Factors associated with disease control failure in acromegaly patients treated with pegvisomant: an ACROSTUDY analysis

Purpose: Aim of this study was to examine the probability of achieving acromegaly disease control according to several patient-, disease- and treatment-related factors longitudinally. Methods: We analyzed data from ACROSTUDY, an open-label, non-interventional, post-marketing safety surveillance study conducted in 15 countries. 1546 patients with acromegaly and treated with pegvisomant, with available information on baseline IGF-1 level, were included. Factors influencing IGF-1 control were assessed up to 10 years of follow-up by mixed effects logistic regression models, keeping into account changing values of covariates at baseline and at yearly visits. Twenty-eight anthropometric, clinical, and treatment-related covariates were examined through univariate and multivariate analyses. We tested whether the probability of non-control was different than 0.50 (50%) by computing effect sizes (ES) and the corresponding 95% confidence intervals (CI). Results: Univariate analysis showed that age <40 years, normal or overweight, baseline IGF-1<300 ug/L or ranged between 300 and 500ug/L, and all pegvisomant dose <20mg/day were associated with a lower probability of acromegaly uncontrol. Consistently, in multivariate analyses, the probability of uncontrolled acromegaly was influenced by baseline IGF-1 value: patients with IGF-1<300 ug/L had the lowest risk of not-controlled acromegaly (ES=0.29, 95%CI:0.23-0.36). The probability of acromegaly uncontrol was also lower for values 300-<500ug/L (ES=0.37, 95%CI:0.32-0.43), while it was higher for baseline IGF-1 values ≥700ug/L (ES=0.58, 95%CI:0.53-0.64). Conclusions: Baseline IGF-l levels were a good predictor factor for long-term acromegaly control. On the contrary, our data did not support a role of age, sex, BMI, and pegvisomant dose as predictors of long-term control of acromegaly.