Biological treatment of ankylosing spondylitis: a nationwide study of treatment trajectories on a patient level in clinical practice

Abstract

Background: There is substantial evidence that patients with ankylosing spondylitis (AS) have high response rates to tumour necrosis factor inhibitors (TNFi), a low likelihood of successful treatment termination, but yet a limited drug retention. Whereas several reports have assessed drug retention rates for TNFi in AS, there are few, if any, studies investigating the actual treatment trajectories on a patient level, including subsequent therapy changes and dose reductions, of individual patients. The aim of this study was to describe 5-year treatment trajectories in patients with ankylosing spondylitis (AS) starting a first TNFi.

Methods: Bio-naïve patients with AS starting a TNFi in 2006-2015 were identified in the nationwide Swedish Rheumatology Quality register and followed until 31 December 2015. All changes in their anti-rheumatic treatment during follow-up were recorded. To further increase precision, these data were complimented by information on the amount of prescribed subcutaneous TNFi collected from pharmacies during each year, retrieved from the Swedish Prescribed Drug Register.

Results: Two thousand five hundred ninety patients started a first TNFi 2006-2015, and after 1 year, 74% remained on their first TNFi. However, after 5 years, this figure was only 46%, although at that time 63% were still on treatment with any biologic, while 30% had no anti-rheumatic treatment at all. After discontinuing the first TNFi, 46% switched directly to a second TNFi, but the drug retention for the second and third TNFi grew successively shorter compared to that for the first TNFi. In contrast, patients remaining on treatment with their first subcutaneous TNFi gradually reduced the dose, so that during the fifth year of treatment only 66% had collected ≥ 75% of the defined daily doses for that year.

Conclusion: Less than half of patients with AS will remain on their first TNFi after 5 years, but most are still on a biologic. While patients remaining on treatment with their first TNFi appear to be able to reduce the dose over time, a large proportion cycle through several biologics, and 1/3 have no anti-rheumatic treatment after 5 years. This indicates the importance of thorough follow-up programs as well as a need for alternative therapeutic options.

Keywords: Ankylosing spondylitis; Observational; Treatment; Tumour necrosis factor inhibitor.

Fig. 1

a, b Current treatment after one to five whole years since starting a first TNFi. The figure describes the treatment status for bio-naïve patients with ankylosing spondylitis, 1–5 years after starting a first ever TNFi. (a) Patients who have either used > 3 different TNFi or cycled back to previous TNFi. (b) The solid black line indicates the percentage of the patients who are still on their first TNFi at the end of each year, and who have collected at least 75% of that year’s defined dose from a pharmacy. (c) The dotted black line indicates the percentage who were lost to follow-up (censored) due to death, emigration, “uncertain treatment status (see Methods)” or past the end of the study period. DDD = defined daily dose; csDMARDs = conventional synthetic disease-modifying anti-rheumatic drugs; TNFi = tumour necrosis factor alpha inhibitor; AS = ankylosing spondylitis

Fig. 2

Treatment trajectories for bio-naïve AS patients starting a first TNFi in 2006–2015. a The trajectories for all patients discontinuing their first TNFi within the study period 2006–2015 and prior to censoring (N = 1129). b All patients changing their treatment trajectory also a second time within the study period (N = 378). TNFi = tumour necrosis factor alpha inhibitor; AS = ankylosing spondylitis

Fig. 3

Survival probability plots, for drug retention in patients with ankylosing spondylitis starting a first TNFi 2006–2015. a Comparing the five different available TNFi, used as the first ever TNFi. b Comparing the first, second and third TNFi, with hazard ratios for TNFi discontinuation also adjusted for sex and age at the respective treatment start. TNFi = tumour necrosis factor alpha inhibitor; ADA = adalimumab; CER = certolizumab pegol; ETN = etanercept; GOL = golimumab; IFX = infliximab