Abatacept for the Treatment of Myositis-associated Interstitial Lung Disease

Inclusion Criteria

• Age ≥ 18 years.
• Anti-synthetase syndrome defined as the patient possessing 1 antisynthetase autoantibody (Jo-1, PL-12, PL-7, KS, OJ, EJ, Zo) in the presence of autoimmune ILD.
• ILD defined by radiographic (HRCT chest) findings of reticulation, honeycombing or ground glass opacities (GGO) without another plausible explanation. HRCT chest defining ILD for inclusion criteria, should be within last 1 year done as SOC.
• Active ILD (see Section 4.2).
• Baseline FVC a) % = 10% decline in FVC in last 12 months as minimal threshold of ILD severity (PFT done within last 3 months is acceptable for inclusion criteria determination)
• SOC immunosuppressive therapy (IS) therapy:
• Steroids (prednisone or other forms of steroid in equivalent doses) OR one of the other immunosuppressive agent (either Mycophenolate (MMF) or Azathioprine (AZA) OR a combination of steroid and an immunosuppressive agent. MMF (maximum of 3 gm/day) or azathioprine (maximum of 200 mg/day).Goal is to start the trial drug (or placebo) soon after starting SOC (MMF/AZA/Steroids) and their doses are stable. Note that patients on steroids alone as well as not on steroids can be enrolled in the trial as well.
• Desired dose of the SOC therapy should be reached 4 weeks prior to first study visit (Visit 1). No dose changes are allowed 4 weeks prior to first study visit.
• Dose of concomitant therapy (SOC) cannot be changed during the 24 weeks of the trial unless safety/toxicity issues supervene.
• If on steroid, the steroid dose must be stable for 2 weeks prior to Visit 1.
• No other concomitant IS medications including methotrexate, cyclosporine, intravenous immunoglobulin (IVIG), tacrolimus, cyclophosphamide or tofacitinib.
• No concomitant biologic agents (i.e. rituximab, anti-tumor necrosis factor (TNF) agents, tocilizumab).
• Additional IS therapy: Patient cannot begin any new IS therapy or new steroid taper for the 24-week study period, except if severe clinical worsening (flare up) of the disease requiring rescue therapy occurs (i.e. documentation of worsening of PFT/HRCT and patient and physician determination of worsening). See section of rescue medication below for details.
• If the enrolling physician is planning to discontinue current IS agent or steroid before clinical trial, then following washout period is required prior to Visit 1.

Medication Washout Period methotrexate 4 weeks Other IS agent (e.g. azathioprine, cyclosporine, tacrolimus, leflunomide, mycophenolate mofetil) 4 weeks IVIg or cyclophosphamide 3 months rituximab 6 months infliximab or adalimumab 8 weeks glucocorticoids 2 weeks etanercept 2 weeks anakinra 1 week pirfenidone 4 weeks

• Men and women of reproductive potential must agree to use an acceptable method of birth control during the trial period.
• Subject has provided written informed consent.

Exclusion Criteria

A patient will be excluded if any of the following Exclusion Criteria are met:

• Severe end stage lung disease:
• FVC ≤30% or Forced expiratory volume (FEV1) ≤ 30% or
• Requirement of high O2 requirement ≥ 6 L/min at rest for >1 month before the study enrollment or
• Listed for lung transplantation or
• PI feels that ILD is severe and end stage fibrosis is such that there is low potential for improvement with any disease modifying intervention.
• Subjects under the age of 18.
• Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of nail beds).
• Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening.
• Active tuberculosis (TB) requiring treatment within the previous 3 years. Patients should be screened for latent TB using purified protein derivative (PPD)/or quantiferon gold within last 1 year and, if positive, t