flares in those with sero-reversion, renal flares occurred more frequently in the latter group of patients (16% vs 38%; p=0.02).

Conclusions Immunogenicity of the quadrivalent HPV vaccine was retained in 79% of SLE patients at 5 year post-vaccination. Antibody titers to HPV serotypes 6 and 16 were significantly lower in SLE patients than controls. Patients who had more SLE flares, especially renal flares, and had received higher cumulative doses of glucocorticoids, mycophenolate mofetil and tacrolimus were more likely to have sero-reversion of one or more anti-HPV antibodies. Re-vaccination of these patients should be considered.

Disclosure of Interest None declared