Anti-tumour necrosis factor alpha treatment in patients affected by rheumatoid arthritis with anti-Ro/SSA antibodies

Background

Anti-tumour necrosis factor alpha (anti-TNF-α) treatment could induce the onset of new autoantibodies [1, 2] or clinical features of other autoimmune diseases than rheumatoid arthritis (RA) [2].

Aim

To analyse the efficacy and safety of anti-TNF-α treatment in six patients affected by RA with anti-Ro/SSA antibodies and to evaluate the clinical and laboratory changes during the treatment.

Patients and methods

Antinuclear antibodies (IFI on HEp-2 cells), anti-dsDNA (Farr assay), anticardiolipin (aCL, ELISA) and anti-ENA (CIE) were evaluated before the treatment and every 6–12 months. Anti-Ro/SSA antibodies were confirmed by ELISA, using recombinant 52 and 60 kDa Ro proteins (Pharmacia).

Results

Six patients had anti-Ro/SSA antibodies before anti-TNFα treatment. Anti-Ro/SSA was detected in four sera using both CIE and ELISA, while two sera showed anti-60 kDa Ro antibodies only by ELISA. Six patients (mean age, 58 years; standard deviation [SD], 9.8) were affected by long-acting RA (mean duration, 7 years; range, 5–22 years), not responding to common disease-modifying anti-rheumatic drugs (mean, 5 disease-modifying anti-rheumatic drugs; SD, 2.3). All the patients were treated for a mean of 31 months (SD, 20.4 months), four subjects with Infliximab and two with Etanercept. Before the treatment the patients showed active arthritis with a mean of 25.3 tender joints (SD, 2.16), 17.3 swollen joints (SD, 8.6) and Disease Activity Score (DAS) of 5.5 (SD, 1.04); after 6, 12, 18, and 24 months all the patients showed a rapid and sustained improvement with reduction of DAS value (see Table 1).

Table 1 Clinical response to anti-tumour necrosis factor alpha treatment in patients with rheumatoid arthritis and anti-Ro/SSA antibodies

All the patients were affected by Sjögren syndrome (SS), associated to RA, clinically stable during the treatment. One subject was also affected by primary biliary cirrhosis, which remained clinically and histologically stable. Three patients developed anti-dsDNA at low titre after 6 months and a fourth after 12 months of treatment. Only one patient developed skin lesions after 6 months of Infliximab, clinically and histologically similar to subacute cutaneous lupus with IgM deposits at basal membrane. No patients developed aCL, while the titre of anti-Ro antibodies by ELISA was stable during the treatment. One subject, affected by RA and HCV hepatitis, stopped the etanercept treatment due to severe increase of hepatic enzymes.

Conclusions

Anti-TNF treatment in RA-SS patients with anti-Ro/SSA showed a good and sustained efficacy until the 24th month. Four patients (66.7%) showed anti-dsDNA after 6–12 months, while only one developed subacute cutaneous lupus-like symptoms. No other autoantibodies nor an increase of the anti-Ro titre were observed.