Long‐term, real‐world efficacy of biologics for psoriasis: a single centre's experience

Dear Editor, Biologic therapies have revolutionized the management of moderate‐to‐severe chronic plaque psoriasis and have been life transforming for many patients. The first biologic to be licensed for psoriasis in the U.K. was efalizumab in 2004 and there are now nine licensed by the European Medicines Agency for the indication of moderate‐to‐severe disease. A key determinant in choosing a biologic for an individual patient is the likelihood of long‐term efficacy, and for some there is compelling evidence that monotherapy can result in long‐term disease control. Prospectively collected registry data in the U.K., primarily from the British Association of Dermatologists Biologics and Immunomodulators Register,1 and focused on biologic‐naive patients with psoriasis, demonstrate that survival of response with biologic therapies decreases over time from 77% in the first year to 53% in the third year.2 Studies in other countries have shown similar results.3,4,5,6 Secondary failure occurs when there is inadequate control of the disease after an initial response to biologic therapy. Drug levels, immunogenicity, compliance, female sex, body mass index and smoking status have all been implicated as playing a role in biologic failure.3 However, the mechanism of drug failure is not fully understood. Stratified medicine studies, such as Psoriasis Stratification to Optimise Relevant Therapy (PSORT), are ongoing to ascertain the key, reproducible clinical, genetic and immune biomarker predictors of response of psoriasis in an individual to any given biologic.7 Further research is needed to elucidate why this occurs at different time intervals in individual patients on the same drug. We conducted a retrospective descriptive study at a single U.K. dermatology centre (Salford Royal NHS Foundation Trust, Manchester) to report real‐world long‐term data of patients with chronic plaque psoriasis on infliximab, etanercept, adalimumab and ustekinumab. Patients with psoriasis maintained on these drugs as monotherapy for 8 years or longer were included. Clinical data, including Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), were collected prior to starting the biologic and at each subsequent outpatient visit. At the time of analysis a total of 560 patients with psoriasis were on the aforementioned biologics (17 infliximab, 38 etanercept, 239 adalimumab, 266 ustekinumab), of whom 68 (12%) had sustained clinical efficacy on the same biologic for at least 8 years; their demographics are shown in Table 1. The other 492 patients were excluded as they did not meet the eligibility criteria. There was a higher proportion of men (n = 47, 69%) with a sustained response compared with women (n = 21, 31%). Smoking status was recorded, with 47% (n = 32) being ex‐smokers, 26% (n = 18) current smokers and 26% (n = 18) nonsmokers. Most patients (81%) were obese, with a body mass index between 30 and 35 kg m−2. Summary of patient characteristics and response to biologics BMI, body mass index; PASI, Psoriasis Area and Severity Index; DLQI, Dermatology Life Quality Index. Summary of patient characteristics and response to biologics BMI, body mass index; PASI, Psoriasis Area and Severity Index; DLQI, Dermatology Life Quality Index. The age at onset of psoriasis ranged from 1 to 61 years, with most patients developing psoriasis in their twenties. Forty per cent (n = 27) had confirmed psoriatic arthritis and 69% (n = 47) had a positive family history. All patients were on the same biologic for 8 years or longer (nine infliximab, seven etanercept, 28 adalimumab, 24 ustekinumab). The mean PASI values at baseline and after 8 years are shown in Table 1. There was also a sustained improvement in DLQI after 8 years. There were no serious side‐effects reported with etanercept, ustekinumab or adalimumab in this cohort. Recurrent chest and skin infections were the most common adverse events reported with infliximab. These data are from a single centre and are limited in number. However, to our knowledge this is one of the longest reported real‐world studies on patients with psoriasis, maintaining efficacy and acceptable safety on biologic monotherapy for 8 years or longer. There are still unanswered questions as to why biologics fail to sustain an adequate clinical response in all patients. Our data show that in a small proportion of patients (12%) a long‐term satisfactory clinical response is possible. Further studies, as exemplified by PSORT, are needed to understand better the determinants of drug failure and persistent response, but these long‐term responders evince clues that may allow identification of key reasons for such success. This may ultimately lead to a personalized approach in developing and choosing the ideal biologic for any patient first time. Funded in part by the NIHR Manchester Biomedical Research Centre. Conflicts of interest: C.E.M.G. has acted as a consultant and/or speaker for AbbVie, Almirall, Bristol‐Myers Squibb, Celgene, Eli Lilly, Galderma, Janssen, LEO Pharma, MSD, Novartis, Pfizer Sandoz, Sun Pharmaceuticals and UCB. D.L. has acted as a consultant and/or speaker for AbbVie, Almirall, Celgene, Dermal, Janssen‐Cilag U.K., Lilly, Novartis, Pfizer U.K., Sanofi and UVB Pharma. R.B.W. has acted as a consultant and/or speaker for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sanofi, UCB and Xenoport.