1. Long-term Pegvisomant treatment outcomes in Patients with Acromegaly: Spanish ACROSTUDY data A.Pico1, E.Venegas2, T.Lucas3, C. Alvarez-Escolá4, J.A. García Arnés5, M. Marazuela6, P Jonsson7, N. Mir8, R. Gomez9, Spanish ACROSTUDY Group10, I.Bernabeu11 1Hospital General de Alicante, Alicante, Spain. 2 Hospital Virgen del Rocío, Sevilla, Spain. 3Hospital General Universitario Puerta de Hierro, Madrid, Spain. 4Hospital La Paz, Madrid, Spain. 5Hospital Carlos Haya, Málaga, Spain. 6Hospital de La Princesa, Madrid, Spain. 7 Pfizer Endocrine Care, Sollentuna, Sweden. 8Pfizer Medical Department, Spain. 9Pfizer Medical Affairs, Europe 10ACROSTUDY centers Spain, Spain. 11Hospital Universitario de Santiago, Santiago de Compostela, Spain.
SUN-0610
Introduction
At start of ACROSTUDY 135 patients had normal glucose metabolism and 61 had diabetes mellitus (DM) (3 patients data not reported). 48.2% of patients received PEG monotherapy and 51.8% received PEG in combination with other drugs. 97.5% of patients took PEG daily at treatment start.
All patients were observed for safety, using biochemical methods in 99% of patients and local MRI evaluations in 92.5% of patients.
Fifteen patients had follow-up visits at year nine; of these, 66.7% had IGF-I levels that were below the LLN (Figure 4).
85.5% (165 out of 193 patients) showed an IGF-I sample normal or < LLN) at any time after PEG start (Figure 4).
The mean±SD daily PEG dose (mg) during follow-up visits was 15.2±1 for patients with normal IGF-I levels and 17.6±1.6 for patients with IGF-I levels above the ULN (Figure 4).
Figure 6. IGF-I normalization and PEG dose (mg/day) throughout the course of treatment in patients with (A) and without (B) DM (cross-sectional data)  
ACROSTUDY is a global non-interventional safety surveillance study designed to evaluate long-term safety and treatment outcomes of pegvisomant (PEG; Somavert®) treatment. A
IGF-I normalized or
below LLN (%)
Objective
Results
To evaluate the long-term safety of PEG in the Spanish cohort of ACROSTUDY. The main outcome measure was IGF-I levels.
The mean±SD daily dose (mg) of PEG during the study ranged between 14.7 ± 6.60 in the first year and to 17.1 ± 9.18 in the ninth year of follow-up (Figure 2).
Figure 4. Percentage of patients with IGF-I normalization (A) or above ULN (B) and PEG dose (mg/day) throughout the course of treatment (cross-sectional data)
Patients and Methods A
199 Spanish patients from 41 centers were included in ACROSTUDY as of July Patient´s demographic characteristics are presented in Table 1.
Statistical analysis: Data analyses were performed using SAS 9.2. Within group comparisons were analyzed with the Wilcoxon sign-rank test. Significance was accepted at p < 0.05.
Figure 2. Daily doses of PEG during the study
IGF-I normalized or
below LLN (%)
PEG dose (mg/day) N= Q3 Q1
90th percentile
10th percentile
Median
Mean B
IGF-I normalized or
below LLN (%)
Table 1: Demographics Characteristics
Male
Female
All
Number (%)
85 (42.7)
114 (57.3)
199
Age at diagnosis of acromegaly, years, mean (±SD)
38.9 (11.73)
46.5 (14.52)
46.13 (13.89)
Duration of acromegaly before PEG start, years, mean (±SD)
7.1 (7.70)
5.9 (6.37)
6.4 (6.97)
Age at PEG start, years, mean (±SD)
45.9 (11.94)
52.4 (15.27)
49.6 (14.29)
Years on PEG, mean (±SD)
6.9 (2.02)
6.6 (2.12)
6.7 (2.08)
Years in ACROSTUDY, mean (±SD)
5.5 (0.99)
4.8 (1.07)
4.9 (1.04) B
Mean,
11.9
14.7
15.3
16.2
16.5
16.6
16.8
17.8
15.2
17.1
IGF-I above ULN (%) N=
188
183
177
168
142
108 81 53 27 N=
Years of therapy
Years in Acrostudy
Mean dose PEG (mg/day)
The mean daily doses (mg) were similar for both in males and females; however, doses were higher in female patients when doses were adjusted by weight (Figure 3).
SAFETY
Serious AEs (SAEs) were described in 31 patients (15.6%) and in three cases (1.5%) the SAEs were considered to be treatment-related.
91% patients had received other medical treatments for acromegaly before the start of PEG (Figure 1).
Figure 3. PEG doses (mg/kg) by gender N=
Conclusion
Figure 1: Treatment modalities used prior to initiation of PEG
Years of therapy
Mean dose PEG (mg/day)
(TE: Transphenoidal; TC: Craniotomy; RDT: Radiation; CONV: Conventional; STE: Stereotactic) 28
(14.1%) 87
(43.7%) 6
(3%) 66
(33.2%) 4
(2%) 1
(0.5%) 7
(3.5%)
(0%)
MEDICAL
THERAPY
RADIATION
NO TREATMENT REPORTED OR
UNKNOWN
SURGERY
In this non interventional study of the Spanish cohort previously unresponsive to surgical, medical therapy with Somatostatin analogs and/or radiation treatments, long-term data for up to 9 years showed that PEG is an effective and safe medical treatment for acromegaly with normalization of IGF-I reported in 85.5% of patients at any time. After start of treatment the uncontrolled patients were receiving sub-optimal doses of the drug.
Figure 5. Mean daily PEG dose in controlled (CTR) and uncontrolled (UNCTR) patients at last observation.
At the last observation (LO), the mean daily PEG dose was 15.2 mg for the group with normal IGF-I levels (N=107) and 17.6 mg for the controlled group (N=77) (Figure 5).
Disclosures
A.P., E.V., C.A-E., JA.G, M.M and I.B. received honoraria from Pfizer as speakers fees as Advisor fees. A.P , M.M and I.B. also received an IIR from Pfizer. T.L. received honoraria from Pfizer as speaker fees.
P.J., N.M., R.G. are full time employees of Pfizer.
TREATMENT OUTCOMES
The % of patients with IGF-I normal or < lower limit of normal (LLN), ranged from 60.2% (N=113) of patients assessed after 1 year of start PEG treatment to 67.9% (N=112) of patients assessed after 5 years of PEG treatment (Figure 4).
There were no differences in the disease control (ie, normalization of IGF-I) between acromegalic patients with DM (57.6%) vs. those without DM (60.5%) (Figure 6).