While being treated with MMF, five patients had worsening respiratory symptoms, pulmonary physiology, or HRCT scans a median of 700 days (range, 211 to 1,105 days) after MMF initiation, which prompted either an increase in daily MMF or in prednisone dose. The average increase in daily prednisone dose over baseline in these cases was 14.5 mg; the average maximal prednisone dose during these episodes was 21 mg/d. The average duration that patients were receiving higher-than-baseline doses of prednisone for these episodes prior to returning to their usual dose was 12 weeks.
During a total of 36 patient-years of follow-up, five patients had identified side effects from MMF, which occurred a median 470 days (range, 31 to 792 days) after MMF initiation. No patient discontinued MMF because of side effects, and only two patients in the cohort discontinued MMF for any reason. No patient had more than one side effect; in each case, the side effect resolved with MMF dose reduction. One patient, with a history of peptic ulcer disease and GI bleeding had MMF discontinued as a precaution when she was found to be anemic, most likely due to a GI source. Another patient had MMF discontinued because it did not control arthralgias.
The most common side effect of MMF was diarrhea (n = 2). One patient had MMF-related leuco-penia. This patient was started on MMF as an alternative to CYC after completing 15 months of CYC. With MMF at 1,500 mg bid, his total WBC count fell to < 4,000/^L. The MMF dose was reduced to 1,000 mg bid, and his total WBC rose and has remained > 8,000/^L. More info
Pulmonary physiology data from at least two time points—one prior to and one after starting MMF— were available for the majority of patients. Pulmonary physiology remained stable from time points prior to MMF initiation to most recent evaluations while receiving MMF therapy (Fig 1). Since MMF initiation, the average cohort percentage of predicted FVC (FVC%), percentage of predicted TLC (TLC%), and percentage of predicted Dlco (Dlco%) had increased by 2.3%, 4.0%, and 2.6%, respectively. Similar changes and a trend toward statistical significance was observed in Dlco% (Table 3). From the time of MMF initiation to the most recent pulmonary physiology study (ie, over the course of interval two), FVC% in four patients, TLC% in three other patients, and Dlco% in two other patients increased by > 10%. Over the same time interval, the FVC% in one patient, the TLC% in another patient, and the Dlco% in another patient decreased by > 10%.
Figure 1. Box plots for FVC in liters (top this page, A), TLC in liters (bottom this page, B), and Dlco in milliliters per minute per millimeter Hg (top next page, C) before, at the time of, and after MMF initiation. Numbers equal p values from the longitudinal analysis and are for comparisons between indicated time points. + within box plot = median value; horizontal line within box plot = mean value.
Table 3—Mean Differences in Pulmonary Physiology Over the Two Time Intervals in this Study
|Variables||Time Interval 1, From the First PFT Before MMF Initiation to MMF Initiation||Time Interval 2, From MMF Initiation to the Most Recent PFT||p Value|
|Duration, d||166 (50-646)||371 (32-1,299)|
|FVC, L||0.02 (0.25)t||0.08 (0.27)t||0.45|
|FVC%||0.67 (6.55)t||2.3 (7.38)t||0.47|
|TLC, L||0.06 (0.36)|||0.22 (0.50)|||0.33|
|TLC%||1.6 (6.82)|||4.01 (9.6)|||0.42|
|Dlco, mL/min/mm Hg||— 0.73 (2.95)§||0.81 (2.05)§||0.09|
|Dlco%||— 2.12 (10.79)§||2.58 (7.24)§||0.14|