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An abstract of the article "Effects of meloxicam treatment on renal function in cats with degenerative joint disease," by R. A. Gowan and colleagues is presented.

Background: Idiopathic pulmonary fibrosis (IPF) predominantly affects individuals aged > 60 years who have several comorbidities. Nintedanib is an approved treatment for IPF, which reduces the rate of decline in forced vital capacity (FVC). We assessed the efficacy and safety of nintedanib in patients with IPF who were elderly and who had multiple comorbidities., Methods: Data were pooled from five clinical trials in which patients were randomised to receive nintedanib 150 mg twice daily or placebo. We assessed outcomes in subgroups by age < 75 versus ≥ 75 years, by < 5 and ≥ 5 comorbidities, and by Charlson Comorbidity Index (CCI) ≤ 3 and > 3 at baseline., Results: The data set comprised 1690 patients. Nintedanib reduced the rate of decline in FVC (mL/year) over 52 weeks versus placebo in patients aged ≥ 75 years (difference: 105.3 [95% CI 39.3, 171.2]) (n = 326) and < 75 years (difference 125.2 [90.1, 160.4]) (n = 1364) (p = 0.60 for treatment-by-time-by-subgroup interaction), in patients with < 5 comorbidities (difference: 107.9 [95% CI 65.0, 150.9]) (n = 843) and ≥ 5 comorbidities (difference 139.3 [93.8, 184.8]) (n = 847) (p = 0.41 for treatment-by-time-by-subgroup interaction) and in patients with CCI score ≤ 3 (difference: 106.4 [95% CI 70.4, 142.4]) (n = 1330) and CCI score > 3 (difference: 129.5 [57.6, 201.4]) (n = 360) (p = 0.57 for treatment-by-time-by-subgroup interaction). The adverse event profile of nintedanib was generally similar across subgroups. The proportion of patients with adverse events leading to treatment discontinuation was greater in patients aged ≥ 75 years than < 75 years in both the nintedanib (26.4% versus 16.0%) and placebo (12.2% versus 10.8%) groups. Similarly the proportion of patients with adverse events leading to treatment discontinuation was greater in patients with ≥ 5 than < 5 comorbidities (nintedanib: 20.5% versus 15.7%; placebo: 12.1% versus 10.0%)., Conclusions: Our findings suggest that the effect of nintedanib on reducing the rate of FVC decline is consistent across subgroups based on age and comorbidity burden. Proactive management of adverse events is important to reduce the impact of adverse events and help patients remain on therapy., Trial Registration: ClinicalTrials.gov NCT00514683, NCT01335464, NCT01335477, NCT02788474, NCT01979952.

Background: Nintedanib is an approved therapy for idiopathic pulmonary fibrosis (IPF). Some patients treated with nintedanib experience weight loss. Exploratory data suggest that low body mass index or weight loss are associated with worse outcomes in patients with IPF. We investigated whether BMI at baseline or weight loss over 52 weeks was associated with FVC decline, or influenced the effect of nintedanib, in patients with IPF., Methods: Using pooled data from the two INPULSIS trials, we analysed the rate of decline in FVC (mL/yr) over 52 weeks in patients treated with nintedanib and placebo in subgroups by baseline BMI (< 25; ≥25 to < 30; ≥30 kg/m 2 ) and by weight loss over 52 weeks (≤5; > 5%) using random coefficient regression., Results: In the placebo group, the mean rate of FVC decline over 52 weeks was numerically greater in patients with lower baseline BMI (- 283.3 [SE 22.4], - 207.9 [20.9] and - 104.5 [21.4] in patients with BMI < 25 kg/m 2 , ≥25 to < 30 kg/m 2 and ≥ 30 kg/m 2 , respectively). Nintedanib reduced the rate of FVC decline versus placebo in all subgroups by BMI, with a consistent treatment effect across subgroups (interaction p = 0.31). In the placebo group, the mean rate of FVC decline was numerically greater in patients with > 5% than ≤5% weight loss over 52 weeks (- 312.7 [SE 32.2] versus - 199.5 [SE 14.4] mL/year). Nintedanib reduced the rate of FVC decline versus placebo in both subgroups by weight loss, with a greater treatment effect in patients with > 5% weight loss (interaction p = 0.0008). The adverse event profile of nintedanib was similar across subgroups., Conclusions: In patients with IPF, lower BMI and weight loss may be associated with faster decline in FVC. Nintedanib reduces the rate of FVC decline both in patients who lose weight on treatment and those who do not., Trial Registration: ClinicalTrials.gov ; Nos. NCT01335464 and NCT01335477 ; URL: www.clinicaltrials.gov .

Background and Objective: The efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis (IPF) were investigated in the placebo-controlled INPULSIS® trials. All patients who completed an INPULSIS® trial could receive open-label nintedanib in the extension trial INPULSIS®-ON., Methods: We assessed the long-term efficacy and safety of nintedanib in patients of Asian race who were treated in INPULSIS®-ON. Analyses were descriptive., Results: A total of 215 Asian patients were treated in INPULSIS®-ON, of whom 121 continued nintedanib in INPULSIS®-ON and 94 initiated nintedanib in INPULSIS®-ON having received placebo in an INPULSIS® trial. At baseline of INPULSIS®-ON, the mean (SD) age of Asian patients was 66.3 (7.5) years, 80.5% were males and mean (SD) forced vital capacity (FVC) was 78.9 (19.3) % predicted. Median total exposure to nintedanib in both INPULSIS® and INPULSIS®-ON was 42.2 months; maximum exposure was 64.1 months. In INPULSIS®, the annual rate (SE) of decline in FVC over 52 weeks in Asian patients was -124 (20) mL/year in the nintedanib group and -218 (24) mL/year in the placebo group. In INPULSIS®-ON, the annual rate (SE) of decline in FVC over 192 weeks in Asian patients was -127 (11) mL/year. Diarrhoea was reported in Asian patients at event rates of 58.8 and 82.5 events per 100 patient exposure-years in patients who continued and initiated nintedanib in INPULSIS®-ON, respectively., Conclusion: The effect of nintedanib on slowing disease progression in Asian patients with IPF is sustained over the long term. Long-term treatment with nintedanib has an acceptable safety and tolerability profile., (© 2019 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Background: In the Phase III INPULSIS® trials, treatment of patients with idiopathic pulmonary fibrosis (IPF) with nintedanib significantly reduced the annual rate of decline in forced vital capacity (FVC) versus placebo, consistent with slowing disease progression. However, nintedanib was not associated with a benefit in health-related quality of life (HRQoL) assessed using the St George's respiratory questionnaire (SGRQ). We aimed to further examine the impact of IPF progression on HRQoL and symptoms, and to explore the effect of nintedanib on HRQoL in patients from the INPULSIS® trials stratified by clinical factors associated with disease progression., Methods: Patient-reported outcome (PRO) data from the INPULSIS® trials were included in three post hoc analyses. Two analyses used the pooled data set to examine PRO changes from baseline to week 52 according to 1) decline in FVC and 2) occurrence of acute exacerbations. In the third analysis, patients were stratified based on clinical indicators of disease progression (gender, age and physiology [GAP] stage; FVC % predicted; diffusing capacity of the lung for carbon monoxide [DL CO ] % predicted; composite physiologic index [CPI]; and SGRQ total score) at baseline; median change from baseline was measured at 52 weeks and treatment groups were compared using the Wilcoxon two-sample test., Results: Data from 1061 patients (638 nintedanib, 423 placebo) were analyzed. Greater categorical decline from baseline in FVC % predicted over 52 weeks was associated with significant worsening of HRQoL and symptoms across all PRO measures. Acute exacerbations were associated with deterioration in HRQoL and worsened symptoms. In general, patients with advanced disease at baseline (defined as GAP II/III, FVC ≤ 80%, DL CO  ≤ 40%, CPI >  45, or SGRQ > 40) experienced greater deterioration in PROs than patients with less-advanced disease. Among patients with advanced disease, compared with placebo, nintedanib slowed deterioration in several PROs; benefit was most apparent on the SGRQ (total and activity scores)., Conclusions: In patients with advanced IPF, compared with placebo, nintedanib slowed deterioration in HRQoL and symptoms as assessed by several PROs. HRQoL measures have a higher responsiveness to change in advanced disease and may lack sensitivity to capture change in patients with less-advanced IPF.

Background: We explored the impact of FVC decline on subsequent FVC decline and mortality in the INPULSIS trials of nintedanib in patients with IPF and their open-label extension, INPULSIS-ON., Methods: Changes in FVC and mortality between weeks 24 and 52 of the INPULSIS trials were assessed in patients with an increase/no decline in FVC % predicted and with declines in FVC <10% and ≥10% predicted from baseline to week 24. Changes in FVC and mortality in the first year of INPULSIS-ON were assessed in patients treated with nintedanib in the preceding INPULSIS trial who did and did not have a decline in FVC ≥10% predicted at week 52., Results: The proportion of placebo-treated patients with decline in FVC ≥10% predicted between weeks 24 and 52 of INPULSIS was similar in patients with increase/no decline in FVC and with decline in FVC ≥10% predicted between baseline and week 24 (20.5% and 18.9%, respectively). Mortality between weeks 24 and 52 of INPULSIS was higher in patients with FVC decline ≥10% predicted than <10% predicted between baseline and week 24 (13.2% vs 3.8%). Among nintedanib-treated patients in INPULSIS who had decline in FVC ≥10% versus <10% predicted at week 52, 34.0% versus 21.4%, respectively, had decline in FVC ≥10% predicted in the first year of INPULSIS-ON. Mortality in the first year of INPULSIS-ON was 21.3% vs 5.7% in these groups, respectively., Conclusions: Decline in FVC did not predict FVC decline but was associated with mortality in patients with IPF., (Copyright © 2019 Elsevier Ltd. All rights reserved.)