Severe interstitial lung disease in connective tissue disease: rituximab as rescue therapy

Abstract

In very severe interstitial lung disease associated with connective tissue disease (CTD-ILD), progressing despite maximal conventional immunosuppression, there is no effective medical rescue therapy.The aim of the present study was to test whether rituximab, a monoclonal antibody that depletes peripheral B lymphocytes, is effective as rescue therapy in very severe CTD-ILD, unresponsive to conventional immunosuppression.We performed a retrospective assessment of eight patients with severe and progressive CTD-ILD treated with rituximab. In six patients, change in pulmonary function tests (PFTs) compared with pre-rituximab levels, was assessed at 9-12 months post-treatment. In two patients, who were mechanically ventilated at the time of treatment, clinical and HRCT changes were assessed.Seven out of eight patients had a favourable treatment response to rituximab, while in one patient disease severity did not change. In contrast with previous progression, we observed a median significant improvement of 22% in diffusing capacity for carbon monoxide (from a median baseline of 25%; range 16-32%; p50.04), and a median significant improvement of 18% in forced vital capacity (from a median baseline of 45%; range 37-59%; p50.03), in the 9-12 months following treatment with rituximab.In very severe CTD-ILD unresponsive to conventional immunosuppression, rituximab may represent an effective, potentially life-saving, therapeutic intervention.

C-X-C Motif Chemokine 13 (CXCL13) Is a Prognostic Biomarker of Idiopathic Pulmonary Fibrosis

“…However, these nonspecific agents are similarly ineffectual as primary (or sole) therapy of numerous (if not all) other antibody-mediated lung diseases, including granulomatosis with polyangitis (Wegener's) (or antineutrophil cytoplasmic antibody-associated pulmonary vasculitides); Goodpasture syndrome; interstitial lung diseases (especially acute exacerbations) associated with polymyositis, scleroderma, and other conventional connective tissue diseases; or donor-specific antibodies in lung transplant recipients with chronic allograft rejection. Conversely, therapeutic modalities that deplete antibodies or target the B cells that produce these immunoglobulins often have beneficial clinical effects (25)(26)(27)(28)(29). A preliminary report indicates that autoantibody-targeted therapies may similarly benefit patients with Definitions of abbreviations: CXCL13 = C-X-C motif chemokine 13; DL CO = diffusing capacity of carbon monoxide; IPF = idiopathic pulmonary fibrosis.…”

“…These cumulative findings could ultimately influence incremental investigations and approaches to treatment of this morbid and heretofore inexorable lung disease. In addition to currently available regimens for treatment of antibody-mediated syndromes (25)(26)(27)(28)(29)48), the development of biologic response modifiers with specific actions at discrete, critical steps of pathologic B-cell response pathways is a very active area of ongoing research, and there is reason to believe that even more efficacious therapies will be available in the not-too-distant future (7,35,49). n…”

“…As an example, antibody-mediated lung diseases are resistant to treatment with nonspecific immunosuppressants (e.g., glucocorticoids), as is IPF, whereas approaches that physically remove antibodies, or target the B cells that produce these immunoglobulins, more often have favorable clinical effects (25)(26)(27)(28)(29). If B cells play an important role in IPF pathogenesis, analogous, more mechanistically focused treatment regimens might also benefit patients with this otherwise inexorable syndrome (30).…”

Significance of connective tissue diseases features in pulmonary fibrosis

“…Diagnosing CTD may impact on patient management, with more frequent use of corticosteroids and immunosuppressive therapy [25,26], and possibly newer biological agents such as rituximab [27]. Beyond the consequences that diagnosing the underlying CTD may have on managing the ILD, diagnosing a CTD may directly impact on the information delivered to the patient regarding the potential risk of systemic manifestations, with further ensuing consequences on the choice of disease modifying drugs or screening for systemic complications (e.g.…”

Recent Advances in Systemic Scleroderma in Childhood

“…In non-responders, a rescue rituximab treatment option is available [25]. As a last resort, a bilateral lung transplant or autologous bone marrow transplant are options [25][26][27]. Patients who underwent pulmonary transplants have similar survival rates to those with idiopathic pulmonary fibrosis.…”