The following recommendations consider monitoring of Fabry-related symptoms and organ involvement in patients with Fabry disease. Recommendations regarding α-Gal A and lyso-Gb3 monitoring should also be considered.
All patients with Fabry disease should have a mental health assessment at BL and every 12 months thereafter conducted by an HCP, using a validated screening tool (statements 3B and 3C; strong consensus [1.5 and 1.2, respectively]). After the evaluation, as part of routine care, patients should be referred to an appropriate HCP, who can provide guidance/treatment for any identified issues (e.g., genetic counselor, licensed therapist, social worker, psychologist) (statement 3E; moderate consensus [0.9]). All patients with Fabry disease should be evaluated for pain and GI symptoms at BL prior to treatment initiation (statement 3A; strong consensus [1.6]). All patients with Fabry disease should have evaluations with PROs (e.g., EQ-5D, SF-36) every 6–12 months, depending on disease severity, patient needs, and the usual frequency of specialist appointments (statement 3D; strong consensus [1.2]). All patients with Fabry disease should have an evaluation of renal function, cardiac function (statement 4B; strong consensus [1.4]), and Fabry-related symptoms (statement 4A; strong consensus [1.5]) at BL and every 6–12 months thereafter, and neurological function at BL and every ≤3 years thereafter (statement 4D; strong consensus [1.2]). Frequency of follow-up evaluations should be decided based on disease severity, clinical presentation, and patient needs (statements 4B and 4A). For any patient presenting with severe or rapidly declining symptoms and/or organ involvement from BL on two consecutive readings at least 6 months apart, more frequent follow-up evaluations (approximately every 3 months) should be considered (statement 4C; strong consensus [1.4]). A one-time follow-up evaluation 3 months post-initiation or treatment switch should be considered before deciding on the frequency of subsequent follow-up evaluations (statement 4E; moderate consensus [0.8]).
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Patients should be given an overview of all suitable available therapies (statement 5A; strong consensus [1.8]). Patients should be encouraged to be involved in treatment decisions, and their choice taken into consideration for any decision to start, change, or stop treatment (statements 5B and 5C; strong consensus [1.8 and 1.6, respectively]). There should be a single set of guidelines to follow for treatment initiation (statement 6M; moderate consensus
[0.8]) and cessation (statement 6J; strong consensus [1.3]) of both migalastat and ERT, capturing the similarities and differences between criteria for these treatments (e.g., approved indication and the requirement for amenability to migalastat).
Treatment initiation (in eligible patients according to licensed indications):
Family history (e.g., history of organ involvement, symptoms or clinical events that could be related to Fabry disease, and/or history of Fabry disease diagnosis) should be considered when deciding whether to initiate treatment, but is not the only factor for this decision (statement 6K; strong consensus [1.3]). All patients with Fabry disease (male, female, classic, late-onset) and an amenable mutation may be started on migalastat if they have evidence of Fabry-related symptoms and/or organ involvement (statements 6A, 6B, 6D, 6E, 6F, and 6H; strong consensus [range 1.4–1.6]). Male patients with Fabry disease and a classic, amenable mutation may be started on migalastat, even in the absence of organ involvement (statement 6L; strong consensus [1.3]). Female patients with Fabry disease and a classic, amenable mutation may be started on migalastat if they have ≥1 Fabry-related symptom (statement 6I; strong consensus [1.4]). Female patients with Fabry disease and a classic, amenable mutation should begin treatment (with either ERT or migalastat) if they have evidence of organ involvement (statement 6C; strong consensus [1.6]). Male and female patients with late-onset, amenable mutations should begin treatment (with either ERT or migalastat) if they have evidence of organ involvement (statement 6G; strong consensus [1.5]).
Treatment switch/stop
When considering whether to switch or stop treatment in patients with Fabry disease, treatment adherence, PROs, and patient choice should be considered (statement 7A; strong consensus [1.5]). Migalastat treatment should be continued in patients with stable or improving Fabry-related symptoms, even if they show no improvement in organ function from BL (statement 7B; strong consensus [1.2]). On two consecutive assessments ≥6 months apart: Relative deterioration of renal, neurological, or cardiac organ function (or architecture) compared with BL disease progression is an indication to consider switching treatment (ERT or migalastat) (statement 7C; moderate consensus [1.0]) Relative deterioration of symptoms alone compared with BL disease progression is not an indication to consider switching or stopping treatment (ERT or migalastat); organ involvement, PROs, and patient choice should also be considered (statement 7D; moderate consensus [0.9]) Patients with stabilization or improvement compared with BL disease progression in ≥1 organ should consider remaining on treatment (ERT or migalastat), even if function of another organ deteriorates (statement 7E; moderate consensus [0.9]).
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