Research ArticleArticle

Longterm Treatment with Endothelin Receptor Antagonist Bosentan and Iloprost Improves Fingertip Blood Perfusion in Systemic Sclerosis

Maurizio Cutolo, Barbara Ruaro, Carmen Pizzorni, Francesca Ravera, Vanessa Smith, Giuseppe Zampogna, Sabrina Paolino, Bruno Seriolo, Marco Cimmino and Alberto Sulli
The Journal of Rheumatology May 2014, 41 (5) 881-886; DOI: https://doi.org/10.3899/jrheum.131284

Article Figures & Data

Figures

  • Figure 1.
    Figure 1.

    Reported trends at baseline (T0) and during further 3 years (T1, T2, T3) for peripheral blood perfusion at both basal skin temperature (A) and at 36°C (B), difference of perfusion between basal and 36°C laser Doppler flowmetry assessment (C), nailfold videocapillaroscopy score for capillary loss (D). ILO: iloprost; BOS: bosentan; PU: perfusion units; NVC: nailfold videocapillaroscopy; T0: at study entry; T1: after 1 year of study; T2: after 2 years of study; T3: after 3 years of study.

Tables

  • Table 1.

    Baseline clinical characteristics of the study patients.

    CharacteristicsTotal SSc PatientsILO GroupILO + BOS Group
    No. patients261313
    Age, yrs ± SD62 ± 1265 ± 459 ± 18
    Sex, male/female4/221/123/10
    SSc duration, yrs ± SD8 ± 47 ± 39 ± 3
    Raynaud duration, yrs ± SD16 ± 420 ± 1514 ± 4
    NVC pattern (early/active/late)0/7/190/5/80/2/11
    ANA indirect immunofluorescence pattern (centromeric/speckled/homogeneous/nucleolar)16/7/0/312/1/0/04/6/0/3
    Specific autoantibody positivity (ACA or Scl-70)16/612/14/6
    Skin involvement, limited/diffuse13/137/66/7
    Gastrointestinal involvement, yes/no2/241/121/12
    Lung involvement, yes/no2/241/121/12
    Pulmonary arterial hypertension, yes/no1/250/131/12
    Heart involvement, yes/no0/260/130/13
    Renal involvement, yes/no0/260/130/13
    Digital ulcers, yes/no13/260/1313/13
    Treatments (cardioaspirin/PPI/antihypertensive drugs/cyclosporine/MTX)22/23/9/8/411/11/3/4/111/12/6/4/3

    • SSc: systemic sclerosis; ILO: iloprost; BOS: bosentan; NVC: nailfold videocapillaroscopy; ANA: antinuclear antibodies; ACA: anticentromere antibodies; Scl-70: topoisomerase; PPI: proton pump inhibitors; MTX: methotrexate.

  • Table 2A.

    Mean values along with SD of clinical variables at different times in both groups of patients.

    AGroupMean ± SD
    PBP T0ILO85 ± 49
    basal temp. (PU)ILO+BOS53 ± 29
    PBP T1ILO81 ± 45
    basal temp. (PU)ILO+BOS74 ± 35
    PBP T2ILO71 ± 45
    basal temp. (PU)ILO+BOS92 ± 34
    PBP T3ILO66 ± 47
    basal temp. (PU)ILO+BOS93 ± 31
    PBP T0ILO132 ± 57
    36°C (PU)ILO+BOS89 ± 50
    PBP T1ILO120 ± 55
    36°C (PU)ILO+BOS112 ± 54
    PBP T2ILO107 ± 59
    36°C (PU)ILO+BOS128 ± 57
    PBP T3ILO95 ± 62
    36°C (PU)ILO+BOS125 ± 47
    Delta PBP T0ILO46 ± 32
    (PU)ILO+BOS36 ± 32
    Delta PBP T1ILO39 ± 30
    (PU)ILO+BOS37 ± 35
    Delta PBP T2ILO36 ± 30
    (PU)ILO+BOS36 ± 33
    Delta PBP T3ILO29 ± 37
    (PU)ILO+BOS32 ± 31
    NVC score for capillary number T0ILO1.77 ± 0.60
    ILO+BOS2.23 ± 0.60
    NVC score for capillary number T1ILO2.08 ± 0.28
    ILO+BOS2.00 ± 0.41
    NVC score for capillary number T2ILO2.15 ± 0.38
    ILO+BOS1.85 ± 0.38
    NVC score for capillary number T3ILO2.23 ± 0.44
    ILO+BOS1.77 ± 0.44
  • Table 2B.

    Statistical data.

    GroupT1 Statistical Significance, Mean Difference, 95% Lower, 95% Upper CIT2 Statistical Significance, Mean Difference, 95% Lower, 95% Upper CIT3 Statistical Significance, Mean Difference, 95% Lower, 95% Upper CI
    PBP T0 basal temp. (PU)ILOp = 0.35p = 0.14p = 0.09
    −4.68−14.40−19.58
    5.79, −15.145.55, −34.363.59, −42.75
    ILO+BOSp = 0.0007p = 0.0002p = 0.01
    21.6739.1940.95
    32.06, 11.2749.82, 28.5651.17, 30.73
    PBP T1 basal temp. (PU)ILOp = 0.14p = 0.07
    —−9.72−14.90
    3.81, −23.261.41, −31.21
    ILO+BOS—p = 0.004p = 0.04
    —17.5319.28
    29.44, 5.6129.68, 8.89
    PBP T2 basal temp. (PU)ILOp = 0.10
    ——−5.18
    1.07, −11.42
    ILO+BOSp = 0.72
    ——1.76
    12.35, −8.84
    PBP T0 36°C (PU)ILOp = 0.12p = 0.03p = 0.03
    −12.29−24.54−36.76
    3.92, −28.49−0.08, −48.99−6.01, −67.52
    ILO+BOSp = 0.003p = 0.0001p = 0.002
    22.9839.436.49
    36.40, 9.5654.85, 23.9557.15, 15.83
    PBP T1 36°C (PU)ILOp = 0.08p = 0.04
    —−12.25−24.48
    1.84, −26.34−2.71, −46.25
    ILO+BOSp = 0.01p = 0.11
    —16.4213.51
    28.76, 4.0830.57, −3.55
    PBP T2 36°C (PU)ILOp = 0.06
    ——−12.23
    0.32, −24.77
    ILO+BOSp = 0.70
    ——−2.91
    13.27, −19.08
    Delta PBP T0 (PU)ILOp = 0.05p = 0.26p = 0.09
    −7.61−10.13−17.19
    −0.02, −15.208.38, −28.653.22, −37.59
    ILO+BOSp = 0.69p = 0.97p = 0.58
    1.320.21−4.46
    8.33, −5.6911.77, −11.3612.54, −21.46
    Delta PBP T1 (PU)ILOp = 0.69p = 0.05
    —−2.53−9.58
    11.04, −16.09−0.05, −19.11
    ILO+BOS—p = 0.79p = 0.40
    −1.11−5.77
    7.70, −9.928.78, −20.33
    Delta PBP T2 (PU)ILOp = 0.26
    ——−7.05
    5.92, −20.03
    ILO+BOSp = 0.41
    ——−4.66
    7.17, −16.50
    NVC score for capillary number T0ILOp = 0.04p = 0.04p = 0.05
    0.310.380.46
    0.60, 0.020.69, 0.080.86, 0.06
    ILO+BOSp = 0.19p = 0.05p = 0.05
    −0.23−0.38−0.46
    0.13, −0.59−0.08, −0.69−0.15, −0.78
    NVC score for capillary number T1ILOp = 0.34p = 0.16
    —0.080.15
    0.24, −0.090.38, −0.07
    ILO+BOSp = 0.16p = 0.08
    —−0.15−0.23
    0.07, −0.380.03, −0.50
    NVC score for capillary number T2ILOp = 0.34
    ——0.08
    0.24, −0.09
    ILO+BOSp = 0.34
    ——−0.08
    0.09, −0.24

    • Delta is difference expressed in PU between basal and 36°C temperature at laser Doppler flowmetry assessment. ILO: iloprost; BOS: bosentan; PBP: peripheral blood perfusion; T0: baseline; T1: first year; T2: second year; T3: third year; NVC: nailfold videocapillaroscopy; PU: perfusion units.

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Keywords

SYSTEMIC SCLEROSIS
RAYNAUD PHENOMENON
LASER DOPPLER FLOWMETRY
NAILFOLD VIDEOCAPILLAROSCOPY
ENDOTHELIN-1 ANTAGONIST
ILOPROST

Keywords