One-Year Italian Experience with Off-Label rhGH Treatment in SHOX-Deficient Children to Overcome the Shortage of Authorized rhGH Somatropin

Background/Objectives: The global landscape of growth hormone (GH) therapy is increasingly affected by supply shortages, posing risks to treatment continuity, particularly in rare diseases with a single authorized GH brand. In Italy, a prolonged shortage of the only approved recombinant human GH (rhGH) for SHOX-deficient (SHOXD) patients (Somatropin, Humatrope®) raised concerns about treatment interruption. As growth impairment is a key clinical feature of SHOXD, uninterrupted rhGH therapy is essential. To address this issue, the Italian Medicines Agency (AIFA) temporarily authorized the off-label use of alternative rhGH formulations. This study aimed to evaluate growth outcomes and safety over one year of off-label rhGH treatment in SHOXD patients and to compare these data with prior Humatrope® treatment. Methods: Fifty SHOXD patients (25 females), aged 2–17 and still in the growth phase, previously treated with Humatrope®, were switched to an alternative rhGH therapy. Height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS) were recorded 12 and 6 months before and after the switch. Growth trends were analyzed using repeated-measures ANOVA. Results: No statistically significant differences in HSDS or HVSDS were observed after switching to alternative rhGH compared with prior treatment (p > 0.05). IGF-1 SDS values remained stable within age- and puberty-appropriate reference ranges. No adverse events were reported. Conclusions: In this real-world pediatric cohort, one year of off-label rhGH treatment during a drug shortage was not associated with relevant changes in growth parameters or safety concerns. These findings may support treatment continuity during temporary disruptions in rhGH availability.