The emerging role of mycophenolate mofetil in interstitial lung diseases

Figures & data

Figure 1. Spectrum of ILDs in India from prospective studies

ILDs: Interstitial lung diseases; IPF: Idiopathic pulmonary fibrosis; CTD-ILD: Connective tissue disease associated interstitial lung diseases; HP: Hypersensitivity pneumonitisHypersensitivity pneumonitis was the most prevalent ILD followed by CTD-ILD and IPF in the cohort studied in India ILD Registry. The other prospective studies also highlight the high prevalence of ILDs other than IPF. The numbers represent percentage of subjects diagnosed with the condition.

Table 1. Summary of Evidence from Various Clinical Studies with MMF in ILDs

Authors	No. of Patients	Design	Treatment Duration	FVC	DLco			Steroid Dose (mg)
				Before mycophenolate mofetil initiation	After mycophenolate mofetil treatment	Before mycophenolate mofetil initiation	After mycophenolate mofetil treatment	Before mycophenolate mofetil initiation	After mycophenolate mofetil treatment
Chronic HP
Morisset et al. (2017)	51	Retrospective trial	12 months	65.2% predicted	Increased by 1.3% (P = .103)	49.8% predicted	Increased by 3.9% (P < .001)	12.33	3.7
D Mac Donald et al. (2017)	38	Retrospective trial	24 months	61.1 ± 12.3% predicted	65.1 ± 12.9% predicted	45.3 ± 14.9% predicted	50.9 ± 14.5% predicted	18.9 ± 11.1	5.4 ± 6.1
Fiddler CA et al. (2019)	18	Retrospective trial	12 months	–111 ± 295 mL	Increased by 2.3 ± 319 mL (P = 0.22)	NA		16.2 ± 9.7	8.2 ± 4.2 (P = 0.002)
Systemic Sclerosis-ILD
Tashkin DP et al (2016)	69	Randomized, double-blind, parallel group	24 months	66.5% predicted	Increased by 2.19%	54.0% predicted	Stabilized	NA	NA
Shenoy PD et al. (2016)	34	Retrospective trial	6 months	53.44 ± 13.69% predicted	55.99 ± 13.47% predicted; (P = 0.003); numerical increase in FVC reported in 78.5% of patients	NA	NA	NA	NA
Highland KB et al. (2021)	139	Randomized, double-blind, placebo-controlled trial	52 weeks			NA	NA	NA	NA
Gerbino AJ et al. (2008)	13	Retrospective trial	12 months	Decreased by 5.4% in previous 12 months (P = 0.02)	Increased by 4.2% predicted (P = 0.002)	Decreased by 5.2% in previous 12 months (P = 0.01)	Increased by 1.2% predicted (P = 0.57)	NA	NA
Liossis SNC et al. (2006)	5	Prospective trial	4– 6 months	65.6% predicted	76.2% predicted (P = 0.057)	64.2% predicted	75.4% predicted (P = 0.033)	NA	NA
Owen C et al. (2016)	22	Prospective trial	36 months	Stabilized and/improvement	Stabilized and/improvement			NA	NA
Swigris JJ et al. (2006)	28	Retrospective observational study	35.9 patient-years	65% predicted	Increased by 2.3% (P = 0.47)	38% predicted	Increased by 2.6% (P = 0.14)	15	10
Other Connective Tissue Disease-ILD
Fischer A et al. (2013)	125	Retrospective trial	156 weeks	66.7 ± 16.0% predicted	Increased by 7.3% ± 2.6% (P = 0.004)	47.4 ± 16.4% predicted	Increased by 7.8% ± 4.1% (P = 0.05)	20 mg	5 mg
Santhanam S and Rahulan V (2018) - MCTD - RA - Others	33	Retrospective observational study	24 months	62% predicted 59% predicted 64% predicted	65% predicted 62% predicted 65% predicted	NA	NA	NA	NA
Polymyositis/Dermatomyositis-ILD
Morganroth PA et al. (2010)	4	Case report	1 year	Complete normalization of pulmonary function				15–60	4
Mira-Avendano IC et al. (2013)	9	Retrospective study	12 months	64% predicted	64% predicted	58% predicted	63% predicted	40	10
Koyama RVL et al. (2017)	1	F/62 years	25 months	Improvement in pulmonary function				10	5
Huapaya JA et al. (2019)	44	Retrospective trial	24 months	72 ± 22.2% predicted	Improved by 3.3% (P = .021)	66.6 ± 26.2% predicted (P = .657)	NA	18.1 ± 12.2	Decreased by 6.9 (P < .001)
Chronic/Refractory Sarcoidosis
Brill KA et al. (2013)	10	Retrospective trial	12 months	78.8 ± 11.9% predicted	85 ± 9.6% predicted (P = 0.057)	62.9 ± 14.4% predicted	60.3 ± 11.8% predicted (P = 0.721)	14.3 ± 13.3	6.5 ± 2.3 (P = 0.043)
Papiris S et al. (2019)	8	Retrospective trial	12 months	86.2% predicted	92.4% predicted	68.8% predicted	81.1% predicted	15	2.5
Idiopathic Pulmonary Fibrosis
Nambiar AM et al. (2017)	11	Retrospective trial	12 months	Trend toward decreased decline in FVC by 76.3 mL, 2.4% predicted (P = NS)	NA		NA	NA	NA

MMF = Mycophenolate mofetil; ILDs = Interstitial lung diseases; Chronic HP = Hypersensitivity pneumonitis; FVC = Forced vital capacity; DLco = Diffusing capacity of lung for carbon monoxide; NA = Not available

Figure 2. Prednisone Dose and Pulmonary Function Test Following Initiation with MMF

MMF: Mycophenolate mofetil; DLco: Diffusing capacity of lungs for carbon monoxide; FVC: Forced vital capacityTreatment with MMF in patients with cHP over a 2-year period was associated with a reduction in the CS dose and stabilisation of both DLco % predicted and FVC% predicted.

Table 2. Trends in FVC Decline in IPF patients at 1-Year Follow-up

	No Treatment	Triple-Drug Combination (prednisone, azathioprine plus N-acetylcysteine)	MMF	P value
Change in FVC from the baseline (mL)	–239	–165	–76.3	NS
% of patients with absolute change in FVC <10%	50	57	87.5	NS
% of patients with absolute change in FVC ≥10%	50	43	12.5	NS

FVC: Forced vital capacity; IPF: Idiopathic pulmonary fibrosis; MMF: Mycophenolate mofetil; NS: Not significant.

Table 3. Comparative AEs with Immunosuppressive Therapies

AEs
Chronic HP	Prednisolone	MMF	Azathioprine	Cyclophosphamide
Adegunsoye A et al. (2017)	104 events	30 events; 66% less frequent compared with steroids (P = 0.002)	45 events (P = 0.04)	NS
Morisset et al. (2017)	NS	13.7%	15.8%	NS
Myositis-ILD
Huapaya et al. (2019)	NS	13.6%	33.3% (P = .04)	NS
Systemic Sclerosis
Tashkin DP et al. (2016)
Leukopenia	NS	6%	NS	41%
Neutropenia	NS	4%	NS	7%
Anemia	NS	12%	NS	18%
Thrombocytopenia	NS	0	NS	6%
Hematuria	NS	4%	NS	3%
Pneumonia	NS	7%	NS	6%
Owen C et al. (2016)	NS	18.2%	26.5%	NS

AEs: Adverse events; Chronic HP: Chronic hypersensitivity pneumonitis; MMF: Mycophenolate mofetil; NS: Not studied