Use of mycophenolate mofetil for systemic sclerosis and systemic sclerosis-associated interstitial lung disease: Information from a Japanese hospital claims database.

Limited information is available on patients with systemic sclerosis (SSc) or SSc-associated interstitial lung disease (SSc-ILD) receiving mycophenolate mofetil (MMF) in Japan. The dose, treatment duration, and patient characteristics of SSc and SSc-ILD patients receiving MMF were investigated. We used data from a Japanese hospital claims database (2008-2020). Data on 486 SSc patients ≥18 years old receiving MMF were captured; 314 had SSc complicated with ILD. The most common initial daily doses were 1000 mg (SSc, 39.5%; SSc-ILD, 38.1%) and 500 mg (SSc, 36.6%; SSc-ILD, 34.6%). The most common maximum daily doses were 1000 mg (SSc, 33.3%; SSc-ILD, 34.9%), 1500 mg (SSc, 24.4%; SSc-ILD, 23.1%), and 2000 mg (SSc, 23.8%; SSc-ILD, 24.4%). Doses ranged from 250 to 3000 mg/day and were similar for SSc and SSc-ILD patients. Over 27% of patients received treatment for >1 year. There was a gradual decrease in steroid doses during MMF treatment. Our study suggests that the off-label use of MMF for SSc and SSc-ILD has been increasing annually since 2015 in Japan. The doses used in patients with SSc and SSc-ILD were similar to the approved doses of MMF for lupus nephritis in Japan.

Funatogawa T ，Narita Y ，Tamura A ，Mii K ，Sugitani Y ，Uchida T ... -  《-》

Mycophenolate mofetil as a therapeutic agent for interstitial lung diseases in systemic sclerosis.

Systemic sclerosis (SSc) is an intractable disease that causes fibrosis in all organs. Approximately 40% of patients with SSc have some degree of interstitial lung disease (ILD). One third of patients with SSc and ILD, approximately 15% of all patients, have pulmonary lesions, which slowly progress to respiratory failure resistant to corticosteroid and other treatments. A randomized controlled trial conducted in the United States indicated that one year of treatment with oral cyclophosphamide in patients with SSc-ILD had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and health-related quality of life. However, all the effects, except for a sustained impact on dyspnea, disappeared approximately one year after stopping oral administration of cyclophosphamide. A randomized controlled trial using cyclophosphamide and mycophenolate mofetil (MMF) was then held in the United States for 142 patients with SSc-ILD. Treatment of SSc-ILD with MMF for two years or cyclophosphamide for one year both resulted in significant improvements in lung function over the 2-year course of the study. Leukopenia and thrombocytopenia occurred less often in patients administered MMF than in those administered cyclophosphamide. MMF is currently not approved for the treatment of SSc-ILD in Japan. Both MMF and cyclophosphamide were effective against ILD associated with SSc and, in particular, MMF was useful in terms of tolerability. When MMF is approved, it should be positioned as one of the first treatment options for SSc-ILD, which will further enhance the treatment of this disease in Japan.

Ueda T ，Sakagami T ，Kikuchi T ，Takada T ... -  《-》

Cyclophosphamide versus mycophenolate mofetil in scleroderma interstitial lung disease (SSc-ILD) as induction therapy: a single-centre, retrospective analysis.

Shenoy PD ，Bavaliya M ，Sashidharan S ，Nalianda K ，Sreenath S ... -  《-》

Interstitial Lung Disease: How Should Therapeutics Be Implemented?

Systemic sclerosis-interstitial lung disease (SSc-ILD) is a major complication of SSc resulting in important morbidity and mortality. Next to cyclophosphamide and mycophenolate mofetil, tocilizumab and nintedanib have proven efficacy in the treatment of SSc-ILD. The highly variable course of SSc-ILD, the complexity in determining and predicting the progression of SSc-ILD, and the diversity of treatment options for SSc-ILD, pose many challenges for everyday clinical practice. In this review, currently available evidence for monitoring and treatment of SSc-ILD is summarized and areas where additional evidence is highly desirable are discussed.

Bruni C ，Campochiaro C ，de Vries-Bouwstra JK 《-》

Improved Cough and Cough-Specific Quality of Life in Patients Treated for Scleroderma-Related Interstitial Lung Disease: Results of Scleroderma Lung Study II.

Cough is a common symptom of scleroderma-related interstitial lung disease (SSc-ILD), but its relationship to other characteristics of SSc-ILD, impact on cough-specific quality of life (QoL), and response to therapy for SSc-ILD have not been well studied. We investigated frequent cough (FC) in patients with SSc-ILD (N = 142) enrolled in the Scleroderma Lung Study II, a randomized controlled trial comparing mycophenolate mofetil (MMF) and oral cyclophosphamide (CYC) as treatments for interstitial lung disease (ILD). We determined the impact of FC on QoL (Leicester Cough Questionnaire [LCQ]), evaluated the change in FC in response to treatment for SSc-ILD, and examined the relationship between gastroesophageal reflux disease (GERD) and cough during the trial. Study participants who reported FC at baseline (61.3%) reported significantly more dyspnea, exhibited more extensive ILD on high-resolution CT, had a lower diffusing capacity for carbon monoxide, and reported more GERD symptoms than did those without FC. Cough-specific QoL was modestly impaired in patients with FC (total LCQ score, 15.4 ± 3.7; normal range, 3-21 [higher scores indicate worse QoL]). The proportion of patients with FC at baseline declined by 44% and 41% over 2 years in the CYC and MMF treatment arms, respectively, and this decline was significantly related to changes in GERD and ILD severity. FC occurs commonly in SSc-ILD, correlates with both the presence and severity of GERD and ILD at baseline, and declines in parallel with improvements in both ILD and GERD over a 2-year course of therapy. Frequent cough might serve as a useful surrogate marker of treatment response in SSc-ILD trials. ClinicalTrials.gov; No.: NCT00883129; URL: www.clinicaltrials.gov.

Tashkin DP ，Volkmann ER ，Tseng CH ，Roth MD ，Khanna D ，Furst DE ，Clements PJ ，Theodore A ，Kafaja S ，Kim GH ，Goldin J ，Ariolla E ，Elashoff RM ... -  《-》