From the Guidelines
For advanced scleroderma, treatment typically involves immunosuppressive medications such as mycophenolate mofetil (1-3g daily), cyclophosphamide (1-2mg/kg/day orally or monthly IV pulses), or rituximab (two 1000mg infusions two weeks apart), with autologous hematopoietic stem cell transplantation considered as a last-resort option for severe, rapidly progressive disease. The management of scleroderma is complex and depends on the specific symptoms and organ involvement. According to the most recent guidelines, including the EULAR recommendations for the treatment of systemic sclerosis: 2023 update 1, treatment decisions should be individualized based on disease subtype, organ involvement, and patient factors.
Treatment Options
- Immunosuppressive medications: mycophenolate mofetil, cyclophosphamide, or rituximab
- Autologous hematopoietic stem cell transplantation for severe, rapidly progressive disease
- Organ-specific therapies, such as nintedanib for SSc pulmonary fibrosis and phosphodiesterase 5 inhibitors for pulmonary arterial hypertension
The state-of-the-art evidence in the treatment of systemic sclerosis, as reviewed in Nature Reviews Rheumatology 1, highlights the importance of early treatment and the use of organ-specific therapies to improve morbidity and mortality. Autologous hematopoietic stem cell transplantation has shown promise in some cases of severe scleroderma by potentially inducing long-term remission, but this aggressive approach carries significant risks, including infection and treatment-related mortality.
Key Considerations
- Disease subtype and organ involvement
- Patient factors, such as age and comorbidities
- Access to biologic agents and other treatments
- Multidisciplinary care coordination
In practice, the most common first-line drug for skin manifestations in patients with dcSSc is mycophenolate mofetil, although methotrexate is also commonly used as an alternative first-line treatment or second-line after MMF 1. If the patient worsens, other treatments, such as rituximab, tocilizumab, cyclophosphamide, or AHSCT, can be considered. Treatment decisions should always be individualized and based on the latest evidence, with care coordinated through a multidisciplinary team experienced in managing scleroderma.
From the Research
Current Treatment Options for Scleroderma
- The goal of treatment for scleroderma is to target vascular damage, fibrosis, and regulation of inflammation as well as autoimmune responses 2.
- Current treatment modalities include canonical medications such as glucocorticoids, immunosuppressants, and vasodilators, which have had some success in treating various manifestations in SSc patients 2.
- Biologic agents targeting collagen, cytokines, and cell surface molecules may have promising therapeutic effects in SSc 2.
- Hematopoietic stem cell transplantation (HSCT), mostly autologous, has made great progress as a promising treatment option in severe and refractory SSc 2.
Treatment for Specific Complications of Scleroderma
- For scleroderma renal crisis (SRC), first-line therapy is an angiotensin-converting enzyme inhibitor (ACEi), followed by addition of a calcium channel blocker (CCB) or angiotensin receptor blocker (ARB) and then an alpha-blocker 3.
- For pulmonary arterial hypertension (PAH), endothelin receptor agonists (ERAs) are the first treatment in mild cases, followed by addition of a phosphodiesterase-5 inhibitor (PDE5i) and then a prostanoid 3.
- For interstitial lung disease/pulmonary fibrosis, induction treatment usually involves intravenous cyclophosphamide and mycophenolate mofetil (MMF) or azathioprine, while maintenance treatment typically involves MMF 3.
Emerging Therapies for Scleroderma
- Therapies targeting the vasculature, such as ET-1 receptor antagonists, phosphodiesterase-5 (PDE-5) inhibitors, and prostacyclins, are being evaluated in SSc 4.
- Advanced approaches, reserved for unresponsive SSc patients, include autologous hematopoietic stem cell transplantation (HSTC) and intravenous immunoglobulins (IVIG) 4.
- Combination therapy in SSc seems to be the best approach, together with early intervention on the major hallmarks of the disease in "at risk" patients 4.
Comparison of Treatment Options
- A study comparing mycophenolate mofetil and oral cyclophosphamide in scleroderma-related interstitial lung disease found that both treatments resulted in significant improvements in lung function, but mycophenolate mofetil was better tolerated and associated with less toxicity 5.
- Another study found that cyclophosphamide and mycophenolate mofetil have potential clinical effectiveness for progressive scleroderma-related interstitial lung disease, with mycophenolate mofetil being preferred due to its better tolerability and toxicity profile 5.