Background/Purpose: Tumor necrosis factor-α inhibitors (TNFi) have been widely used in patients who failed conventional DMARDs in the treatment of rheumatoid arthritis (RA). While most patients respond well to TNFi, some patients experience loss of efficacy over time possibly due to forming TNFi antibodies. Studies have shown that concomitant use of methotrexate (MTX) with TNFi is associated with increased drug survival compared with TNFi monotherapy. However, whether hydroxychloroquine (HCQ) may also prolong TNFi persistence is unknown and was the purpose of this study.

Methods: We analyzed patients with RA and ≥1 year participation in the National Data Bank for Rheumatic Diseases (NDB), an ongoing US-wide longitudinal observational study with biannual questionnaires since 1998. Patients initiating 3 TNFi’s, infliximab, adalimumab, or etanercept, were categorized according to concomitant DMARD use: none (monotherapy), HCQ +/- other DMARDs but no MTX, MTX +/- other DMARDs but no HCQ, and HCQ and MTX +/- other DMARDs. Patients who have previously taken other biologics were also enrolled into our study. Patients were considered as continuing the TNFi if it was on hold for less than 12 months due to infection or surgery and the same TNFi was resumed after that. Baseline characteristics (including all prior therapies) were collected via self-report at enrollment while therapy continuation was collected on each follow-up questionnaire. We followed patients until TNFi discontinuation, censoring, or death. We compared the discontinuation rate and mean drug survival time between subgroups using Pearson chi-square tests and Kruskal-Wallis tests with Dunn’s tests.

Results: A total of 8611 patients were included with mean (SD) age of 59 (13) years, 81% female and RA duration 14 (11) years. Patients who received concomitant HCQ with TNFi initiation had similar therapy discontinuation rates compared to TNFi monotherapy. Concomitant HCQ use was associated with a longer drug survival compared to etanercept (p=0.007) or infliximab (p<0.001) monotherapy. Concomitant MTX use has the largest impact in infliximab comparing to monotherapy, associated with both lower discontinuation rate (p<0.001) and longer drug survival time (p<0.001). Concomitant MTX use is also associated with longer drug survival in adalimumab (p<0.001), while such association was not found with concomitant HCQ use (p=0.183). Otherwise, concomitant HCQ use has similar effect in prolonging TNFi survival comparing to concomitant MTX use.

Table 1. Discontinuation and mean drug survival of TNFi by concomitant HCQ and MTX use (+) and nonuse (–)

Conclusion: Concomitant use of HCQ with TNFi’s is associated with increased TNFi persistence. Our initial findings show promise for increased TNFi effectiveness with either HCQ or MTX, and followup studies examining TNFi-antibody levels may help explain this association.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/concomitant-hydroxychloroquine-impact-on-anti-tnf-persistence-in-patients-with-rheumatoid-arthritis/