Gaucher disease is a heterogeneous disorder that requires patient-centric management; however, with the availability of effective therapies, patients can demonstrate improvements in many of the long-term symptoms of the disease.1
Recommendations for the management of patients with Gaucher disease Type 1 and Gaucher disease Types 2 and 3, and for patients with Gaucher disease during pregnancy, are available.2-9 Moreover, support and counselling can be provided to patients with Gaucher disease.10
In terms of treatment, three intravenous enzyme replacement therapies are available for patients with Gaucher disease: imiglucerease, velaglucerase alfa and taliglucerase alfa.11-13 Additionally, two oral substrate reduction therapies, miglustat and eliglustat, are available.14,15 There are a variety of factors that could influence treatment decisions for patients with Gaucher disease. These include country-level directives, insurance or reimbursements issues, medical contraindications specific to the patient, patient preference, and physicians’ previous experience in managing Gaucher disease.16
The availability of these treatments differs between countries. For further information, please consult your local prescribing information.
Real-world treatment patterns of Gaucher disease: analysis from the Gaucher Outcome Survey (GOS)
The GOS is an ongoing, international registry (sponsored by Shire, now part of Takeda), established in 2010 for patients with Gaucher disease, irrespective of disease type or treatment status. As of October 2015, 34 treatment centres from 10 countries, specialising in Gaucher disease and other lysosomal storage diseases, had provided real-world data for 1003 patients with Gaucher disease. These data include information on Gaucher disease manifestations and treatment history. According to the 2015 report, the highest number of patients included in the GOS were from Israel (n=460), followed by the US (n=344) and the UK (n=108). The remaining patients were from Brazil (n=33), Paraguay (n=16), France (n=11), Russia (n=10), Italy (n=9), Spain (n=7) and Argentina (n=5). Information on specific treatments for Gaucher disease, received at any time, was available for 64.5% of patients (647/1003) in the GOS. Across countries, the majority of patients had received treatment for their Gaucher disease, particularly in the highest-enrolling countries: Israel (n=301), the US (n=207) and the UK (n=66).16
Within the analysis, 151 patients (47.0% male) were identified as having never been treated for their Gaucher disease (aged ≥18 years, n=130; aged <18 years, n=21). Almost all of these patients had Gaucher disease Type 1 (only one adult patient had Gaucher disease Type 3) and were of Ashkenazi Jewish ethnicity (aged ≥18 years, 93.8%; aged <18 years, 95.2%). For untreated patients with GBA1 data, most were homozygous for the N370S (c.1226A>G; p.Asp409Ser) mutation (aged ≥18 years, 76.6%; aged <18 years, 76.9%).16 These findings may correlate with late symptom onset and mild haematological and visceral disease generally observed in patients with Gaucher disease with the N370S/N370S genotype.16,17 Moreover, this is the most frequently observed genotype in patients of Ashkenazi Jewish ethnicity, which could explain the high number of untreated patients in Israel (140/460) compared with other countries, such as the US (6/344) or the UK (4/108).16,18
Of the 647 treated patients, the majority (87.9%) were aged ≥18 years (43.6% male), were of Ashkenazi Jewish ethnicity (65.0%), and had Gaucher disease Type 1 (98.8%). Seven of these adult patients had Gaucher disease Type 3 (1.2%; data missing for three patients). Of the 78 treated patients aged <18 years (56.4% male), most patients were of non-Ashkenazi Jewish ethnicity (74.4%) and had Gaucher disease Type 1 (80.5%); 14 had Gaucher disease Type 3 (18.2%; data missing for one patient). In both age groups, most patients had not been splenectomised (aged ≥18 years, 72.6%; aged <18 years, 98.7%). In those treated patients aged ≥18 years with GBA1 data, 39.2% were homozygous for the N370S (c.1226A>G; p.Asp409Ser) mutation (N370S/N370S), and 21.1% were heterozygous (N370S/OTHER). In this age group, 13.0% had the N370S/L444P (c.1448T>C; p.Leu483Pro) genotype. In patients aged <18 years with Gaucher disease, OTHER/OTHER was the most frequently noted genotype (34.4%), followed by N370S/OTHER (18.0%) and N370S/L444P (14.8%). GBA1 genotypes varied between the three highest-enrolling countries; the most common genotype among all treated patients in Israel was N370S/N370S, with a frequency of 58.4%, compared with 26.1% in the US and 5.9% in the UK.16
At the time of the analysis (30 October 2015), 573 patients were currently receiving treatments specific for Gaucher disease (Figure 1). The majority of these patients were administered velaglucerase alfa (55.1%) or imiglucerase (32.1%). Most patients had received velaglucerase alfa for ≤5 years (60.2%), whereas the duration of exposure to imiglucerase was more widespread (≤5 years, 27.3%; 5‒10 years, 22.4%; 10‒15 years, 22.8%; and 15‒20 years, 19.8%). Of the 647 patients who had received specific treatment for Gaucher disease at any time, 56.9% had only been administered one form of therapy. The remaining patients had changed therapies once or more; the most common switch was from imiglucerase to velaglucerase alfa (40.9%; n=114/279) (Figure 2).16
Variances in local prescribing practices and market authorisation of each therapy for Gaucher disease likely account for the differences in treatment administration between countries observed in this study. These findings also emphasise that management of Gaucher disease differs globally, and may be influenced by a range of factors, including treatment availability, treatment cost, local prescribing practices and disease severity.16
Gaucher disease-specific treatments received by patients included in the GOS at the time of data analysis (N=573). Reproduced with permission from Deegan P, et al. Blood Cells Mol Dis 2018; 68: 218-225.16
Treatment patterns of Gaucher disease in European- and US-based studies
The French Gaucher disease Registry was initiated in 2009, and includes all patients with Gaucher disease living in France and having ≥1 consultation since 1980, either hospitalisation or outpatient appointment with a Gaucher disease specialist. In 2011, 562 patients with Gaucher disease were enrolled in the French Gaucher disease Registry. After an initial evaluation, data were available for 378 patients who had ≥1 follow-up visit (median follow-up duration [range] of 16.2 [0.1‒67.6] years). The majority of followed patients had Gaucher disease Type 1 (92%), whereas 4% each had Type 2 or Type 3. Gaucher disease-specific treatment was administered in 298 (78.8%) patients. Most patients were treated with imiglucerase (75.2%), followed by alglucerase (20.8%), velaglucerase alfa (13.4%), miglustat (2.3%) and taliglucerase alfa (0.3%). The median time from diagnosis to first treatment (range) was 9.1 (0‒61.4) years; however, this was shorter for the 145 patients diagnosed after 1991 (1.4 [0‒16] years).19
Treatment outcomes were assessed in 93 patients (mean age [range], 62.1 [25‒91] years) with Gaucher disease Type 1 at the University Research Foundation for Lysosomal Storage Diseases South Florida, which enrolled patients into the International Collaborative Gaucher Group Registry (sponsored by Sanofi Genzyme) from 1991 to 2011. Initial and serial assessments indicated that 15 patients had a clinically mild phenotype and did not receive disease-specific treatment. At last evaluation, through June 2011, 49 patients were treated with imiglucerase, 10 patients received velaglucerase alfa and four patients were administered miglustat.20
Data from the Spanish Registry of Gaucher disease were used to assess access to enzyme replacement therapy in paediatric patients with Gaucher disease. Patients were divided into two subgroups depending on whether the diagnosis was made in or before 1994 (Cohort A) or after 1994 (Cohort B). Diagnosis of Gaucher disease in childhood, before patients were aged 18 years, was made in 124 of 386 patients enrolled in the registry. In total, 98 (79.1%) patients were suspected to have Gaucher disease Type 1 and 20.9% had Gaucher disease Type 2. Of the 98 patients with suspected Gaucher disease Type 1, 18 (14.5%) had a GBA1 genotype other than N370S, developed neurological symptoms and were reclassified as Gaucher disease Type 3. The median time of follow-up (range) was 8.8 (0.3‒17.5) years. During this time period, 12 (26.7%) patients from Cohort A and 42 (79.2%) patients from Cohort B initiated enzyme replacement therapy during childhood. For patients in Cohort A, the median time from diagnosis to treatment initiation (range) was 5.2 (0.1‒11.9) years and for Cohort B was 1.6 (0.1‒11.2) years. These data highlight that, after the introduction of imiglucerase in 1994, paediatric patients with Gaucher disease were more likely to receive enzyme replacement therapy earlier following diagnosis compared with patients diagnosed in or before 1994. These findings also highlight the increasing awareness of Gaucher disease and the enhanced efforts of physicians to diagnoses patients earlier once Gaucher disease-specific treatments became available.21
Non-specific medication and management of Gaucher disease
Prior to the introduction of treatments specific for Gaucher disease, symptomatic management of disease manifestations included splenectomy and orthopaedic surgery. Some patients may have also undergone allogeneic bone marrow transplantation.2
Alongside pharmacological treatments specific for Gaucher disease, complementary therapies such as physical therapy or orthopaedic measures to restore bone complications associated with the disease (e.g. fractures or destroyed hip joints) may still be used.7 Orthopaedic surgery may still be needed in some patients who have experienced avascular necrosis prior to the initiation of Gaucher disease-specific therapies.2 Treatment of chronic bone pain and bone pain crises may also require administration of analgesics. Oral bisphosphonates are indicated in adults in the event of vertebral compression and osteoporosis, in conjunction with treatment specific for Gaucher disease. In the cases of osteomyelitis and for intercurrent infections, curative antibiotic therapy may also be necessary for patients.6 Generally, common clinical practices to ensure optimal skeletal health should be followed, including appropriate calcium and vitamin D therapy according to local guidelines.22
In the event of multiple disabilities, adjustments to everyday life may be required for some patients. These adjustments may include: anti–pressure-sore mattress, aspiration equipment, bedside or portable peripheral or central venous infusion kit, central venous access device, crutches, corsets, day and/or night splints, home oxygen, manual or electric wheelchair, medicalised bed, moulded chair, nasogastric or gastrostomy tube, orthopaedic shoes, osteosynthesis of fractures, plaster casts, prosthesis or a walker. Patients may also require help from department houses for the disabled and specialised centres.6
Clinicians should encourage self-management education to help patients understand Gaucher disease, their treatment options, how to cope with symptoms, manage medications and communicate with clinicians. Patients with Gaucher disease should also be made aware of the specific warning signs of their disease that require medical attention, and be encouraged to seek medical help if there is any change or worsening in their symptoms.6
C-ANPROM/INT//7568; Date of preparation: September 2020
- Mistry PK, Weinthal JA, Weinreb NJ. Disease state awareness in Gaucher disease: a Q&A expert roundtable discussion. Clin Adv Hematol Oncol 2012; 10(6 Suppl 8): 1-16.
- Revel-Vilk S, Szer J, Mehta A, et al. How we manage Gaucher disease in the era of choices. Br J Haematol 2018; 182: 467-480.
- Biegstraaten M, Cox TM, Belmatoug N, et al. Management goals for Type 1 Gaucher disease: an expert consensus document from the European Working Group on Gaucher disease. Blood Cells Mol Dis 2018; 68: 203-208.
- Weiss K, Gonzalez A, Lopez G, et al. The clinical management of Type 2 Gaucher disease. Mol Genet Metab 2015; 114: 110-122.
- Roshan Lal T, Sidransky E. The spectrum of neurological manifestations associated with Gaucher disease. Diseases (Basel, Switzerland) 2017; 5: 10.
- Haute Autorité de Santé. Gaucher disease: national diagnosis and treatment protocol. January 2007. Available at https://www.has-sante.fr/upload/docs/application/pdf/ven_gaucher_web.pdf. Accessed September 2020.
- German Society for Child and Youth Medicine Working Group on Pediatric Metabolic Disorders. Gaucher's disease guidelines. March 2006. Available at https://www.ggd-ev.de/wp-content/uploads/mgaucher-22-12-2007.pdf. Accessed September 2020.
- The Belgian Working Group on Gaucher disease. Guidelines for diagnosis, treatment and monitoring of Gaucher's disease. May 2016. Available at https://cema.uza.be/static/documenten/informatie_metabole_ziekten/Belgian%20Expert%20Opinion%20for%20Diagnosis,%20Treatment%20an%20Monitoring%20of%20Gaucher.pdf. Accessed September 2020.
- Granovsky-Grisaru S, Belmatoug N, vom Dahl S, et al. The management of pregnancy in Gaucher disease. Eur J Obstet Gynecol Reprod Biol 2011; 156: 3-8.
- Futerman AH, Zimran A. Gaucher disease. Boca Raton, FL; Taylor & Francis, 2007.
- Sanofi Genzyme. Cerezyme® EU Summary of Product Characteristics. Last updated March 2020.
- Shire Pharmaceuticals Ltd. VPRIV® EU Summary of Product Characteristics. Last updated August 2020.
- Pfizer Canada Inc. ELELYSO® Product Monograph. Last updated August 2017.
- Accord-Healthcare Ltd. Zavesca® EU Summary of Product Characteristics. Last updated July 2019.
- Sanofi Genzyme. Cerdelga® EU Summary of Product Characteristics. Last updated January 2020.
- Deegan P, Fernandez-Sasso D, Giraldo P, et al. Treatment patterns from 647 patients with Gaucher disease: an analysis from the Gaucher Outcome Survey. Blood Cells Mol Dis 2018; 68: 218-225.
- Taddei TH, Kacena KA, Yang M, et al. The underrecognized progressive nature of N370S Gaucher disease and assessment of cancer risk in 403 patients. Am J Hematol 2009; 84: 208-214.
- Zimran A, Gelbart T, Westwood B, et al. High frequency of the Gaucher disease mutation at nucleotide 1226 among Ashkenazi Jews. Am J Hum Genet 1991; 49: 855-859.
- Stirnemann J, Vigan M, Hamroun D, et al. The French Gaucher's disease registry: clinical characteristics, complications and treatment of 562 patients. Orphanet J Rare Dis 2012; 7: 77.
- Orenstein M, Barbouth D, Bodamer OA, et al. Patients with type 1 Gaucher disease in South Florida, USA: demographics, genotypes, disease severity and treatment outcomes. Orphanet J Rare Dis 2014; 9: 45.
- Andrade-Campos M, Alfonso P, Irun P, et al. Diagnosis features of pediatric Gaucher disease patients in the era of enzymatic therapy, a national-base study from the Spanish Registry of Gaucher Disease. Orphanet J Rare Dis 2017; 12: 84.
- Hughes D, Mikosch P, Belmatoug N, et al. Gaucher disease in bone: from pathophysiology to practice. J Bone Miner Res 2019; 34: 996-1013.