Connective Tissue Disease-Associated Interstitial Lung Disease (CTD-ILD) Medication

Updated: Aug 06, 2020
  • Author: Aniruddh Kapoor, MBBS; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
  • Print

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications. Drugs used to manage connective tissue disease (CTD) associated with interstitial lung disease (ILD) (CTD-ILD) include nintedanib, corticosteroids, and antineoplastic agents. [99]



Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body’s immune response to diverse stimuli.

Prednisone (Deltasone, Rayos)

Prednisone is used as an immunosuppressant in the treatment of autoimmune disorders. It has anti-inflammatory properties and produces multiple glucocorticoid and mineralocorticoid effects. Prednisone therapy is best prescribed in consultation with a pulmonary disease specialist.

Prednisolone (FloPred, Millipred, Millipred DP, Prelone)

Prednisolone elicits mild mineralocorticoid activity and moderate anti-inflammatory effects; controls or prevents inflammation by controlling rate of protein synthesis, suppressing migration of polymorphonuclear leukocytes (PMNs) and fibroblasts, reversing capillary permeability, and stabilizing lysosomes at cellular level.


Pulmonary, Tyrosine Kinase Inhibitors

Class Summary

Nintedanib is a tyrosine kinase inhibitor that targets growth factors (eg, vascular endothelial growth factor receptor [VEGFR], fibroblast growth factor receptor [FGFR], platelet-derived growth factor receptor [PDGFR] 1-3, colony-stimulating factor 1 receptor [CSFIR]) that are implicated in the pathogenesis of interstitial lung diseases.

Nintedanib (Ofev)

Nintedanib is indicated to slow the rate of decline in pulmonary function in patients who have interstitial lung disease (ILD) associated with scleroderma. It is also indicated for chronic fibrosing ILDs with a progressive phenotype. Unclassifiable ILDs, autoimmune ILDs, chronic hypersensitivity pneumonitis, sarcoidosis, myositis, Sjögren syndrome, coal worker pneumoconiosis, and idiopathic forms of interstitial pneumonias (eg, idiopathic nonspecific interstitial pneumonia [NSIP]) are among the diseases that may develop a progressive form of chronic fibrosing ILD.



Class Summary

These agents inhibit key factors involved in immune reactions.

Azathioprine (Imuran, Azasan)

Azathioprine is an imidazolyl derivative of 6-mercaptopurine (6-MP). Many of its biologic effects are similar to those of the parent compound. Both compounds are eliminated rapidly from blood and are oxidized or methylated in erythrocytes and liver. No azathioprine or 6-MP is detectable in the urine 8 hours after being taken.

Azathioprine antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. The mechanism whereby it affects autoimmune diseases is unknown. It works primarily on T cells, suppressing hypersensitivities of the cell-mediated type and causing variable alterations in antibody production. Immunosuppressive, delayed hypersensitivity, and cellular cytotoxicity test results are suppressed to a greater degree than antibody responses. Azathioprine works very slowly; a 6- to 12-month trial may be required before effects are observed.

As many as 10% of patients may have idiosyncratic reactions that rule out the use of azathioprine. Do not allow the white blood cell (WBC) count to drop below 3000/µL or the lymphocyte count to drop below 1000/µL. The drug is available in tablet form for oral administration or in 100-mg vials for intravenous (IV) injection.

Cyclosporine (Gengraf, Neoral, Sandimmune)

Cyclosporine is a cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions. Suppresses mRNA expression of Th2 cytokines (interleukins 4 and 13) in peripheral blood mononuclear cells.


Antineoplastic Agents

Class Summary

Antineoplastic agents inhibit cell growth and proliferation.


Cyclophosphamide is primarily used for treating several types of cancer and autoimmune disorders. It is related to the nitrogen mustard group, and its mode of action involves alkylation and cross-linking of DNA. Cyclophosphamide is used for several different types of rheumatic disease, including systemic lupus erythematosus (SLE) and sometimes rheumatoid arthritis (RA).

Methotrexate (Trexall, Rheumatrex, Otrexup, Rasuvo)

Methotrexate is an antimetabolite used in the treatment of certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. It inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be used as carriers of single-carbon groups in the synthesis of purine nucleotides and thymidylate. Methotrexate therefore interferes with DNA synthesis, repair, and cellular replication.