Pegvisomant and not somatostatin receptor ligands (SRLs) is first-line medical therapy for acromegaly

Current guidelines recommend the use of long-acting somatostatin receptor ligands (SRLs) first when surgery fails to correct GH/IGF-I hypersecretion in patients with acromegaly. In this issue of the journal, a pro- and contra debate will outline which arguments are in favour and which are against positioning pegvisomant (PEGV), a GH receptor antagonist, as the first-line treatment modality of acromegaly. The task of the pros was to promote a paradigm shift towards repositioning PEGV as first-line treatment as PEGV is safe and more effective than the first- and second-generation of SRLs. SRLs, when prescribed together with PEGV can still reduce tumour size when necessary, while they decrease the necessary dose of PEGV by around 50% in the average patient. They conclude that PEGV must move up towards the first-line treatment. For the cons, SRLs remain the first-line medical treatment. Indeed, even if, in recent studies, the remission rate is lower than initially claimed, SRLs are still effective not only for normalizing GH/IGF-I levels in half of the patients but also for inducing tumour shrinkage, improving comorbidities and headaches and reversing excess mortality. They are more convenient for use with their monthly administration and have a remarkable safety profile as demonstrated by the very prolonged experience acquired by more than 30 years of use. Finally, the cost-effectiveness of first-generation SRLs is better than that of PEGV. For all these reasons, cons consider that SRLs remain the best first medical treatment in patients requiring medical therapy.

Download Full-text

Clinical and Radiological Predictors of Biochemical Response to First-Line Treatment With Somatostatin Receptor Ligands in Acromegaly: A Real-Life Perspective

Frontiers in Endocrinology ◽

10.3389/fendo.2021.677919 ◽

2021 ◽

Vol 12 ◽

Author(s):

Federica Nista ◽

Giuliana Corica ◽

Lara Castelletti ◽

Keyvan Khorrami ◽

Claudia Campana ◽

...

Keyword(s):

Logistic Regression ◽

Somatostatin Receptor ◽

Biochemical Response ◽

Line Treatment ◽

Receptor Ligands ◽

First Line ◽

Multivariable Logistic Regression ◽

Somatostatin Receptor Ligands ◽

Younger Age ◽

First Line Treatment

BackgroundFirst-generation somatostatin receptor ligands (fg-SRLs) represent the first-line medical treatment for acromegaly, recommended in patients with persistent disease after neurosurgery, or when surgical approach is not feasible. Despite the lack of strong recommendations from guidelines and consensus statements, data from national Registries report an increasing use of medical therapy as first-line treatment in acromegaly.ObjectiveWe retrospectively evaluated the potential role of a large number of clinical and radiological parameters in predicting the biochemical response to 6-month treatment with fg-SRLs, in a cohort of naïve acromegaly patients referred to a single tertiary center for pituitary diseases.MethodsUnivariable and multivariable logistic regression and linear regression analyses were performed. Biochemical response was defined based on IGF-1 levels, represented as both categorical (tight control, control, >50% reduction) and continuous (linear % reduction) variables.ResultsFifty-one patients (33 females, median age 57 years) were included in the study. At univariable logistic regression analysis, we found that younger age (≤ 40 years; OR 0.04, p=0.045) and higher BMI (OR 0.866, p=0.034) were associated with a lower chance of achieving >50% IGF-1 reduction. On the contrary, higher IGF-1 xULN values at diagnosis (OR 2.304, p=0.007) and a T2-hypointense tumor (OR 18, p=0.017) were associated with a significantly higher likelihood of achieving >50% IGF-1 reduction after SRL therapy. Of note, dichotomized age, IGF1 xULN at diagnosis, and T2-hypointense signal of the tumor were retained as significant predictors by our multivariable logistic regression model. Furthermore, investigating the presence of predictors to the linear % IGF-1 reduction, we found a negative association with younger age (≤ 40 years; β -0.533, p<0.0001), while a positive association was observed with both IGF-1 xULN levels at diagnosis (β 0.330, p=0.018) and the presence of a T2-hypointense pituitary tumor (β 0.466, p=0.019). All these variables were still significant predictors at multivariable analysis.ConclusionsDichotomized age, IGF-1 levels at diagnosis, and tumor T2-weighted signal are reliable predictors of both >50% IGF-1 reduction and linear % IGF-1 reduction after 6 month fg-SRL treatment in naïve acromegaly patients. These parameters should be considered in the light of an individualized treatment for acromegaly patients.

Download Full-text

Biliary adverse events in acromegaly during somatostatin receptor ligands: predictors of onset and response to ursodeoxycholic acid treatment

Pituitary ◽

10.1007/s11102-020-01102-7 ◽

2020 ◽

Author(s):

N. Prencipe ◽

C. Bona ◽

D. Cuboni ◽

M. Parasiliti-Caprino ◽

A. M. Berton ◽

...

Keyword(s):

Adverse Events ◽

Ursodeoxycholic Acid ◽

Somatostatin Receptor ◽

Stone Disease ◽

Receptor Ligands ◽

First Line ◽

Metabolic Markers ◽

Somatostatin Receptor Ligands ◽

Igf I

Abstract Purpose Somatostatin receptor ligands (SRL) are the first-line medical treatment for acromegaly. Gallbladder alterations are one of most important SRL side effect, but according to some authors growth hormone hypersecretion itself is a risk factor for gallstones. This single center, longitudinal retrospective study evaluated the incidence and the predictors of biliary adverse events (BAE) in acromegaly during SRL therapy and their response to ursodeoxycholic acid (UDCA). Methods 91 acromegaly patients with indication to SRL were enrolled. Evaluations of acromegaly activity (GH, IGF-I, IGF-I/ULN) and metabolic profile were collected before starting treatment, yearly during follow-up and at BAE onset. In patients developing BAE we searched for predictors of UDCA effectiveness. Results 61.5% of patients developed BAE (58.9% cholelithiasis; 41.1% only sludge). IGF-I and IGF-I/ULN proved to be positive predictor of BAE, which occur about 5 years after SRL starting. None of metabolic markers proved to be associated with BAE. Only five patients (5.5%) underwent cholecystectomy for symptomatic cholelithiasis. 71% of patients started UDCA treatment, achieving regression of BAE in 60% of cases (88% in patients developing only sludge and 30% in patients affected by cholelithiasis, p < 0.001). BMI and obesity were negative predictors of UDCA efficacy. In 50% of the subjects BAE resolved after 36 months of therapy with a lower rate if cholelithiasis was present. Conclusion Biliary stone disease is a frequent SRL adverse event, although it is often symptomless. Ultrasound follow-up mainly in the first 5 years of therapy, early UDCA starting and proper lifestyle represent a valid strategy in their detection and management.

Download Full-text

Medical Therapy of Acromegaly

International Journal of Endocrinology ◽

10.1155/2012/268957 ◽

2012 ◽

Vol 2012 ◽

pp. 1-22 ◽

Cited By ~ 15

Author(s):

U. Plöckinger

Keyword(s):

Medical Therapy ◽

Mechanism Of Action ◽

Present Status ◽

Therapeutic Efficacy ◽

Dopamine Agonists ◽

Somatostatin Receptor ◽

Postoperative Treatment ◽

Receptor Ligands ◽

Somatostatin Receptor Ligands ◽

Remission Criteria

This paper outlines the present status of medical therapy of acromegaly. Indications for permanent postoperative treatment, postirradiation treamtent to bridge the interval until remission as well as primary medical therapy are elaborated. Therapeutic efficacy of the different available drugs—somatostatin receptor ligands (SRLs), dopamine agonists, and the GH antagonist Pegvisomant—is discussed, as are the indications for and efficacy of their respective combinations. Information on their mechanism of action, and some pharmakokinetic data are included. Special emphasis is given to the difficulties to define remission criteria of acromegaly due to technical assay problems. An algorithm for medical therapy in acromegaly is provided.

Download Full-text

MON-320 Inter-Rater Reliability of T2 MRI Intensity of Somatotroph Adenomas; Endocrinologists vs. Neuroradiologist Pilot Study

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.970 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Elena V Varlamov ◽

José Miguel Hinojosa-Amaya ◽

Dawn Lim Shao Ting ◽

Maria Fleseriu ◽

Joao Prola

Keyword(s):

White Matter ◽

Pilot Study ◽

Medical Therapy ◽

Somatostatin Receptor ◽

Biochemical Response ◽

Receptor Ligands ◽

Rater Reliability ◽

Post Surgery ◽

Somatostatin Receptor Ligands ◽

T2 Mri

Abstract Background MRI T2 hypointensity of growth hormone (GH) secreting pituitary adenomas (PA) has been associated with better biochemical response to somatostatin receptor ligands and has been suggested to be useful in selecting patients with expected favorable response for pre- and post-surgery medical therapy. However, in most imaging centers, T2 intensity measurement is not part of standard neuroradiologist (NR) reporting. Objective To assess whether endocrinologists (Es) can reliably measure PA T2 signal intensity by calculating inter-rater reliability between Es and NR. Methods Retrospective review of MRI in 20 patients with pituitary somatotroph macroadenoma randomly selected from an IRB-approved PA database who had preoperative MRI available. T2 MRI intensity of the solid portion of the PA was compared to the temporal gray matter (GM) and white matter (WM): hypo- (PA< WM), hyper- (PA> GM), and isointense (WM <PA <GM). Measurements were performed separately by a NR and by two Es trained to take measurements by the same NR. Statistics: SPSS 25; Cohen kappa (κ). Results Patient mean age was 47 ± 20 years, with 12 females; mean largest PA diameter was 22.6 mm (range 11-45 mm). NR measured 12 hyper-, 7 iso- and 1 hypo-intense PA. Agreement was moderate between NR and E#1 (κ 0.72, 95%CI 0.751-1.0, p<0.001) and NR and E#2 (κ 0.638, 95%CI 0.351-0976, p<0.001) and strong between E#1 and E#2 (κ=0.90, 95%CI 0.309-0.903, p=0.001). Hypointense PA (by NR) was read by both Es as isointense. One hyperintense PA (by NR) was read by both Es as isointense. One isointense PA was read by E#2 as hypointense. Overall adenomas were; 9 densely granulated GH, 5 sparsely granulated GH, 3 mixed GH and prolactin, 1 plurihormonal, 1 not classified, and 1 no surgical intervention. Discussion Inter-rater reliability between the 2 Es was strong, however, it was moderate between each E and the NR. Factors that likely contributed to difference in measurement are heterogeneity of the PA, MRI quality, selection bias in choosing “most appropriate” site to measure intensity of adenoma, gray and white matter. Es could be trained to interpret the T2 intensity, although reliability with NR is only moderate. Interestingly, in this sample majority of T2 PA were hyperintense, but densely granulated, suggesting that preoperative identification of densely granulated tumors, which are also predictive of favorable SRL response, might be limited. More studies are needed to assess T2 correlation with pathology. Conclusion As T2 intensity (hyper-, hypo- or iso-) on MRI might be predictive of biochemical response to medical therapy in some patients with PA, we recommend T2 intensity to be part of neuroradiology reporting protocol. Our pilot study showed that endocrinologists could read MRIs after adequate training, but there is only moderate correlation with neuroradiologists.

Download Full-text

Machine Learning-based Prediction Model for Treatment of Acromegaly With First-generation Somatostatin Receptor Ligands

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab125 ◽

2021 ◽

Author(s):

Luiz Eduardo Wildemberg ◽

Aline Helen da Silva Camacho ◽

Renan Lyra Miranda ◽

Paula C L Elias ◽

Nina R de Castro Musolino ◽

...

Keyword(s):

Machine Learning ◽

Support Vector Machine ◽

Prediction Model ◽

Predictive Value ◽

First Generation ◽

Somatostatin Receptor ◽

Support Vector ◽

Receptor Ligands ◽

Somatostatin Receptor Ligands ◽

Igf I

Abstract Context Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly. Objective To develop a prediction model of therapeutic response of acromegaly to fg-SRL. Methods Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included. Patients were considered controlled if they presented growth hormone (GH) <1.0 ng/mL and normal age-adjusted insulin-like growth factor (IGF)-I levels. Six AI models were evaluated: logistic regression, k-nearest neighbor classifier, support vector machine, gradient-boosted classifier, random forest, and multilayer perceptron. The features included in the analysis were age at diagnosis, sex, GH, and IGF-I levels at diagnosis and at pretreatment, somatostatin receptor subtype 2 and 5 (SST2 and SST5) protein expression and cytokeratin granulation pattern (GP). Results A total of 153 patients were analyzed. Controlled patients were older (P = .002), had lower GH at diagnosis (P = .01), had lower pretreatment GH and IGF-I (P < .001), and more frequently harbored tumors that were densely granulated (P = .014) or highly expressed SST2 (P < .001). The model that performed best was the support vector machine with the features SST2, SST5, GP, sex, age, and pretreatment GH and IGF-I levels. It had an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5%. Conclusion We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.

Download Full-text

Three Technologies That Will Guide Revascularization of Chronic Coronary Syndrome Patients into the 21st Century: A Review

International Journal of Angiology ◽

10.1055/s-0041-1735201 ◽

2021 ◽

Author(s):

Michael A. Winkler ◽

Ripa Patel ◽

Weibo Fu ◽

Vishal Arora ◽

Neal L. Weintraub

Keyword(s):

Computed Tomography ◽

Medical Therapy ◽

21St Century ◽

Cardiac Computed Tomography ◽

Line Treatment ◽

First Line ◽

Intracoronary Imaging ◽

Coronary Syndrome ◽

Diagnostic Technologies ◽

First Line Treatment

AbstractAlthough medical therapy is the preferred first-line treatment for patients with chronic coronary syndrome (CCS), revascularization remains an important consideration. We present a review that identifies the three diagnostic technologies most important to guiding the decision to revascularize patients with CCS: (1) cardiac computed tomography, (2) intracoronary imaging, and (3) lesion-specific physiological guidance.

Download Full-text

Somatostatin receptor ligands induce TSH deficiency in thyrotropin-secreting pituitary adenoma

Acta Endocrinologica ◽

10.1530/eje-20-0484 ◽

2021 ◽

Vol 184 (1) ◽

pp. 1-8

Author(s):

Frédéric Illouz ◽

Philippe Chanson ◽

Emmanuel Sonnet ◽

Thierry Brue ◽

Amandine Ferriere ◽

...

Keyword(s):

Pituitary Adenoma ◽

Somatostatin Receptor ◽

Receptor Ligands ◽

First Line ◽

First Line Therapy ◽

Line Therapy ◽

Somatostatin Receptor Ligands ◽

Central Hyperthyroidism ◽

Long Acting ◽

Tsh Deficiency

Objective Somatostatin receptor ligands (SRL) are useful to control central hyperthyroidism in patients with thyrotropin-secreting pituitary adenoma (TSH pituitary adenoma). The aim of this study was to describe the frequency of thyrotropin deficiency (TSH deficiency) in patients with TSH pituitary adenoma treated by SRL. Design Retrospective study. Methods Patients with central hyperthyroidism due to TSH pituitary adenoma treated by short or long-acting SRL were retrospectively included. TSH deficiency was defined by a low FT4 associated with non-elevated TSH concentrations during SRL therapy. We analysed the frequency of TSH deficiency and the characteristics of patients with or without TSH deficiency. Results Forty-six patients were included. SRL were used as the first-line therapy in 21 of 46 patients (46%). Central hyperthyroidism was controlled in 36 of 46 patients (78%). TSH deficiency appeared in 7 of 46 patients (15%) after a median time of 4 weeks (4–7) and for a median duration of 3 months (2.5–3). The TSH deficiency occurred after one to three injections of long-acting SRL used as first-line therapy in 6/7 cases. There were no differences in terms of clinical and hormonal features, size of adenomas or doses of SRL between patients with or without TSH deficiency. Conclusions SRL can induce TSH deficiency in patients with central hyperthyroidism due to TSH pituitary adenoma. Thyrotropic function should be assessed before the first three injections of SRL in order to track TSH deficiency and reduce the frequency of injections when control of thyrotoxicosis rather than tumour reduction is the aim of the treatment.

Download Full-text

A Phase 3 Large International Noninferiority Trial (MPOWERED): Assessing Maintenance of Response to Oral Octreotide Capsules in Comparison to Injectable Somatostatin Receptor Ligands

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1056 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A517-A517

Author(s):

Maria Fleseriu ◽

Alexander V Dreval ◽

Yulia Pokramovich ◽

Irina Bondar ◽

Elena Isaeva ◽

...

Keyword(s):

Somatostatin Receptor ◽

Safety Data ◽

Biochemical Response ◽

Receptor Ligands ◽

Phase 3 ◽

Landmark Analysis ◽

End Point ◽

Noninferiority Trial ◽

Somatostatin Receptor Ligands ◽

Igf I

Abstract Background: MPOWERED, a large phase 3 trial, assessed maintenance of response to oral octreotide capsules (OOC; MYCAPSSA®) compared to injectable somatostatin receptor ligands (iSRLs) in patients with acromegaly who responded to OOC and iSRLs (octreotide or lanreotide). OOC were recently approved in the US for patients with acromegaly who responded to and tolerated iSRLs. Methods: Eligibility criteria included age 18-75 years at screening, acromegaly diagnosis, disease evidence, biochemical control (insulin-like growth factor I [IGF-I] <1.3 × upper limit of normal [ULN] and mean integrated growth hormone [GH] <2.5 ng/mL) at screening, and ≥6 months’ iSRL treatment. Effective OOC dose was determined in a 26-week Run-in phase. Eligible patients (IGF-I <1.3 × ULN and mean integrated GH <2.5 ng/mL, week 24) were randomized to a 36-week controlled treatment phase (RCT), receiving OOC or iSRLs starting at week 26. The primary end point was a noninferiority assessment of proportion of patients biochemically controlled in the RCT (IGF-I <1.3 × ULN using time-weighted average). Other end points included nonresponse imputation of the primary end point, landmark analysis using proportion of responders based on average of last 2 IGF-I values at end of RCT, and change from baseline RCT (week 26) IGF-I and GH levels. Results: Of 146 enrolled patients, 92 entered the RCT (OOC, n=55; iSRLs, n=37). Both arms were well balanced for age, sex, and acromegaly duration. OOC demonstrated noninferiority to iSRLs in maintaining biochemical response, with 91% (CI, 80%-97%) of OOC and 100% (CI, 91%-100%) of iSRL groups maintaining control during the RCT. Of those responding at end of Run-in, 96% of patients on OOC maintained response during RCT. Using nonresponse imputation, 89% of OOC and 95% of iSRL groups were biochemically controlled in RCT. Landmark analysis of those respnding at end of Run-in showed that 94% of patients in each group maintained response at RCT end. In both groups, IGF-I levels were stable in the RCT, average IGF-I at baseline and RCT end being 0.9 × ULN (OOC) and 0.8 × ULN (iSRL). Mean change in GH from RCT start to RCT end was -0.03 ng/mL (OOC) and +0.29 ng/mL (iSRL). Safety data were mostly similar between groups; the OOC group did not experience injection site reactions. Conclusion: In this noninferiority trial in patients with acromegaly, OOC demonstrated maintenance of biochemical response compared to iSRLs. Results support the efficacy of OOC as a possible iSRL alternative.

Download Full-text

Pasireotide in the Personalized Treatment of Acromegaly

Frontiers in Endocrinology ◽

10.3389/fendo.2021.648411 ◽

2021 ◽

Vol 12 ◽

Author(s):

Manel Puig-Domingo ◽

Ignacio Bernabéu ◽

Antonio Picó ◽

Betina Biagetti ◽

Joan Gil ◽

...

Keyword(s):

First Generation ◽

Somatostatin Receptor ◽

Receptor Ligands ◽

First Line ◽

First Line Therapy ◽

Somatostatin Receptor Ligands ◽

Therapeutic Algorithm ◽

Surgical Failure ◽

Positive Effect ◽

T2 Mri

The delay in controlling the disease in patients who do not respond to first-line treatment with first generation somatostatin receptor ligands (first-generation SRLs) can be quantified in years, as every modification in the medical therapy requires some months to be fully evaluated. Considering this, acromegaly treatment should benefit from personalized medicine therapeutic approach by using biomarkers identifying drug response. Pasireotide has been positioned mostly as a compound to be used in first-generation SRLs resistant patients and after surgical failure, but sufficient data are now available to indicate it is a first line therapy for patients with certain characteristics. Pasireotide has been proved to be useful in patients in which hyperintensity T2 MRI signal is shown and in those depicting low SST2 and high expression of SST5, low or mutated AIP condition and sparsely granulated immunohistochemical pattern. This combination of clinical and pathological characteristics is unique for certain patients and seems to cluster in the same cases, strongly suggesting an etiopathogenic link. Thus, in this paper we propose to include this clinico-pathologic phenotype in the therapeutic algorithm, which would allow us to use as first line medical treatment those compounds with the highest potential for achieving the fastest control of GH hypersecretion as well as a positive effect upon tumor shrinkage, therefore accelerating the implementation of precision medicine for acromegaly. Moreover, we suggest the development, validation and clinical use of a pasireotide acute test, able to identify patients responsive to pasireotide LAR as the acute octreotide test is able to do for SRLs.

Download Full-text

MON-LB55 Biochemical Control of Most Patients Reverting to Injectable Long-Acting Somatostatin Receptor Ligands Is Achieved After One Dose: Results From the Phase 3, Randomized, Double Blind, Placebo-Controlled Optimal Study

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2123 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Maria Fleseriu ◽

Susan Leanne Samson ◽

Lisa B Nachtigall ◽

Artak Labadzhyan ◽

Atanaska Elenkova ◽

...

Keyword(s):

Rescue Therapy ◽

Somatostatin Receptor ◽

Clinical Signs ◽

Placebo Treatment ◽

Receptor Ligands ◽

Biochemical Control ◽

Double Blind ◽

Double Blind Placebo ◽

Somatostatin Receptor Ligands ◽

Igf I

Abstract Background: Injectable somatostatin receptor ligands (SRLs) are currently the most widely used medical therapy for acromegaly worldwide. Oral octreotide capsules (OOC) have been formulated as a potential therapy for this disorder and the safety and efficacy were evaluated in the CHIASMA OPTIMAL pivotal study (Samson et al. ENDO 2020). As reported, mean IGF-I levels of the OOC treatment group were maintained within normal range at the end of treatment in all patients. However, some patients may not respond to OOC treatment (25% of OOC group and 68% of placebo groups required rescue, P=0.003). This analysis describes the degree and rapidity with which patients achieve biochemical control (IGF-I ≤1.0 x ULN) when reverted to their prior injectable SRL treatment. Methods: Patients with confirmed acromegaly and receiving a stable dose of injectable SRL (≥3 months) were randomized to OOC (40mg/day; N=28) or placebo (N=28) for 36 weeks. Patients were dose titrated to 60 or 80mg of OOC (or placebo) through week 24 at investigator discretion based on increased IGF-I levels and/or worsening acromegaly signs/symptoms. Patients could be rescued via reversion to prior injectable SRL therapy if they met the predefined withdrawal criteria (i.e., IGF-I ≥1.3 x upper limit of normal [ULN] for 2 consecutive visits on the highest dose, and exacerbation of clinical signs/symptoms) or discontinued treatment early for any other reason. In the study, 7 patients in the OOC group and 19 in the placebo group required rescue. The change in IGF-I from Baseline was compared to the end of the Double-blind Placebo Controlled period. Results: In patients rescued up to week 32 and in whom there were at least 4 weeks of follow up, baseline IGF-I levels (mean of Screening Visit 2 and Baseline) were 0.80 and 0.87 x ULN in the OOC and placebo groups, respectively. In patients receiving rescue therapy, the end of study IGF-I levels (mean of week 34 and 36) were 0.80 and 0.89 x ULN in the OOC and placebo groups, respectively, virtually unchanged. The median time to return to normal baseline IGF-I values following loss of response was 4.0 weeks after discontinuing OOC and 4.0 weeks after discontinuing placebo treatment. Therefore, most patients who required rescue following a short trial of therapy with OOC returned to their baseline values following a single SRL injection. Conclusion: Most treatment failures in the CHIASMA OPTIMAL trial (on either OOC or placebo) rescued with injectable SRL re-established their baseline response levels after a single injectable SRL administration (at pre-study dose). Based on this data, patients may potentially be treated with OOC and for those not responding, either not biochemically controlled or who have adverse effects, they may be able to return to injectable SRLs with immediate IGF-I control after one SRL injection.

Download Full-text