Presentation: Promising Effects of Mycophenolate Mofetil on Autoimmune Related Pulmonary Fibrosis (2007)

27 Promising Effects of Mycophenolate Mofetil on Autoimmune Related Pulmonary Fibrosis

Purpose: To share this small proof of concept series of 9 patients with autoimmune related pulmonary fibrosis (ARPF) started on mycophenolate mofetil (MMF). To encourage large scale investigations of MMF as a first line agent in ARPF assessing long term outcomes on morbidity and mortality.
Methods: We observed the progression of 9 patients with either scleroderma (Scl), RA, polymyositis (PM) or SLE/Sjogren related PF whose treatment included MMF due to intolerance of cyclophosphamide (CYC) or need to reduce prednisone dose. MMF reached total dose of 3000mg daily in all patients. Measures include HRCT, PFT, ABG, patient symptom report (cough, dyspnea, fatigue, walking), physical exam assessing for alveolitis , quality of life (QOL) and development of adverse effects while on MMF. At time of submission duration ranges from 3 to 9 months.
Results: All patients experienced symptomatic relief with marked increase in activity levels. All patients requiring oxygen before MMF was initiated, reversed their oxygen requirement. All patients had increase in QOL except for KT who had worsening fibromyalgia.
Table of Results:
Patient1 EK2 LG3 KG4 RR5 KT6 JL7 CB8 IT9 JC
DiagnosisSclPMPMRASclSclSLE/
Sjogren
SclRA
MMF start9/068/061/071/0712/062/0711/062/063/07
CYC: months
Received
620066000
HRCT comparisonImpvStableStableStableStablePendPendPendPend
PFTImpvImpvStableStableStablePendPendPendPend
Physical ExamImpvImpvImpvImpvImpImpvImpvImpvImpv
Pt ReportImpvImpvImpvImpvImpvImpvImpvImpvImpv
QOLImpvImpvImpvImpvStableImpvImpvImpvImpv
Prednisone pre
post
60 mg 2.560mg 2.560mg
0
60mg
10
60mg
5
60mg
10
60mg
5
40mg
0
60mg
10
Oxygen useStopStopNoNoNoStopStopNoNo
New
symptoms
transient
diarrhea

Key: Impv: improved; Pend: pending; Stop: stopped while on MMF
Very importantly, averaged prednisone dosage decrease was from 58 mg to 4.4 mg. All patients on oxygen were able to discontinue use. One of 5 repeat HRCTs improved and 4 of 5 stabilized after at least 2 months from start of MMF compared to HRCT from 6 months ago or greater. Two of 5 repeat PFTs improved and 3 of 5 stabilized after at least 2 months of MMF. All patients showed improvement in symptoms, alveolitis and QOL except KT who had worsening fibromyalgia. The only side effect observed was transient diarrhea. This observational study is in progress. In November, data will include months until 9/2007 and reflect quantitative differential with statistical significance described.
Conclusions: The effects of MMF on objective and subjective changes observed on ARPF are favorable with little side effects. These observations potentially herald hope for a condition with a poor prognosis. At the very least, MMF allows reduction or discontinuation of prednisone. In addition to MMF’s specific inhibition of lymphocyte proliferation and migration, observations seen likely result from MMF’s ability to inhibit fibroblast proliferation consequently causing downstream interruption of fibroblastic interplay of autocrine and paracrine secretion of TFG-β, PDGF, CTGF and fibronectin effecting deposition of collagen and extracellular matrix proteins. MMF, being a less toxic and potentially more effective agent, is likely to supplant the use of CYC in the treatment of ARPF.

 L. Saketkoo, None; L.R. Espinoza, None.