mycophenolate as primary treatment for sjogren associated ILD
- related: Interstitial Lung Disease ILD
- tags: #literature #pulmonary
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The patient has systemic sclerosis or scleroderma by American College of Rheumatology criteria (skin thickening proximal to the metacarpal phalangeal joints), with associated interstitial lung disease on the basis of crackles on lung examination, restriction on pulmonary function testing, and chest CT imaging compatible with nonspecific interstitial pneumonia type interstitial lung disease (bilateral basilar predominant ground-glass opacities with traction bronchiectasis but no honeycombing and extreme peripheral sparing as seen in Figure 2). The preferred initial treatment for such a patient would be with mycophenolate mofetil (choice B is correct).
Up to 80% of patients with systemic sclerosis have interstitial lung disease, which is now the leading cause of mortality in systemic sclerosis. Both diffuse systemic sclerosis, which is defined by the skin thickening beyond the metacarpal phalangeal joints, and a positive Scl-70 antibody are associated with increased risk of interstitial lung disease.
About 25% to 30% of patients with scleroderma will have interstitial lung disease that is severe (generally thought to be FVC <70% predicted) or progressive for which medical therapy is recommended. There are a number of rigorous clinical trials of therapy in systemic sclerosis–associated interstitial lung disease, including randomized trials of immunosuppressive agents. These include cyclophosphamide vs placebo, cyclophosphamide vs mycophenolate mofetil, and the antifibrotic agent nintedanib (tyrosine kinase inhibitor that targets several growth factor receptors) vs placebo that have demonstrated efficacy in terms of FVC and in some cases skin thickening. In Scleroderma Lung Study I, cyclophosphamide for 12 months as compared with placebo was associated with a modest improvement in FVC and decreased skin thickening at 12 months. The benefit did not persist at 24 months, possibly because the cyclophosphamide was stopped after 12 months of therapy to minimize the risk of future serious adverse effects, such as bladder cancer and leukemia. In the follow-up Scleroderma Lung Study II, mycophenolate mofetil for 24 months was as effective as cyclophosphamide given for 12 months in improving FVC at 24 months and was associated with fewer adverse effects. In the SENSCIS trial, nintedanib slowed the decline in FVC as compared with placebo over 12 months, with half the patients in each arm on background mycophenolate mofetil therapy.
Because the side effect profile is much better for mycophenolate mofetil than for cyclophosphamide, both based on the potency of the immunosuppression (greater for cyclophosphamide) and incidence of adverse effects seen in Scleroderma Lung Study II (lower for those taking mycophenolate mofetil), in this patient with worsening interstitial lung disease, mycophenolate mofetil would be the medical therapy of choice (choice B is correct; choice A is incorrect). While IV rituximab infusion may be associated with improved lung function in some patients with scleroderma interstitial lung disease, the data demonstrating benefit is less rigorous, and the potency and duration of immunosuppression, potential risk of infection, and cost preclude this as initial therapy in those with mild to moderate interstitial lung disease (choice C is incorrect). Pirfenidone has not been demonstrated to be efficacious in systemic sclerosis–associated interstitial lung disease (choice D is incorrect). Scleroderma Lung Study III is an ongoing phase 2, randomized, double-blind trial of pirfenidone and mycophenolate mofetil vs placebo and mycophenolate mofetil for 18 months in patients with active and symptomatic scleroderma-related interstitial lung disease that is previously untreated or within 6 months of starting other therapy.
At present, there are no official pulmonary or rheumatology society guidelines to recommend when to initiate therapy with the antifibrotic agent nintedanib. Nintedanib is generally reserved for use after the initiation of mycophenolate mofetil, especially in the setting of progressive pulmonary fibrosis. Unlike mycophenolate mofetil, nintedanib has no beneficial effect on skin thickening. Because both nintedanib and mycophenolate mofetil can cause diarrhea, if both agents are used together, patients need to be monitored for gastrointestinal toxicity and electrolyte abnormalities.1