Dose reduction of biologics in patients with plaque psoriasis: a review.

Dose reduction (DR) of first-generation biologics for plaque psoriasis (TNF-alpha inhibitors (i) and interleukin (IL)-12/23i) has been described in a previous scoping review. The literature on the DR of the newest generation of biologics (IL-17/23i) was scarce. The current review provides a literature update on the previous scoping review on the DR of all biologics, including the newest generation, with a focus on the uptake and implementation of DR in practice. The current literature search on DR revealed 14 new articles in addition to those in the previous review. Four of the newly found articles tested DR strategies, mostly focusing on first-generation biologics; only guselkumab (IL-23i) was included in one study. The other 10 studies showed data on regaining response after failure of DR, safety, cost-effectiveness, and uptake and implementation, as well as information about IL-17/23i. The eligibility criteria to start DR included both absolute and relative Psoriasis Area and Severity Index (PASI) scores (PASI ≤3/≤5/PASI 75-100) and/or Dermatology Life Quality Index (DLQI) ≤3/≤5, or BSA ≤1/≤2, or Physician Global Assessment (PGA) ≤1/0-2 during a period ranging from 12 weeks to ≥1 year. Most studies used PASI ≤5 and/or DLQI ≤5 or PGA ≤1 for ≥6 months. DR strategies were mostly performed by stepwise interval prolongation in two steps (to 67% of the standard dose, followed by 50%). Some studies of IL-17/23i reduced the dose to ±25%. The tested DR strategies on stepwise or fixed DR on TNF-αi and IL-12/23i (three studies), as well as one "on-demand" dosing study on IL-23i guselkumab, were successful. In the case of relapse of DR on TNF-αi and IL-12/23i, clinical effectiveness was regained by retreatment with the standard dose. All studies showed substantial cost savings with the biologic DR of TNF-αi and IL-12/23i. The identified barriers against the implementation of DR were mainly a lack of guidelines and scientific evidence on effectiveness and safety, and a lack of time and (technical) support. The identified facilitators were mainly clear guidelines, feasible protocols, adequate education of patients and physicians, and cost reduction. In conclusion, DR seems promising, but a research gap still exists in randomized, prospective studies testing DR strategies, especially of IL-17/23i, hampering the completion of guidelines on DR. Taking into account the identified barriers and facilitators most likely results in a more successful implementation of biologic DR in practice.

Steps towards implementation of protocolized dose reduction of adalimumab, etanercept and ustekinumab for psoriasis in daily practice.

BACKGROUND: Dose reduction (DR) of adalimumab, etanercept and ustekinumab has proven to be (cost-)effective in psoriasis patients with low disease activity. Further implementation is needed to establish application of DR for eligible patients. OBJECTIVES: To evaluate the implementation of protocolized biologic DR in daily practice. METHODS: A pilot implementation study was performed in 3 hospitals during 6 months. By combining education and protocol development, involved healthcare providers (HCPs) were directed toward the adoption of protocolized DR. DR of adalimumab, etanercept, and ustekinumab was achieved by stepwise injection interval prolongation. Implementation outcomes (fidelity, feasibility) were assessed. Factors for optimizing implementation were explored in interviews with HCPs. Uptake was measured in patients by chart review. RESULTS: The implementation strategy was executed as planned. Implementation fidelity was less than 100% as not all provided tools were used across study sites. HCPs indicated the feasibility of implementing protocolized DR, although time investment was needed. Identified additional factors for successful implementation included support for patients, uptake of DR into guidelines, and supportive electronic health record systems. During the 6 months intervention period, 52 patients were eligible for DR of whom 26 (50%) started DR. The proposed DR protocol was followed in 22/26 patients (85%) on DR. CONCLUSION: Additional staff for support, extra time during consultations, education on DR for HCPs and patients, and effective tools such as a feasible protocol can lead to more patients on biologic DR.

Patients' perspectives towards biologic dose reduction in psoriasis: a qualitative study.

Dose reduction of biologics for psoriasis could contribute to more efficient use of these expensive medicines. Evidence on opinions of patients with psoriasis regarding dose reduction is sparse. The objective of this study was therefore to explore patients' perspectives towards dose reduction of biologics for psoriasis. A qualitative study was conducted, comprising semi-structured interviews with 15 patients with psoriasis with different characteristics and treatment experiences. Interviews were analyzed by inductive thematic analysis. Perceived benefits of biologic dose reduction according to patients were minimizing medication use, lowering risks of adverse effects and lowering societal healthcare costs. Patients reported to have experienced a large impact of their psoriasis, and expressed concerns about loss of disease control due to dose reduction. Fast access to flare treatment and adequate monitoring of disease activity were among reported preconditions. According to patients, they should have confidence in dose reduction effects and should be willing to change their effective treatment. Moreover, addressing information needs and involvement in decision-making were deemed important among patients. In conclusion, addressing patients' concerns, fulfilling information needs, providing the possibility of resuming standard dose, and involving patients in decision-making are important according to patients with psoriasis when considering biologic dose reduction.

National consensus on biologic dose reduction in psoriasis: a modified eDelphi procedure.

BACKGROUND: Dose reduction of biologics for psoriasis is applied in daily practice, although guidelines are lacking. Striving for clear criteria is important, as it leads to a consistent application of dose reduction. OBJECTIVE: To achieve consensus on criteria for biologic dose reduction in psoriasis patients with stable and low disease activity. METHODS: An online Delphi procedure (eDelphi) was conducted. Dutch dermatologists were invited to participate in a maximum of 3 voting rounds. Proposed statements were selected based on literature review and included criteria for the application of dose reduction and dosing schedules. Biologic dose reduction was defined as 'application of injection interval prolongation'. Proposed statements were rated using a 9-point Likert scale; consensus was reached when ≥70% of all voters rated 'agree' (7-9) and <15% rated 'disagree' (1-3). RESULTS: A total of 27 dermatologists participated and reached a consensus on 15 recommendations over 2 voting rounds. Agreed statements included criteria for dose reduction eligibility, criteria for dose reduction (dis)continuation, and dosing schedules for adalimumab, etanercept, and ustekinumab. Based on the eDelphi outcomes, an algorithm fit for implementation in current practice was developed. CONCLUSIONS: Recommendations of this national consensus process can guide clinicians, and consequently their patients, toward consistent application of biologic dose reduction.

Drug Survival, Safety, and Effectiveness of Biologics in Older Patients with Psoriasis: A Comparison with Younger Patients-A BioCAPTURE Registry Study.

BACKGROUND: Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data specifically on this growing population are available, e.g. regarding the safety and performance of biological treatment. AIMS: We aimed to give insight into this specific population by comparing the drug survival and safety of biologics in older patients with that in younger patients. METHODS: In this real-world observational study, data from 3 academic and 15 non-academic centers in The Netherlands were extracted from the prospective BioCAPTURE registry. Biologics included in this study were tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors. Patients were divided into two age groups: ≥ 65 years and < 65 years. The Charlson Comorbidity Index (CCI) was used to measure comorbid disease status, and all adverse events (AEs) that led to treatment discontinuation were classified according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. All AEs that led to treatment discontinuation were studied to check whether they could be classified as serious AEs (SAEs). Kaplan-Meier survival curves for overall 5-year drug survival and split according to reasons of discontinuation (ineffectiveness or AEs) were constructed. Cox regression models were used to correct for possible confounders and to investigate associations with drug survival in both age groups separately. Psoriasis Area and Severity Index (PASI) scores during the first 2 years of treatment and at the time of treatment discontinuation were assessed and compared between age groups. RESULTS: A total of 890 patients were included, of whom 102 (11.4%) were aged ≥ 65 years. Body mass index, sex, and distribution of biologic classes (e.g. TNFα, IL12/23) were not significantly different between the two age groups. A significantly higher CCI score was found in older patients, indicative of more comorbidity (p < 0.001). The 5-year ineffectiveness-related drug survival was lower for older patients (44.5% vs. 60.5%; p = 0.006), and the 5-year overall (≥ 65 years: 32.4% vs. < 65 years: 42.1%; p = 0.144) and AE-related (≥ 65 years: 82.1% vs. < 65 years: 79.5%; p = 0.913) drug survival was comparable between age groups. Of all AEs (n = 155) that led to discontinuation, 16 (10.3%) were reported as SAEs but these only occurred in younger patients. After correcting for confounders, the same trends were observed in the drug survival outcomes. Linear regression analyses on PASI scores showed no statistical differences at 6, 12, 18, and 24 months of treatment between age groups. CONCLUSIONS: This study in a substantial, well-defined, prospective cohort provides further support that the use of biologics in older patients seems well-tolerated and effective. Biologic discontinuation due to AEs did not occur more frequently in older patients. Older patients discontinued biologic treatment more often due to ineffectiveness, although no clear difference in PASI scores was observed. More real-world studies on physician- and patient-related factors in older patients are warranted.

Children with psoriasis and COVID-19: factors associated with an unfavourable COVID-19 course, and the impact of infection on disease progression (Chi-PsoCov registry).

BACKGROUND: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. OBJECTIVES: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments. METHODS: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms. RESULTS: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01). DISCUSSION: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.

Two-year follow-up of a dose reduction strategy trial of biologics adalimumab, etanercept, and ustekinumab in psoriasis patients in daily practice.

BACKGROUND/OBJECTIVES: Tightly-controlled dose reduction was possible during 1 year in psoriasis patients on adalimumab, etanercept or ustekinumab with low disease activity (CONDOR trial). Extended observation is needed to ensure long-term effectiveness and safety of the strategy. With prolonged follow-up, we investigated the clinical effects and safety of the strategy, the proportion of patients with successful dose reduction, and assessed if patients with a disease flare regained remission. METHODS: Two-year follow up of a subgroup of patients previously included in a randomized pragmatic study comparing usual care (UC) with stepwise dose reduction (DR). Effectiveness (Psoriasis Area and Severity Index, PASI), Dermatology Life Quality Index (DLQI), adverse events, proportion of patients with successful DR and proportion of persistent disease flares were analyzed. RESULTS: DR leads temporarily to a slightly increased PASI groupwise, but on the long-term patients regained low PASI. DLQI scores remained stable during follow-up. No serious adverse events due to DR were reported. Forty-one percent of patients remained on a low dose up to 2 years. The number of persistent flares was low in DR and UC. CONCLUSIONS: The proposed dose reduction strategy is effective for a significant part of patients and remains safe up to 2 years of follow-up.

Attitudes and behaviour regarding dose reduction of biologics for psoriasis: a survey among dermatologists worldwide.

Dose reduction (DR) of biologics, where possible, seems promising for more efficient use of expensive biologics. For implementation of DR strategies, it is essential to get insight in factors that influence implementation. The objective of this study was to evaluate the attitudes and behaviour regarding dose reduction of biologic therapies for psoriasis among psoriasis expert dermatologists worldwide. A 27-question e-survey was sent through the International Psoriasis Council (IPC) to its 114 dermatologist councilors worldwide. The survey assessed demographics, general and DR prescription behaviour, and motivations for and barriers against application of DR. Of 57 respondents, 53 respondents who prescribed biologics were included for analysis. Thirty-seven (69.8%) applied DR (i.e., 'DR dermatologists'), and 16 (30.2%) did not (i.e., 'Non-DR dermatologists'). DR strategies varied among respondents. Regarding criteria for starting DR, differences were reported in required treatment duration, and interpretation and duration of stable low disease activity. In addition, the prolongation of intervals between injections varied between respondents. For most 'DR dermatologists' (n = 32/37, 86.5%), cost savings were one of the main reasons to apply DR. Fifteen out of 16 'Non-DR dermatologists' (94%) did not apply DR due to lack of scientific evidence. In conclusion, DR of biologics for psoriasis is part of clinical practice in psoriasis experts globally. Barriers for applying DR included lack of evidence or guidelines, and uncertainty on DR effects and risks. Although growing evidence shows DR feasibility, future studies are needed to accumulate and broaden evidence, along with development of (inter)national guidelines on DR strategies.

Unmet Personal Patient Needs in Psoriasis Patients with Low Disease Activity on Adalimumab, Etanercept or Ustekinumab.

BACKGROUND: Personal treatment goals have been systematically investigated in psoriasis patients with active but not in controlled disease. OBJECTIVES: To explore patient needs in psoriasis patients with controlled disease due to biologic therapy with adalimumab, etanercept or ustekinumab. METHODS: Treatment needs in patients on adalimumab, etanercept or ustekinumab with a stable low disease activity for ≥ 6 months and preferably a Psoriasis Area and Severity Index (PASI) < 5, were explored with the Patient Needs Questionnaire (PNQ). Goal importance was expressed as overall mean importance score, percentage of patients that reported a goal to be quite/very important, and per PNQ subscale. Data were analysed separately for treatment, gender, age group (< 50 vs. ≥ 50 years), biologic naivety and willingness to participate in a pragmatic dose-reduction strategy. RESULTS: Sixty-five patients were included. 'To be free of itching', 'to be healed of all skin defects' and 'to have confidence in the therapy' were rated quite/very important in 78.5% of the patients, followed by 'to have no fear the disease will progress' (75.4%) and 'to get better skin quickly' (75.4%). Goals related to the subscale 'confidence in healing' were still of high importance in controlled disease. Least importance was attributed towards social goals. For female patients, it was significantly more important than for males to 'feel less depressed' and 'be comfortable showing yourself more in public'. CONCLUSIONS: Psoriasis patients with controlled disease still report substantial treatment needs, with high importance ascribed to confidence in healing. To apply personalized medicine, treatment needs should be explored on an individual level.

In psoriasis patients, a large reduction in disease severity can lead to a significant improvement in health-related quality of life. In addition to quality-of-life measurements, individual treatment goals can be assessed to evaluate patients' preferences regarding their psoriasis treatment. As opposed to patients with more severe psoriasis, unmet treatment needs in psoriasis patients with stable, low disease activity have barely been reported. In this study, the personal treatment aims of patients with controlled disease due to treatment with adalimumab, etanercept or ustekinumab were explored using the Patient Needs Questionnaire. Sixty-five patients with sustained low disease activity for ≥ 6 months were included. We found that despite low disease activity, these patients still have substantial patient needs. Patients attributed the highest importance to goals on confidence in healing, in contrast to social goals, which were valued of least importance. For female patients, it was significantly more important to 'feel less depressed' and 'be comfortable showing yourself more in public' compared to male patients. Previous treatment with biologic therapy was not associated with an altered attitude towards specific treatment goals. Our population with low disease activity seemed to award a lower level of importance to all treatment goals compared to groups of patients with more severe psoriasis that have been described in literature. Since treatment goals differ per patient, individual treatment could be optimized by actively inquiring about the patient's personal treatment goals. Clinicians should be aware that even in patients with controlled disease, substantial personal treatment needs remain.

Dose Tapering of Biologics in Patients with Psoriasis: A Scoping Review.

INTRODUCTION: Biologics serve as a cornerstone in psoriasis treatment, with low disease activity or sometimes even clinical remission as a realistic treatment outcome. So far, it is unclear whether biologics should be tapered when this target is achieved. Dose tapering could offer potential benefits by decreasing side effects, the burden of repetitive injections and costs of biological therapy. However, clinical guidelines on dose tapering of biologicals in psoriasis patients are lacking. This scoping review was conducted to provide an overview of the current literature on dose tapering and offer guidance for clinicians in daily clinical practice. METHODS: Dose tapering is defined as the administration of a lower dose per administration, or the prolongation of the regular dose interval, after initial treatment according to the standard dosing. Four electronic databases (PubMed, EMBASE, Cochrane, and Web of Science) were systematically searched for literature on tapering of biologics in adult patients with psoriasis from 1 January 2000. RESULTS: We included 19 original articles on biologic tapering in psoriasis patients: four randomized controlled trials and 15 observational studies. Tapering eligibility criteria, tapering strategies, tapering outcomes, and recapture of response after relapse were assessed. Furthermore, the available evidence on possible predictors for successful tapering, and the effect of tapering on safety, quality of life and costs is summarized. The definition of low disease activity as a measure for tapering eligibility varied widely. Beside tapering criteria, tapering strategies were also heterogeneous. Of note, quality-of-life measurements were barely integrated in the evaluation of tapering outcomes. Literature on regaining response after relapse due to tapering was limited, but restored remission has been described. The included studies did not proclaim a significant effect of tapering on the occurrence of (severe) adverse events. Even though cost savings have been reported, no proper cost-effectiveness analysis has been conducted yet. CONCLUSION: Biologic tapering seems to be effective and safe in psoriasis patients with stable low disease activity or clinical remission. Available data on biologic dose tapering in patients with psoriasis are promising, but more research is warranted to fill the current gaps in knowledge.

Biologics are effective in treating psoriasis amongst other diseases, such as rheumatoid arthritis and Crohn's disease. However, biologics are costly, and can cause side effects, such as an increased risk of infection. In patients with rheumatoid arthritis, it is not uncommon to lower the dose of these biologics (also called "dose tapering"), once stable low disease activity, or even remission, is reached. However, in psoriasis patients, dose tapering of biologics is not common practice. In this "scoping review," we provide an overview of the available literature on dose tapering of biologics in adult patients with plaque psoriasis in order to address the current gaps in literature. We found 19 studies that addressed dose tapering. These studies used different criteria to determine which patients were eligible for tapering, which led to various interpretations of tapering success. This made it difficult for us to draw general conclusions on which tapering criteria and strategies should be further investigated. Dose tapering seems to be effective and safe in patients with a stable low disease activity, although more (high-quality) research is needed. Future studies should focus on generating more data on long-term safety, finding predictors for successful tapering, calculating the cost-effectiveness of dose tapering, and evaluating dose tapering in the newest generation of biologics.

Response to IL-17A inhibitors secukinumab and ixekizumab cannot be explained by genetic variation in the protein-coding and untranslated regions of the IL-17A gene: results from a multicentre study of four European psoriasis cohorts.

BACKGROUND: Genetic predictors for treatment response could optimize allocation of biological treatment in patients with psoriasis. There is minimal knowledge about pharmacogenetics of anti-IL-17 agents. OBJECTIVES: To assess whether genetic variants in the protein-coding region or untranslated regions of the IL-17A gene are associated with response to IL-17A inhibitors in patients with psoriasis. METHODS: This was a multicenter European cohort study investigating pharmacogenetics of IL-17A inhibitors in patients with psoriasis. Patients with plaque psoriasis treated with secukinumab or ixekizumab in daily practice were included. For all participants, the protein-coding region and untranslated regions of the IL-17A gene were analysed using Sanger sequencing. Identified genetic variants were tested for association with response to secukinumab/ixekizumab, measured as ∆PASI, after 12 weeks (primary outcome) and after 24 weeks (secondary outcome). Association was tested using a linear regression model with correction for baseline PASI as a fixed covariate and for biological naivety and body mass index as additional covariates. RESULTS: In total, 134 patients treated with secukinumab or ixekizumab were included. Genotyping of the cohort identified genetic variants present in untranslated regions and intronic DNA, but not in the protein-coding region of the IL-17A gene. Five genetic variants in non-coding DNA with a known or suspected functional effect on IL-17A expression were selected for association analyses: rs2275913, rs8193037, rs3819025, rs7747909 and rs3748067. After 12 weeks, 62% of patients achieved PASI75 and 39% achieved PASI90. At week 24, PASI75 and PASI90 response rates were 72% and 62%, respectively. No associations were found between the five genetic variants and ∆PASI, PASI75 or PASI90 after 12 and 24 weeks of anti-IL-17A treatment. CONCLUSIONS: Response to IL-17A inhibitors secukinumab and ixekizumab cannot be explained by genetic variation in the protein-coding and untranslated regions of the IL-17A gene. Pharmacogenetics of IL-17A inhibitors in the treatment of psoriasis requires further exploration.

Female patients are less satisfied with biological treatment for psoriasis and experience more side-effects than male patients: results from the prospective BioCAPTURE registry.

BACKGROUND: Female sex has been reported as a predictor for treatment discontinuation with biological therapies for psoriasis, although reasons remain unclear. It can be hypothesized that lower satisfaction with biological treatment in women might add to the lower drug survival rates. OBJECTIVES: To identify possible differences in satisfaction with biological treatment between female and male patients using the Treatment Satisfaction Questionnaire for Medication (TSQM). METHODS: Data of psoriasis patients treated with biologics were obtained from the prospective, multicentre, daily-practice BioCAPTURE registry. Longitudinal TSQM data were analysed by linear mixed models. Relevant patient characteristics were incorporated as possible confounding factors. Post hoc analysis of adverse events was performed in order to investigate differences between sexes. RESULTS: We included 315 patients with 396 corresponding treatment episodes (137 adalimumab, 90 etanercept, 137 ustekinumab, 24 secukinumab and 8 infliximab). Almost forty per cent of the patients were female. Women had significantly lower baseline PASI scores (P = 0.01). Longitudinal analyses demonstrated lower TSQM scores for 'side-effects' (P = 0.05) and 'global satisfaction' (P = 0.01) in female patients compared with male patients over 1 year of treatment. Women reported more relevant adverse events in the context of biologic treatment compared to men (rate ratio 1.79; P < 0.001), with more fungal (rate ratio 2.20; P = 0.001) and herpes simplex infections (rate ratio 3.25; P = 0.005). CONCLUSIONS: This study provides a prospective, longitudinal analysis of treatment satisfaction with biologics in female and male patients with psoriasis. Women were slightly less satisfied with treatment regarding side-effects and global satisfaction. Differences in treatment satisfaction and side-effects might add to the fact that women discontinue biological treatments more often.

The journey of adult psoriasis patients towards biologics: past and present - Results from the BioCAPTURE registry.

BACKGROUND: A considerable disease period often precedes initiation of a biologic in patients with psoriasis. Little is known about this important period in patients' lives. Evaluation of this 'journey' can reveal important insights and opportunities for physicians and healthcare decision makers. OBJECTIVES: (i) To describe patient and treatment characteristics until the start of biologic treatment in patients with severe psoriasis, (ii) to assess shifts in early (2005-2009) versus established (2010-2015) biologics prescription periods, (iii) to assess changes in hospital/day care admissions before vs. after starting biologics. METHODS: Explorative, retrospective study on the treatment characteristics of the disease period until first biologic, presented with descriptive statistics of patients included in the BioCAPTURE registry. Journeys of 2005-2009 and 2010-2015 were compared with statistical tests to identify important shifts. RESULTS: Median TUS (time until conventional systemic) was 11.0 years and median TUB (time until biologic) was 18.9 years for all patients treated from 2005 to 2015. Most patients received three different conventional antipsoriatic systemic therapies. We noticed a small trend towards a shorter journey (TUB) with only two conventional systemic agents instead of three before initiating a biologic in later years (2010-2015, vs. 2005-2009). We also noticed a significant decrease in (day care) admissions comparing the two years before, versus the first two years after the start of a biologic treatment (17.7 vs. 8.6 admissions/100 follow-up years, P < 0.001). Cyclosporine, intensive topical treatment (dithranol), retinoids and PUVA therapy lost popularity in recent years. CONCLUSION: The 'journey' of patients with psoriasis towards a biologic is still long and characterized by many different treatments. Shifts towards fewer conventional drugs before biologic initiation and a clear decrease in hospital and day care admissions before vs. after a biologic are seen. Improvement of this journey, especially in young or recently diagnosed patients, can decrease negative influences on patients' lives and reduce societal impact.