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Antinuclear antibody formation following administration of anti‐tumor necrosis factor agents in Japanese patients with psoriasis

Dear Editor, Recent data suggest that anti-tumor necrosis factor (TNF) agents induce the formation of antinuclear antibodies (ANA) and the development of autoimmune diseases in psoriasis patients. The present study demonstrated that treatment of psoriasis patients with anti-TNF agents, unlike ustekinumab, significantly increased the proportion of patients who were positive for ANA without the development of autoimmune diseases or loss of response. We retrospectively evaluated the clinical records of 66 Japanese patients with psoriasis treated with anti-TNF agents (infliximab, n = 20; adalimumab, n = 28) or ustekinumab (n = 18) for at least 3 months. The mean ( standard deviation) followup period for patients on anti-TNF agents or ustekinumab was 7.4 3.5 and 9.0 6.7 months, respectively. Patients who had been treated with any other biologics were excluded from the study, and none of the included patients had a history of autoimmune disease or concomitant treatment with retinoids, cyclosporin or methotrexate. ANA were identified by indirect immunofluorescence using an ANA test system (BML, Tokyo, Japan). Fisher’s exact probability test was used to compare frequencies. Statistical significance was defined as a P-value of less than 0.05. When ANA positivity was determined at a dilution of 1:40, ANA positivity in psoriasis patients was significantly increased from 48% to 69% during treatment with anti-TNF agents (P = 0.038, Table 1). When a dilution of 1:80 was used, 21% of the patients with psoriasis were positive for ANA at baseline, but 40% were positive for ANA during anti-TNF treatment (P = 0.045). At a dilution of 1:160, the positivity was raised from 13% to 25% during treatment with anti-TNF agents, although the change was not statistically significant (P = 0.117). There were no statistical differences in ANA positivity between infliximab and adalimumab (data not shown). By contrast, ANA positivity was not significantly changed by ustekinumab at these three different cut-off dilutions. Furthermore, 75% reduction of Psoriasis Area and Severity Index score (PASI-75) response rates were not significantly different between psoriasis patients whose ANA became positive during treatment with anti-TNF agents and those whose ANA were not changed throughout anti-TNF treatment (71% vs 73%, 68% vs 63% and 72% vs 57%, at 1:40, 1:80 and 1:160 dilutions, respectively). None of these patients developed autoimmune disease during treatment. Thus, treatment with anti-TNF agents, unlike ustekinumab, increased the proportion of patients with ANA positivity without affecting efficacy. According to recent reports, the development of ANA is associated with loss of response, but it has been also shown not to be associated with loss of efficacy. Fifty-three percent of psoriasis patients became positive for ANA during infliximab treatment, but PASI-75 response rates were not affected in these patients. Although this study showed that ANA development appeared not to affect the efficacy of antiTNF agents, future studies should examine the longitudinal changes in ANA titers and efficacy for longer observation periods. Furthermore, evaluation of the emergence of various autoantibodies and antidrug antibodies is required. Nonetheless, our findings suggest that it is not necessary to terminate anti-TNF treatment immediately because of the observed elevations in ANA titers, although careful observation is needed.