Risdiplam in non‐sitter patients aged 16 years and older with 5q spinal muscular atrophy

Abstract

Introduction/Aims Risdiplam has been approved for the treatment of patients with 5q spinal muscular atrophy (SMA), but data from type 2 non‐sitter patients are lacking. In this study we describe our experience regarding the use of risdiplam in a series of type 2 non‐sitter patients. Methods Type 2 SMA patients over 16 years of age were administered risdiplam through the expanded access program (NCT04256265). Patients were followed‐up with a battery of scales and clinical measures. Results Six non‐sitter patients (17 to 46 years old) were treated with risdiplam. One patient reported mild adverse events (dyspepsia and headache). After 1 year of treatment, all patients showed clinically meaningful improvements in at least one scale and none of them showed any clinically meaningful deterioration. Two patients showed a clinically meaningful increase in body mass index (>5%) and two others scored higher on the Revised Upper Limb Module (>2 points). Moreover, five patients had clinically meaningful improvements on the Egen Klassifikation 2 scale (>2 points), including the motor (axial and upper limbs), bulbar (speech and swallowing), and respiratory (coughing) domains. Four subjects achieved at least one of the goals set with the Goal Attainment Scale (GAS). Discussion This series suggests that risdiplam is safe and may be effective in non‐sitter SMA patients older than 16 years of age. In these patients, functional scales and the GAS would be more sensitive than motor scales to detect changes, because they include axial, bulbar, and respiratory domains. Larger studies are needed to confirm these results.

Motor function and treatment satisfaction in adult patients with 5q-spinal muscular atrophy treated with risdiplam: real-world experience from a single neuromuscular center in Germany

“…Contrary to that, Ñungo Garzón et al reported no clinically meaningful deteriorations in RULM (worsening of RULM score ≥ 2 vs. baseline) during their 12 months follow-up period of six SMA type 2 patients [17]. A possible explanation for this might be a oor effect in their study as half of the patients scored 0 for their baseline RULM assessment [17]. McCluskey et al reported clinically meaningful improvement in RULM scores in two patients and stabilization in the other three (n = 6, one patient lost to follow-up) [16].…”

“…In the study of Ñungo Garzón et al, two patients had previously been treated with nusinersen. Out of them, one patient remained stable, while the other one showed clinically meaningful improvement (improvement of RULM score ≥ 2 vs. baseline) after 12 months of treatment [17].…”

“…To date, there are two previous reports on motor function during risdiplam therapy in adult SMA patients in a real-world setting, each comprising six patients with SMA type 2 [16,17]. McCluskey et al [16] showed no change in the Revised Upper Limb Module (RULM) score after 6 months of treatment, while Ñungo Garzón et al [17] observed improvements in RULM in two out of six non-sitter patients > 16 years of age after 12 months. Larger multicentric and longitudinal data regarding safety, tolerability, and e cacy of risdiplam in adults with SMA are lacking.…”

Evaluation of risdiplam efficacy in 5q spinal muscular atrophy: A systematic comparison of electrophysiologic with clinical outcome measures

“…Furthermore, clinical characteristics are hererogeneously distributed and show a preponderance of severely diseased non‐sitters and sitters, restricting the applicability of our findings to this patient population. However, the patients studied here resemble the previously reported risdiplam‐treated patient cohorts [9, 23, 24]. The cohort assessing the course of disease prior to pharmacotherapy is imbalanced to some degree regarding symptom duration and a tendency towards less severely affected patients, possibly biasing comparative analyses.…”

Efficacy of risdiplam in spinal muscular atrophy: A systematic review and meta‐analysis

“…Another aspect to highlight was the improvement in patient‐reported outcome measures in SMA which include physical function, mental health and cognition, fatigue, communication and speech, pain, and systemic issues 45 . Although not included as an outcome in our review due to the large number of variables, the observations of some of the included studies should be highlighted 32,35 . These studies in adults showed improvements in some participants' fatigue, cognition, overall strength, manual dexterity and strength, speech, well‐being, and quality of life.…”