Monitoring and Caring for Adult Patients with Progressive Pulmonary Fibrosis

Dr. Ekaterini Zapantis partnered with Boehringer Ingelheim to share the health messages below. Dr. Zapantis is a paid consultant for Boehringer Ingelheim.

Progressive pulmonary fibrosis (PPF) is a progressive lung condition that can cause a decline in lung function.^1,2 It affects around 100,000 people in the U.S.^2,3

While PPF can arise from unknown causes, it is most often linked to an underlying clinical interstitial lung disease (ILD) diagnosis.^1,4 Sometimes caused by exposure to external environmental substances and/or occupational dusts or fibers, PPF is also associated with autoimmune diseases, including rheumatoid arthritis, scleroderma, and mixed connective tissue disease.^4,5

“ILD’s nonspecific symptoms can delay or lead to misdiagnosis, which can allow further loss of lung function,” says Ekaterini Zapantis, MD, Managing Partner and Chief Medical Officer, Rheumatology Center of WNY. “Because PPF can occur at any stage of an autoimmune disease, as rheumatologists, it is important that we monitor our patients closely for the clinical signs of PPF progression — including worsened respiratory symptoms, declines in forced vital capacity, and/or increases in the fibrotic changes seen on imaging scans — so disease progression can be identified on a timely basis.”

Collaborative Care for those with PPF

Rheumatologists play an important role in the collaborative care model often used to manage those with PPF.

“Management of my patients with PPF is highly collaborative with pulmonologists,” shares Dr. Zapantis. “We co-manage these patients through shared decision-making strategies. Pulmonologists typically guide lung-specific monitoring while I focus on systemic disease control. We work closely to ensure all aspects of a patient’s care plan are considered and keep each other informed of our clinical findings.”

Treatment options for PPF have historically been limited, but in December 2025 the U.S. Food and Drug Administration (FDA) approved JASCAYD (nerandomilast) tablets for the treatment of adults with PPF.⁶

IMPORTANT SAFETY INFORMATION
ADVERSE REACTIONS

• The most common adverse reactions with an incidence of ≥5% in patients treated with JASCAYD were diarrhea, COVID-19, upper respiratory tract infection, depression, weight decreased, decreased appetite, nausea, fatigue, headache, vomiting, back pain, and dizziness.

Please see additional Important Safety Information below.

JASCAYD is the first and only preferential inhibitor of phosphodiesterase 4B (PDE4B) approved by the FDA for the treatment of adults with PPF.^7,8,9 It inhibits phosphodiesterase 4 with at least nine-fold preferential inhibition of the PDE4B isoenzyme over PDE4A, PDE4C and PDE4D based on in vitro data.⁷ JASCAYD exerts both antifibrotic and immunomodulatory effects, thereby slowing the decline in lung function in PPF patients.⁷

Clinical Efficacy and Safety Data for JASCAYD in PPF

The FDA approval of JASCAYD in PPF was based on data from FIBRONEER™-ILD.⁷

At 52 weeks, JASCAYD demonstrated a significantly smaller decline in absolute change from baseline in FVC compared to placebo in adults with PPF.⁷ Patients receiving JASCAYD 18 mg or 9 mg showed an adjusted mean reduction of -86 mL and -69 mL in FVC, respectively, compared to -152 mL with placebo.⁷ The respective treatment difference compared with the placebo group was 65 mL (95% CI: 30, 101) and 83 mL (95% CI: 48, 118).⁷

Over the blinded duration of the trial (up to 109 weeks), there was no statistically significant treatment difference in the hazard ratio (HR) for the JASCAYD 18 mg or 9 mg groups compared to placebo for the key secondary composite endpoint (JASCAYD 18 mg or 9 mg groups, respectively, compared to placebo: HR 0.77 [95% CI: 0.59, 1.01] and HR 0.88 [95% CI: 0.68, 1.14]).⁷ An exploratory analysis over the blinded trial duration (up to 109 weeks) showed a nominally significant reduction in the risk of acute ILD exacerbations with JASCAYD 18 mg versus placebo (HR 0.60 [95% CI: 0.38, 0.94]), and a numerical reduction in the risk of hospitalization for respiratory cause with JASCAYD 18 mg versus placebo (HR 0.82 [95% CI: 0.61, 1.11]).⁷ Values shown here are for descriptive purposes.

Additionally, in the FIBRONEER™-ILD trial population, the HRs for all-cause mortality assessed until the end of the trial (up to 114 weeks) for JASCAYD 18 mg and 9 mg compared to placebo were 0.51 (95% CI: 0.34, 0.78) and 0.51 (95% CI: 0.34, 0.78), respectively.⁷ These results were not prespecified for multiplicity control.⁷

The most common adverse reactions in patients with PPF treated with JASCAYD were generally consistent with those observed in patients with idiopathic pulmonary fibrosis (IPF).⁷ In patients with IPF (FIBRONEER-IPF™ Trial), the most common adverse reactions with an incidence of ≥5% and more common than placebo in patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo were diarrhea (42%, 31%, and 17%, respectively), COVID-19 (13%, 16%, and 12%, respectively), upper respiratory tract infection (13%, 11%, and 10%, respectively), depression (12%, 11%, and 10%, respectively), weight decreased (11%, 10%, and 8%, respectively), decreased appetite (9%, 9%, and 5%, respectively), nausea (8%, 9%, and 7%, respectively), fatigue (7%, 8%, and 6%, respectively), headache (7%, 6%, and 5%, respectively), vomiting (6%, 5%, and 5%, respectively), back pain (6%, 5%, and 4%, respectively), and dizziness (5%, 6%, and 5%, respectively).⁷

Diarrhea was more common in patients using JASCAYD with concomitant nintedanib.⁷ In patients taking nintedanib, diarrhea occurred in 49%, 50%, and 37% of patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively.⁷ In patients without concomitant use of nintedanib, diarrhea occurred in 27%, 16%, and 16% of patients using JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively.⁷ In FIBRONEER™-ILD, diarrhea was the most common adverse reaction associated with treatment discontinuation and occurred most frequently in patients treated with JASCAYD 18 mg (4%) or JASCAYD 9 mg (3%) with background antifibrotic therapy versus patients receiving placebo (1%) and background antifibrotic therapy.⁷

Diarrhea leading to treatment discontinuation occurred in 1% of patients treated with JASCAYD 18 mg twice daily and in no patients treated with JASCAYD 9 mg or placebo without concomitant use of nintedanib.⁷ In most patients treated with JASCAYD, diarrhea was of mild to moderate intensity and generally occurred within the first three months of treatment.⁷

Weight decrease was more common in patients who received JASCAYD concomitantly with nintedanib, which occurred in 12%, 10%, and 9% of patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively.⁷ In patients without concomitant use of nintedanib, weight decrease occurred in 13%, 8%, and 5% of patients treated with JASCAYD 18 mg twice daily, JASCAYD 9 mg twice daily, and placebo, respectively.⁷

Among patients with PPF, neoplasms (benign, malignant, or unspecified) were reported in more patients with PPF treated with JASCAYD 18 mg (5%) or JASCAYD 9 mg (5%) than placebo (3%) over the entire study duration.⁷ Malignancies such as non-melanoma skin cancers and small cell lung cancer were observed in patients who received JASCAYD (basal cell carcinoma: JASCAYD 18 mg n=2 [1%] vs. JASCAYD 9 mg n=3 [1%] vs. placebo n=1 [0.3%]; squamous cell carcinoma of skin: JASCAYD 18 mg n=4 [1%] vs. JASCAYD 9 mg n=2 [0.5%] vs. placebo n=0; and small cell lung cancer: JASCAYD 18 mg n=4 [1%] vs. JASCAYD 9 mg and placebo n=0).⁷

Less common adverse reactions in the PPF population following administration of JASCAYD include atrial fibrillation (3% JASCAYD 18 mg twice daily, 2% JASCAYD 9 mg twice daily, and <1% placebo).⁷

JASCAYD in a Collaborative Care Model

“PPF can progress at different rates from person to person, so it is important to closely monitor patients for signs of worsening lung function and adjust their care strategy as needed,” says Dr. Zapantis. “The approval of JASCAYD represents an important expansion of therapeutic options for patients with PPF, an expansion that I hope encourages deeper collaboration between rheumatology and pulmonology.”

IMPORTANT SAFETY INFORMATION (CONTINUED)
DRUG INTERACTIONS
Effects of Other Drugs on JASCAYD

• Strong CYP3A Inhibitors: Reduce the dosage of JASCAYD to 9 mg twice daily when used concomitantly with strong CYP3A inhibitors. Nerandomilast is a CYP3A substrate. Concomitant use of JASCAYD with a strong CYP3A inhibitor increases exposure of nerandomilast, which may increase the risk of JASCAYD adverse reactions.
• Strong or Moderate CYP3A Inducers: Avoid concomitant use of strong CYP3A inducers with JASCAYD. Recommended dosage of JASCAYD is 18 mg twice daily when used concomitantly with moderate CYP3A inducers. Do not reduce the dosage to 9 mg twice daily. Nerandomilast is a CYP3A substrate. Concomitant use of JASCAYD with strong or moderate CYP3A inducers decreases exposure of nerandomilast, which may decrease the efficacy of JASCAYD.
• Pirfenidone: Recommended dosage of JASCAYD is 18 mg twice daily when used concomitantly with pirfenidone. Do not reduce the dosage to 9 mg twice daily. Concomitant use of JASCAYD with pirfenidone decreases exposure of nerandomilast. When JASCAYD was used concomitantly with pirfenidone in patients with IPF in FIBRONEER-IPF, efficacy was not observed with the JASCAYD 9 mg twice daily dosage.

USE IN SPECIFIC POPULATIONS

• Pregnancy: Advise female patients to contact their healthcare provider if they become pregnant or suspect they may be pregnant during treatment with JASCAYD. Advise female patients of the potential risk of fetal loss.
• Lactation: The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for JASCAYD and any potential adverse effects on the breastfed infant from JASCAYD or from the underlying maternal condition.
• Renal Impairment: Use of JASCAYD is not recommended in patients with end stage renal disease (eGFR <15 mL/minute/1.73 m²).
• Hepatic Impairment: Use of JASCAYD is not recommended in patients with severe (Child-Pugh Class C) hepatic impairment.

Please see full Prescribing Information for JASCAYD, including Patient Information.

References

1. Kondoh Y, Inoue Y. Adv Ther. 2025;42(7):2988–3001. DOI: 10.1007/s12325-025-03215-6.
2. Montero IE, Hernandez-Gonzalez F and Sellares J. Pulm Ther. 2025;11, 347–363. DOI: 10.1007/s41030-025-00302-5.
3. Monthly Population Estimates for the United States: April 1, 2020 to December 1, 2026. U.S. Census Bureau, Population Division; 2026. Accessed September 10, 2026. https://www2.census.gov/programs-surveys/popest/tables/2020-2025/national/totals/NA-EST2025-POP.xlsx.
4. Raghu G, Remy-Jardin M, Richeldi L, et al. Am J Respir Crit Care Med. 2022;205(9). DOI: 10.1164/rccm.202202-0399ST.
5. Cottin V, Hirani NA, Hotchkin DL, et al. Eur Respir Rev. 2018;27(150): 180076. DOI: 10.1183/16000617.0076-2018.
6. FDA Press Release. December 2025. Accessed February 4, 2026. Available at: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-treat-chronic-progressive-lung-disease.
7. JASCAYD® (nerandomilast). Prescribing Information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2026.
8. Drugs@FDA: FDA-approved drugs. US Food and Drug Administration. Accessed July 23, 2026. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=205832.
9. Drugs@FDA: FDA-approved drugs. US Food and Drug Administration. Accessed September 9, 2026. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022535.
10. Mulhall A, Droege C, Ernst, N, et al. Expert Opinion on Investigational Drugs. 2015 Sep 20; 24(12), 1597–1611. DOI: 10.1517/13543784.2015.1094054.