Background/Purpose: The well-known positive effect of pregnancy on improving Rheumatoid Arthritis (RA) disease activity suggests that hormonal changes may play a role in disease pathogenesis and raises a concern that anti-estrogen therapy (AET) including Aromatase Inhibitors [AI] and selective estrogen receptor modulators [SERMs] may have an adverse effect on RA. AI can cause musculoskeletal symptoms including AI induced arthritis. Recent observations by our group suggest an increased incidence of RA among patients using either AI or SERMs (1). We intended to examine the effect of AET on disease activity in patients with established RA.

Methods: We searched the electronic medical records in 2 medical centers for patients with the diagnoses of both breast cancer and RA.  Of 435 charts reviewed, we identified 40 who had validated RA diagnosis, used SERMs or AI for breast cancer and had appropriate rheumatology evaluation. Data collected included age, BMI, smoking, RA disease duration, clinical status, serology and medication use.  The primary outcome measure was worsening of disease within 6 months of AET initiation compared to the most recent evaluation prior to AET, using 2 visits before and 2 after AET. Worsening was defined as an increase in swollen & tender joint count, patient and/or physician global assessment, or documented flare/worsening by rheumatologist assessment, including the need to discontinue AET or modify RA therapy.  Worsening could not be attributed to changes or discontinuation of RA therapy. We also reviewed patients who developed RA following initiation of AET.

Results: Thirty eight patients were analyzed. Mean age was 59 years and median duration of RA prior to cancer diagnosis was 8.2 years. AETs used included tamoxifen (6), anastrazole (23) and other AI (9). RA clinical status prior to AET initiation was classified as complete remission (25%), stable (55%) and active (20%), 76.7% were seropositive. Seven patients developed new onset seropositive RA with a mean of 12 months (1-24 months) following initiation of AI (5 patients) and tamoxifen (2). RA worsened in 18 out of 31 patients (58%) after initiating AET, primarily after AI (16/18 patients). On comparing patients who worsened to those who did not (table 1), worsening group was significantly more likely to be younger and seropositive, while age and BMI did not differ between groups. Eighty three percent of patients who were not on DMARDs or biologics worsened while the patients who were maintained on biologics did not.

Conclusion: Our study includes the largest reported number of new onset RA cases following the initiation of AET, Our data suggest that use of AET may worsen RA in patients with established disease, especially in those who are not on DMARDs or biologic therapy.

References: 1-Chen JY, Ballou SP. The Effect of Antiestrogen Agents on Risk of Autoimmune Disorders in Patients with Breast Cancer. J Rheumatol. 2014 Oct 1

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