State-of-the-art evidence in the treatment of systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease with multi-organ involvement, fibrosis and vasculopathy. Treatment in SSc, including early diffuse cutaneous SSc (dcSSc) and the use of organ-specific therapies, has improved, as evident from randomized clinical trials. Treatments for early dcSSc include immunosuppressive agents such as mycophenolate mofetil, methotrexate, cyclophosphamide, rituximab and tocilizumab. Patients with rapidly progressive early dcSSc might be eligible for autologous haematopoietic stem cell transplantation, which can improve survival. Morbidity from interstitial lung disease and pulmonary arterial hypertension is improving with the use of proven therapies. Mycophenolate mofetil has surpassed cyclophosphamide as the initial treatment for SSc-interstitial lung disease. Nintedanib and possibly perfinidone can be considered in SSc pulmonary fibrosis. Pulmonary arterial hypertension is frequently treated with initial combination therapy (for example, with phosphodiesterase 5 inhibitors and endothelin receptor antagonists) and, if necessary, the addition of a prostacyclin analogue. Raynaud phenomenon and digital ulcers are treated with dihydropyridine calcium channel blockers (especially nifedipine), then phosphodiesterase 5 inhibitors or intravenous iloprost. Bosentan can reduce the development of new digital ulcers. Trial data for other manifestations are mostly lacking. Research is needed to develop targeted and highly effective treatments, best practices for organ-specific screening and early intervention, and sensitive outcome measurements.

A Rare Case of Polymyositis and Systemic Sclerosis Overlap Syndrome: Diagnosis and Treatment

“…In many cases of systemic sclerosis, anti-topoisomerase has been shown to be a key factor in determining the risk of ILD as well as the severity of the disease that the patient may eventually show [ 13 ]. In terms of treating the ILD itself, MMF and cyclophosphamide, as well as nintedanib (INBUILD trial), rituximab, and tocilizumab, have all been shown to be the new standards of treatment, but the availability and cost of these medications should be brought into the equation as well, as we try and determine the best course of action for our patient [ 14 ].…”

“…Throughout the course of treatment, blood transfusions were provided, and while this provided some respite, it did not completely cure the patient, and in retrospect, this was probably the cause of worsening heart failure as well. New studies have shown that autologous stem cell transplant might be the way forward in these types of cases, as these have shown not only to improve the anemia but also to reduce skin manifestations in diffuse SSC, and these have been proven to be significantly better than cyclophosphamide [ 14 ].…”

Scleroderma pulmonary arterial hypertension: the same as idiopathic pulmonary arterial hypertension?

“…SSc patients with coexisting pulmonary hypertension and ILD pose a unique therapeutic challenge. To date, no studies have investigated the safety or efficacy of pulmonary vasodilators in SSc patients with pulmonary hypertension driven by their ILD [84]. However, a cohort of patients with pulmonary hypertension secondary to connective tissue disease-related ILD was included in the INCREASE trial, which demonstrated improvement in 6 min walk distances (6MWD), NT-proBNP levels, and time to clinical worsening for patients who received inhaled treprostinil compared with placebo [85].…”

Targeting B cells for treatment of systemic sclerosis

“…As a result, these immune cells further contribute to the inflammatory and fibrotic processes associated with SSc. Targeting B cells and their activity has become a therapeutic approach in SSc [7–9]. For example, rituximab, a monoclonal antibody that selectively depletes B cells, has been used in SSc patients with promising results [10,11,12 ▪ ,13–18].…”