Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

An Open Label Trial of the Endothelin Receptor Antagonist Bosentan in Scleroderma Renal Crisis (BIRD-1)

Penn1,  Henry, Burns1,  Aine, Black2,  Carol M., Denton3,  Christopher P.

Royal Free Hospital, London, United Kingdom
Royal Free Hospital, London
UCL Medical School, London, United Kingdom


Scleroderma renal crisis (SRC) is a life-threatening complication affecting approximately 5% of cases of systemic sclerosis. Endothelin-1 is a potent vasoconstrictor peptide which has proliferative effects on endothelium and is found at high levels in plasma and in renal biopsy material in SRC. The non-selective endothelin receptor antagonist (ETRA) bosentan is an established therapy for SSc associated pulmonary arterial hypertension and ischaemic digital ulceration. We have undertaken an open label pilot study of bosentan in SRC (BIRD-1).


Cases within 6 weeks of confirmed of SRC received six months bosentan at a dose of 62.5mg for 1 month then 125mg twice daily for 5 months. 10 cases were screened, and six enrolled. Outcome measures included 1 year mortality, renal function, and blood pressure control. These were compared with a recent historic cohort of 49 SRC cases managed at our centre from 2000–2004.


The mean (SD) age of the BIRD-1 cohort was 52 (11.5) years. 5 were female and only one was classified as lcSSc. The median duration of SSc at time of SRC was 6 months (range 2–72). Demographic and baseline clinical variables were not significantly different for the comparator cohort. All cases were treated with ACE inhibitors at full therapeutic doses. Clinical outcomes are summarised in Table 1. One case withdrew from the study after developing encephalopathy attributable to SRC. One case died at 2 months of multi-organ failure after discontinuing bosentan and dialysis. Bosentan was well tolerated with no significant drug related serious adverse events occurring. Three of five patients developed rebound phenomena on withdrawing bosentan – two with severe Raynaud's phenomenon, and three developed hypertension requiring one or two additional anti-hypertensive agents. Levels of ET-1 were elevated in all cases at SRC (median healthy controls 0.50pg/ml; SRC 1.48 pg/ml; p<0.0005), and increased further with bosentan therapy (1.46 pg/ml vs 3.05; t test p<0.05). N-terminal pro brain natriuretic peptide levels were also elevated, and high levels prior at presentation were associated with requiring dialysis (log values dialysed 3.61, non-dialysed 2.36, p=0.028).

Table 1.

  2000–5 cohort (n=49)BIRD-1 cohort (n=6)
Median (range) BP at presentation 195/114 (130–250/80–180)194/118 (150–253/90–140)
Median (range) serum creatinine at presentation (microMol/L) 191 (82–1123)185 (94–251)
Dialysis rates in survivorsat 1 mth34/49 (69%)3/6 (50%)
 at 12 mths21/43 (48%)2/5 (40%)
eGFR median (range) ml/min for cases not on dialysisat 3 mths31 (21–83)66 (43–85)
 at 6 mths36.5 (19–66)68 (59–107)
 at 12 mths41 (23–70)72 (62–107)
Mortality at 1 year 6/49 (12%)1/6 (16%)


Bosentan appears safe and well tolerated in conjunction with ACEi therapy for SRC. Overall, mortality and dialysis rates were not significantly different to our recent historic comparator cohort. A larger controlled study would be needed to fully assess therapeutic potential.

To cite this abstract, please use the following information:
Penn, Henry, Burns, Aine, Black, Carol M., Denton, Christopher P.; An Open Label Trial of the Endothelin Receptor Antagonist Bosentan in Scleroderma Renal Crisis (BIRD-1) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :451
DOI: 10.1002/art.25533

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