Abstract PD4-1: Timing, severity and risk factors for arthralgia in the IBIS-II trial: A retrospective and exploratory analysis
Authors: Sestak Ivana , Howell Anthony , Forbes John F , Neven Patrick , Cuzick Jack 
Published: May 2015

Abstract
Background: Arthralgia is a well known side effect of aromatase inhibitors and low oestrogen levels and postmenopausal status are associated with this event. Anastrozole reduced the incidence of oestrogen receptor positive, invasive breast cancer by 58% in the IBIS-II trial. However, timing, severity and risk factors for arthralgia have not been assessed in detail in this trial.
Methods: The IBIS-II trial randomised postmenopausal women at high risk to receive 1mg anastrozole or matching placebo for 5 years. Date of occurrence of arthralgia along with severity (mild, moderate, severe) were recorded at each yearly follow-up visit. Age, body mass index (BMI), and previous hormone replacement therapy (HRT) were investigated as potential risk factors for arthralgia. All analyses were done by the use of logistic regression.
Results: 3864 postmenopausal women (anastrozole: 1920, placebo: 1944) were enrolled in the IBIS-II trial. 58.5% of women randomised to anastrozole reported arthralgia at any time during the trial compared with 52.8% on placebo (OR=1.26 (1.11-1.43), P=0.0004). The majority of arthralgias were reported within the first 18 months of randomisation, with a decline thereafter (Table). 17.5% of women who reported arthralgia withdrew from the trial compared to 13.9% without any of these symptoms (OR=1.31 (1.10-1.57)), and the withdrawal was significantly greater for those with severe symptoms compared to mild (OR=5.97 (4.27-8.33)). Women who used HRT before trial entry had a significant higher risk of developing arthralgia than their counterparts irrespective of allocated treatment (OR=1.45 (1.27-1.64), P&lt;0.001). Increasing BMI (lowest vs. highest BMI group: OR=1.30 (1.11-1.53)) and age (lowest vs. highest age group: OR=1.23 (1.01-1.50)) were also significant risk factors for arthralgia. HRT and BMI remained highly significant in a multivariate model.
Conclusion: Arthalgia was common in the IBIS-II trial irrespective of treatment. However it increased in severity in the active treatment arm mainly in the 18 month period after randomisation. Severe arthralgia led to significantly more withdrawals from the trial than mild symptoms irrespective of treatment. Major risk factors for arthralgia in both arms were previous HRT use and obesity.
Number and percentages (%) of arthralgia of any severity according to treatment allocation and time point.Overall0-18 months18-30 months30-42 months42-54 months&gt;54 monthsAnastrozoleWomen at risk19201150842673543401Number with arthralgia1123770170865344Percentage (%)58.567.020.212.89.811.0PlaceboWomen at risk19441294979782618481Number with arthralgia10266501531096945Percentage (%)52.850.315.613.911.29.4OR (95% CI) (A vs. P)1.26 (1.11-1.43)1.33 (1.17-1.52)1.29 (1.01-1.65)0.92 (0.67-1.25)0.87 (0.59-1.29)1.17 (0.74-1.86)
Citation Format: Ivana Sestak, Anthony Howell, John F Forbes, Patrick Neven, Jack Cuzick. Timing, severity and risk factors for arthralgia in the IBIS-II trial: A retrospective and exploratory analysis [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD4-1.