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Table 1 Phase I, II and III trials in systemic sclerosis with lung assessed as a primary or secondary endpoint

From: The need for a holistic approach for SSc-ILD – achievements and ambiguity in a devastating disease

Publication

No. patients included

Treatment

Primary

endpoint

Secondary

endpoint

Distler et al. NEJM 2019 [28]

576

Phase III

Nintedanib

150 mg × 2

Annual rate of Decline in FVC

Absolute changes in:

 • mRSS

 • SGRQ at week 52

 • FVC (ml)

 • %DLCO

 • Net digital ulcer burden

 • HAQ-DI

 • FACIT–Dyspnea questionnaire

Annual rate of decline in %FVC

Time to death from any cause

Sircar et al. Rheumatology 2018 [20]

64

Phase II

Monthly pulses of CYC 500 mg/m2 or RTX 1000 mg × 2 doses at 0, 15 days

%FVC at 6 months

Absolute change in:

 • FVC (l)

 • mRSSa

 • 6MWTD

 • Medsgers scorea

 • New onset/ worsening of pulmonary hypertension

Hsu et al. J Rheumatol 2018 [43]

23

Phase II

Pomalidomide 1 mg q.d.

FVC

Total UCLA SCTC GIT V2.0 score

mRSS

BDI/TDI

Pulse oximetry (SpO2)

UCLA SCTC GIT 2.0 subscale scores

SHAQ

Khanna et al.

Ann Rheum. Dis. 2017 [22]

87

Phase II

Tocilizumab 162 mg sc

mRSS

%FVC

%DLCO

VAS (Clinician Global)

HAQ-DI,

Patient Global VAS

FACIT-Fatigue Score

Pruritus 5-D Itch Scale.

Tashkin et al.

LRM 2016 [16]

142

Phase II

Oral CYC 2 mg/kg/day or MMF 1500 mg b.i.d.

%FVC at 24 months

%DLCO

TDI

mRSS

LCQ

Change in HRCT extent

Khanna et al.

J Rheumatol 2016 [27]

63

Phase II

Pirfenidone 801 mg t.i.d.

Safety

UCLA SCTC GIT V2.0 score

FVC

DLCO

Mahlers dyspnea score

TDI

HAQ-DI

PtGA

mRSS

Burt et al.

Lancet Resp. Med. 2011 [44]

19

Phase II

HSCT vs. monthly pulses of IV CYC

1 g/m2

mRSS, 25% decrease

FVC, 10% improvement

CT volume of lung disease

DLCO

TLC

Spiera et al.

Ann Rheum Dis 2011 [45]

30

Phase IIa

Imatinib 400 mg q.d.

mRSS

FVC

DLCO

SF36

SHAQ-DI

VAS (global, SOB, pain, Raynaud)

Seibold et al. Arthrit. Rheum. 2010 [46]

163

Phase II

Bosentan 125 (62.5 mg) mg b.i.d.

6MWTD

Death

FVC

DLCO

BDI

mRSS

Medsgers score

SHAQ-DI

VAS

Denton et al. Arthrit. Rheum. 2007 [47]

45

Phase I/II

Recombinant Human Anti–Transforming Growth Factor

Antibody Therapy (CAT-192)

mRSS

FVC

TLC

DLCO

HAQ

VAS (global, Raynaud, lung disease, GO disease, digital ulcers)

Tashkin et al.

NEJM 2006 [14]

158

Phase II

Oral CYC 1–2 mg/kg q.d.

FVC

DLCO

TLC

HAQ

SF36

Mahler dyspnea score

VAS breathing

Hoyles et al.

Arthrit. Rheum. 2006 [15]

45

Phase II

20 mg oral prednisolone (alternate days), 6 monthly IV pulses of CYC 600 mg/m2 followed by AZA 2.5 mg/kg/day

FVC

DLCO

Dyspnea score

Change in HRCT extent and pattern

Nadashkevich et al.

Clin Rheumatol. 2006 [48]

60

Phase I/II

Oral CYC 2 mg/kg for 12 months, then 1 mg/kg for 12 months vs. Aza 2.5 mg/kg for 12 months, then 2 mg/kg for 18 months

 

mRSSb

Raynaud frequency

%FVC

%DLCO

Binks et al.

Ann. Rheum. Dis. 2001 [49]

41

Phase I/II

HSCT

Mortality

Disease progression

mRSS

VC

DLCO

LVEF by echocardiography

  1. Bold: Significant change; a CYC improved only mRSS and Medsgers score; RTX improved all secondary outcomes. bImprovement with CYC, no improvement with Aza
  2. FVC Forced vital capacity, DLCO Diffusing capacity for carbon monoxide, TLC Total lung capacity, VC vital capacity, mRSS modified Rodnan skin score, 6MWTD 6 min walk test distance, SGRQ St. Georges respiratory Questionnaire, HAQ-DI Health Assessment Questionnaire Disability Index, FACIT–Dyspnea Functional Assessment of Chronic Illness Therapy – Dyspnea, UCLA SCTC GIT University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract, BDI/TDI Baseline and transition dyspnea index, LCQ Leicester Cough Questionnaire, SHAQ Scleroderma Health Assessment Questionnaire, PtGA Patients global assessment of disease activity, CYC cyclophosphamide, MMF mycophenolate mofetil, HSCT hematopoic stamcell transplantation, LVEF left ventricular ejection fraction, VA Visual Analogic Scale