Table 1 Characteristics of studies included in the meta-analysis (n = 14 studies)

Daoussis et al. 2012

SSc-ILD

Case series

8

One cycle: IV, 375 mg/ m², once weekly*4 weeks, every 6 months

4 cycles

None

FVC;

DLCO

2 years

2 Respiratory infections requiring hospitalization, 1 with associated leukopenia, 1 infusion reaction

Keir et al. 2012

CTD-ILD

Case series

6

One cycle: 5-IV, 1000 mg administered on day 0 and day 14

1 patient: 375 mg/ m², once weekly*4 weeks

1 cycle

None

FVC;

DLCO

9–12 months

None

Fitzgerald et al. 2015

CTD-ILD

Case series

10

a. 1–1000 mg monthly

b. 2-IV, 375 mg/ m², monthly

c. 7-IV, 1000 mg administered

on day 0 and day 14

a, b*4 months;

c*6 months

CYC*3

FVC;

DLCO

3–27 months

None

Chen et al. 2016

Sjögren’s syndrome-ILD

Case series

10

One cycle: IV, 1000 mg administered on day 0 and day 14

Repeated the same protocol every half a year depending on

Individual response

Hydroxychloroquine

FVC;

DLCO

6 months

None

Lepri et al. 2016

CTD-ILD

Case series

21

Cumulative mean dose:

SYN: 1.91 g;

SSc: 1.75 g;

MCTD: 1.4 g

2 years

ASS: Azathioprine* 8, MTX*1, IVIG*1, cyclosporine*1, CYC*3;

SSc: MTX*9, MMF*1

MCTD: MMF, CYC, MTX

FVC;

DLCO

2 years

1 Arrhythmia; 3 fatigue;

8 infections (2 serious with hospitalization)

Sharp et al. 2016

CTD-ILD

Case series

24

One cycle: IV, 1000 mg administered on day 0 and day 14

1–2 cycles

Oral immunosuppression

FVC;

DLCO

6–12 months

None

Daoussis et al. 2017

SSc-ILD

Cohort (prospective)

33

One cycle: IV, 375 mg/ m², once weekly*4 weeks, every 6 months

 ≥ 2 cycles

MTX*2; Hydroxychloro-quine*1;

MMF*10

FVC;

DLCO

2 years

2 Infusion reactions

Md Yusof et al. 2017

RA-ILD

Cohort (retrospective)

56

One cycle:

IV, 1000 mg administered on day 1 and day 14

 ≥ 1 cycle

CYC

FVC;

DLCO

6-12 months

12 Chest infections (none hospitalized)

Sari et al. 2017

SSc-ILD

Case series

14

One cycle: IV, 1000 or 500 mg, 2 infusions biweekly

4 received 1 cycle;

2 received 2 cycles;

2 received 3 cycles;

4 received 4 cycles;

2 received 5 cycles

None

FVC

15 months

None

Doyle et al. 2018

ASS-ILD

Case series

12

Not mentioned

Mean time to initiation of RTX after ILD identification: 4.4 years

Azathioprine, MMF, CYC, IVIG

FVC;

DLCO

2 years

1 Anaphylaxis and 2 serious gastrointestinal complications requiring surgery (not described), but later resumed RTX

Sircar et al. 2018

SSc-ILD

RCT

30

One cycle: IV, 1000 mg administered on day 0 and day 15, every 6 months

2 cycles

None

FVC

6 months

1 Severe pulmonary arterial hypertension, 3 infusion reactions

Duarte et al. 2019

CTD-ILD

Case series

49

One cycle: IV, 1000 mg, 2 infusions biweekly

Median number of cycles was 2

None

FVC;

DLCO

1 year

None

Ebata et al. 2019

SSc-ILD

Non-randomized study (retrospective)

9

One cycle: IV, 375 mg/ m.², once weekly*4 weeks

1 up to 3 cycles

Maintenance therapy with immunosuppressant agents

FVC;

DLCO

2 years

None

Fui et al. 2019

RA-ILD

Cohort (retrospective)

14

One cycle: IV, 1000 mg administered on day 0 and day 14

Treated for more than 1 year

None

FVC;

DLCO

1 year

Discontinued in 2 patients with refractory severe arthritis