Rituximab in the treatment of systemic sclerosis-associated
interstitial lung disease. Comment on the article by Yoo
Dimitrios Daoussis, M.D. and Andrew P. Andonopoulos, M.D., FACP.
Division of Rheumatology, Department of Internal Medicine, Patras University
Hospital, University of Patras Medical School , Patras, Greece.
Address correspondence and reprint requests to: Dr. D. Daoussis, Department of
Internal Medicine, Division of Rheumatology, Patras University Hospital, 26504
Rion, Patras, Greece. Tel: +30-2610-999 693, FAX: +30-2610-993 982.
Several lines of evidence from basic research indicate that B cells may contribute to
the pathogenesis of systemic sclerosis. Clinical studies as well, have provided
preliminary data pointing to the direction that B cell depletion with rituximab might
be a therapeutic option for patients with this debilitating disease.
Key words: systemic sclerosis; scleroderma; rituximab; interstitial lung disease; B
cells; fibrosis; skin thickening; rheumatic diseases
We read with interest the article by Yoo which reported a case of successful treatment
of systemic sclerosis (SSc)-associated interstitial lung disease (ILD) with rituximab
(RTX) in a patient resistant to steroid and cyclophosphamide (CYC) therapy. The
author mentions that there is only one case report of improvement of SSc-associated
ILD with RTX so far. This is incorrect. We have previously shown that RTX may
improve lung function in patients with SSc-associated ILD, in a randomized,
controlled, proof of principle study, of one year duration. (1) This study was
available online (Epub ahead of print) since May 2009, six months prior of the date
this article was submitted. This is why we were surprised to notice that our study was
not included in the references even though the author has performed an exhaustive
literature search and has included all the articles regarding the use of rituximab in
SSc, including two in abstract form.
Three studies so far have explored the potential clinical efficacy of RTX in SSc. (1-3)
Our study, however, was the only one specifically designed to test the effect of RTX
on SSc-associated ILD, since the presence of ILD was an inclusion criterion and most
patients had severe ILD. On the contrary the other two studies excluded patients with
severe ILD and only a fraction of patients had evidence of mild ILD. We evaluated
14 patients with SSc. Eight patients were randomized to receive 2 courses of RTX at
baseline and 24 weeks, whereas 6 patients (control group) received standard treatment
alone. The median percentage of improvement of FVC in the RTX group was
10.25% whereas that of deterioration in the controls was 5.04% (p=0.002). The
median percentage of improvement of DLco in the RTX group was 19.46% whereas
that of deterioration in the control group was 7.5% (p=0.023). We also found
evidence of skin remodelling with reduction of collagen deposition in most patients
treated with RTX which correlated with skin B cell depletion. We have also
published a case report describing dramatic improvement of lung function and skin
fibrosis in a patient with severe, diffuse scleroderma following long term treatment
with RTX. (4) Our data indicate a possible disease modifying role of RTX in SSc,
particularly in SSc-associated lung disease. (5)
The case report by Yoo is in agreement with our data and suggests that RTX may
have beneficial effects on SSc-associated ILD. It is worth mentioning that this
particular patient showed a dramatic improvement in HRCT findings something that
was not observed in our cohort, probably due to the longer disease duration of our
patients which had more established fibrosis.
SSc is a multisystem disease with poor prognosis since no disease modifying drugs
exist so far. Cyclophosphamide has shown modest results, however its toxicity
restricts its long term use. Clinical, as well as basic research data indicate that
targeting B cells with RTX may be a promising therapeutic approach in SSc. We
propose that further exploration of the clinical efficacy of RTX in SSc-associated ILD
is highly needed. A direct comparison of RTX versus cyclophosphamide, the gold
standard of care so far, in a large, multicentre, randomized, double blind study, would
seem a reasonable approach.
(1) Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Kazantzi A,
Sirinian C et al. Experience with rituximab in scleroderma: results from a 1-
year, proof-of-principle study. (2010) Rheumatology (Oxford); 49:271-280.
(2) Lafyatis R, Kissin E, York M, Farina G, Viger K, Fritzler MJ et al. (2009) B cell
depletion with rituximab in patients with diffuse cutaneous systemic sclerosis.
Arthritis Rheum; 60:578-583.
(3) Smith V, Van Praet JT, Vandooren B, Van der CB, Naeyaert JM, Decuman S et
al. (2010) Rituximab in diffuse cutaneous systemic sclerosis: an open-label
clinical and histopathological study. Ann Rheum Dis; 69:193-197.
(4) Daoussis D, Liossis SN, Tsamandas AC, Kalogeropoulou C, Kazantzi A,
Korfiatis P et al. Is There a Role for B-cell Depletion as Therapy for
Scleroderma? A Case Report and Review of the Literature. Semin Arthritis
Rheum 2009. Epub ahead of print
(5) Simms RW, Lafyatis R. (2010) Rituximab: a potential therapeutic advance in
scleroderma: what is the evidence? Rheumatology (Oxford); 49:201-202.