Persistence with second-line biologic therapies in patients with psoriasis: a prospective observational cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR)

Patients with psoriasis who fail treatment with one biologic therapy, either due to adverse events (AEs) or ineffectiveness, are frequently switched to a second one. However, little is known about the persistence of second-line biologic therapy in routine clinical practice or whether the reason(s) for failing the first-line biologic is predictive of failure of the second. We assessed the persistence of second-line biologic therapies and estimated the risk of recurrent discontinuation due to AEs and ineffectiveness in a prospective cohort of 1239 psoriasis patients (adalimumab,538; etanercept,104; ustekinumab,597) registered with BADBIR,who failed their first biologic for any reason,and had ≥1 dermatology follow-ups after switching to the second biologic. The persistence rates were compared using persistence analysis techniques and predictors of discontinuation were analyzed using a multivariable Cox proportional hazard model.
Overall, 1181(95.3%) of those patients who were switched to a second-line biologic failed first-line tumour necrosis factor inhibitors (TNFIs), while 47(3.8%) and 11(0.9%) patients failed first-line ustekinumab and other biologics, respectively. Patients who failed first-line TNFIs were switched to second-line ustekinumab (50.4%), adalimumab (41.7%), and etanercept (7.9%); while 89.4% of patients failing first-line ustekinumab were switched to second-line adalimumab. Persistence data were available for a mean follow-up of 2.7±1.6 person-years. The overall persistence rate in the first year after switching was 77%, falling to 58% by the third year. A sensitivity analysis investigating the impact of switching from first-line TNFIs showed a similar overall persistence rate as the overall patient cohort. Multivariable regression analysis showed that female gender, multiple comorbidities, concomitant therapy with ciclosporin, and a higher psoriasis area severity index at the time of switching were predictors of discontinuation. Following switching, compared to adalimumab, patients on etanercept were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist. First drug discontinuation due to AEs was associated with an increased rate of second drug discontinuation due to this reason (hazard ratio 2.48; 95% confidence intervals: 1.48-4.16). There was no increased risk of drug discontinuation due to ineffectiveness in those patients who discontinued their first biologic for this reason (0.97;0.65-1.44).
Psoriasis patients who are switched to a second biologic have high rates of one-year persistence. Second-line discontinuation due to AEs was more common among those who discontinued first-line treatment for this reason. This large prospective cohort study from the UK provides the first estimates of the magnitude of this effect in patients with psoriasis.The results of this study will aid clinical decision making when choosing second-line biologic therapy for psoriasis patients.