ABSTRACT

Context: Methylxanthines continue to play a role in the management of chronic respiratory diseases; however, real-world evidence on the etophylline-theophylline combination remains limited. Aims: To evaluate the safety and effectiveness of Deriphyllin (Fixed-dose combination of etophylline + theophylline manufactured by Zydus Healthcare Limited) as add-on therapy in patients with asthma, chronic obstructive pulmonary disease (COPD), and related respiratory disorders in routine clinical practice. Settings and Design: Prospective, multicenter, observational real-world study conducted across 400 sites in India. Methods and Material: A total of 4,001 adults (>18 years) newly initiated on etophylline + theophylline combination were followed for up to 3 months. The primary outcome was safety assessed through adverse event monitoring. Secondary outcomes included changes in modified Medical Research Council (mMRC) dyspnea grade, COPD Assessment Test (CAT), and Asthma Control Test (ACT) scores, along with physician global assessment and patient satisfaction. Results: The cohort (mean age 52.09 ± 13.56 years; 70.71% male) included asthma (52.84%) and COPD (38.67%) patients. Severe dyspnea (mMRC grades 3-4) decreased from 62.70% at baseline to 0.20% at 3-month follow-up (X² = 5185.18; p < 0.0001). CAT scores improved from 30.65 ± 4.8 to 9.32 ± 6.54 (p < 0.0001) for COPD patients and ACT scores from 12.58 ± 4.3 to 20.96 ± 2.64 (p < 0.0001) for asthma patients. Adverse events occurred in 7.17%, predominantly mild gastrointestinal symptoms. All patients underwent cardiac monitoring, and no arrhythmias were observed during the study period. Physician and patient satisfaction ratings were excellent/very good in 89.72% and 91.30% of cases, respectively. Conclusion: In this large real-world study, etophylline-theophylline as add-on therapy demonstrated clinically meaningful improvements in mMRC, CAT, and ACT scores exceeding minimal clinically important difference (MCID) thresholds, a favorable safety profile (7.17% adverse events; no cardiac arrhythmias), and high physician (89.72%) and patient (91.30%) satisfaction, supporting its role as a safe and effective first oral add-on option in persistent respiratory disease.