Mycophenolate Mofetil Is Safe, Well Tolerated, and Preserves Lung Function in Patients With Connective Tissue Disease-Related Interstitial Lung Disease: Results

A total of 67 patients were being treated with MMF. Twenty-eight patients received MMF primarily for CTD-ILD. The other 39 patients were excluded for the following reasons: (1) 29 patients had CTD but no ILD; (2) 6 patients with CTD-ILD had not yet returned for a follow-up visit; and (3) 4 patients had an idiopathic interstitial pneumonia (nonspecific interstitial pneumonia). Sixty-four percent (n = 18) of the patients in our cohort were women, and most were white (Table 1). Nine patients had scleroderma, five had poly-/dermatomyo-sitis, and five had UCTD. Among the patients with UCTD, all had esophageal disease in addition to physical examination or otherwise unexplained serologic abnormalities suggestive of an underlying CTD. A diagnosis of ILD was made by surgical lung biopsy in 13 patients. The primary pathologic pattern seen in the biopsy specimens was fibrosing nonspecific interstitial pneumonia. On average, mild-to-moder-ate restrictive lung physiology and a severely reduced Dlco were observed at the time of MMF initiation (median FVC, 2.4 L, 65% of predicted; median Dlco, 11.2 mL/min/mm Hg, 38% of predicted).
Twenty-two patients received at least one other immunomodulatory agent prior to the institution of MMF (Table 2). CYC was the initial agent in 13 patients and AZA in 9 patients. Link
The most common reason for starting MMF was intolerance to the initial agent (n = 16). Four patients had leukopenia, three had nausea, and two had hemorrhagic cystitis leading to discontinuation of CYC. Azathioprine was discontinued in four patients because of nausea and in three patients because of elevated transaminases.
The median length of follow-up after initiating MMF was 371 days (interquartile range, 187 to 632 days), and no patient died. The median dose of MMF was 2,000 mg/d in divided doses. At MMF initiation, the median daily dose of prednisone was 12.5 mg (range, 0 to 60 mg). There was a trend toward a significant difference in daily prednisone dose when comparing the two study intervals (15 mg during interval one vs 10 mg during interval two, p = 0.09). The median daily prednisone intake while receiving MMF was lower than the median daily prednisone intake while receiving other immunomodulatory agents (also 10 mg vs 15 mg, p = 0.13).

Table 1—Baseline Characteristics of Patients With CTD-Associated ILD (n = 28)

Characteristics Data
Age, yr 59(49-66)
Female gender 18
Ethnicity
White 19
Black 4
Hispanic 1
Pacific Islander 1
Uncertain 3
Smoking history
Never 16
Former 11
Current 1
CTD
Mixed CTD 1
Overlap, SLE/limited scleroderma 2
Overlap, DM/Sjogren disease 1
PM/DM 5
SLE 1
Sjogren disease 4
Sine scleroderma 2
Diffuse scleroderma 2
Limited scleroderma 5
UCTD 5
Time since CTD diagnosis, yr 4.4 (1.8-5.5)
Mode of ILD diagnosis
Clinical/HRCT 15
Radiographic pattern
NSIP 12
UIP 1
Indeterminate 2
Surgical lung biopsy 13
Pathologic pattern
NSIP 4
NSIP plus BOOP 2
NSIP plus DAD 2
Organizing pneumonia 2
End-stage lung disease 1
Lymphocytic bronchiolitis 1
Pleuritis and nonspecific interstitial cellularity 1
Time since ILD diagnosis, yr 3.5 (2.0-4.8)
Pulmonary physiology at MMF initiation
FVC, L 2.4 (2.1-2.9)
FVC% 65 (56-76)
TLC, L 4.3 (3.7-4.9)
TLC% 75(67-103)
Dlco, mL/min/mm Hg 11.2 (9-14.3)
Dlco% 38 (33-49)

Table 2—Treatment for CTD-Related ILD

Variables Data
Received immunomodulatory agent prior to 22
MMF
One agent 14
Two agents in succession 8
Days of immunomodulatory therapy prior to starting MMF 288 (42-634)
Reason for initiating MMF
Adverse effect of prior agent 15
MMF was first immunomodulatory agent 6
ILD progression 6
Concern about duration of CYC exposure 1
Time of MMF follow-up, d 371(187-632)
Median daily dose of MMF, mg 2,000 (2,000-2,500)
Able to discontinue long-term, daily prednisone after starting MMF 5
Median daily dose of prednisone during interval one (before MMF), mg 15 (6-20)
Median daily dose of prednisone during interval two (receiving MMF), mg 10(4-15)
Prednisone bursts for respiratory symptoms while on MMF
No burst 23
One burst 4
Two bursts 1
MMF side effects
Diarrhea 2
Hiccups 1
Leukopenia 1
Oral ulcer 1
Recurrent pneumonia 1
Discontinued MMF as a result of side effects 0
Discontinued MMF 2
This entry was posted in Pulmonary Function and tagged connective tissue disease, interstitial lung disease, mycophenolate mofetil.