ACR Interstitial Lung Disease Treatment Instructions
- June 13, 2024
- ACR
Table of Contents
AMERICAN COLLEGE
of RHEUMATOLOGY
Empowering Rheumatology Professionals
Interstitial Lung Disease Treatment
2023 American College of Rheumatology (ACR) Guideline for the Treatment of
Interstitial Lung Disease in People with Systemic Autoimmune
Rheumatic Disease
Guideline Summary
This guideline provides evidence-based recommendations for the treatment of
Interstitial Lung Disease (ILD) in adults with Systemic Autoimmune Rheumatic
Diseases (SARDs) at greatest risk of ILD, including systemic sclerosis (SSc),
rheumatoid arthritis (RA), idiopathic inflammatory myopathies (IIM including
polymyositis, dermatomyositis, antisynthetase syndrome, immune-mediated
necrotizing myopathy), mixed connective tissue disease (MCTD), and Sjögren’s
Disease (SjD). This document summarizes 36 treatment recommendations for
first-line ILD treatment, treatment for ILD progression despite first-line
treatment, and treatment of Rapidly Progressive ILD (RP-ILD).
Table 1. Summary of Recommendations for Management of SARD-ILD: First-line ILD
Treatment
Recommendations
For people with SARD-ILD other than SSc-ILD, we conditionally recommend
glucocorticoids as a first-line ILD treatment.
For people with SSc-ILD, we strongly recommend against glucocorticoids as a
first-line ILD treatment.
For people with SARD-ILD, we conditionally recommend mycophenolate,
azathioprine, rituximab, and cyclophosphamide as first-line ILD treatment
options.
For people with SSc-ILD and MCTD-ILD, we conditionally recommend tocilizumab
as a first-line ILD treatment option.
For people with SARD-ILD, we conditionally recommend against leflunomide,
methotrexate, TNFi, and abatacept as first-line ILD treatment options.
For people with SjD-ILD, IIM-ILD, and MCTD-ILD, we conditionally recommend
against nintedanib as a first-line ILD treatment option.
For people with SSc-ILD, we conditionally recommend nintedanib as a first-line
ILD treatment option.
For people with RA-ILD, the Panel was not able to come to consensus on whether
to recommend nintedanib as a first-line ILD treatment option.
For people with SARD-ILD, we conditionally recommend against pirfenidone as a
first-line ILD treatment option.
For people with SARD-ILD receiving mycophenolate without evidence of ILD
progression, we conditionally recommend against adding nintedanib or
pirfenidone to mycophenolate.
For people with SARD-ILD, we conditionally recommend against upfront
combination of nintedanib or pirfenidone with mycophenolate over mycophenolate
alone as first-line ILD treatment options.
For people with IIM-ILD, we conditionally recommend JAK inhibitors as a first-
line ILD treatment option.
For people with SARD-ILD other than IIM-ILD, we conditionally recommend
against JAK inhibitors as a first-line ILD treatment option.
For people with IIM-ILD, we conditionally recommend CNI as a first-line ILD
treatment option.
For people with SARD-ILD other than IIM-ILD, we conditionally recommend
against CNI as a first-line ILD treatment option.
For people with SARD-ILD, we conditionally recommend against IVIG or plasma
exchange as first-line ILD treatment options.
For people with SARD-associated ILD, we conditionally recommend optimal
medical management over referral for stem cell or lung transplant as first-
line ILD treatment options.
Figure 1: Initial treatment options for the treatment of interstitial lung disease associated with systemic autoimmune rheumatic diseases of interest.
- Decisions on GC dose and use of oral versus intravenous therapy depend on severity of disease. GCs should be used cautiously in patients with MCTD with a systemic sclerosis phenotype who may be at increased risk of renal crisis.
- Treatments are listed in order based on a hierarchy established by head-to-head votes, although the panel noted that decisions on which first-line therapy to use were dependent on specific situations and patient factors. In all diseases, mycophenolate was conditionally recommended over the other listed therapies. Therapies here are divided into “preferred” options and “additional options” based on the rank-order hierarchy.
MCTD = mixed connective tissue disease; GCs = glucocorticoids; CNI = calcineurin inhibitor; JAKi = janus kinase inhibitor
Figure 1. Recommendations for Management of SARD-ILD: First-line ILD Treatment
Table 2. Recommendations for Management of SARD-ILD Progression Despite First-line ILD Treatment
Recommendations
For people with SSc-ILD progression despite first ILD treatment, we strongly
recommend against using longterm glucocorticoids, and in other SARD-ILD we
conditionally recommend against using long-term glucocorticoids.
For people with SARD-ILD progression despite first ILD treatment, we
conditionally recommend mycophenolate, rituximab, cyclophosphamide, and
nintedanib as treatment options.
For people with RA-ILD progression despite first ILD treatment, we
conditionally recommend adding pirfenidone as a treatment option.
For people with SARD-ILD, other than RA-ILD, progression despite first ILD
treatment, we conditionally recommend against adding pirfenidone as a
treatment option.
For people with SSc-ILD, MCTD-ILD, and RA-ILD progression despite first ILD
treatment, we conditionally recommend using tocilizumab as a treatment option.
For people with SjD-ILD and IIM-ILD progression despite first ILD treatment,
we conditionally recommend against using tocilizumab as a treatment option.
For people with IIM-ILD progression despite first ILD treatments, we
conditionally recommend using a calcineurin inhibitor as a treatment option.
For people with SARD-ILD, other than IIM-ILD, progression despite first ILD
treatments, we conditionally recommend against using a calcineurin inhibitor
as a treatment option.
For people with IIM-ILD progression despite first ILD treatment, we
conditionally recommend using JAK inhibitors as a treatment option.
For people with IIM-ILD and MCTD-ILD progression despite first ILD treatment,
we conditionally recommend adding IVIG as a treatment option.
For people with SARD-ILD progression despite first ILD treatment, we
conditionally recommend against using plasma exchange as a treatment option.
For people with SSc-ILD progression despite first ILD treatment, we
conditionally recommend referral for stem cell transplantation and/or lung
transplantation.
If intolerance leads to suboptimal dosing of first-line therapy consider
switch to an alternative first-line therapy.
Therapies are generally listed in order based on a hierarchy established by
head-to-head votes, but decisions depend on specific clinical situations.
Decision on whether to switch therapy or add to current therapy depends on
current therapy and on which therapy is being initiated. Cyclophosphamide is
not typically used in combination with other therapies, while others may be
used individually or in combination.
- Decision on use of nintedanib vs immunosuppression depends on pace of progression and amount of fibrotic disease or presence of a usual interstitial pneumonia pattern on CT chest.
JAKi conditionally recommended as an option particularly in patients with anti-MDA-5.
short-term glucocorticoids may be of use in some patients with disease flares or as a bridge when switching therapy MCTD = mixed connective tissue disease; CNI = calcineurin inhibitor; AHSCT = autologous hematopoetic stem cell transplant; GCs = glucocorticoids
Figure 2. Recommendations for Management of SARD-ILD Progression Despite First-line ILD Treatment
Table 3. Recommendations for Management of SARD with Rapidly Progressive ILD (RP-ILD)
Recommendations
For people with SARD and RP-ILD, we conditionally recommend pulse intravenous methylprednisolone as a first-line RP-ILD treatment.
For people with SARD and RP-ILD, we conditionally recommend rituximab, cyclophosphamide, IVIG, mycophenolate, CNI, and JAK inhibitors as first-line RP-ILD treatment options.
For people with SARD and RP-ILD, we conditionally recommend against methotrexate, leflunomide, azathioprine, TNF inhibitors, abatacept, tocilizumab, nintedanib, pirfenidone, and plasma exchange as first-line RP-ILD treatment options.
For people with RP-ILD, we conditionally recommend up-front combination therapy (triple therapy for those with confirmed or suspected MDA-5 and double or triple therapy for those without confirmed or suspected MDA-5) over monotherapy as first-line treatment
For people with SARD and RP-ILD, we conditionally recommend against referral for stem cell transplantation over optimal medical management as a first-line RP-ILD treatment.
For people with SARD and RP-ILD, we conditionally recommend early referral for lung transplantation over later referral after progression on optimal medical management. In rare patients with systemic sclerosis with rapidly progressive ILD, there was no consensus on whether or not to use glucocorticoids — if used, patients should be monitored closely for evidence of renal crisis. - Rituximab and cyclophosphamide recommended over IVIG, but IVIG may be preferred if there is high concern for infection.
ILD = interstitial lung disease; IV = intravenous; IVIG = intravenous immune globulin; JAKi = janus kinase inhibitor
Figure 3. Recommendations for Management of SARD with Rapidly progressive ILD (RP-ILD)
This summary was approved by the ACR Board of Directors on 12 August 2023. These recommendations are included in a full manuscript, pending peer review, which was submitted for publication in Arthritis & Rheumatology and Arthritis Care and Research.
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