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Outcome of pulse oral cyclophosphamide therapy in scleroderma interstitial lung disease

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Abstract

Introduction

Standard regimens for scleroderma interstitial lung diseases (SSc-ILDs) are pulse intravenous (IV) and oral daily cyclophosphamide (CYC). However, IV CYC has limited access to diffuse cutaneous SSc, and oral daily CYC is associated with febrile neutropenia and hemorrhagic cystitis. Pulse oral CYC regimen has never been studied.

Objective

To determine the effectiveness of pulse oral CYC therapy in SSc-ILDs, predictors of effectiveness, and side-effects.

Methods

A historical cohort study enrolled SSc-ILDs from the SSc database registry at Srinagarind Hospital, Thailand from 1 January 2012 to 1 October 2018. All patients received monthly oral dosages of CYC 600–750 mg/m2, Mesna, and daily prednisolone of 10 mg for 2 years. Changes of FVC, chest radiography, HRCT, 6MWT, and side effects were recorded for the baseline and at the end of the treatment. Response to treatment was defined by (a) stable FVC or a decline ≤ 10% of predicted, (b) unchanged or improved radiographic findings, or (c) a decline 6MWT of ≤ 30 m compared with the baseline.

Results

A total of 76 patients with female 52 patients (68.4%) and with a median age of 54.2 years (IQR 46.6–59.6). The majority was dcSSc subset (59 patients; 78.6%). Fifty-four patients (71%) were defined as responsive to therapy. The mean FVC improvement was 1 ml (SD 9.5). The only factor associated with treatment response was limited cutaneous SSc (OR 7.69, 95% CI (1.01, 339.68), p = 0.029). Hemorrhagic cystitis was found in 1 patient.

Conclusions

Nearly three-quarters of SSc-ILDs patients had a good response to the pulse oral CYC therapy for 2 years with a few serious side effects. Pulse oral CYC therapy had been effective for SSc-ILDs in case of difficult IV access.

Key Point

• Pulse oral cyclophosphamide has been used for scleroderma lung disease. It has shown efficacy and safety in scleroderma patients. In patients who have difficulty with intravenous access, pulse oral cyclophosphamide can be an alternative regimen.

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Acknowledgments

The authors extend their gratitude to the Faculty of Medicine and the Scleroderma Research Group, Khon Kaen University for the support.

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Authors and Affiliations

  1. Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand

    Itthiphat Arunsurat, Ajanee Mahakkanukrauh, Chingching Foocharoen, Siraphop Suwannaroj & Ratanavadee Nanagara

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  1. Itthiphat Arunsurat
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  2. Ajanee Mahakkanukrauh
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  3. Chingching Foocharoen
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  4. Siraphop Suwannaroj
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  5. Ratanavadee Nanagara
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the scleroderma research group

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Historical-cohort research and manuscript preparation: all authors.

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Correspondence to Ajanee Mahakkanukrauh.

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This research was approved by the Human Research Ethics Committee of Khon Kaen University (HE611252)

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Arunsurat, I., Mahakkanukrauh, A., Foocharoen, C. et al. Outcome of pulse oral cyclophosphamide therapy in scleroderma interstitial lung disease. Clin Rheumatol 40, 205–211 (2021). https://doi.org/10.1007/s10067-020-05217-x

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