Clinical features of joint symptoms observed in the ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial

Abstract

551 Background: Aromatase inhibitors have been associated with higher rates of adverse events associated with the joints, or ‘joint symptoms’ (JS) than tamoxifen. Details of these were reviewed in the ATAC study. JS were reported spontaneously at a higher frequency with anastrozole (A) than with tamoxifen (T), and here we present a detailed assessment of these events. Methods: Adverse events related to the joints were coded into four COSTART terms: arthralgia, arthritis, arthrosis and joint disorder. Time of onset, duration of symptoms and their effect on treatment adherence were reviewed. Results: At 68 months’ median follow-up 1100/3092 (35.6%) patients in the A arm and 911/3094 (29.4%) patients in the T arm experienced JS. Almost half (46%) of patients with JS reported these as an exacerbation of a pre-existing condition in the joints and in most cases the location was generalized. The majority of first events developed within 24 months of initiation of treatment (A 68%, T 59%) with a peak occurrence at 6 months (A 29%, T 20%). Review of all available data showed that half of the patients who recovered from JS were symptom-free within 6 months of onset and in 75%, symptoms resolved within 18 months. Median time to resolution for these events was 5.5 months for the A arm and 5.9 months for the T arm. Sixty percent of patients experiencing JS received treatment, with >90% of these patients managed with an NSAID alone or in combination with mild analgesics. Although the difference in overall prevalence between treatment arms was statistically significant (p<0.0001), a similar occurrence of serious adverse events of JS was reported (A 10.6%, T 10.4%), and only a small number of patients experiencing JS required treatment withdrawal (A 2.1%, T 0.9%). Conclusion: 68-month data from the ATAC trial showed that treatment with A was associated with a modest increase in the incidence of JS compared with T. In most patients the events were mild-to-moderate in intensity and did not lead to withdrawal of treatment. [Table: see text]