Combo Medications May Reduce Need for Prednisone in Lung Disease Treatment

Adding rituximab to mycophenolate mofetil may necessitate a lower average daily dose of prednisone in patients with recalcitrant connective tissue disease–associated interstitial lung disease, but the combination treatment may not improve pulmonary function, shows a new study.

Interstitial lung disease affects many patients with connective tissue diseases, including patients with rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, systemic sclerosis, dermatomyositis, polymyositis and mixed connective tissue disease.

The condition is typically been treated with immunosuppressants, such as cyclophosphamide and mycophenolate mofetil. However, the treatment is ineffective in one-quarter of patients. Corticosteroids have been shown to lead to some improvements in patients, but it is associated with the risk of infections, hypertension, hyperglycemia, neuropsychiatric effects and osteoporosis.

In this brief report, published this week in ACR Open Rheumatology, set out to assess whether the combination treatment would improve pulmonary function in these patients and whether the treatment may require a change in prednisone dosage.

Led by Lorinda Chung, M.D., of Stanford University, the study included 15 patients who received rituximab and mycophenolate mofetil and 68 patients who received mycophenolate mofetil only.

While they found that the average daily prednisone dose score decreased in patients treated with rituximab group, the dosage remained unchanged in the control group.

They also found that the median interstitial lung disease duration at the start of treatment was longer in the rituximab group at 47 months versus 6.5 months in the control group. Forced vital capacity (FVC) decreased by 3.0% (range: 11%‐21%) after treatment in the rituximab group, but it increased by 2.0% (range: 14%‐25%) in the control group (p = 0.025). Diffusing capacity of carbon monoxide (DLCO) decreased by 3.0% (range: 10%‐12%) after treatment in the rituximab group, whereas it increased by 4.5% (range: 30%‐36%) in the control group (p = 0.046). Mixed model analysis controlling for lung disease duration, baseline diffusing capacity of carbon monoxide (DLC), systemic sclerosis, pulmonary hypertension, and prednisone use showed no significant difference in FVC or DLCO between groups at 6 months or one year.

“Patients in the rituximab group demonstrated a decline in FVC and DLCO posttreatment compared with pretreatment, whereas patients in the control group demonstrated an increase in FVC and DLCO. However, mixed model analysis did not reveal a significant difference in either parameter over time. Notably, despite the fact that patients in the rituximab group had longer disease duration and lower DLCO at baseline, they were able to reduce their average daily prednisone dose posttreatment to a greater degree compared with those treated with mycophenolate mofetil alone,” the authors wrote. “Our data add to the existing body of evidence and support the need for research clinical trials to investigate the use of rituximab in recalcitrant connective tissue disease–associated interstitial lung disease.”

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REFERENCE

Lisa Zhu MD,Melody P. Chung MD,Laurence Gagne MD, et al. "Rituximab Versus Mycophenolate in the Treatment of Recalcitrant Connective Tissue Disease–Associated Interstitial Lung Disease," ACR Open Rheumatology. First published: 04 December 2020 https://doi.org/10.1002/acr2.11210