https://www.farm.ucl.ac.be/FARM2129/2008-2009/Tulkens/anemie-neutropenie/Veronese-Pegylation-Drug-Discovery-Today-2005-10-1451-1458.pdf

PEGylation, successful approach to drug delivery.

Once a rarely used subset of medical treatments, protein therapeutics have increased dramatically in number and frequency of use since the introduction of the first recombinant protein therapeutic--human insulin--25 years ago. Protein therapeutics already have a significant role in almost every field of medicine, but this role is still only in its infancy. This article overviews some of the key characteristics of protein therapeutics, summarizes the more than 130 protein therapeutics used currently and suggests a new classification of these proteins according to their pharmacological action.

Protein therapeutics: a summary and pharmacological classification

Objective: The aim was to formulate clinical practice guidelines for acromegaly. Participants: The Task Force included a chair selected by the Endocrine Society Clinical Guidelines Subcommittee (CGS), five experts in the field, and a methodologist. The authors received no corporate funding or remuneration. This guideline is cosponsored by the European Society of Endocrinology. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. The Task Force reviewed primary evidence and commissioned two additional systematic reviews. Consensus Process: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society and the European Society of Endocrinology reviewed drafts of the guidelines. Conclusions: Using an evidence-based approach, this acromegaly guideline addresses impor...

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Acromegaly: An Endocrine Society Clinical Practice Guideline

This review focuses on the systemic complications of acromegaly. Mortality in this disease is increased mostly because of cardiovascular and respiratory diseases, although currently neoplastic complications have been questioned as a relevant cause of increased risk of death. Biventricular hypertrophy, occurring independently of hypertension and metabolic complications, is the most frequent cardiac complication. Diastolic and systolic dysfunction develops along with disease duration; and other cardiac disorders, such as arrhythmias, valve disease, hypertension, atherosclerosis, and endothelial dysfunction, are also common in acromegaly. Control of acromegaly by surgery or pharmacotherapy, especially somatostatin analogs, improves cardiovascular morbidity. Respiratory disorders, sleep apnea, and ventilatory dysfunction are also important contributors in increasing mortality and are advantageously benefitted by controlling GH and IGF-I hypersecretion. An increased risk of colonic polyps, which more frequently recur in patients not controlled after treatment, has been reported by several independent investigations, although malignancies in other organs have also been described, but less convincingly than at the gastrointestinal level. Finally, the most important cause of morbidity and functional disability of the disease is arthropathy, which can be reversed at an initial stage, but not if the disease is left untreated for several years.

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Systemic complications of acromegaly: epidemiology, pathogenesis, and management.

https://digital.csic.es/bitstream/10261/134282/5/ADVANCED%20TARGETED.pdf

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.

Background Patients with acromegaly are treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone–receptor antagonist that blocks the action of growth hormone. Methods We conducted a 12-week, randomized, double-blind study of three different daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly. Results The mean (±SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0±16.8 percent in the placebo group, 26.7± 27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1±26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5±21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score for total symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P«0.05). The incidence of adverse effects was similar in all groups. Conclusions On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone–receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement. (N Engl J Med 2000;342:1171-7.)

https://www.nejm.org/doi/pdf/10.1056/NEJM200004203421604

Hackett S

Papers

Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.