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Systemic sclerosis (SSc) is characterised by skin fibrosis together with a dysfunction of the immune system and vasculopathy. Until now, only a few accepted treatment options have existed for patients with progressive disease.1 A similar skin fibrosis is seen in graft-versus-host disease, an immunologically mediated disease in recipients of haematological stem cells.2 In graft-versus-host disease, targeting of CD25-positive lymphocytes with a monoclonal antibody (basiliximab) has been shown to reduce its syptoms and complications.3 CD25 is the cluster designation for the high-affinity interleukin-2 receptor expressed on T and B lymphocytes after their activation. Activated lymphocytes are also thought to play a role in the pathogenesis of SSc as patients have elevated serum interleukin-2 receptor levels and the levels correlate with mortality and disease duration.4 5 As we had already treated one rapidly progressive SSc patient refractory to other forms of treatment with the monoclonal antibody basiliximab,6 we started a small open-label study and evaluated the possible effects and tolerance of basiliximab.
Ten patients with rapidly progressive disease and organ involvement were treated after protocol approval of the ethics committee. Further inclusion criteria were short disease duration, stable immunosuppressive therapy and concomitant medication. Patients were included after informed consent and received six infusions of 20 mg basiliximab every 4 weeks. The development of symptoms and complaints was monitored continuously and the disease activity was evaluated 24, 44 and partly 68 weeks after the start of the study as well as 6 months (±2 months) before (if available). Statistical analysis was performed using Graphpad Prism 4.0 software.
In total, 10 patients, eight women/two men, with SSc were included, all of these had the diffuse subtype. The main disease features are listed in table 1. The concomitant immunosuppressive and vasoactive treatment was not changed during the time of the study, except for three patients who were subsequently excluded from the final analysis (because of rapidly progressive myositis, autologous stem cell transplantation and severe pulmonary arterial hypertension). Apart from a high median modified Rodnan skin score (mRSS 26/51), our patients had frequent organ involvement (table 1).
The median mRSS was reduced from 26/51 to 11/51 at week 68 (p=0.015) (figure 1A) and lung function parameters changed over 44 weeks: the mean forced vital capacity increased from 82.1% to 88.4% expected (week 44, p=0.078) (figure 1B). The mean carbon monoxide diffusing capacity improved slightly to 57.8% expected (week 44, p=0.578) (figure 1C). Four patients had an improvement of forced vital capacity by greater than 10% and in two patients the carbon monoxide diffusing capacity increased more than 10%. In six of seven finally evaluated patients the mRSS had decreased by over 10 at week 68. Generally, the treatment with basiliximab was well tolerated. Although transient nausea, erythema, fatigue and weakness were common (3–4/10 patients), severe reactions with significant dyspnoea occurred in only one case. No patient had a documented severe infection and only one patient needed antibacterial therapy because of suspected respiratory infection.
In summary, we observed a significant improvement of skin thickness after 68 weeks and an improvement of pulmonary restriction during treatment with basiliximab and stable concomitant medication. However, as there was no control group in this preliminary study, these effects cannot be clearly attributed to the specific treatment. However, the reduction in skin thickness is more than expected by cyclophosphamide treatment alone7 or the natural course of the disease in clinical trials.8 The side-effects recorded were mostly minor and, in general, therapy was well tolerated. Our data show promising effects of an additional therapy with basiliximab and encourage a further evaluation of its possible therapeutic option in SSc patients, for example, in a controlled trial with a larger and more defined patient population.
Funding The study was partly financially supported by a grant from Novartis, Germany.
Competing interests None.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the local ethics committee.
Provenance and peer review Not commissioned; externally peer reviewed.