Rituximab Versus Mycophenolate in the Treatment of Recalcitrant Connective Tissue Disease–Associated Interstitial Lung Disease

Zhu, Lisa; Chung, Mo; Gagne, Laurence; Guo, H. Henry; Guenther, Z.; Li, Shufeng; Jacobs, Susan S.; Morisset, Julie; Mooney, Joshua J.; Raj, Rishi; Chung, Lorinda

doi:10.1002/acr2.11210

Cited by 5 publications

(7 citation statements)

References 12 publications

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“…Our data support previous studies reporting that B-cell depletion positively impacts lung and skin outcomes in patients with SSc [30][31][32][33][34]. Interestingly, if compared to other available studies, our experience is supported by a longer-term follow-up.…”

Section: Discussionsupporting

confidence: 90%

A 3-Year Observational Study of Patients with Progressive Systemic Sclerosis Treated with an Intensified B Lymphocyte Depletion Protocol: Clinical and Immunological Response

Rossi

Sciascia

Cecchi

et al. 2021

JCM

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Background: B-cells have been suggested to play a role in the pathogenesis of systemic sclerosis (SSc), representing, therefore, a potential therapeutic target. Objectives: We aimed at investigating the 36-month outcomes of 20 SSc patients who underwent an intensified B-depletion therapy (IBCDT) scheme, including both Rituximab (RTX) and cyclophosphamide (CYC). Methods: Data from 20 severe patients (18 females and 2 males, mean age 66.7 ± 11.0 years) with diffuse SSc (anti-topoisomerase I antibody in 95%) patients with multiorgan involvement including interstitial lung disease (ILD) treated with an IBCDT were prospectively collected. IBCDT comprehended: RTX 375 mg/m2 administered for four weekly doses (on days 1, 8, 15, and 22), followed by two additional doses after 30 and 60 days, in addition to two administrations of 10 mg/kg of intravenous CYC plus three methylprednisolone pulses (15 mg/kg) and subsequently followed by oral prednisone rapidly tapered to low minimum dosage of 5 mg daily. In addition, 10 patients with more severe functional respiratory impairment at baseline were also treated with RTX 500 mg every 4 months during the first year and two times a year during the second and the third year. Results: After 36 months of follow-up, we recorded significant amelioration in N-terminal-pro-brain natriuretic peptide (NT-proBNP) levels (mean 385.4 ± 517 pg/mL at baseline to 279 ± 543 after 36 months). In addition, a significant radiological improvement of ILD in 20% of patients (4/20) and a radiological stabilization with no sign of progression of interstitial involvement in 13/20 (65%) were documented. A total of 3 out of 20 (15%) patients experienced a worsening of the ILD. No patient showed further decrease in functional respiratory parameters, including forced vital capacity, forced expiratory volume in one second, and mean values of diffusing capacity for carbon monoxide Moreover, no patient showed any change in the ejection fraction and pulmonary artery pressure when comparing values at baseline and after 24 and 36 months of observation. No severe infection, renal flare, RTX-related side effects were observed. No patient died. Conclusions: Our findings support that the IBCDT was well tolerated and might be a promising therapeutic option for the management of SSc, especially in those subjects with multiorgan involvement that includes ILD.

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Section: Discussionsupporting

confidence: 90%

A 3-Year Observational Study of Patients with Progressive Systemic Sclerosis Treated with an Intensified B Lymphocyte Depletion Protocol: Clinical and Immunological Response

Rossi

Sciascia

Cecchi

et al. 2021

JCM

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“…22 In a further retrospective study on CTD-ILD patients, the addition of RTX to MMF reduced daily prednisone requirements, although no significant changes in lung function were seen. 63 In a 2018 open-label, randomized trial on 60 patients with early SSc-ILD treated with RTX versus CYC for 6 months, there was a significant improvement in FVC in the RTX group (from 61% to 68%) and a non-significant decline in the CYC group. 20 Other studies have had similarly positive findings.…”

Section: Mycophenolate Mofetilmentioning

confidence: 99%

“… 22 In a further retrospective study on CTD-ILD patients, the addition of RTX to MMF reduced daily prednisone requirements, although no significant changes in lung function were seen. 63 …”

Section: Immunomodulatory Therapiesmentioning

confidence: 99%

“…CTD-ILD, IPAF Prednisone First line 10,31,32,41 MMF First line with prednisone or second line 13,40,41,79 AZA First line with prednisone or second line 16 RTX Third line 22,62,63,68 CYC Third line 58,80 RA-ILD MTX Second line if required for joint disease 81,82 Tocilizumab Fourth line 83 SSc-ILD MMF First line 11 CYC Second line 11,52 RTX Third line 20,64 Tocilizumab Third line 84 Vasculitis or Dermatomyositis with hypoxemic respiratory failure Methylprednisolone pulse First line 85 CYC First line 59 RTX Second line 75,86 AZA Third line (maintenance only) 87 MMF Third line (maintenance only) 13,88 NSIP Prednisone First line 89 MMF Second line 79 AZA Second line 89 CYC Third line 19,89 (Continued)…”

Section: Condition Treatments Approachmentioning

confidence: 99%

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Immunomodulatory treatment of interstitial lung disease

Bosch

Luppi

Ferrara

et al. 2022

Ther Adv Respir Dis

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Interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) have an array of immunomodulatory treatment options compared with IPF, due to their inflammatory component. However, there is a relative paucity of guidance on the management of this heterogeneous group of diseases. In ILDs other than IPF, immunosuppression is the cornerstone of therapy, with varying levels of evidence for different immunomodulatory agents and for each specific ILD. Classification of ILDs is important for guiding treatment decisions. Immunomodulatory agents mainly include corticosteroids, mycophenolate mofetil (MMF), azathioprine, methotrexate, cyclophosphamide and rituximab. In this review, the available evidence for single agents in the most common ILDs is first discussed. We then reviewed practical therapeutic approaches in connective tissue disease–related ILD and interstitial pneumonia with autoimmune features, scleroderma-related ILD, vasculitis and dermatomyositis with hypoxemic respiratory failure, idiopathic non-specific interstitial pneumonia, hypersensitivity pneumonitis sarcoidosis, fibrosing organizing pneumonia and eosinophilic pneumonia. The treatment of acute exacerbations of ILD is also discussed. Therapy augmentation in ILD is dictated by the recognition of progression of disease. Criteria for the evaluation of progression of disease are then discussed. Finally, specific protocol and measures to increase patients’ safety are reviewed as well, including general monitoring and serologic surveillance, Pneumocystis jirovecii prophylaxis, patients’ education, genetic testing for azathioprine, MMF serum levels and cyclophosphamide administration protocols. Immunomodulatory therapies are largely successful in the management of ILDs and can be safely managed with the application of specific protocols, precautions and monitoring.

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“…However, Zhu et al conducted a retrospective controlled trial comparing the effects of combined RTX plus MMF treatment in patients with CTD-ILD ( n = 15) (RTX group) vs. MMF treatment alone ( n = 68) in patients with CTD-ILD (control group) ( 13 ). The evaluation of PFTs between the two groups reveals the following: the absolute change in FVC (% predicted, post-treatment—baseline) was −3.0 in the RTX group thus showing a significant decrease.…”

Section: Retrospective Studies In Ctd–ildmentioning

confidence: 99%

Treating Autoimmune-Related Interstitial Lung Disease With B Cell Depletion

Liossis

Bounia

2022

Front. Med.

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Autoimmune rheumatic diseases may affect vital organs with lung involvement being severe and difficult to treat manifestation. Systemic sclerosis (SSc) commonly affects the lung in the form of interstitial lung disease (ILD). ILD may be also seen in patients with rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), inflammatory myositis (IM), antisynthetase syndrome (AS), and the ANCA-associated vasculitides (AAV). Rituximab (RTX) is an anti-CD20 B lymphocyte depleting mAb, often administered in the treatment of autoimmune rheumatic diseases. Although RTX is an off-label treatment for CTD–ILD, there are numerous reports providing data that is effective in improving both pulmonary function tests (PFTs) and chest computed tomography findings consistent with ILD. There are retrospective uncontrolled studies that assess RTX as a treatment of ILD in autoimmune diseases. These studies, apart from one, do not include patients with AAV-ILD. In SSc-ILD, in particular, there are both controlled and uncontrolled studies displaying encouraging results following B cell depletion. In addition, a number of retrospective uncontrolled studies and fewer prospective studies evaluate RTX in connective tissue diseases CTD–ILD. Although RTX is an approved treatment for AAV there are scarce only data focusing on patients with AAV-ILD specifically. The results of a handful of studies comparing treatment of CTD-ILD with RTX to treatment with other agents are in favor of RTX. Results from large, still ongoing controlled trials are awaited to ascertain RTX effects in ILD encountered in autoimmune rheumatic diseases. We review herein the results of the different RTX trials in patients with autoimmune disease–associated with ILD. Despite the heterogeneity of these studies, RTX may be considered an alternative and safe but still off-label treatment for patients with refractory CTD–ILD.

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Rituximab Versus Mycophenolate in the Treatment of Recalcitrant Connective Tissue Disease–Associated Interstitial Lung Disease

Cited by 5 publications

References 12 publications

A 3-Year Observational Study of Patients with Progressive Systemic Sclerosis Treated with an Intensified B Lymphocyte Depletion Protocol: Clinical and Immunological Response

A 3-Year Observational Study of Patients with Progressive Systemic Sclerosis Treated with an Intensified B Lymphocyte Depletion Protocol: Clinical and Immunological Response

Immunomodulatory treatment of interstitial lung disease

Treating Autoimmune-Related Interstitial Lung Disease With B Cell Depletion

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