Table 1

Primary and secondary outcomes in three randomised controlled trials and corresponding effect sizes

Reference
Outcomes
Effect size
Safety

1. Hoyles, et al. [3], 2006
Follow-up after 1 year Primary endpoints:

3 withdrawals in the active group due to side effects (1 patient had intolerable nausea and 1 patient had abnormal findings on liver function tests during treatment with AZA) and no withdrawals in the placebo group (NNH = 11)

FVC: no change P = 0.08 versus placebo
ES = 0.35 (CI -0.24, 0.94)


DLCO: no change P = 0.64 versus placebo
ES = -0.01 (CI -0.59, 0.58)


TLC: no change P = 0.61
ES = 0.06 (CI -0.53, 0.64)


FEV1: no change P = 0.16
ES = 0.28 (CI -0.31, 0.86)


Kco: no change
ES = 0.3 (CI -0.29, 0.88)


Secondary endpoint:



HRCT: trends toward to improve P = 0.39
NNT = 5

2. Tashkin, et al. [2], 2006
Skin score: decreased
ES = -0.24 (CI 0.09, -0.56)
20 patients withdrew in the active group and 13 patients in the placebo group, mostly due to adverse events or serious adverse events within 12 months. (NNH = 11.2)

Diffuse
ES = -0.06 (CI 0.27, -0.38)


Limited
ES = -0.04 (CI 0.28, -0.37)


Primary outcome:



FVC: increased (P < 0.03) favouring Cyc
ES = 0.14 (CI -0.18, 0.47)


Secondary outcomes:



TLC: increased (P = 0.026) favouring Cyc
ES = 0.19 (CI -0.13, 0.52)


DLCO: no change
ES = -0.06 (CI -0.38, 0.27)


SF-36 score:



     Physical: no change versus placebo
ES = 0.24 (CI -0.09, 0.56)


     Mental: no change versus placebo
ES = 0.27 (CI -0.06, 0.6)


HAQ-DI: decreased
ES = -0.37 (CI -0.04, -0.69)


Transitional dyspnea score: improvement
Not possible to calculate


P < 0.001


3. Nadashkevich, et al. [11], 2006
MRSS: decreased after 12 (P < 0.001) and 18 months (P < 0.01) of therapy in
ES = -1.31 (CI -0.74, -1.85) after 6 months
No withdrawals Adverse events on Cyc included hair loss, nausea, dyspepsia, and leucopenia.

Cyc group versus baseline; P < 0.001 versus controlled patients
ES = -5.94 (CI -4.7, -7.03) after 12 months



ES = -9.21 (CI -7.39, -10.79) after 18 months


Attack frequency of Raynaud: decreased after 12 (P < 0.001) and 18 months (P < 0.01) of therapy in Cyc group versus baseline; P < 0.001 versus controlled patients
ES = -1.99 (CI -1.34, -2.58) after 6 months



ES = -8.35 (CI -6.69, -9.81) after 12 months



ES = -11.68 (CI -9.41, -13.66) after 18 months NNT = 1.3


FVC: no change in Cyc group (P = NS), worsening in AZA group (P < 0.01) after 6, 12, and 18 months of therapy versus baseline; P < 0.001 versus controlled patients
ES = 3.38 (CI 2.56, 4.12) after 6 months



ES = 4.92 (CI 3.85, 5.86) after 12 months



ES = 7.38 (CI 5.89, 8.68) after 18 months


DLCO: no change in Cyc group (P = NS), worsening in AZA group (P < 0.01) after 6, 12, and 18 months of change in Cyc group (P = NS), worsening in AZA group (P < 0.001) after 12 and 18 months of therapy versus baseline; P < 0.001 versus controlled patients
ES = 2.46 (CI 1.76, 3.1) after 6 months



ES = 5.12 (CI 4.02, 6.09) after 12 months



ES = 7.72 (CI 6.16, 9.07) after 18 months


AZA, azathioprine; CI, confidence interval; Cyc, cyclophosphamide; DLCO, diffusing lung capacity for carbon monoxide; ES, effect size; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HAQ-DI, Health Assessment Questionnaire-Disability Index; HRCT, high-resolution computed tomography; Kco, monoxide transfer coefficient; MRSS, modified Rodnan skin score; NNH, number needed to harm; NNT, number needed to treat; NS, not significant; SF-36, short form-36; TLC, total lung capacity.

Miniati et al. Arthritis Research & Therapy 2009 11:103   doi:10.1186/ar2576