You are here

Article Text

Article menu

Download PDFPDF

Systemic sclerosis
Original article
Rituximab in early systemic sclerosis
  1. Maaike Boonstra1,
  2. Jessica Meijs1,
  3. Annemarie L Dorjée1,
  4. Nina Ajmone Marsan2,
  5. Anne Schouffoer1,3,
  6. Maarten K Ninaber4,
  7. Koen D Quint5,
  8. Femke Bonte-Mineur6,
  9. Tom W J Huizinga1,
  10. Hans U Scherer1 and
  11. Jeska K de Vries-Bouwstra1
  1. 1 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3 Department of Rheumatology, Haga Hospital, The Hague, The Netherlands
  4. 4 Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands
  5. 5 Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands
  6. 6 Department of Rheumatology, Maasstad Hospital, Rotterdam, The Netherlands
  1. Correspondence to Maaike Boonstra; m.boonstra{at}lumc.nl

Abstract

Objectives (1) Hypothesis testing of the potency of rituximab (RTX) in preventing fibrotic complications and (2) assessing acceptability and feasibility of RTX in early systemic sclerosis (SSc).

Methods A small, 24-month, randomised, double-blind, placebo-controlled, single-centre trial in patients with SSc diagnosed <2 years was conducted. Patients received RTX or placebo infusions at t=0, t=15 days and t=6 months. Patients were clinically evaluated every 3 months, with lung function tests and high-resolution CT every other visit. Skin biopsies were taken at baseline and month 3. Immunophenotyping of peripheral blood mononuclear cells was performed at every visit, except at months 9 and 18. Adverse events, course of skin and pulmonary involvement and B cell populations in skin and peripheral blood were evaluated.

Results In total 16, patients (rituximab n=8, placebo n=8) were included. Twelve patients had diffuse cutaneous SSc. Eighty-eight adverse events (RTX n=53, placebo n=35, p=0.22) and 11 serious adverse events (RTX n=7, placebo n=4, p=0.36) occurred. No unexpected RTX-related events were observed. Mean skin score over time did not differ between the groups. Over time, forced vital capacity and extent of lung involvement slightly improved with RTX, but this difference was insignificant. In peripheral blood B cells depletion was demonstrated.

Conclusions No unexpected safety issues were observed with RTX in early SSc. Although this small trial could not confirm or reject potential efficacy of RTX in these patients, future placebo-controlled trials are warranted, specifically in the subgroup of patients with pulmonary involvement.

Trial registration number EudraCT 2008-07180-16; Results.

  • Systemic Sclerosis
  • B Cells
  • Treatment

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/rmdopen-2016-000384

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • Contributors TWJH, HUS, JKdVB, AS, NAM, MKN, JM all participated in study design and data collection. ALD, KDQ and MB performed immunohistologic scoring. AS and LK assessed HRCTs according to Goh criteria. NAM assessed cardiac echos. MB conducted statistical analyses. JKdVB and MKN helped with clinical interpretation. All authors contributed to refinement of the study protocol.

    • Funding This work was supported by Roche B.V., donating medication. Roche was not involved in study design; collection, analysis and interpretation of data; writing of the manuscript or in the decision to submit the manuscriptfor publication.

    • Competing interests MB is supported by a grant of Actelion Pharmaceuticals Nederland BV (Woerden, The Netherlands). ActelionPharmaceuticals had no role in the study design; collection, analysis and interpretation of data; writing of themanuscript or in the decision to submit the manuscript for publication.

    • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

    • Ethics approval Medical Ethical Committee (METC) of the Leiden University Medical Center.

    • Provenance and peer review Not commissioned; externally peer reviewed.