Weight change in patients with psoriasis using tumour necrosis factor‐α inhibitors

Dear Editor, Psoriasis is a chronic, inflammatory, immune‐mediated disease, characterized by erythematous scaly plaques, and occurs in about 2–3% of the population. Tumour necrosis factor (TNF)‐α plays a role not only in the inflammatory cascade but also in body weight homeostasis, which could be disrupted by TNF‐α inhibitors, such as adalimumab, infliximab and etanercept, used for treatment of moderate‐to‐severe psoriasis. The goal of this study was to determine the association between the use of TNF‐α inhibitors and weight gain in patients with plaque psoriasis, based on available clinical trials. Ethics review is not required for this type of research at our institutions. The study was registered at PROSPERO (CRD42018104232). We included observational studies (cohort, case–control and cross‐sectional) and randomized controlled trials with adult patients (over 18 years old). Psoriasis diagnosis was confirmed by physicians, and severity based on Psoriasis Area and Severity Index score. This review was completed in accordance with PRISMA guidelines. The quality of individual publications was evaluated using the U.S. Preventive Services Task Force Quality Rating Criteria. Only studies considered ‘good’ or ‘fair’ were included. Meta‐analysis was based on the random‐effects model using Open Meta[Analyst] software (Brown University, Providence, RI, U.S.A.). Our search identified 2953 articles and 16 were selected for analysis. Of these, 15 were observational studies (six prospective and nine retrospective) and one was a randomized controlled trial. There were a total of n = 2935 patients with psoriasis. Three studies were of adalimumab, including a total of 125 patients. Two of these studies showed significant weight gain while on treatment. One retrospective study found a 2·23‐kg (P < 0·014) weight gain over 24 weeks,1 while another retrospective study revealed a (mean ± SD) 2·4 ± 6·4‐kg (P < 0·05) gain over the same duration of treatment.2 In the study by Al‐Mutairi and Nour, a 0·5‐kg weight gain was noted in patients over 24 weeks.3 Ten studies were of infliximab, including a total of 631 patients. Nine of the studies showed significant weight gain throughout the duration of treatment. Two studies showed significant weight increase of 2·5 ± 5·4 kg (P < 0·005)2 and 1·53 kg (P < 0·001)1 after 48 weeks of treatment. A prospective cohort study found a significant (2·5 ± 3·3‐kg; P = 0·004) increase in body weight after 7 months of treatment.4 A retrospective study revealed a 4·8 ± 5‐kg (P = 0·005) weight increase in 16 patients after 3 years of follow‐up.5 A cross‐sectional prospective multicentre study reported a 1·6‐kg increase over a 1‐year period where 48·2% of patients experienced a weight increment.6 Two studies over a treatment period of 24 weeks found a weight gain of 2·5 ± 3·3 kg (P = 0·004) in 40 patients,7 and a 2‐kg increase in 81 patients.3 Six studies were of etanercept, including a total of 371 patients. Four of the studies showed significant weight gain. A retrospective study found a significant weight increase of 1·5 ± 2·7 kg (P < 0·001) in 58 patients over a 24‐week treatment period.7 Another reported a significant increase of 2·18 kg at week 48 of treatment.1 Esposito et al. found a significant weight gain of 3·1 ± 6·3 kg over 24 weeks of treatment.8 Another retrospective study revealed a 0·1 ± 6·5‐kg loss (P > 0·1) over 48 weeks.2 Finally, in the study by Al‐Mutairi and Nour, mean weight gain was 1·6 kg over 24 weeks.3 Eight studies, comprising 685 patients, were selected for meta‐analysis to determine the association between treatment with a TNF‐α inhibitor and weight gain. Data for infliximab was reported in five studies (412 patients) and for etanercept (219 patients) in three studies. There was one study remaining for adalimumab with a complete set of results and a meta‐analysis could not be performed for this therapy. The forest plot for all of the TNF‐α inhibitors combined found a 2·08‐kg increase [95% confidence interval (CI) 1·56–2·61], over an average duration of therapy of 39 weeks, with measure of consistency (I2) equal to 50·78% (P = 0·039) (Fig.1). Body mass index (BMI) change in all TNF‐α inhibitors combined found a 0·98‐unit increase (95% CI 0·18–1·77) with I2 = 97·65% (P < 0·001) (data not shown). Weight gain of 2·33 kg over 40 weeks was found for infliximab (95% CI 1·88–2·78) with I2 = 50·78% (P = 0·671). For etanercept, there was a 1·57‐kg (95% CI 0·08–3·05) weight increase over 34 weeks with the resulting I2 = 80·35% (P = 0·006). Forest plot of weight gained in kg after treatment period with a tumour necrosis factor‐α inhibitor. CI, confidence interval. The study has limitations, as most reports include data for up to 24–48 weeks of follow‐up, so it is difficult to determine the trajectory of weight change over time. Most studies report change in body weight or BMI; however, this does not specify change in percentage of body fat or central adiposity, which is a more sensitive predictor of increased morbidity. Our meta‐analysis suggests there is an association between TNF‐α inhibitors and increased body weight in patients with psoriasis, with infliximab leading to more substantial weight gain compared with etanercept. Clinicians should monitor patient weights at each clinic visit and provide appropriate lifestyle counselling during treatment. A.M. and P.F. had full access to all of the data in the study and take responsibility for the acquisition, integrity, analysis and interpretation of the data; the accuracy of the data analysis; and drafting of the manuscript. All authors were responsible for study concept and design, and critical revision of the manuscript for important intellectual content. A.M. carried out the statistical analysis. A.M. and W.P.G. undertook study supervision. Funding sources: none. Conflicts of interest: P.F. has received honoraria and/or consulting fees for AbbVie, Galderma, L'Oréal and Eli Lilly, and has attended investigator meetings for Glenmark and Incyte. W.P.G. has received honoraria from AbbVie, Amgen, Celgene, Cipher, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, Pfizer, Roche and Valeant for participation on advisory boards, consultant services and speaker engagements; he has also received grant/research support/clinical trials from AbbVie, Amgen, Astellas, Celgene, Lilly, Novartis, Pfizer and Regeneron. A.M. has no conflicts of interest to declare.

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