RESUMO
Purpose: The 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, noninterventional, post-marketing safety surveillance study conducted in 15 countries. A total of 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, taking 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% CI. Results: Univariate analysis showed that age <40 years, normal or overweight, baseline IGF-1 <300 µg/L or ranged between 300 and 500 µg/L, and all pegvisomant dose <20 mg/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 µg/L had the lowest risk of un-controlled acromegaly (ES = 0.29, 95% CI: 0.23-0.36). The probability of acromegaly uncontrol was also lower for values 300-500 µg/L (ES = 0.37, 95% CI: 0.32-0.43), while it was higher for baseline IGF-1 values ≥700 µg/L (ES = 0.58, 95% CI: 0.53-0.64). Conclusion: 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. Significance statement: Among factors that could influence and predict the efficacy of pegvisomant therapy in controlling acromegaly, a central role of baseline IGF-1 values on the probability of achieving a biochemical control of acromegaly during the treatment with pegvisomant was identified, in a real-life setting.
RESUMO
Objective: To analyze the effectiveness and safety of growth hormone (GH) replacement treatment in adult patients with Langerhans cell histiocytosis (LCH) and GH deficiency (GHD) enrolled in KIMS (Pfizer International Metabolic Database). Patients and methods: Patients with LCH and GHD were studied at baseline and some of them after 1 year of GH treatment. The effectiveness of GH is presented as change after 1 year of treatment (mean, 95% CI). The LCH population was compared to two other groups of patients enrolled in KIMS, granulomatous and lymphocytic hypophysitis. Results: At baseline, 81 adults with LCH (27 with childhood onset, 56% females), mean age at GHD onset of 29 (15) years were studied. Diabetes insipidus was diagnosed in 86% of patients. Analysis of 1 year of GH treatment was possible in 37 patients. One-year cross-sectional values for the GH dose were 0.39 (s.d.± 0.21) mg and -0.5 (-1.2 to 0.2) for insulin-like growth factor-1 s.d. Total cholesterol decreased 0.9 (-1.5 to -0.3 (mmol/L); P < 0.05); AGHDA-QoL-score (n = 20) was improved by 2.8 points (-5.6 to 0.0; P < 0.05), while mean BMI increased 0.6 ± 3 kg/m2 (95% CI: -0.2 to 1.4). All these effects did not differ from the two other groups after adjusting for age, gender, and baseline values. In 20 of 77 patients included in the safety analysis, 36 serious adverse events were reported during 435 patient-years (82.8/1000); no new safety signals were reported. Conclusion: After 1 year of GH treatment in patients with LCH, metabolic variables and quality of life improved, with no new safety signals.
