EXTENDED REPORT

Do rheumatoid arthritis patients in clinical practice benefit from switching from infliximab to a second tumor necrosis factor alpha inhibitor?

Elisabeth Hjardem¹, Mikkel Østergaard², Jan Pødenphant³, Ulrik Tarp⁴, Lis Smedegaard Andersen⁵, Jette Bing⁶, Elisabeth Peen⁷, Hanne Merete Lindegaard⁸, Vibeke Stevenius Ringsdal⁹, Anne Rødgaard¹⁰, Jens Skøt¹¹, Annette Hansen¹², Hans Henrik Mogensen¹³, Janne Unkerskov¹⁴, Merete Lund Hetland²

¹ Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark
² The Danish Database for Biological Therapies in Rheumatology (DANBIO), Hvidovre, Denmark
³ Copenhagen University Hospital, Herlev, Denmark
⁴ Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark
⁵ Rheumatism Hospital, University of Southern Denmark, Odense, Denmark
⁶ Department of Rheumatology, Copenhagen University Hospital, Frederiksberg, Denmark
⁷ Department of Rheumatology, Sydvestjysk Sygehus, Esbjerg, Denmark
⁸ Department of Internal Medicine, Section of Rheumatology, University Hospital, Odense, Denmark
⁹ Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark
¹⁰ Department of Rheumatology, Copenhagen University Hospital, Glostrup, Denmark
¹¹ Department of Rheumatology, Copenhagen University Hospital, Gentofte, Denmark
¹² Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
¹³ Department of Rheumatology, Hoersholm Hospital, Hoersholm, Denmark
¹⁴ Institute for Rational Pharmacotherapy, Danish Medicines Agency, Copenhagen, Denmark

Correspondence to:
Dr Merete Lund Hetland
Copenhagen University Hospital at Hvidovre, Department of Rheumatology 232, Kettegård Alle 30, DK 2650 Hvidovre, Denmark; merete.hetland{at}dadlnet.dk

Objective: To investigate the efficacy of switching to a second biological drug in rheumatoid arthritis (RA) patients.

Methods: Since 2000, Danish RA patients (n = 1021) receiving biological therapy have been registered in the nationwide DANBIO database. The first and second treatment series of patients, who switched therapy before 2005 (n = 235), were analysed for their reasons for switching, Disease Activity Score 28 (DAS28), DAS28 improvement, European League against Rheumatology (EULAR) response and drug survival. Most patients switched from infliximab to etanercept or adalimumab.

Results: Median survivals for switchers’ first/second treatment were 37/92 weeks (all patients’ first treatment 119 weeks). Reasons for switching were lack of efficacy (LOE; 109 patients), adverse events (AE; 72), other reasons (54). If patients experienced AE to the first drug, 15% had AE to the second. Median DAS28 improvements in first/second treatment at 3 months were: LOE switchers 1.1/1.6; AE switchers 1.5/0.8. In LOE switchers, a good/moderate EULAR response was more prevalent during the second treatment course than during the first (63% versus 54%, p = 0.02). AE switchers achieved similar EULAR responses to both treatments (59% versus 50%, p = 0.38).

Conclusion: LOE switchers had a better clinical response to the second treatment. AE switchers responded equally well to both treatments, with a low risk of discontinuing the second drug as a result of AE. Drug survival of the switchers’ second biological therapy was higher than of the first, but lower than that of non-switchers. No difference between various sequences of drugs were found. Danish post-marketing data thus support that RA patients may benefit from switching biological therapy.

Abbreviations: AE, Adverse event; DAS28, Disease Activity Score 28; DMARD, disease-modifying antirheumatic drug; EULAR, European League against Rheumatology; LOE, lack of efficacy; RA, rheumatoid arthritis; TNF, tumor necrosis factor alpha

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