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Table 1 Randomized controlled trials evaluating immunosuppressive/immunomodulatory drugs in patients with SSc.

From: Molecular targets for therapy in systemic sclerosis



Number and main inclusion criteria of SSc patients

Study duration

Clinical effect

Furst DE et al.

Arthritis Rheum


Chlorambucil p.o. 0.05-0.1 mg/kg/day versus placebo

65 SSc

3 years

NS effect

O'Dell JR et al. J Rheumatol


Total lymphoid irradiation versus untreated control

6 SSc with internal organ involvement

Follow-up of 1-4 years

NS effect

Casaes JA et al.

Ann Rheum Dis


5-fluorouracil i.v. 4 × 12 mg/kg daily, followed by 4 × 6 mg/kg every two days and maintenance therapy with 12.5 mg/kg weekly versus placebo

70 SSc (diffuse or limited with visceral involvement)

6 months

Significant improvement in skin score, Raynaud's score and patient's general assesment scores

Sharada B et al.

Rheumatol Int


Dexamethasone i.v. 100 mg/month versus placebo

35 diffuse SSc

6 months

Significant improvement in skin score

Van den Hoogen FH et al.

Br J Rheumatol


Methotrexate i.m. 15 mg/week versus placebo

29 SSc with <3 years of skin involvement or with disease progression

24 weeks

Trend towards improvement in skin score (p = 0.06 in comparison with placebo)

Clements PJ et al. Arthritis Rheum


D-penicillamine p.o. high (750-1000 mg/d) versus low (125 mg every second day) dose

134 early diffuse SSc

2 years

NS effect

Pope JE et al.

Arthritis Rheum


Methotrexate p.o. 15 mg/week versus placebo

71 early diffuse SSc

1 year

Improvement in skin scores, borderline significance

Tashkin DP et al. N Eng J Med


Cyclophosphamide p.o. 1-2 mg/kg/d versus placebo

154 SSc with early (<7 years duration) SSc, symptomatic SLD and alveolitis

1 year

Significant improvement in lung volumes, dyspnoea and some measures of health related quality of life.

Significant improvement in skin score in diffuse SSc as a secondary outcome measure

Hoyles Rk et al.

Arthritis Rheum


Cyclophosphamide 6 × i.v. 600 mg/m2/month plus oral predonisone 20 mg every second day followed by azathioprine (p.o. 2.5 mg/kg/day) versus placebo

45 SSc with SLD

1 year

Trend towards improvement of FVC (p = 0.08), but low power

Nadashkevich O et al.

Clin Rheumatol


Cyclophosphamide p.o. 2 mg/kg/d for 12 months, then 1 mg/kg/d for another 6 months versus asathioprine 2.5 mg/kg/d for 12 months and then 2 mg/kg/d for 18 months

60 early diffuse SSc (<12 months duration)

18 months

Significant improvement in skin score, lung function tests and frequency of attacks of Raynaud's phenomenon

  1. i.v. = intravenous, i.m. = intramuscular, p.o. = peroral, NS = not significant, SLD = scleroderma interstitial lung diseases, SSc = systemic sclerosis. This list is not complete and is only a selection of potential molecules for targeted therapies. Modified from Distler O: Screloderma-modern aspects of pathogenesis, diagnosis and therapy. UNI-MED 2009.