Ustekinumab In Patients Research Articles

27476 Increased benefit of secukinumab vs ustekinumab in patients with psoriasis regardless of previous systemic psoriasis therapy: Pooled analysis of the phase 3 CLEAR and CLARITY trials

27476 Increased benefit of secukinumab vs ustekinumab in patients with psoriasis regardless of previous systemic psoriasis therapy: Pooled analysis of the phase 3 CLEAR and CLARITY trials

28169 Psoriasis in routine clinical care: Complete skin clearance rates with guselkumab increase through week 52—Results from the real-life PERSIST study

Introduction: The prospective, noninterventional, multicenter PERSIST study evaluates effectiveness and safety of guselkumab and ustekinumab in patients with moderate-to-severe plaque psoriasis in a German real-world setting. Week (W) 52 data of 303 patients treated with guselkumab are presented.

Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with ulcerative colitis: a GETAID cohort study.

Phase III trials have demonstrated the efficacy and safety of ustekinumab in ulcerative colitis (UC), but few real-life long-term data are currently available. To assess the real-world effectiveness and safety of ustekinumab in patients with UC. From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined as a partial Mayo Clinic score ≤2. We included 103 patients with UC (62 men; mean age: 41.2±16.2years; 52% pancolitis E3) with an insufficient response to immunosuppressants, anti-TNFs and/or vedolizumab. At week 52, 45 (44%) patients had discontinued ustekinumab mainly due to lack of effectiveness (n=41). The cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7% and 58.4% after 3, 6, 9 and 12months respectively. The overall steroid-free clinical remission rate at week 52 was 32% of whom 71% had subscores of null for rectal bleeding and stool frequency. Ten patients underwent colectomy within a median of 6.7 [4.3-10.6] months. Adverse effects were observed in 15 (16.9%) patients; 4 (4.5%) were severe, including one patient who died from a myocardial infarction. After 52 weeks, over one-half of patients with refractory UC were still treated by ustekinumab and one-third were in steroid-free clinical remission.

Approach to medical therapy in perianal Crohn's disease.

Perianal Crohn’s disease remains a challenging condition to treat and can have a substantial negative impact on quality of life. It often requires combined surgical and medical interventions. Anti-tumor necrosis factor (anti-TNF) therapy, including infliximab and adalimumab, remain preferred medical therapies for perianal Crohn’s disease. Infliximab has been shown to be efficacious in improving fistula closure rates in randomized controlled trials. Clinicians can be faced with a number of questions relating to the optimal use of anti-TNF therapy in perianal Crohn’s disease. Specific issues include evaluation for the presence of perianal sepsis, the treatment target of therapy, the ideal time to commence treatment, whether additional medical therapy should be used in conjunction with anti-TNF therapy, and the duration of treatment. This article will discuss key studies which can assist clinicians in addressing these matters when they are considering or have already commenced anti-TNF therapy for the treatment of perianal Crohn’s disease. It will also discuss current evidence regarding the use of vedolizumab and ustekinumab in patients who are failing to achieve a response to anti-TNF therapy for perianal Crohn’s disease. Lastly, new therapies such as local injection of mesenchymal stem cell therapy will be discussed.

Ustekinumab for the Treatment of Giant Cell Arteritis

To evaluate the efficacy and safety of ustekinumab (UST) in giant cell arteritis (GCA). We conducted a prospective, open-label trial of UST in patients with active new-onset or relapsing GCA. Active disease was defined as the presence of GCA symptoms and elevation of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level within 6 weeks of baseline. All patients received a 24-week prednisone taper and subcutaneous UST 90 mg at baseline and at weeks 4, 12, 20, 28, 36, and 44. The primary endpoint, prednisone-free remission, was defined as the absence of relapse through week 52 and normalization of the ESR and CRP level. Relapse was defined as the recurrence of GCA symptoms requiring treatment intensification. A sensitivity analysis excluding ESR/CRP level normalization from the prednisone-free remission definition was performed. The study enrolled 13 patients (target sample size 20). Enrollment was closed prematurely after 7 of the initial 10 patients relapsed. Five patients (39%) had new-onset disease. The initial prednisone doses were 20 mg (1 patient), 40 mg (9 patients), and 60 mg (3 patients). All patients entered disease remission within 4 weeks of baseline. Only 3 (23%) achieved the primary endpoint. Of the 10 patients (77%) who failed to achieve the primary endpoint, 7 relapsed after a mean period of 23 weeks. The remaining 3 patients met the alternative definition of prednisone-free remission that did not require ESR/CRP level normalization. One serious adverse event occurred. UST combined with 24 weeks of prednisone was associated with a high rate of treatment failure in this prospective GCA trial.

P389 Efficacy and safety of ustekinumab in patients with Crohn’s disease refractory to anti-tumour necrosis factor: real clinical practice

Abstract Background The efficacy of ustekinumab in patients with Crohn’s disease (CD) refractory to anti-TNF is worse than in anti-TNF naïve patients. Methods Retrospective study of patients with CD refractory or intolerant to TNF initiating ustekinumab between January 2013 and March 2020, with a minimum follow-up of 12 months, and without corticosteroid treatment. Our aim was evaluated clinical response (reduction of CDAI >100), clinical remission (CDAI <150) and biochemical remission (CDAI <100 and CRP <1 mg/L and faecal calprotectin <100 µg/g) in short and long term. Results A total of 49 patients with a medium follow-up of 28 months (IQR:13-37) were included. Patients baseline characteristics are reflected in Table 1. In 20% patients the induction was made subcutaneous (90 mg/week for 4 weeks). At week 52, clinical response, clinical remission and biochemical remission was 93%, 82% and 54% respectively (Figure 1). In the long term (3 years), 62% had clinical response, 52% remained in clinical remission, and 48% showed biochemical remission. 1/3 of patients needed intensification every year. Ustekinumab treatment discontinuation was observed in 13 patients (27%) mainly due to lack of response (6[12%]: primary, 7[14%]: secondary). No serious adverse effects have been reported. Conclusion About 50% of the patients are in clinical and biochemical remission at week 152 in a real-life cohort of anti-TNF-exposed CD patients. With a harder remission definition including biochemical parameters, our results in real life are similar to pivotal studies at week 152. Nevertheless, at week 52 our remission rates were higher.

P388 Agreement between locally and centrally reviewed Mayo endoscopic subscores in the UNIFI study of ustekinumab in patients with Ulcerative Colitis

Abstract Background In the UNIFI clinical study of ustekinumab (UST) in ulcerative colitis (UC), an endoscopic subscore (ES) was assigned by a local endoscopist, and the video was reviewed by central readers who provided an independent ES. Here, we determined ES agreement between local and central readers. Methods UNIFI (NCT02407236) was a placebo-controlled double-blind trial consisting of randomized induction and maintenance studies.1 Endoscopies were performed at screening (I-0), induction Wk 8 (I-8), and maintenance Wk 44 (M-44). Mayo ESs (range 0-3) were assigned by local endoscopists and a central reader reviewing the endoscopy video. The local reader was blinded to treatment, and the central reader was blinded to local ESs, treatment, and visit. If local and central readers assigned the same ES, that was the final ES (FES). If local and central reader ESs did not agree, videos were reviewed by an adjudicator who was blinded to the two previous ESs. If the adjudicator assigned the same ES as the local or central reader, that was the FES. If not, the FES was the median of the 3 ESs. Results Agreement between individual local and central reader ESs was fair (κ=0.25-0.33, Figure 1) and was less than the agreement between central reader and adjudicator (κ=0.55–0.56) at all timepoints. However, at I-0, when determining study entry eligibility (ES≥2), local and central reader agreed more than 85% of the time. At I-0, 98.2% of 1051 endoscopies with FES 2/3 were also scored 2/3 by local ES, while for the 104 with FES 0/1, 49% had a local ES 2/3. At I-8 and M-44 (primary endpoint timepoints), the local ES and FES agreed 87% (785/899) and 80% (497/625), respectively. The proportions of subjects with clinical remission and endoscopic improvement were slightly higher when using the local ES compared to the FES (Figure 2), whereas clinical response rates when using the local ES were similar to FES. Despite these findings, treatment differences between UST and placebo were generally similar when local ES and FES were used to calculate clinical remission at I-8 and M-88. Approximately 90% of endoscopies had an image quality considered “optimal” or “readable with certainty but with minor technical difficulties” by central readers. Overall, image adequacy did not impact agreement between readers. Conclusion Even though agreement between local and central readers was fair and less than that between the central reader and adjudicator, the overall impact on primary and secondary study endpoints was minimal. Overall, the use of both local and central ES to determine the FES yielded a robust and reliable measure for study endpoint determination, however, efforts facilitating reproducible endoscopic assessments in UC are warranted.

Prior Immunogenicity to Anti-TNF Biologics Is Not Associated with Increased Anti-drug Antibodies to Vedolizumab or Ustekinumab

Patients with inflammatory bowel disease (IBD) on biologic therapy may lose response to anti-tumor necrosis factor agents (anti-TNFs) due to the development of anti-drug antibodies (ADAs). A history of anti-TNF ADA increases the risk of developing ADA to subsequent anti-TNFs; however, it is not known whether ADA to anti-TNFs increases the risk of ADA development to vedolizumab (VDZ) or ustekinumab (UST). We aimed to investigate whether prior history of ADA to anti-TNF increases the risk of ADA to VDZ and UST. We conducted a retrospective cohort study of patients at a tertiary care IBD center over the course of four years who had previous anti-TNF drug and ADA level data during maintenance treatment and subsequent VDZ or UST drug and antibody levels, all collected as standard of care. The primary outcome was the rate of ADA development to VDZ and UST in patients with and without prior anti-TNF immunogenicity. Descriptive statistics summarized the data and univariate tested associations. Of the 152 IBD patients analyzed, 41 (27%) had a history of previous anti-TNF ADA with 22 (53.7%) having simultaneously undetectable anti-TNF drug levels. There was no significant difference in the rates of ustekinumab and vedolizumab ADA development between patients with prior ADA and patients without prior ADA (1/41 [2.7%] vs 1/111 [0.9%]; p = 0.54). There was also no difference in concomitant immunomodulator use with ustekinumab or vedolizumab initiation in patients with or without prior ADA (13/41 [31.7%] vs 31/111 [27.9%], p = 0.84). Neither patient who developed ADA to VDZ or UST was on concomitant immunomodulator at drug initiation, and both patients had detectable drug levels at the time of antibody detection. We observed that prior immunogenicity to anti-TNF agents does not confer an increased risk of immunogenicity to ustekinumab or vedolizumab. Our data support the use of vedolizumab or ustekinumab as monotherapy for the treatment of IBD.

Dermatology Life Quality Index in Patients with Moderate-to-Severe Plaque Psoriasis Treated with Brodalumab or Ustekinumab.

IntroductionTargeted biological therapies for psoriasis have resulted in significant benefits, with therapeutic goals such as clear or almost clear skin accompanied by improvements in health-related quality of life (HRQoL). The objective of this study was to compare the effects of 52 weeks of treatment with brodalumab or ustekinumab on HRQoL in patients with moderate-to-severe plaque psoriasis.MethodsData were pooled from two randomised controlled phase 3 trials (AMAGINE-2 and -3) which included patients with moderate-to-severe plaque psoriasis treated with brodalumab 210 mg or ustekinumab 45 or 90 mg for 52 weeks. HRQoL outcomes were measured using the Dermatology Life Quality Index (DLQI) as well as the DLQI-Relevant (DLQI-R) version which excludes ‘not relevant’ responses.ResultsA total of 929 patients were included, 339 in the brodalumab group and 590 in the ustekinumab group. A significantly greater reduction (improvement) in DLQI score from baseline was observed in the brodalumab group compared with the ustekinumab group at weeks 4 [least-squares (LS) mean difference − 2.9, 95% confidence interval [CI] − 3.6 to − 2.2; p < 0.001), 12 (LS mean difference − 0.85, 95% CI − 1.5 to − 0.2; p = 0.01) and 52 (LS mean difference − 0.94, 95% CI − 1.6 to − 0.2; p = 0.009)]. Significantly greater proportions of patients treated with brodalumab achieved a DLQI score of 0 at weeks 4 (15.0 vs. 5.4%; p < 0.0001), 12 (37.5 vs. 28.0%; p = 0.0140) and 52 (46.3 vs. 30.3%; p < 0.0001), or of ≤ 1 [DLQI (0/1): 33.9 vs. 15.4%, 59.9 vs. 45.6% and 54.9 vs. 39.8%, respectively; all p < 0.0001]. Similar results were observed using the DLQI-R scoring system. Significantly more patients achieved a ≥ 4 or ≥ 5 improvement in DLQI with brodalumab compared to ustekinumab at weeks 4 and 52. Treatment with brodalumab was associated with significantly more patients achieving a DLQI of 0 compared to ustekinumab for all domains after 4 and 52 weeks.ConclusionBrodalumab was associated with a significantly greater improvement in HRQoL compared to ustekinumab in patients with moderate-to-severe psoriasis.

Infectious risk of vedolizumab compared with other biological agents in the treatment of inflammatory bowel disease.

Vedolizumab is a gut-selective anti-integrin (α4β7) antibody for the treatment of inflammatory bowel disease with a well-known optimal safety profile. We aimed to compare its risk of infections with that of anti-TNF drugs and ustekinumab in patients with both ulcerative colitis and Crohn's disease. All Crohn's disease and ulcerative colitis patients undergoing biological treatment at our centre between 2013 and 2019 were retrospectively included. All infectious complications were registered, considering both inpatient and outpatient events. A comparison of the exposure-adjusted infection rates of vedolizumab, anti-TNF drugs and ustekinumab was carried out, with a specific focus on the rate of gut infections. All infection rates were expressed in events per patient-years (PYs). The overall exposure-adjusted infection rate was 11.5/100 PYs. The most common infections were respiratory tract infections, cutaneous infections, HSV infections/reactivations and gut infections. The rate of serious infections was 1.3/100 PYs. The infection rate of vedolizumab was 17.5/100 PYs, with Crohn's disease patients having a lower infection risk compared with ulcerative colitis patients (P = 0.035). Gut infections were observed in 3.0% of the whole patient population (1.5/100 PYs) and were more common in the vedolizumab group (P = 0.0001). Our study confirms the good safety profile of vedolizumab. Among patients treated with vedolizumab, those with ulcerative colitis have a higher risk of developing infectious complications. Patients treated with vedolizumab have a higher risk of gut infections compared with patients treated with anti-TNF drugs or ustekinumab. Presumably, this is due to the gut-selective mechanism of action of vedolizumab.

Comparison of short- and long-term effectiveness between ustekinumab and vedolizumab in patients with Crohn's disease refractory to anti-tumour necrosis factor therapy.

The best option between vedolizumab and ustekinumab after anti-tumour necrosis factor (TNF) failure remains unclear in Crohn's disease. To compare the short- and long-term effectiveness of vedolizumab and ustekinumab in Crohn's disease patients with prior anti-TNF exposure. All Crohn's disease patients treated with ustekinumab or vedolizumab after exposure to at least one anti-TNF agent were included from two referral centres. Primary endpoint was corticosteroid-free clinical remission defined as Crohn's disease activity index <150 at week 54. Deep remission (corticosteroid-free clinical remission and faecal calprotectin <100µg/g) was assessed at week 14. Propensity-matched analyses were applied to make the two groups comparable. Overall, 312 patients (ustekinumab=224 and vedolizumab=88) were included. After propensity score analysis, ustekinumab was more effective to achieve corticosteroid-free clinical remission at week 54 (49.3% vs 41.2%, P=0.04) and deep remission at Week 14 (25.9% vs 3.8%, P=0.02) than vedolizumab. The rate of primary nonresponders (6.7% vs 14.8%, P=0.034) and the long-term risk of drug discontinuation due to therapeutic failure (HR=1.53 [1.04-2.07], P=0.029) were lower in patients treated with ustekinumab compared with vedolizumab. Predictors of ustekinumab failure were complicated phenotype (odds ratio [OR]=2.35 [1.31-4.22]; P=0.004) and anti-TNF primary non-response (OR=2.55 [1.27-5.12]; P=0.008). We did not find any predictor of corticosteroid-free clinical remission in patients treated with vedolizumab. Vedolizumab was less effective than ustekinumab in patients >35 years old (OR=0.41 [0.19-0.87]), with noncomplicated phenotype (OR=0.42 [0.18-0.96]), no prior bowel resection (OR=0.49 [0.24-0.96]), and no steroids at baseline (OR=0.47 [0.23-0.97]). Ustekinumab was more effective to achieve early and long-term effectiveness than vedolizumab in Crohn's disease patients who previously failed response to anti-TNF agents.

Эффективность и безопасность устекинумаба у пациентов с болезнью Крона в реальной клинической практике

Эффективность и безопасность устекинумаба у пациентов с болезнью Крона в реальной клинической практике

Twelve-week secukinumab treatment is consistently efficacious for moderate-to-severe psoriasis regardless of prior biologic and non-biologic systemic treatment: Post hoc analysis of six randomised trials.

BackgroundThe efficacy of biologic therapies is greater among biologic‐naïve vs. biologic‐experienced psoriasis patients. However, little is known as to whether prior use of other systemic therapies impacts secukinumab efficacy in patients with moderate‐to‐severe psoriasis.ObjectiveTo investigate the impact of prior exposure to systemic therapies upon the efficacy and safety of secukinumab 300 mg for moderate‐to‐severe psoriasis.Methods Post hoc analysis of six randomised controlled trials (RCTs) comparing secukinumab with placebo, ustekinumab or etanercept at 12 weeks of treatment. Data comparing secukinumab with placebo and ustekinumab were meta‐analysed, while comparisons between secukinumab and etanercept were from a single RCT. Four subgroups of patients were assessed: (i) naïve to non‐biologic systemics (NBS) and biologics; (ii) exposed to NBS but naïve to biologics; (iii) naïve to NBS but exposed to biologics; and (iv) exposed to NBS and biologics. Outcomes of interest included the following: investigator’s global assessment (IGA) score, absolute psoriasis area and severity index (PASI) response, PASI 75, PASI 90 and PASI 100 responses, and dermatology life quality index (DLQI). Safety was also assessed.ResultsOne thousand three hundred and eighty‐three patients were included in the secukinumab vs. placebo meta‐analysis: 1776 in the secukinumab vs. ustekinumab meta‐analysis and 653 in the within‐trial analyses of secukinumab vs. etanercept. For all subgroups, secukinumab was significantly more efficacious than placebo for all outcomes measured. Secukinumab generated greater responses in biologic‐naïve patients, while prior NBS had a negligible impact on treatment response. Furthermore, secukinumab was more efficacious than both ustekinumab and etanercept on many outcomes, with an even greater difference for biologic‐naïve than biologic‐exposed patients. Safety results were consistent with individual clinical trial results.ConclusionsTwelve‐week treatment with secukinumab 300 mg is consistently more efficacious than placebo, etanercept and ustekinumab in patients with moderate‐to‐severe psoriasis, regardless of prior exposure to biologics or NBS. Secukinumab had a comparable safety profile to both etanercept and ustekinumab.

Ustekinumab for Ulcerative Colitis

Ustekinumab for Ulcerative Colitis

Re-induction With Intravenous Ustekinumab in Patients With Crohn's Disease and a Loss of Response to This Therapy.

A significant percentage of patients treated with ustekinumab may lose response. Our aim was to evaluate the short-term efficacy and safety of intravenous re-induction with ustekinumab in patients with Crohn's disease who have lost the response to the treatment. This is a retrospective, observational, multicenter study. Treatment efficacy was measured at week 8 and 16; clinical remission was defined when the Harvey-Bradshaw Index was ≤4 points, and clinical response was defined as a decrease of ≥3 points in the index compared with the baseline. Adverse events and treatment decisions after re-induction were also collected. Fifty-three patients from 13 centers were included. Forty-nine percent had previously failed to respond to 2 biological treatments, and 24.5% had failed to respond to 3. The average exposure time to ustekinumab before re-induction was 17.7 ± 12.8 months. In 56.6% of patients, the administration interval had been shortened to every 4 to 6 weeks before re-induction. At week 8 and 16 after re-induction, 49.0% (n = 26) and 43.3% (n = 23), respectively, were in remission, whereas 64.1% (n = 34) and 52.8% (n = 28) had a clinical response. Patients who achieved remission at week 16 had lower C-reactive protein levels than those who did not respond (2.8 ± 1.6 vs 12.5 ± 9.5 mg/dL; P = 0.001). No serious adverse events related to re-induction were observed. Intravenous re-induction with ustekinumab is an effective and safe strategy that recovers the response in approximately half of the patients with refractory Crohn's disease who experience a loss of response. Re-induction can be attempted before switching out of the therapy class.

Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID): efficacy and safety from a 52-week, multicentre, double-blind, active comparator and placebo controlled phase 3 trial

There is an unmet need for a treatment for psoriasis that results in complete skin clearance with a reliably quick response. Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A. We aimed to compare the efficacy and safety of bimekizumab with placebo and ustekinumab in patients with moderate to severe plaque psoriasis over 52 weeks. BE VIVID was a multicentre, randomised, double-blind, active comparator and placebo controlled phase 3 trial done across 105 sites (clinics, hospitals, research units, and private practices) in 11 countries in Asia, Australia, Europe, and North America. Adults aged 18 years or older with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] score ≥12, ≥10% body surface area affected by psoriasis, and Investigator's Global Assessment [IGA] score ≥3 on a five point scale) were included. Randomisation was stratified by geographical region and previous exposure to biologics; patients, investigators, and sponsors were masked to treatment assignment. Patients were randomly assigned (4:2:1) using an interactive response technology to bimekizumab 320 mg every 4 weeks, ustekinumab 45 mg or 90 mg (baseline weight-dependent dosing) at weeks 0 and 4, then every 12 weeks, or placebo every 4 weeks. At week 16, patients receiving placebo switched to bimekizumab 320 mg every 4 weeks. All study treatments were administered as two subcutaneous injections. Coprimary endpoints were the proportion of patients with 90% improvement in the PASI (PASI90) and the proportion of patients with an IGA response of clear or almost clear (score 0 or 1) at week 16 (non-responder imputation). Efficacy analyses included the intention-to-treat population; safety analysis included patients who received at least one dose of study treatment. This trial was registered at ClinicalTrials.gov, NCT03370133 (completed). Between Dec 6, 2017, and Dec 13, 2019, 735 patients were screened and 567 were enrolled and randomly assigned (bimekizumab 320 mg every 4 weeks n=321, ustekinumab 45 mg or 90 mg every 12 weeks n=163, placebo n=83). At week 16, 273 (85%) of 321 patients in the bimekizumab group had PASI90 versus 81 (50%) of 163 in the ustekinumab group (risk difference 35 [95% CI 27-43]; p<0·0001) and four (5%) of 83 in the placebo group (risk difference 80 [74-86]; p<0·0001). At week 16, 270 (84%) patients in the bimekizumab group had an IGA response versus 87 (53%) in the ustekinumab group (risk difference 30 [95% CI 22-39]; p<0·0001) and four (5%) in the placebo group (risk difference 79 [73-85]; p<0·0001). Over 52 weeks, serious treatment-emergent adverse events were reported in 24 (6%) of 395 patients in the bimekizumab group (including those who switched from placebo at week 16) and 13 (8%) of 163 in the ustekinumab group. Bimekizumab was more efficacious than ustekinumab and placebo in the treatment of moderate to severe plaque psoriasis. The bimekizumab safety profile was consistent with that observed in previous studies. UCB Pharma.

Evaluation of a One-step Dose Reduction Strategy of Adalimumab, Etanercept and Ustekinumab in Patients with Psoriasis in Daily Practice.

Dose reduction of biologics for psoriasis could contribute to lower drug exposure. This study evaluated a one-step, tightly controlled, biologic dose reduction strategy in a prospective daily practice cohort. In patients with psoriasis with low disease activity using adalimumab, etanercept or ustekinumab for at least 6 months, the dosing interval was prolonged with 33%. Patients could return to their normal dosing interval in case of disease flare. Of 108 eligible patients, 80 started dose reduction and were analysed. In total, 36/80 patients (45.0%) discontinued dose reduction after 19 months (95% confidence interval 14.9–23.1 months). Of 67 patients with 1-year follow-up, 45 (67.2%) still used the lower dose after 1 year. No serious adverse events related to dose reduction occurred. Cumulative dose and costs decreased by 22.7% during 1 year. In conclusion, a one-step tightly controlled dose reduction strategy for adalimumab, etanercept and ustekinumab has considerable potential to safely decrease biologic dosages in patients with psoriasis in daily practice.

Real-World Effectiveness and Safety of Ustekinumab for Ulcerative Colitis From 2 Tertiary IBD Centers in the United States.

Ustekinumab has been recently approved for the treatment of moderately to severely active ulcerative colitis (UC). The registry trials for ustekinumab in UC demonstrated efficacy and safety, but data on real-world outcomes are limited. We describe the effectiveness and safety of ustekinumab in patients with UC from 2 US tertiary inflammatory bowel disease centers. Patients with moderately to severely active UC treated with ustekinumab at NYU Langone Health (New York, New York) and University of Chicago Medical Center (Chicago, Illinois) between January 2016 and March 2020 were retrospectively included. The primary outcome was clinical remission at 3 and 12 months, defined as a partial Mayo score of ≤2, with a combined rectal bleeding and stool frequency subscore of ≤1. Sixty-six UC patients were included. Ninety-two percent of patients had prior exposure to biologics or tofacitinib. Forty-three percent and 45% of patients achieved clinical remission by 3 and 12 months, respectively. Anti-TNF nonresponse and endoscopic Mayo score of 3 were negative predictors of clinical remission. Thirty-three percent of those followed for a year achieved concurrent endoscopic and histologic healing, which was significantly associated with lower partial Mayo score (P < 0.01) and lower stool frequency (P = 0.02). Serious adverse events occurred in 4 (6%) patients (3 UC exacerbations, 1 vasculitis). In this cohort of mostly biologic-refractory UC patients, treatment with ustekinumab achieved remission in nearly half of them at 12 months, and was associated with an overall favorable safety profile. These results are modestly better than the pivotal trials.

Randomized Trial Replication Using Observational Data for Comparative Effectiveness of Secukinumab and Ustekinumab in Psoriasis

Treatments for psoriasis may be less effective in everyday practice than in clinical trials. Emulating a target trial using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) can provide treatment effect estimates that are robust and can inform both clinicians and regulatory bodies. To assess the comparative effectiveness of ustekinumab and secukinumab in patients with psoriasis, and to test whether the relative effectiveness estimate of the CLEAR trial, a randomized clinical trial that compared secukinumab with ustekinumab for psoriasis, can be replicated. This comparative effectiveness research study used a target trial emulation approach and was performed between November 2007 and August 2019. Data were obtained from BADBIR, a multicenter longitudinal pharmacovigilance register of patients with moderate to severe psoriasis in the United Kingdom and Republic of Ireland. Participants had chronic plaque psoriasis, were 18 years or older, and had at least 1 record of a Psoriasis Area and Severity Index (PASI) of 12 or higher before their initiation to secukinumab or ustekinumab. Propensity score (PS) 1:1 matched analysis and inverse probability treatment weighted analysis were performed. The primary outcomes were the risk ratio (RR) and the risk difference (RD) for achieving PASI of 2 or lower after 12 months of therapy for secukinumab compared with ustekinumab. Methods to account for missing outcome data were complete case analysis, nonresponder imputation, last observation carried forward, inverse probability of censoring weighting, and multiple imputation. Regulatory and estimate agreement metrics were used to benchmark the effect estimates in this study against those in the CLEAR trial. A total of 1231 patients were included in the analysis, with 917 receiving ustekinumab and 314 receiving secukinumab. Secukinumab was superior to ustekinumab in all analyses, except under the nonresponder imputation method, in the proportion of participants achieving a PASI of 2 or lower (PS-weighted complete case analysis: RR, 1.28 [95% CI, 1.06-1.55]; RD, 11.9% [1.6-22.1]). All analyses, except for nonresponder imputation, reached regulatory agreement in both PS-matching and PS-weighted analyses. This comparative effectiveness study found that secukinumab resulted in more patients achieving a PASI of 2 or lower after 12 months of therapy compared with ustekinumab in patients with psoriasis. Target trial emulation in this study resulted in regulatory and estimate agreement with the CLEAR randomized clinical trial; further such studies may help fill the evidence gap when comparing other systemic therapies for psoriasis.

Ustekinumab in patients with Crohn’s disease with extraintestinal manifestations (psoriasis)

Ulcerative colitis and Crohn’s disease are severe immune-mediated diseases. Extraintestinal manifestations of inflammatory bowel disease (IBD) significantly increase the burden to the patient. The most common extraintestinal manifestations include erythema nodosum, ankylosing spondylitis, and primary sclerosing cholangitis. Some of the extraintestinal manifestations depend on the activity of the inflammatory process in the intestine and can be reversed during treatment of IBD, while the others require specific therapy, since it does not depend on the degree of inflammation in the intestine. Patients with IBD are at increased risk of developing complications caused by other organ systems, such as osteoporosis, venous thromboembolism, and cardiovascular diseases. Immunemediated diseases such as multiple sclerosis and psoriasis have been associated with inflammatory bowel disease, but these conditions can also be complications of IBD therapy. In this regard, patients and healthcare providers should exercise vigilance in identifying extraintestinal manifestations and complications of IBD, and the therapy should be aimed both at treating the underlying disease and reversing extraintestinal manifestations as much as possible. Interleukin-12/23 is an important cytokine in the inflammatory process development in the immune-mediated diseases. Ustekinumab is effective in treating not only IBD, but also psoriasis by blocking interleukin 12/23. The drug shows a higher survival index of the therapy as compared to tumour necrosis factor-α inhibitors. The article describes the experience of using ustekinumab in severe concomitant pathology – Crohn’s disease in the form of ileocolitis and psoriasis vulgaris with initial manifestations of psoriatic arthritis against ineffectiveness of tumour necrosis factor-α inhibitors.