Cyclophosphamide for connective tissue disease-associated interstitial lung disease

Barnes, Hayley; Holland, Anne E; Westall, Glen P.; Goh, Nicole; Glaspole, Ian

doi:10.1002/14651858.cd010908.pub2

Cited by 77 publications

(57 citation statements)

References 60 publications

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“…The main mechanism of cyclophosphamide is the ability to covalently bind an alkyl group, affecting mainly the DNA (61). This interaction is irreversible and leads to inhibition of DNA replication and apoptosis, producing cell death amongst resting and dividing white blood cells and leading to impaired humoral and cellular immune responses (62). Rapidly proliferating cells are most sensitive to cyclophosphamide (41).…”

Section: Discussionmentioning

confidence: 99%

Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study

et al. 2020

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Introduction: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease with high symptom burden, of unknown etiology, with no established treatment. We observed patients with long-standing ME/CFS who got cancer, and who reported improvement of ME/CFS symptoms after chemotherapy including cyclophosphamide, forming the basis for this prospective trial. Materials and methods: This open-label phase II trial included 40 patients with ME/CFS diagnosed by Canadian criteria. Treatment consisted of six intravenous infusions of cyclophosphamide, 600-700 mg/m 2 , given at four-week intervals with follow-up for 18 months, extended to 4 years. Response was defined by self-reported improvements in symptoms by Fatigue score, supported by Short Form 36 (SF-36) scores, physical activity measures and other instruments. Repeated measures of outcome variables were assessed by General linear models. Responses were correlated with specific Human Leukocyte Antigen (HLA) alleles. Results: The overall response rate by Fatigue score was 55.0% (22 of 40 patients). Fatigue score and other outcome variables showed significant improvements compared to baseline. The SF-36 Physical Function score increased from mean 33.0 at baseline to 51.5 at 18 months (all patients), and from mean 35.0 to 69.5 among responders. Mean steps per 24 h increased from mean 3,199 at baseline to 4,347 at 18 months (all patients), and from 3,622 to 5,589 among responders. At extended follow-up to 4 years 68% (15 of 22 responders) were still in remission. Patients positive for HLA-DQB1 * 03:03 and/or HLA-C * 07:04 (n = 12) had significantly higher response rate compared to patients negative for these alleles (n = 28), 83 vs. 43%, respectively. Nausea and constipation were common grade 1-2 adverse events. There were one suspected unexpected serious adverse reaction (aggravated POTS) and 11 serious adverse events in eight patients. Conclusion: Intravenous cyclophosphamide treatment was feasible for ME/CFS patients and associated with an acceptable toxicity profile. More than half of the patients Rekeland et al. Intravenous Cyclophosphamide in ME/CFS responded and with prolonged follow-up, a considerable proportion of patients reported ongoing remission. Without a placebo group, clinical response data must be interpreted with caution. We nevertheless believe a future randomized trial is warranted.

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Section: Discussionmentioning

confidence: 99%

Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study

et al. 2020

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“…Cyclophosphamide (CYC) demonstrated a modest advantage in systemic sclerosis-related ILD (SSc-ILD) and other CTD-ILD [50][51][52][53][54], especially in combination with methylprednisolone pulses, although a metanalysis doubted the efficacy of CYC in SSc-related lung fibrosis [55].…”

Section: Cyclophosphamide and Mycophenolate Mofetilmentioning

confidence: 99%

“…In patients with progressive lung disease and mild articular involvement, immunosuppressants, such as CYC and MMF, should be considered [51][52][53][54][55][56][61][62][63][64]. On the other hand, the recent data about nintedanib allow us to suppose the future use of antifibrotic agents in ILD secondary to RA [185].…”

Section: Proposal For Patient Management and Treatmentmentioning

confidence: 99%

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows

Cassone

Manfredi

Vacchi

et al. 2020

JCM

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Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease affecting 0.5–1% of the population worldwide. Interstitial lung disease (ILD) is a serious pulmonary complication of RA and it is responsible for 10–20% of mortality, with a mean survival of 5–8 years. However, nowadays there are no therapeutic recommendations for the treatment of RA-ILD. Therapeutic options for RA-ILD are complicated by the possible pulmonary toxicity of many disease modifying anti-rheumatic drugs (DMARDs) and by their unclear efficacy on pulmonary disease. Therefore, joint and lung involvement should be evaluated independently of each other for treatment purposes. On the other hand, some similarities between RA-ILD and idiopathic pulmonary fibrosis and the results of the recent INBIULD trial suggest a possible future role for antifibrotic agents. From this perspective, we review the current literature describing the pulmonary effects of drugs (immunosuppressants, conventional, biological and target synthetic DMARDs and antifibrotic agents) in patients with RA and ILD. In addition, we suggest a framework for the management of RA-ILD patients and outline a research agenda to fill the gaps in knowledge about this challenging patient cohort.

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“…As reported in 2004, 15% of patients with ILD had underlying CTD, 1 or one-third of patients with ILD were connected with CTD in 2018. 2 The percentage may vary due to inadequate classification and diagnostic criteria. 3 Immune reaction, excessive collagen deposition, fibroblast proliferation, alveolar fibrillation, pulmonary interstitial substance, and tissues around the trachea are also involved, but their mechanism is still poorly understood.…”

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confidence: 99%

Association of Interstitial Lung Disease With Clinical Characteristics of Chinese Patients With Systemic Lupus Erythematosus

et al. 2020

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Objectives: This study aims to evaluate the frequency and clinical and laboratory features of interstitial lung disease (ILD) in Chinese patients with systemic lupus erythematosus (SLE) and to evaluate the association of ILD with the clinical features. Patients and methods: The study included 505 SLE patients (64 males, 441 females; mean age 35.3±15.3 years; range, 14 to 87 years) who were categorized into two groups as 449 patients without ILD and 56 patients with ILD based on evidence obtained from high-resolution computed tomography images. The demographic data, clinical and laboratory findings, SLE disease activity index score, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index of all patients were also recorded and statistically analyzed. Results: The ILD frequency in patients with SLE was 11.1%. Compared to the group of SLE patients without ILD, the group of SLE patients with ILD possessed the following statistical differences: elderly age, longer illness duration, lower level of anti-double-stranded deoxyribonucleic acid, and higher level of serum complement 3, increased ratios of Raynaud's phenomenon, moist rales and tachypnea. Multivariate logistic regression results suggested that elderly age (≥60 years), long illness duration (1-10 years, ≥10 years), Raynaud's phenomenon, and tachypnea were statistically associated with the occurrence of ILD in SLE patients. Conclusion: Chinese SLE patients who possessed the factors that were statistically associated with ILD, namely, elderly age (≥60 years old), long illness duration (≥1 years), Raynaud's phenomenon, and tachypnea, were recommended to be monitored for the possibility of ILD.

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Cyclophosphamide for connective tissue disease-associated interstitial lung disease

Cited by 77 publications

References 60 publications

Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study

Intravenous Cyclophosphamide in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. An Open-Label Phase II Study

Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows

Association of Interstitial Lung Disease With Clinical Characteristics of Chinese Patients With Systemic Lupus Erythematosus

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