Current and future perspectives on management of systemic sclerosis-associated interstitial lung disease

Figures & data

Figure 1. ILD occurs early in the course of SSc

Adapted with permission from: Incidences and risk factors of organ manifestations in the early course of systemic sclerosis: A longitudinal EUSTAR study. Jaeger et al. [9].

Figure 2. Nintedanib reduces the rate of decline in forced vital capacity in patients with SSc-ILD: results of the randomized placebo-controlled SENSCIS trial [55]. From Distler et al. Copyright © (2019) Massachusetts Medical Society

Reprinted with permission.

Table 1. Ongoing and recently (2019) completed randomized controlled Phase II/III trials of investigational therapies for SSc-ILD in which change in lung function is the primary endpoint

Drug (company/funding of study)	Type of molecule	Trial name (ClinicalTrials. gov identifier)	Phase	Patient population	Sample size (random-ized)	Primary endpoint	Estimated primary completion date*
Nintedanib (Boehringer Ingelheim)	Tyrosine kinase inhibitor	SENSCIS® (NCT02597933)	III	SSc-ILD	580	Annual rate of decline in FVC (mL/year) over 52 weeks	Completed
Nintedanib (Boehringer Ingelheim)	Tyrosine kinase inhibitor	INBUILD® (NCT02999178)	III	Non-IPF fibrosing ILDs with progressive phenotype	663	Annual rate of decline in FVC (mL/year) over 52 weeks	Completed
Rituximab (study funded by UK Medical Research Council and National Institute for Health Research)	CD20-directed cytolytic antibody	RECITAL (NCT01862926)	II/III	CTD-ILDs	116	Change from baseline in FVC (mL) at week 24	November 2020
Rituximab (study funded by University Hospital, Tours, France)	CD20-directed cytolytic antibody	EvER-ILD (NCT02990286)	III	CTD-ILD or IPAF or idiopathic ILD plus NSIP based on HRCT or histology plus lack of response to immunosuppressant	122	Change from baseline in FVC % predicted at month 6	June 2020
Pirfenidone (Beijing Continent Pharmaceutical Co, Ltd)	Pyridone analogue	N/A (NCT03856853)	III	SSc-ILD	144	Change from baseline in FVC % predicted at week 52	February 2021
Pirfenidone (Roche/Genentech)	Pyridone analogue	SLS III (NCT03221257)	II	SSc-ILD patients taking mycophen-olate	150	Change from baseline in FVC % predicted at month 18	April 2021

*According to ClinicalTrials.gov (accessed 8 August 2019).

Table 2. Ongoing and recently (2019) completed randomized controlled Phase II/III trials of investigational therapies for SSc-ILD in which change in lung function is a secondary endpoint

Drug (company/funding of study)	Type of molecule	Trial name (ClinicalTrials.gov identifier)	Phase	Patient population	Sample size	Primary endpoint	Secondary lung endpoint/s	Estimated primary completion date*
SAR156597 (Sanofi)	Interleukin-4/interleukin-13 directed antibody	N/A (NCT02921971)	II	dcSSc	97	Change in mRSS at week 24	Changes in FVC and DLco at week 24	Completed
Bortezomib (Takeda)	Proteasome inhibitor	N/A (NCT02370693)	II	SSc with pulmonary fibrosis, taking mycophe-nolate	30	Safety over 48 weeks	Change in FVC at week 48	June 2019
Ifetroban (Cumberland Pharmaceuticals)	Antagonist of thromboxane A2/prostaglandin endoperoxide receptor	N/A (NCT02682511)	II	dcSSc or SSc-PAH	34	Safety over 56 weeks	Changes in FVC and DLco at weeks 12, 26 and 52	December 2020
Lenabasum/ anabasum (Corbus Pharmaceuticals)	Synthetic endo-cannabinoid	RESOLVE-1 (NCT03398837)	III	dcSSc	365	CRISS at week 52	Change in FVC at month 12	March 2020
Belimumab (GlaxoSmithKline)	Anti-B-lymphocyte stimulator monoclonal antibody	N/A (NCT03844061)	II	dcSSc	30	CRISS at week 52	Changes in FVC and DLco at week 52	February 2022

*According to ClinicalTrials.gov (accessed 8 August 2019). CRISS, Combined Response Index for Systemic Sclerosis; mRSS, modified Rodnan Skin Score; PAH, pulmonary arterial hypertension.

Jaeger VK, Wirz EG, Allanore Y, et al. Incidences and risk factors of organ manifestations in the early course of systemic sclerosis: a longitudinal EUSTAR study. PLoS One. 2016;11:e0163894.

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Distler O, Highland KB, Gahlemann M, et al. Nintedanib in systemic sclerosis-associated interstitial lung disease. N Engl J Med. 2019;380:2518–2528.

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