Switching anti-TNF therapy in ankylosing spondylitis.

SIR, The introduction of anti-TNF drugs has revolutionized the management of ankylosing spondylitis (AS) [1] and the efficacy of these drugs has been confirmed in clinical trials [2–4]. However, a significant proportion of patients withdraw from treatment because of inadequate efficacy (IE) or adverse effects (AEs). Because there are significant differences between chemical structure of anti-TNF drugs and mechanism of action there is a rationale for switching in these circumstances. Data from patients with RA suggest that switching from one anti-TNF drug to another is effective [5] and now it has become common practice to switch in RA.Very few data however are available regarding the potential benefits of switching in AS. Coates et al. [6] report a favourable clinical outcome from their cohort of whom 15 patients were switched to a second drug; 14 showed a significant and sustained response. To our knowledge, this is the first study addressing anti-TNF drugs and switching in patients with established AS. A retrospective analysis was undertaken of all patients with severe AS treated with anti-TNF therapy at the Norfolk and Norwich University hospital (NNUH) and Northwick Park hospital (NPH). All patients fulfilled the British Society for Rheumatology (BSR) eligibility criteria that requires patients to have met the modified New York Criteria. From these individuals those who switched treatment either due to IE or AEs were identified. Response to treatment was defined as a fall in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) of 50% or 2 units compared with baseline at 3 months (BSR response criteria). Treatment response was evaluated at 3 months and at 6 and 12 months. Infliximab (IFX) was prescribed at 3 or 5 mg/kg, 6–8 weekly intravenously (3 mg/kg, 8 weekly at NNUH; 5 mg/kg, 6–8 weekly at NPH). Etanercept (ETA) and adalimumab (ADA) were prescribed according to the standard licensing regimen. The Wilcoxon signed-rank test was used to assess statistical significance in treatment responses. One hundred and eight AS patients (86 males) received antiTNF therapy (43 IFX, 41 ETA and 24 ADA). The median (IQR) duration of follow-up was 33 (23–46) months, median age 45 (38–54) yrs and median disease duration 13 (7–19) yrs. Sixteen of 108 (15%) patients (12 males) were switched to a second anti-TNF drug and two of them to a third drug, comprising 18 switch episodes. The mean disease duration of the switched patients was 13 (range 3–36) yrs, mean duration of treatment prior to switching 11 (range 5–37) months and mean period of follow-up after switching 13 (range 1–42) months. Switching was due to IE in 67% (IFX: 7, ETA: 5) and AE in 28% (IFX: abnormal LFTs, diverticulitis; ADA: injection site reaction, leukopenia; ETA: abnormal LFTs). Two patients were switched twice, the first from IFX to ADA due to his own choice and from ADA to IFX due to leukopenia.The second patient switched from ETA to IFX due to IE and from IFX to ADA due to IE and stopped treatment 3 months later due to continuing IE. Of the seven patients who switched from IFX due to IE, five were taking IFX 3 mg/kg, 6 weekly (NNUH patients started treatment with 3 mg/kg, 8 weekly) and two were on 5mg/kg (NPH). Eleven of 17 (65%) responded at 3 months and one stopped after 1 month due to AE. Ten of 15 (67%) and six of seven (86%) maintained response at 6 and 12 months, respectively. Table 1 illustrates the changes in the BASDAI post-switching. At 12 months, six of seven (86%) were continuing treatment (IFX: 2, ADA: 2, ETA: 2). No major AEs were seen. Five of 16 patients had IE with their second drug and stopped treatment instead of switching to a third agent. These results may need to be interpreted with caution because of the study design (retrospective observational cross-sectional study with heterogeneous follow-up durations). The data on follow-up ranged from 1 to 42 months and was incompletely available in three patients who had received treatment just over 6 months. Patients who switched because of AE showed a slightly better response than those who changed due to IE. Of the five patients with AE who switched, four responded at their last clinic review; however, of the 12 who switched because of IE only five responded. As many of our patients switched because of IE than AE, the response rate seen in our cohort is slightly less and contrasts with what has been reported by Coates et al. [6]. In our experience, the likelihood of sustained benefit from a second anti-TNF blocker in patients with AS who are intolerant or unresponsive to their first anti-TNFagent is similar to the efficacy seen following initial treatment. This suggests that switching from one anti-TNFdrug to another is an effective and worthwhile treatment strategy in some AS patients.