COMPARISON OF INTERRUPTED AND CONTINUOUS MODULATOR THERAPY IN CYSTIC FIBROSIS: A REAL LIFE EXPERIENCE IN TURKEY

Almala Pinar Ergenekon^1*Merve Selcuk¹GÖKÇEN ÜNAL²Gamzegul Gozen Bayramoglu³Cansu Altuntas⁴Mehmet Kose⁵Abdurrahman Erdem Basaran⁶Sinem Can Oksay⁷Salih Uytun⁸Sedat Oktem⁹Zeynep Seda Uyan¹⁰Yakup Canitez¹¹Esen Demir¹²Velat Sen¹³Veysel Karakulak¹⁴Ela Erdem Eralp¹Bülent Taner Karadağ¹Fazilet Karakoc¹Sevgi Pekcan²Tugba Sismanlar Eyuboglu¹⁵Erkan Cakir⁴Yasemin Gokdemir¹

• ¹Marmara Universitesi, Istanbul, Türkiye
• ²Necmettin Erbakan Universitesi, Meram, Türkiye
• ³Gazi Universitesi, Ankara, Türkiye
• ⁴Istinye Universitesi, Istanbul, Türkiye
• ⁵Erciyes Universitesi, Talas, Türkiye
• ⁶Akdeniz Universitesi, Antalya, Türkiye
• ⁷Istanbul Medeniyet Universitesi, Istanbul, Türkiye
• ⁸Ankara Bilkent Şehir Hastanesi, Ankara, Türkiye
• ⁹Istanbul Medipol Universitesi Tip Fakultesi, Beykoz, Türkiye
• ¹⁰Koc Universitesi Tip Fakultesi, Istanbul, Türkiye
• ¹¹Bursa Uludag Universitesi Tip Fakultesi, Nilüfer, Türkiye
• ¹²Ege Universitesi Tip Fakultesi, Izmir, Türkiye
• ¹³Dicle Universitesi Tip Fakultesi, Diyarbakır, Türkiye
• ¹⁴Cukurova Universitesi Tip Fakultesi, Adana, Türkiye
• ¹⁵Gazi Universitesi Tip Fakultesi, Ankara, Türkiye

Introduction: Cystic fibrosis (CF) transmembrane conductance regulator protein (CFTR) modulators have significantly improved health outcomes in patients with cystic fibrosis (pwCF). However, in Turkey, access is limited due to lack of insurance coverage, and treatment is only granted in 3-month periods via court rulings. This study aimed to compare clinical outcomes between patients receiving continuous versus intermittent modulator therapy. Methods:In this retrospective multicenter study, data from 229 CF patients across 14 centers in Turkey who received highly effective modulator therapy (HEMT) for at least six months were analyzed. Patients were grouped based on whether they received treatment continuously (Group 1) or with interruptions (Group 2). Changes in percent predicted forced expiratory volume in one second (ppFEV₁) and body mass index (BMI) were evaluated at baseline, 3 months, and 6 months. For Group 2, ppFEV₁ was also assessed during interruption periods. Results: Of the 229 patients, 38.4% received continuous treatment while 61.5% experienced treatment interruptions. Both groups showed significant improvements in ppFEV₁ over six months (p < 0.001). However, Group 2 experienced a significant decline during interruption periods (p < 0.001), followed by recovery upon reinitiation. BMI also increased significantly in both groups (p < 0.05). Patients with baseline ppFEV₁ <70% showed greater improvement compared to those with milder disease. Conclusion: Short-term clinical outcomes in ppFEV₁ and BMI were similar between continuous and intermittent treatment. However, treatment interruptions may reduce cumulative benefits, potentially impacting long-term outcomes. Ensuring uninterrupted access to HEMT is essential, especially in low- and middle-income countries.