Background/Purpose

We conducted a single center double-blind, randomized, placebo-controlled trial to determine the effects of oral Tadalafil on lung function and health-related symptoms in patients with scleroderma-related interstitial lung disease (ILD).

Methods

We enrolled 39 patients with scleroderma- related ILD patients who received oral Tadalafil 20 mg or matching placebo every alternate day for 6 months. The primary outcome measure was change in forced vital capacity (FVC, expressed as % of the predicted value) from baseline values  and secondary outcome measures were change in Diffusion Lung Capacity for Carbon Monoxide (DLCO), Total Lung Capacity (TLC), Health Assessment Questionnaire (S HAQ), Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36) and 6 min walk distance at the end of 6 months of treatment with Tadalafil in comparison to placebo group.

Results

Of 39 patients, 30 completed 6 months of treatment and were included in the analysis.  At 6 month, although there was no statistically significant difference in change in FVC (% predicted) from baseline between the 2 groups, patients receiving Tadalafil had shown an improvement in mean (+SE) FVC of 1.82±2.08 whereas patients in placebo group had no change in mean FVC. Out of secondary outcome measures, the only significant difference between the 2 groups was found in patient global assessment scores which was significantly improved in Tadalafil group (p<0.05). There was a trend for improvement in TLC, breathing score in  visual analogue scale (VAS) and  physician global assessment score favoring Tadalafil although the difference between the 2 groups were not significant (P>0.05). There was no significant difference in adverse events between both groups. 

Conclusion

Treatment with 6 month oral Tadalafil (20 mg alternate days) in patients with  scleroderma-related ILD resulted in improvement in patient global assessment score. There was a trend for improvement for lung function, physician global assessment and VAS breathing scores. A larger multicentric study with sufficient power and high dose of Tadalafil may determine the efficacy of Tadalafil in ILD.

Table: Change in  outcome measures  from Baseline to 6 month in Tadalafil vs placebo group

Characteristics	Baseline	Value at 6 month	Difference
Tadalafil Group (n 17)
FVC (%Predicted)	49.18±3.81	51.0 ±4.06	1.82±2.08
TLC (%Predicted)#	75.70±5.18	78.50±7.42	2.8±4.57
DLCO(%Predicted)#	36.30±3.51	35.9±4.95	-0.4±2.24
Mahler Dyspnoea score
Baseline Instrument	7.0±2.58
Transitional Dyspnoea score		2.47±0.77
VAS Breathing(mm)	54.12±9.15	24.71±6.99	-29.41±8.03
Physician global	60.12±5.14	33.41±5.22	-26.70±5.67
Patient global	73.41±5.88	31.35±5.83	-42.05±6.40*
SF36 (physical)	37.2±1.69	45.04±1.71	7.81±1.95
SF36(Mental)	37.02±2.85	45.88±2.88	8.85±3.28
Skin thickness score	17.71±2.11	15.94±2.71	-1.76±1.53
6 min walk test(meters)	426.69±34.08	472.65±22.83	47.06±11.33
RVSP (mm Hg)	31.71±2.67	29.59±2.47	-2.11±2.40
Placebo  Group (n 13)
FVC (%Predicted)	57.46±2.37	57.46±3.05	0±2.41
TLC (%Predicted)	78±3.92	75.29±4.71	-2.71±5.75
DLCO(%Predicted)	45.57±3.92	45.71±4.82	0.14±6.97
Mahler Dyspnoea score
Baseline Instrument	7.77±2.97
Transitional Dyspnoea score		2.31±0.90
VAS Breathing(mm)	22.38±8.28	12.31±4.53	-10.07±6.31
Physician global	45.31±6.67	32.62±8.77	-12.69±4.78
Patient global	49.07±7.51	32±8.84	-17.07±5.69
SF36 (physical)	43.03±2.65	48.64±2.29	5.61±2.43
SF36(Mental)	39.83±3.42	47.9±2.73	8.06±2.46
Skin thickness score	20.23±2.21	17.08±2.20	-3.15±2.08
6 min walk test(meters)	419.23±25.37	464.23±26.29	45±16.93
RVSP (mm Hg)	28.62±2.12	27.77±2.97	-0.84±3.06

Plus-minus values are means±SD. *p <0.05  for comparison with placebo group.

#Paired data for DLCO and TLC were available and analyzed for only 10 and 7 patients in Tadalafil and placebo group respectively.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-double-blind-randomized-control-trial-of-oral-tadalafil-in-interstitial-lung-disease-of-scleroderma/