Staging and managing patients with acromegaly in clinical practice: baseline data from the SAGIT® validation study

Abstract

Purpose: The SAGIT® instrument, designed to assist clinicians to stage acromegaly, assess treatment response and adapt patient management, was well received by endocrinologists in a pilot study. We report an interim analysis of baseline data from the validation phase.

Methods: The SAGIT® validation study (ClinicalTrials.gov NCT02539927) is an international, non-interventional study. Data collection included: demographic/disease characteristics; medical/surgical histories; concomitant acromegaly treatments; investigators' subjective evaluation of disease-control status (clinical global evaluation of disease control [CGE-DC]; controlled/not controlled/yet to be clarified) and clinical disease activity (active/not active); growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels; investigators' therapeutic decision.

Results: Of 228 patients enrolled, investigators considered disease to be controlled in 110 (48.2%), not controlled in 105 (46.1%), and yet to be clarified in 13 (5.7%) according to CGE-DC. Thirty-three patients were treatment-naïve (not controlled, n = 31; yet to be clarified, n = 2). Investigators considered 48.2% patients in the controlled and 95.2% in the not-controlled groups to have clinically active disease. In the controlled group, 29.7% of patients did not exhibit hormonal control (GH ≤ 2.5 µg/L; normalized IGF-1) and 47.3% did not have rigorous hormonal control (GH < 1.0 µg/L; normalized IGF-1) by contemporary consensus. Current acromegaly treatment was continued with no change for 91.8% of patients in the controlled and 40.0% in the not-controlled groups.

Conclusions: These data highlight discrepancies between investigator-evaluated disease-control status, disease activity, hormonal control, and treatment decisions in acromegaly. Once validated, the SAGIT® instrument may assist clinicians in making active management decisions for patients with acromegaly.

Keywords: Acromegaly control; Acromegaly management; Clinician-reported outcomes; SAGIT® instrument.

Conflict of interest statement

AG has been a consultant for Ipsen and Pfizer and has received research Grants from Ipsen and Novartis. MDB has been a consultant for Chiasma, Ipsen, and Novartis, and a speaker and Clinical Trial Investigator for Ipsen and Novartis. PC has received unrestricted research and educational Grants from Ipsen, Novartis and Pfizer (on behalf of the Service of Endocrinology and Reproductive Diseases, Hôpitaux Universitaires Paris-Sud and Association Recherche Endocrinologie Bicêtre); he has served as an investigator for clinical trials funded by Novartis, Pfizer, Ipsen, Italpharmaco, Antisense, and Chiasma and has given lectures for Ipsen, Novartis, and Pfizer (all fees and honoraria paid to his Institution or Research Association). SP has been a speaker and advisory board member for Ipsen, Novartis, and Pfizer. FFC has given lectures and acted as an advisor for Pfizer and Ipsen. SM has received research grants from and acted as an investigator for Pfizer, Ipsen, and Ono; he has also acted as a consultant for Chiasma, Ionis, and Midatech. CS and AH are employees of Ipsen.

Figures

Fig. 1

Patient disposition. aA protocol amendment was introduced to exclude enrolment of patients receiving pegvisomant, to satisfy sample-size requirements for the validation of the SAGIT® instrument (the ‘G’ element of the SAGIT® instrument is not applicable to these patients). bCGE-DC was not available for this patient. cInvestigators determined disease-control status at baseline (classified as controlled, not controlled, or status not yet clarified). CGE-DC clinical global evaluation of disease control

Fig. 2

Patients with GH levels ≤ 2.5/CGE-DC clinical global evaluation of disease control, GH growth hormone, IGF-1 insulin-like growth factor-1

Fig. 3

Investigators’ therapeutic decisions according to CGE-DC categories of disease control. Results are for all patients (enrolled population) and for groups according to CGE-DC status (controlled, not controlled); the enrolled population also included 13 patients for whom disease control status had yet to be clarified (data not shown). aOther investigator therapeutic attitudes at baseline were ‘under evaluation for neurosurgery’ and ‘will initiate a treatment 3 months following surgery’. CGE-DC clinical global evaluation of disease control

Fig. 4

AcroQoL questionnaire global scores at baseline according to CGE-DC categories of disease control. Data are presented as the mean and 95% CIs for the mean (error bars) for all patients (enrolled population) and for subgroups according to CGE-DC categories (controlled, not controlled); the enrolled population also included 13 patients for whom disease control status had yet to be clarified (data not shown). Data are shown by treatment-naïve status as an insert for the group in whom disease was considered not controlled; there are no corresponding data for the group in whom disease was considered controlled, as all patients had received previous treatment. Treatment-naïve is defined as no previous surgery, radiotherapy, or medical treatments for acromegaly. Higher scores indicate better quality of life. *Significantly different based on non-overlapping 95% CIs. AcroQoL acromegaly quality of life questionnaire, CI confidence interval, CGE-DC clinical global evaluation of disease control