Expert Consensus on the Screening, Treatment, and Management of Patients with Systemic Sclerosis-Interstitial Lung Disease, and the Potential Role of Anti-Fibrotics in a Treatment Paradigm for Systemic Sclerosis-Interstitial Lung Disease: A Delphi Consensus Study

Dinesh Khanna^1,2, Mary Strek³, Brian Southern⁴, Rajan Saggar⁵, Vivien Hsu⁶, Maureen D. Mayes⁷, Rick Silver⁸, Virginia D. Steen⁹, Donald Zoz¹⁰ and Franck Rahaghi¹¹, ¹Division of Rheumatology, Department of Internal Medicine, University of Michigan Scleroderma Program, University of Michigan, Ann Arbor, MI, ²Division of Rheumatology, University of Michigan, Ann Arbor, MI, ³Pulmonology, University of Chicago, Chicago, IL, ⁴Pulmonology, Cleveland Clinic Ohio, Cleavland, OH, ⁵Medicine, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, CA, ⁶Rheumatology, Robert Wood Johnson University Scleroderma Program, New Brunswick, NJ, ⁷Rheumatology, University of Texas Medical School at Houston, Houston, TX, ⁸Rheumatology, Medical University of SC, Charleston, SC, ⁹Dept of Rheumatology, Georgetown Univ Medical Center, Washington, DC, ¹⁰Pulmonology, Boehringer Ingelheim, Ridgefield, CT, ¹¹Cleveland Clinic Florida Weston, Weston, FL

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Connective tissue diseases, fibrosis and scleroderma, Lung Disease, Pulmonary Involvement

Session Information

Date: Monday, October 22, 2018

Title: Systemic Sclerosis and Related Disorders – Clinical Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Systemic sclerosis (SSc), or scleroderma, is a rare, autoimmune, multisystem connective tissue disorder characterized by vascular damage, autoimmunity, and fibrosis of the skin and other internal organs ^1–3. Pulmonary manifestations account for 60% of SSc-related deaths, and interstitial lung disease (ILD) is identified more often in SSc than in any other connective tissue disease (CTD), with the prevalence of ILD in SSc patients ranging from 75% to 90% ^1,4. There are many gaps in our understanding of the methodology for screening and the management of SSc-ILD. Hence, the objective of the current Delphi study was to solicit the opinions of rheumatologists and pulmonologists with expertise in the management of patients with SSc-ILD in order to develop consensus on screening and treatment criteria, and to evaluate the potential role of anti-fibrotics in a treatment paradigm for SSc-ILD.

Methods:

A three-stage Delphi method was designed to query rheumatologists and pulmonologists with expertise in SSc-ILD on identifying the criteria for screening, treatment, and management of patients with SSc-ILD. The potential role of anti-fibrotics in the treatment paradigm for patients with SSc-ILD was also explored. Here preliminary data at the completion of the second survey by 9 panelists are presented. Survey two had panelists rate their agreement on a Likert scale from -5 (complete disagreement) to +5 (complete agreement). Consensus was defined as a score of 2.5 or more with standard deviation not crossing zero.

Results:

Preliminary data, based on two rounds of Delphi, show high agreement regarding how to screen, how to identify the patient population to treat, treatment paradigms, and how to monitor progression and eventually successfully manage patients with SSc-ILD (Table 1: Mean ± SD).

Conclusion:

Preliminary data suggest consensus on screening and treatment with initial immunosuppressive therapy in SSc-ILD. The group was amenable to concomitant use of anti-fibrotics with CYC/MMF in SSc-ILD patients. Further guidance should be available in the near future with ongoing and recently completed trials.

Table 1:

How do you screen?

Screening for the general scleroderma population for ILD should include

· Spirometry with DLCO (4.78 ± 0.44)

· Full PFT (4.89 ± 0.33)

· HRCT (3.67 ± 1.94)

· Autoantibody testing (4.22 ± 0.97)

· Echocardiogram and (3.89 ± 1.69)

· Chest auscultation (4.44 ± 1.33)

Who do you screen?

In determining which patients to screen for ILD, I would consider

· Patients with symptoms (4.56 ± 1.01)

· High risk patients (ex: diffuse cutaneous SSc (dcSSc), positive Scl-70 antibodies, African American ethnicity, and/or a high modified Rodnan Skin Score (4.78 ± 0.67)

Who do you treat?

When deciding whether to treat patients for ILD I consider

· Extent of ILD or fibrosis on HRCT (4.44 ± 0.88)

· Clinically meaningful change in PFT value (4.89 ± 0.33)

Based on high resolution computed tomography (HRCT), I treat patients that have

· Worsening HRCT with symptoms or declining PFTs (5.00 ± 0.00)

· >20% involvement on HRCT with abnormal PFTs (4.78 ± 0.44)

Based on forced vital capacity (FVC) and symptom status (assume all patients have ILD on HRCT), I treat patients that have

· FVC >80% with ILD on HRCT in a high-risk patient (early diffuse disease, Topo+) (3.89 ± 0.60)

· Decline in FVC by >10% in one year (4.78 ± 0.44)

To determine the phenotype of patients that are likely to respond to treatment, I would likely employ

· Findings or changes on HRCT (3.56 ± 1.33)

· Findings or changes on PFTs (3.89 ± 1.45)

Additional tests that can help make the decision

· PFTs (Spirometry with DLCO) (1.00 ± 0.0)

· HRCT (2.0 ± 0.0)

· Autoantibodies (3.6 ± 0.89)

How do you treat?

Once I have decided to treat SSc-ILD, the initial therapy I use is

· Mycophenolate Mofetil (CellCept) (4.78 ± 0.44)

The typical/target dose for mycophenolate (MMF) I recommend is

· 3,000 mg daily (4.78 ± 0.44)

With regard to anti-fibrotics…

· I see anti-fibrotics (nintedanib [OFEV] and pirfenidone [Esbriet]) fitting into the management of SSc-ILD as first line therapy (0.44 ± 2.83)

· I see anti-fibrotics (nintedanib [OFEV] and pirfenidone [Esbriet]) fitting into the management of SSc-ILD after CYC/MMF (2.22 ± 3.11)

· I see anti-fibrotics (nintedanib [OFEV] and pirfenidone [Esbriet]) fitting into the management of SSc-ILD concomitant with CYC/MMF: (3.44 ± 1.88)

· I do not see anti-fibrotics fitting into the management of SSc-ILD (-2.56 ± 3.28)

How long do you treat?

I typically treat patients with SSc-ILD for 5 years (3.89 ± 1.17)

What is progression to you, and how do you monitor it?

I monitor progression as follows:

· Changes in PFTs over time (FVC or DLCO) (4.67 ± 0.71)

· Features on HRCT (ILD pattern or extent of fibrosis) (3.56 ± 1.33)

· Changes in HRCT over time (4.11 ± 1.05)

· Changes in symptoms over time (2.78 ± 3.15)

What is success to you?

I consider the following elements in defining success in SSc-ILD:

· FVC improvement (4.33 ± 0.71)

· DLCO improvement (4.11 ± 0.93)

· HRCT improvement (4.22 ± 0.97)

· Symptom stabilization / improvement (3.89 ± 0.93)

References

1. Denton CP, Khanna D. Systemic sclerosis. Lancet. 2017; 390: 1685-99.

2. Gabrielli A, Avvedimento E V, Krieg T. Scleroderma. N Engl J Med. 2009; 360 (19):1989-2003.

3. Renzoni EA. Interstitial lung disease in systemic sclerosis. Monaldi Arch Chest Dis. 2007; 67 (4):217-228.

4. Solomon JJ, Olson AL, Fischer A, Bull T, Brown KK, Raghu G. Scleroderma lung disease. Eur Respir Rev. 2013; 22(127):6-19.

Disclosure: D. Khanna, Eicos Sciences, 1,Pfizer, Inc., 2,Horizon, 2,BMS, 2,Actelion, 5,Bayer, 5,Bayer, 2,Corbus, 5,Cytori, 5,EMD Serono, 5,Genentech, Inc., 5,Sanofi-Aventis, 5,GSK, 5,Boehringer Ingelheim, 5; M. Strek, Boehringer Ingelheim, 5; B. Southern, Boehringer Ingelheim, 5; R. Saggar, Boehringer Ingelheim, 5; V. Hsu, Boehringer Ingelheim, 5; M. D. Mayes, Boehringer-Ingelheim, 2, 5,Corbus, 2,Reata, 2,Sanofi, 2,Mitsubishi-Tanabe, 5,Roche-Genentech, 2; R. Silver, Boehringer-Ingelheim, 5; V. D. Steen, CSL Behring, 2, 5,Bayer, 2, 5,Berhlinger Ingelheim, 2, 5,Roche, 2, 5,Reata, 2, 5,Sanorif, 2,EMD serrano, 2,Corbus, 2, 5,Immune Tolerance Network, 2,cytori, 2, 5; D. Zoz, Boehringer-Ingelheim, 3; F. Rahaghi, Boehringer-Ingelheim, 5.

To cite this abstract in AMA style:

Khanna D, Strek M, Southern B, Saggar R, Hsu V, Mayes MD, Silver R, Steen VD, Zoz D, Rahaghi F. Expert Consensus on the Screening, Treatment, and Management of Patients with Systemic Sclerosis-Interstitial Lung Disease, and the Potential Role of Anti-Fibrotics in a Treatment Paradigm for Systemic Sclerosis-Interstitial Lung Disease: A Delphi Consensus Study [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/expert-consensus-on-the-screening-treatment-and-management-of-patients-with-systemic-sclerosis-interstitial-lung-disease-and-the-potential-role-of-anti-fibrotics-in-a-treatment-paradigm-for-systemi/. Accessed .

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