Search

Prof. Warren reports grants and personal fees from Abbvie, grants and personal fees from Celgene, grants and personal fees from Eli Lilly, grants and personal fees from Novartis, personal fees from Sanofi, grants and personal fees from UCB|, grants and personal fees from Almirall, grants and personal fees from Amgen, grants and personal fees from Janssen, grants and personal fees from Leo, grants and personal fees from Pfizer, personal fees from Arena, personal fees from Avillion, personal fees from Bristol Myers Squibb, personal fees from Boehringer Ingelheim, outside the submitted work. We are grateful to all the patients who have contributed to PsoProtect I Me i , the professional and patient organisations who supported or promoted PsoProtect I M i e and for the input of Prof Lars Iversen, Prof Nick Reynolds, Prof Joel Gelfand, Ms Christine Janus and Ms Melissa Sweeney through their vital contributions. Dr. Di Meglio reports grants and personal fees from UCB, personal fees from Novartis, personal fees from Janssen, outside the submitted work. [Extracted from the article]

Summary: Background: Registry data suggest that people with immune‐mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID‐19) outcomes compared with patients receiving no systemic treatments. Objectives: We used international patient survey data to explore the hypothesis that greater risk‐mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. Methods: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk‐mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed‐effects model. Results: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk‐mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35–1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23–1·56). Shielding was associated with established risk factors for severe COVID‐19 [male sex (OR 1·14, 95% CI 1·05–1·24), obesity (OR 1·37, 95% CI 1·23–1·54), comorbidity burden (OR 1·43, 95% CI 1·15–1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27–1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36–1·80). Modest differences in the proportion shielding were observed across nations. Conclusions: Greater risk‐mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID‐19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence‐based patient communication on risk‐mitigation strategies and may help inform updated public health guidelines as the pandemic continues. What is already known about this topic? At the beginning of the coronavirus disease 2019 (COVID‐19) pandemic, patients with immune‐mediated inflammatory diseases (IMIDs) on targeted systemic therapies were considered to be at higher risk of severe COVID‐19.Subsequent clinician‐reported registry data suggest that targeted systemic therapy use is associated with fewer adverse COVID‐19 outcomes compared with no systemic therapy. What does this study add? We characterize shielding behaviour in 3720 patients with IMIDs from a global self‐report survey.Use of targeted systemic therapy associates with increased shielding behaviour, compared with standard systemics or no therapy, as do demographic risk factors for severe COVID‐19 including male sex and obesity.Greater risk‐mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID‐19 outcomes.Behaviour variation across treatment groups reinforces the need for clear, evidence‐based patient communication on risk‐mitigation strategies.These data may help to inform updated public health guidelines as the pandemic continues. Linked Comment: G. Becher and A.D. Burden. Br J Dermatol 2021; 185:7–8. [ABSTRACT FROM AUTHOR]

Summary: Background: Atopic dermatitis is the most common chronic inflammatory skin disorder, affecting up to 20% of children and 10% of adults in industrialized countries. This highly debilitating condition poses a considerable burden to both the individual and society at large. The pathophysiology of atopic dermatitis is complex, encompassing both genetic and environmental risk factors. Methods: This is a narrative review based on a systematic literature search. Conclusions: Dysregulation of innate and adaptive immunity plays a key role; however, recent epidemiological, genetic and molecular research has focused interest on skin barrier dysfunction as a common precursor and pathological feature. Current understanding of the aetiology of atopic dermatitis highlights disruption of the epidermal barrier leading to increased permeability of the epidermis, pathological inflammation in the skin, and percutaneous sensitization to allergens. Thus, most novel treatment strategies seek to target specific aspects of the skin barrier or cutaneous inflammation. Several studies have also shown promise in preventing atopic dermatitis, such as the early use of emollients in high‐risk infants. This may have broader implications in terms of halting the progression to atopic comorbidities including food allergy, hay fever and asthma. What's already known about this topic? Atopic dermatitis is a common and highly debilitating chronic inflammatory skin disorder.Immune dysregulation plays a key role, but recent evidence has shifted the focus to skin barrier disruption as the key precursor.Loss‐of‐function mutations in the filaggrin gene are the strongest known genetic risk factor, but there are numerous environmental and immunological factors that influence the disease manifestation and course.The current therapeutic armamentarium is limited to simple lipid‐based barrier‐enhancing emollients, topical anti‐inflammatory agents and systemic immunosuppressive therapies. What does this study add? We review how defects in structural epidermal proteins and environmental factors converge to impair skin barrier function, resulting in increased susceptibility to atopic dermatitis.We explore the impact of the defective skin barrier on immune responses and the skin microbiome, highlighting how the complex interplay between the skin barrier and immune activation determines the response to environmental factors such as allergens and microbes.We outline emerging strategies for treating and preventing atopic dermatitis. Linked Comment:Silverberg. Br J Dermatol 2019; 180:447–448. [ABSTRACT FROM AUTHOR]

Skin diseases affect one-third of the global population, posing a major healthcare burden. Deep learning may optimise healthcare workflows through processing skin images via neural networks to make predictions. A focus of deep learning research is skin lesion triage to detect cancer, but this may not translate to the wider scope of >2000 other skin diseases. We searched for studies applying deep learning to skin images, excluding benign/malignant lesions (1/1/2000-23/6/2022, PROSPERO CRD42022309935). The primary outcome was accuracy of deep learning algorithms in disease diagnosis or severity assessment. We modified QUADAS-2 for quality assessment. Of 13,857 references identified, 64 were included. The most studied diseases were acne, psoriasis, eczema, rosacea, vitiligo, urticaria. Deep learning algorithms had high specificity and variable sensitivity in diagnosing these conditions. Accuracy of algorithms in diagnosing acne (median 94%, IQR 86-98; n = 11), rosacea (94%, 90-97; n = 4), eczema (93%, 90-99; n = 9) and psoriasis (89%, 78-92; n = 8) was high. Accuracy for grading severity was highest for psoriasis (range 93-100%, n = 2), eczema (88%, n = 1), and acne (67-86%, n = 4). However, 59 (92%) studies had high risk-of-bias judgements and 62 (97%) had high-level applicability concerns. Only 12 (19%) reported participant ethnicity/skin type. Twenty-four (37.5%) evaluated the algorithm in an independent dataset, clinical setting or prospectively. These data indicate potential of deep learning image analysis in diagnosing and monitoring common skin diseases. Current research has important methodological/reporting limitations. Real-world, prospectively-acquired image datasets with external validation/testing will advance deep learning beyond the current experimental phase towards clinically-useful tools to mitigate rising health and cost impacts of skin disease., (© 2023. Springer Nature Limited.)

Serum adalimumab concentration is a biomarker of treatment response but therapeutic drug monitoring (TDM) is yet to be implemented in routine psoriasis care. We incorporated adalimumab TDM in a national specialized psoriasis service and evaluated it using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) implementation science framework. We undertook pre-implementation planning (validating local assays) and implementation interventions targeted to patients (pragmatic sampling at routine reviews), clinicians (introduction of a TDM protocol), and healthcare systems (adalimumab TDM as a key performance indicator). Over 5 months, 170 of 229 (74%) individuals treated with adalimumab received TDM. Clinical improvement after TDM-guided dose escalation occurred in 13 of 15 (87%) nonresponders with serum drug concentrations <8.3 μg/ml (median PASI reduction of 3.2 [interquartile range = 2.2-8.2] after 23.4 weeks) and in all nonresponders who had TDM-guided switch in biologic due to supratherapeutic drug concentrations (>8.3 μg/ml; n = 2) or positive antidrug antibody (n = 2) (PASI reduction of 7.8 [interquartile range = 7.5-12.9] after 20.0 weeks). Proactive TDM led to dose reduction in five individuals with clear skin and subtherapeutic or supratherapeutic drug concentrations; four (80%) sustained clear skin after 50 weeks (range = 42-52). Adalimumab TDM based on pragmatic serum sampling is clinically viable and may lead to patient benefit. Context-specific implementation interventions and systematic implementation assessment may bridge the biomarker research-to-practice gap., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic., Objectives: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence., Methods: Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence., Results: Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76]. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49)., Conclusions: These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes., Competing Interests: Conflict of interests J.W. has presented talks for Abbott, AbbVie, Bayer, Boehringer Ingelheim, Chiesi, Merck and Roche. K.J.M. reports personal fees from LEO Pharma and Novartis, outside the submitted work. H.M. reports grants from AbbVie, Almirall, Celgene, Dermal Laboratories, Eli Lilly, Janssen, LEO Pharma, T & R Derma and UCB, outside the submitted work. D.U. reports grants from AbbVie, Almirall, Amgen, Celgene, Dermal Laboratories, Eli Lilly, Janssen, LEO Pharma, T & R Derma and UCB, outside the submitted work. L.M. reports personal fees from AbbVie, Celgene, Janssen, LEO Pharma, Novartis and UCB, outside the submitted work. Additional disclosures from L.M. include Almirall, BMS and Lilly. H.B. reports personal fees from AbbVie, Almirall, Biocad, Boehringer-Ingelheim, Janssen, Kyowa Kirin, LEO Pharma, Novartis, Pfizer and UCB, outside the submitted work. F.C. reports consultancy fees from AnaptysBio, grants from Boehringer Ingelheim, outside the submitted work. C.D.l.C. reports personal fees from Boehringer Ingelheim and UCB Pharma; grants from Janssen, Pfizer, Sandoz, Sanofi; grants and personal fees from AbbVie, Novartis, outside the submitted work. P.D.M. reports grants and personal fees from UCB; personal fees from Janssen and Novartis, outside the submitted work. P.G. reports personal fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pierre Fabre, Sandoz and UCB, outside the submitted work. D.J. reports personal fees and nonfinancial support from AbbVie, Celgene, Janssen-Cilag, Lilly, LEO Pharma, MEDAC and Novartis; and personal fees from Amgen, outside the submitted work. L.P. reports grants and personal fees from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Janssen, Lilly, Novartis and UCB; and personal fees from Bristol Myers Squibb, Fresenius-Kabi, Mylan, Pfizer, Samsung-Bioepis, Sandoz, Sanofi, outside the submitted work. P.S. has done consultancies in the past for Sanofi 111017 and AbbVie 041217 (unpaid); has received departmental independent research grants for TREAT NL registry from pharma companies since December 2019; is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of diseases such as psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital; and is chief investigator of the systemic and phototherapy atopic eczema registry (TREAT NL) for adults and children, as well as one of the main investigators of the SECURE-AD registry. T.T. reports grants and personal fees from AbbVie, Almirall, Amgen, Arena Pharmaceuticals, Biocad, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, MSD, Novartis, Pfizer, Samsung-Bioepis and Sandoz, during the conduct of the study. R.B.W. reports grants from AbbVie, Almirall, Amgen, Celgene, Janssen, LEO, Lilly, Medac, Novartis, Pfizer and UCB. R.B.W. also reports consultancy fees from AbbVie, Almirall, Amgen, Arena, Astellas, Avillion, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DiCE, GSK, Janssen, LEO, Lilly, Medac, Novartis, Pfizer, Sanofi, Sun Pharma, UCB and UNION. H.W. is on the Board of the International Federation of Psoriasis Associations who have received grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, Novartis, Pfizer, Sun Pharma and UCB, outside the submitted work. J.B.G. reports personal fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, Sanofi and UCB, outside the submitted work. C.E.M.G. reports grants and personal fees from AbbVie, Janssen, Lilly and Novartis and UCB Pharma; and grants from Almirall, Amgen, BMS, LEO and Pfizer, outside the submitted work. J.N.B. reports grants and personal fees from AbbVie, J&J, Lilly and Novartis during the conduct of the study. J.N.B. has attended advisory boards, and/or received consultancy fees, and/or spoken at sponsored symposia, and/or received grant funding from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Samsung, Sun Pharma and UCB. C.H.S. reports grants from AbbVie, Novartis, Pfizer and Sanofi; and through consortia with multiple academic partners (psort.org.uk, BIOMAP-IMI.eu), outside the submitted work. S.K.M. reports departmental income from AbbVie, Almirall, Eli Lilly, Janssen-Cilag, Novartis, Sanofi and UCB, outside the submitted work., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Targeted biologic therapies can elicit an undesirable host immune response characterized by the development of antidrug antibodies (ADA), an important cause of treatment failure. The most widely used biologic across immune-mediated diseases is adalimumab, a tumor necrosis factor inhibitor. This study aimed to identify genetic variants that contribute to the development of ADA against adalimumab, thereby influencing treatment failure. In patients with psoriasis on their first course of adalimumab, in whom serum ADA had been evaluated 6-36 months after starting treatment, we observed a genome-wide association with ADA against adalimumab within the major histocompatibility complex (MHC). The association signal mapped to the presence of tryptophan at position 9 and lysine at position 71 of the HLA-DR peptide-binding groove, with both residues conferring protection against ADA. Underscoring their clinical relevance, these residues were also protective against treatment failure. Our findings highlight antigenic peptide presentation via MHC class II as a critical mechanism in the development of ADA against biologic therapies and downstream treatment response.

Background: The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited., Objective: Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization., Methods: Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors., Results: Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94)., Conclusion: In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates., (Copyright © 2020. Published by Elsevier Inc.)

Ustekinumab is an effective treatment for psoriasis, but response varies between patients. The formation of anti-drug antibodies (ADAs) may explain part of this variation by reducing the free ustekinumab level. Currently, published analyses of the clinical impact of ADAs are incomplete. In this observational cross-sectional multicenter study of 340 patients, we evaluated the impact of ADAs on ustekinumab level and clinical response as assessed by the PASI. Circulating ADA levels were measured using two assays: a drug-sensitive radioimmunoassay and a drug-tolerant ELISA. Circulating ustekinumab levels were measured using an ELISA. ADAs were detected in 3.8% (95% confidence interval [CI] = 3.2-4.2) and in 10.6% (95% CI = 7.9-13.9) of patients using the radioimmunoassay and drug-tolerant ELISA, respectively. At least 85% of the ADAs were neutralizing. Compared with patients negative for ADAs, ADA positivity in the radioimmunoassay and drug-tolerant ELISA were associated with lower median ustekinumab levels (-0.62 μg/ml [95% CI = -1.190 to -0.30] and -0.74 μg/ml [95% CI = -1.09 to -0.47], respectively) and higher absolute PASI (6.6 [95% CI = 3.0-9.9] and 1.9 [95% CI = 0.4-4.0], respectively). Absence of detectable ustekinumab regardless of ADA status correlated with poor clinical outcome (median sample PASI 10.1, 6.5 [95% CI = 3.9-8.8] compared with patients positive for ustekinumab). In conclusion, substantially reduced drug exposure resulting from ADAs formation is associated with impaired clinical response., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Variation in response to biologic therapy for inflammatory diseases, such as psoriasis, is partly driven by variation in drug exposure. Real-world psoriasis data were used to develop a pharmacokinetic/pharmacodynamic (PK/PD) model for the first-line therapeutic antibody ustekinumab. The impact of differing dosing strategies on response was explored. Data were collected from a UK prospective multicenter observational cohort (491 patients on ustekinumab monotherapy, drug levels, and anti-drug antibody measurements on 797 serum samples, 1,590 measurements of Psoriasis Area Severity Index (PASI)). Ustekinumab PKs were described with a linear one-compartment model. A maximum effect (E max ) model inhibited progression of psoriatic skin lesions in the turnover PD mechanism describing PASI evolution while on treatment. A mixture model on half-maximal effective concentration identified a potential nonresponder group, with simulations suggesting that, in future, the model could be incorporated into a Bayesian therapeutic drug monitoring "dashboard" to individualize dosing and improve treatment outcomes., (© 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Importance: High-cost biologic therapies have transformed the management of immune-mediated inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by measurement of circulating drug levels has been shown to be effective in various settings. However, limited evidence exists for this approach with the interleukin 12 and interleukin 23 inhibitor ustekinumab., Objective: To evaluate clinical utility of therapeutic drug monitoring for ustekinumab in patients with psoriasis., Design, Setting, and Participants: A prospective observational cohort of 491 adults with psoriasis was recruited to the multicenter Biomarkers of Systemic Treatment Outcomes in Psoriasis study within the British Association of Dermatologists Biologic and Immunomodulators Register from June 2009 to December 2017; samples from some patients were taken between 2009 and 2011 as part of a pilot study with the same inclusion criteria., Exposure: Serum ustekinumab level measured at any point during the dosing cycle using an enzyme-linked immunosorbent assay., Main Outcomes and Measures: Disease activity measured using the Psoriasis Area and Severity Index (PASI) score. Treatment response outcomes were PASI75 (75% reduction in PASI score from baseline [primary outcome]), PASI90 (90% reduction of PASI score from baseline), and absolute PASI score of 1.5 or less., Results: A total of 491 patients (171 women and 320 men; mean [SD] age, 45.7 [12.8] years) had 1 or more serum samples (total, 853 samples obtained 0-56 weeks from start of treatment) and 1 or more PASI scores within the first year of treatment. Antidrug antibodies were detected in only 17 of 490 patients (3.5%). Early measured drug levels (1-12 weeks after starting treatment) were associated with PASI75 response 6 months after starting treatment (odds ratio, 1.38; 95% CI, 1.11-1.71) when adjusted for baseline PASI score, age, and ustekinumab dose. However, this finding was not consistent across the other PASI outcomes (PASI90 and PASI score of ≤1.5)., Conclusions and Relevance: This real-world study provides evidence that measurement of early serum ustekinumab levels could be useful to direct the treatment strategy for psoriasis. Adequate drug exposure early in the treatment cycle may be particularly important in determining clinical outcome.

Biologics have transformed management of inflammatory diseases. To optimize outcomes and reduce costs, dose adjustment informed by circulating drug levels has been proposed. We aimed to determine the real-world clinical utility of therapeutic drug monitoring in psoriasis. Within a multicenter (n = 60) prospective observational cohort, 544 psoriasis patients were included who were receiving adalimumab monotherapy and had at least one serum sample and Psoriasis Area and Severity Index (PASI) score available within the first year. We present models giving individualized probabilities of response for any given drug level: a minimally effective drug level of 3.2 μg/ml discriminates responders (PASI75 indicates 75% improvement in baseline PASI) from nonresponders, and gives an estimated PASI75 probability of 65% (95% confidence interval = 60-71). At 7 μg/ml, PASI75 probability is 81% (95% CI = 76-86); beyond 7 μg/ml, the drug level/response curve plateaus. Crucially, drug levels are predictive of response 6 months later, whether sampled early or at steady state. We confirm serum drug level to be the most important factor determining treatment response, highlighting the need to take drug levels into account when searching for biomarkers of response. This real-world study with pragmatic drug level sampling provides evidence to support the proactive measurement of adalimumab levels in psoriasis to direct treatment strategy, and is relevant to other inflammatory diseases., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)