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 (R)) 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 (R) treatment. Methods: Fifty SHOXD patients (25 females), aged 2-17 and still in the growth phase, previously treated with Humatrope (R), 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.