Efficacy of mycophenolate mofetil versus cyclophosphamide in systemic sclerosis-related interstitial lung disease: a systematic review and meta-analysis

Ma, Xinyu; Tang, Rui; Luo, Mei; Zeng, Zhuotong; Shi, Yaqian; Tang, Boyu; Xiao, Rong

doi:10.1007/s10067-021-05794-5

Cited by 10 publications

(6 citation statements)

References 26 publications

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“…The standard of care for SSc-ILD is mycophenolate (MMF) or cyclophosphamide (CYC) based on the seminal scleroderma lung studies I and II [ 53 ••, 54 ••]. Systematic reviews comparing MMF versus CYC have shown equal efficacy for both with possibly lesser adverse effects with MMF [ 55 ]. The role of anti-fibrotic to aid immunosuppressants in SSc-ILD is also promising [ 56 ••].…”

Section: Treatment Of Ctd-ildmentioning

confidence: 99%

Management of Connective Tissue Disease–related Interstitial Lung Disease

Ahmed

Handa

2022

Curr Pulmonol Rep

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Purpose of Review This review aims to collate current evidence on the screening, diagnosis, and treatment of various connective tissue disease (CTD)–associated interstitial lung diseases (CTD-ILD) and present a contemporary framework for the management of such patients. It also seeks to summarize treatment outcomes including efficacy and safety of immunosuppressants, anti-fibrotics, and stem cell transplantation in CTD-ILD. Recent Findings Screening for ILD has been augmented by the use of artificial intelligence, ultra-low dose computerized tomography (CT) of the chest, and the use of chest ultrasound. Serum biomarkers have not found their way into clinical practice as yet. Identifying patients who need treatment and choosing the appropriate therapy is important to minimize the risk of therapy-related toxicity. The first-line drugs for systemic sclerosis (SSc) ILD include mycophenolate and cyclophosphamide. Nintedanib, an anti-fibrotic tyrosine kinase inhibitor, is approved for use in SSc-ILD. The US Food and Drug Administration (FDA) has recently approved tocilizumab subcutaneous injection for slowing the rate of decline in pulmonary function in adult patients with SSc-ILD. Autologous stem cell transplantation may have a role in select cases of SSc-ILD. Summary CTD-ILD is a challenging area with diverse entities and variable outcomes. High-resolution CT is the investigative modality of choice. Treatment decisions need to be individualized and are based on patient symptoms, lung function, radiologic abnormalities, and the risk of disease progression. Precision medicine may play an important role in determining the optimal therapy for an individual patient in the future.

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Section: Treatment Of Ctd-ildmentioning

confidence: 99%

Management of Connective Tissue Disease–related Interstitial Lung Disease

Ahmed

Handa

2022

Curr Pulmonol Rep

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“…Mycophenolate mofetil (MMF) has been shown to have comparable efficacy to cyclophosphamide with a better toxicity profile [85,88] particularly in treatment of SSc lung involvement. Cancer risk data related to MMF are mostly derived from transplant patients, with contradictory results on the increased risk of lymphoproliferative and non-melanoma skin cancer [89][90][91][92].…”

Section: Immunosuppressive Treatment In Ssc Patients and Cancer Riskmentioning

confidence: 99%

“…Cyclophosphamide, an alkylating agent, is the cornerstone of the treatment of SSc, in particular of ILD and skin involvement related to SSc [ 84 , 85 ]. As above mentioned, long-term treatment with cyclophosphamide is associated with an increased risk of developing transitional cell bladder carcinoma [ 56 ] and haematological malignancies [ 86 ].…”

Section: Epidemiological Data On More Frequent Cancers In Ssc Patient...mentioning

confidence: 99%

Systemic Sclerosis Association with Malignancy

Lepri

Catalano

Bellando-Randone

et al. 2022

Clinic Rev Allerg Immunol

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The association of systemic sclerosis (SSc) and cancer is well known from several decades suggesting common genetic and environmental risk factors involved in the development of both diseases. Immunosuppressive drugs widely used in SSc may increase the risk of cancer occurrence and different SSc clinical and serological features identify patients at major risk to develop malignancy. In this context, among serological features, presence of anti-RNA polymerase III and anti-topoisomerase I autoantibodies seems to increase cancer frequency in SSc patients (particularly lung and breast cancers). Lung fibrosis and a long standing SSc pulmonary involvement have been largely proposed as lung cancer risk factors, and the exposure to cyclophosphamide and an upper gastrointestinal involvement have been traditionally linked to bladder and oesophagus cancers, respectively. Furthermore, immune checkpoint inhibitors used for cancer therapy can induce immune-related adverse events, which are more frequent and severe in patients with pre-existing autoimmune diseases such as SSc. The strong association between SSc and cancer occurrence steers clinicians to carefully survey SSc patients performing periodical malignancy screening. In the present review, the most relevant bilateral relationships between SSc and cancer will be addressed.

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“…Numerous systematic reviews and meta-analyses on treatment modalities of CTD-related ILD have been published [16][17][18][19][20][21][22][23][24][25][26][27]. However, there has been no effort to summarize or synthesize the findings of systematic reviews and meta-analyses.…”

Section: Rationalementioning

confidence: 99%

“…However, there has been no effort to summarize or synthesize the findings of systematic reviews and meta-analyses. Further, safety outcomes have not been adequately studied, the comparative effectiveness of treatments remains uncertain, and there is no clear evidence of relative superiority across the different drug classes or the specific agents [16][17][18][19][20][21][22][23][24][25][26][27]. Overviews integrating information from systematic reviews and meta-analyses allow a higher-level synthesis of the evidence and better appreciation of the uncertainties and biases [28,29].…”

Section: Rationalementioning

confidence: 99%

Pharmacological treatment for connective tissue disease-associated interstitial lung involvement: Protocol for an overview of systematic reviews and meta-analyses

et al. 2022

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Background Interstitial lung disease (ILD) is the most important pulmonary manifestation of connective tissue diseases (CTDs) since it is associated with high morbidity and mortality. However, there is uncertainty on what constitutes the optimal treatment options from a variety of competing interventions. The aim of the overview is to summarize existing evidence of the effectiveness and harm of pharmacological therapies for adults with CTD-ILD. Methods A literature search will be conducted in MEDLINE, the Cochrane Database of Systematic Reviews, DARE, the Centre for Reviews and Dissemination Health Technology Assessment database, Epistemonikos.org, KSR Evidence, and PROSPERO. We will search for systematic reviews with or without meta-analysis that examine pharmacological treatment for CTD-ILD. Updated supplemental search will also be undertaken to identify additional randomized controlled trials. The primary outcomes will be changes in lung function measures and adverse events. The methodological quality of the included reviews will be assessed using the AMSTAR 2 tool. The overall quality of the evidence will be evaluated using the GRADE rating. Summarized outcome data extracted from systematic reviews will be described in narrative form or in tables. For each meta-analysis we will estimate the summary effect size by use of random-effects and fixed-effects models with 95% confidence intervals, the between-study heterogeneity expressed by I², and the 95% prediction interval. If feasible, given sufficient data, network meta-analysis will be conducted to combine direct and indirect evidence of class and agent comparisons. Discussion While many factors are crucial in selecting an appropriate treatment for patients with CTD-ILD, evidence for the efficacy and safety of a drug is essential in guiding this decision. Thus, this overview will aid clinicians in balancing the risks versus benefits of the available therapies by providing high-quality evidence to support informed decision-making and may contribute to future guideline development. Systematic review registration MedRxiv: DOI 10.1101/2022.01.25.22269807 PROSPERO: CRD42022303180

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Efficacy of mycophenolate mofetil versus cyclophosphamide in systemic sclerosis-related interstitial lung disease: a systematic review and meta-analysis

Cited by 10 publications

References 26 publications

Management of Connective Tissue Disease–related Interstitial Lung Disease

Management of Connective Tissue Disease–related Interstitial Lung Disease

Systemic Sclerosis Association with Malignancy

Pharmacological treatment for connective tissue disease-associated interstitial lung involvement: Protocol for an overview of systematic reviews and meta-analyses

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