LNSLNS

We would like to respond to this letter to the editor. We have not written in our introduction that theophylline is of little benefit in COPD and associated with risks. We stated that it presently is regarded a third-line treatment (1). The studies conducted so far were generally not aimed at evaluating side effects of theophylline as a primary outcome measure. The one exception is the cohort study of Cyr et al. with 36 492 COPD patients (2). This study, however, did not use a causal method to identify theophylline effects and it found no evidence of severe side effects. Other than that, RCTs have so far been rather small, as stated already in the Discussion section. Therefore, the observed effects could also have occurred randomly, or only the inferiority of theophylline compared with other drugs was demonstrated without evidence of a definitive potential for harm (3). In this respect, we consider our routine data analysis to be an important and complementary contribution, also from an ethical perspective, as we were the first to decidedly demonstrate these effects with regard to exacerbations and hospitalizations. Furthermore, our analysis reveals that theophylline is still a commonly used drug. After all, 5.6% of the patients observed by us received theophylline. Since any matching or adjustments can only be performed with observed or accessible measures, we wrote that the pharmacological efficacy or the side effects can ultimately only be demonstrated in RCTs. Maybe we went too far with our assumption that ethics committees will not approve such studies. We would therefore welcome any suggestions on how such a study could get approved and be realized. Finally, it should be noted that reproducible analyses of routine data represent a valuable addition to evidence from RCTs.

DOI: 10.3238/arztebl.2014.0646b

Dr. med. Michael Mehring

Prof. Dr. med. Antonius Schneider

Johannes Fexer

Institut für Allgemeinmedizin, Technische Universität München

michael.mehring@tum.de

Ewan Donnachie

Dr. rer. nat. Manfred Keller

Dr. rer. nat. Frank Hofmann

Kassenärztliche Vereinigung Bayerns, München

Prof. Dr. oec. Publ. Stefan Wagenpfeil

Institut für Medizinische Biometrie, Epidemiologie und Medizinische Informatik (IMBEI), Universitätsklinikum des Saarlandes, Homburg/Saar

Conflict of interest statement

Prof. Schneider is an external expert for the DMP COPD in the Federal Joint Committee (G-BA). He has received fees for training presentations for DMP Asthma/COPD by the Bavarian Association of Statutory Health Insurance Physicians (KVB).

The remaining authors declare that no conflict of interest exists

1.
Fexer J, Donnachie E, Schneider A, et al.: The effects of theophylline on hospital admissions and exacerbations in COPD patients: audit data from the bavarian disease management program. Dtsch Arztebl Int 2014; 111: 293–300 VOLLTEXT
2.
Cyr MC, Beauchesne MF, Lemiere C, Blais L: Effect of theophylline on the rate of moderate to severe exacerbations among patients with chronic obstructive pulmonary disease. British journal of clinical pharmacology 2008; 65: 40–50 CrossRef MEDLINE PubMed Central
3.
Rossi A, Kristufek P, Levine BE: Comparison of the efficacy, tolerability, and safety of formoterol dry powder and oral, slow-release theophylline in the treatment of COPD. Chest 2002, 121: 1058–69 CrossRef MEDLINE
1.Fexer J, Donnachie E, Schneider A, et al.: The effects of theophylline on hospital admissions and exacerbations in COPD patients: audit data from the bavarian disease management program. Dtsch Arztebl Int 2014; 111: 293–300 VOLLTEXT
2.Cyr MC, Beauchesne MF, Lemiere C, Blais L: Effect of theophylline on the rate of moderate to severe exacerbations among patients with chronic obstructive pulmonary disease. British journal of clinical pharmacology 2008; 65: 40–50 CrossRef MEDLINE PubMed Central
3.Rossi A, Kristufek P, Levine BE: Comparison of the efficacy, tolerability, and safety of formoterol dry powder and oral, slow-release theophylline in the treatment of COPD. Chest 2002, 121: 1058–69 CrossRef MEDLINE

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