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Annals of the Rheumatic Diseases Sep 2023Increased risk of serious adverse events (AEs) was reported for tofacitinib relative to tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis...
Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme.
OBJECTIVE
Increased risk of serious adverse events (AEs) was reported for tofacitinib relative to tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis (RA) aged ≥50 years enriched for cardiovascular (CV) risk (ORAL Surveillance). We assessed post hoc the potential risk of upadacitinib in a similar RA population.
METHODS
Pooled safety data from six phase III trials were evaluated post hoc for AEs in patients receiving upadacitinib 15 mg once a day (with or without conventional synthetic disease-modifying antirheumatic drugs), adalimumab 40 mg every other week with concomitant methotrexate (MTX), or MTX monotherapy in the overall trial population and in a subset of patients with higher CV risk (aged ≥50 years, ≥1 CV risk factor). Higher-risk patients from a head-to-head study of upadacitinib 15 mg versus adalimumab (SELECT-COMPARE) were assessed in parallel. Exposure-adjusted incidence rates for treatment-emergent AEs were summarised based on exposure to upadacitinib or comparators.
RESULTS
A total of 3209 patients received upadacitinib 15 mg, 579 received adalimumab and 314 received MTX monotherapy; ~54% of the patients were included in the overall and SELECT-COMPARE higher-risk populations. Major adverse cardiovascular events (MACE), malignancy (excluding non-melanoma skin cancer (NMSC)) and venous thromboembolism (VTE) were more frequent in the higher-risk cohorts versus the overall population but were generally similar across treatment groups. Rates of serious infections in higher-risk populations and herpes zoster (HZ) and NMSC in all populations were higher with upadacitinib 15 mg than comparators.
CONCLUSIONS
An increased risk of MACE, malignancy (excluding NMSC) and VTE was observed in higher-risk populations with RA, yet risk was comparable between upadacitinib-treated and adalimumab-treated patients. Higher rates of NMSC and HZ were observed with upadacitinib versus comparators across all populations, and increased rates of serious infections were detected in upadacitinib-treated patients at higher CV risk.
TRIAL REGISTRATION NUMBERS
NCT02706873, NCT02675426, NCT02629159, NCT02706951, NCT02706847 and NCT03086343.
Topics: Humans; Adalimumab; Antirheumatic Agents; Arthritis, Rheumatoid; Cardiovascular Diseases; Herpes Zoster; Heterocyclic Compounds, 3-Ring; Methotrexate; Treatment Outcome; Venous Thromboembolism
PubMed: 37308218
DOI: 10.1136/ard-2023-223916 -
Clinical Gastroenterology and... Jul 2024Although biologics have revolutionized the treatment of Crohn's disease (CD), an efficacy ceiling has been reached. Combining biologic therapies may improve remission...
BACKGROUND & AIMS
Although biologics have revolutionized the treatment of Crohn's disease (CD), an efficacy ceiling has been reached. Combining biologic therapies may improve remission rates.
METHODS
EXPLORER, a phase 4, single-arm, open-label study, evaluated triple combination therapy with vedolizumab (300 mg on day 1, weeks 2 and 6, and then every 8 weeks), adalimumab (160 mg on day 2, 80 mg at week 2, then 40 mg every 2 weeks), and methotrexate (15 mg weekly) in biologic-naïve patients with newly diagnosed, moderate- to high-risk CD. Endoscopic remission at week 26 (primary end point; Simple Endoscopic Score for CD ≤2), clinical remission at weeks 10 and 26 (secondary end point; Crohn's Disease Activity Index <150), and incidences of adverse events and serious adverse events were evaluated.
RESULTS
Among 55 enrolled patients, the mean CD duration was 0.4 years, the mean baseline Simple Endoscopic Score for CD was 12.6, and the mean baseline Crohn's Disease Activity Index was 265.5. At week 26, 19 patients (34.5%) were in endoscopic remission. At weeks 10 and 26, 34 (61.8%) and 30 patients (54.5%), respectively, were in clinical remission. Post hoc Bayesian analysis showed that the probabilities that triple combination therapy produced a higher endoscopic remission rate (33.5%; 95% credible interval, 22.4-45.7) than placebo (14%), vedolizumab monotherapy (27%), or adalimumab monotherapy (30%) were 99.9% or higher, 86.3%, and 71.4%, respectively. Six patients had serious adverse events.
CONCLUSIONS
Combination therapy resulted in endoscopic and clinical remission at week 26 in 34.5% and 54.5% of patients, respectively, with no safety signal related to the treatment regimen. This supports further evaluation of combination therapy in CD.
CLINICALTRIALS
gov number: NCT02764762.
Topics: Humans; Crohn Disease; Adalimumab; Antibodies, Monoclonal, Humanized; Male; Female; Adult; Methotrexate; Drug Therapy, Combination; Middle Aged; Treatment Outcome; Young Adult; Adolescent; Drug-Related Side Effects and Adverse Reactions; Gastrointestinal Agents; Aged
PubMed: 37743037
DOI: 10.1016/j.cgh.2023.09.010 -
Clinical, Cosmetic and Investigational... 2023Nail psoriasis (NP) has a prevalence that ranges from 10 to 82% among patients with psoriasis (PsO) and is one of the most common difficult to treat site of psoriasis.... (Review)
Review
BACKGROUND
Nail psoriasis (NP) has a prevalence that ranges from 10 to 82% among patients with psoriasis (PsO) and is one of the most common difficult to treat site of psoriasis. We performed a thorough review of the literature, exploring evidence regarding all available NP systemic treatments, describing also in detail NP dedicated clinical trials.
METHODS
A literature search was conducted in PubMed and Embase prior to February 2023 using a combination of the terms "nail" AND "psoriasis" AND "systemic therapy" AND/OR "systemic treatment". A total of 47 original studies and case reports were reviewed in this article.
RESULTS
Systemic therapies should be considered when the disorder involves more than 3 nails, has extensive skin and joint involvement, and has a significant impact on QoL, due to their best long-term efficacy. In detail, conventional and biologic systemic drugs demonstrated efficacy in recent trials, including acitretin, methotrexate, cyclosporine, apremilast, adalimumab, infliximab, etanercept, certolizumab, golimumab, ustekinumab, secukinumab, ixekizumab, brodalumab, bimekizumab, guselkumab, risankizumab and tildrakizumab.
CONCLUSION
Several therapies have demonstrated efficacy and safety in the treatment of NP; however, the choice of treatment depends not only on the severity of the nail involvement, but also on whether PsA is present, the patient's comorbidities other than PsA, previous treatment history, and the patient's drug preferences.
PubMed: 37519941
DOI: 10.2147/CCID.S417679 -
Cureus Nov 2023This case report focuses on a 40-year-old female with multiple subcutaneous skin nodules presenting to the clinic for worsening skin lesions associated with erythema and...
This case report focuses on a 40-year-old female with multiple subcutaneous skin nodules presenting to the clinic for worsening skin lesions associated with erythema and mild tenderness. A biopsy of the skin lesions showed non-necrotizing granulomas with multinucleated giant cells. The patient was being worked up for non-necrotizing granulomatous skin lesions and was diagnosed with subcutaneous sarcoidosis. Sarcoidosis diagnosis is based on clinical presentation, histopathological changes, and ruling out other granulomatous causes. Our patient is being treated with systemic steroids, hydroxychloroquine, methotrexate, and adalimumab. The patient is nine months into the treatment. A clinically significant reduction in the nodule size was noted. Other systemic involvement of sarcoid was ruled out. This subcutaneous skin involvement is a rare finding called the Darier-Roussy sarcoid. Usually self-resolving but extensive, deformative lesions need to be treated.
PubMed: 38152786
DOI: 10.7759/cureus.49501 -
Drugs Sep 2023Surgery for Crohn's disease (CD) is not curative, as postoperative recurrence (POR) after ileocolonic resection is the rule in the absence of prophylactic treatment. In... (Review)
Review
Surgery for Crohn's disease (CD) is not curative, as postoperative recurrence (POR) after ileocolonic resection is the rule in the absence of prophylactic treatment. In the present article, we critically review available data on the role of anti-tumour necrosis factor (TNF) agents and new biologics (including vedolizumab and ustekinumab) in the prevention and treatment of POR after surgery in CD. Several studies (summarised in various meta-analyses) have confirmed the efficacy of anti-TNFs in the prevention of POR. We identified 37 studies, including 1863 CD patients, with mean endoscopic POR at 6-12 months of 29%. Only few randomised controlled trials (RCTs) have directly compared thiopurines and anti-TNFs, with controversial results, although the superiority of the latter is supported by several meta-analyses. Infliximab and adalimumab seem equally effective. The combination of anti-TNFs and immunosuppressives should be considered in patients previously exposed to anti-TNFs. Several studies have shown that anti-TNFs remain an effective option to prevent POR also in patients with anti-TNF failure before surgery. In fact, the use of the same anti-TNF before and after surgery might be effective for the prevention of POR. Prophylactic anti-TNF treatment, once started, should be continued long term. Anti-TNFs are also effective for the treatment of established POR. Retreatment with anti-TNFs for POR is a valid strategy even after their preoperative failure. In six studies (including 156 patients) evaluating vedolizumab, mean endoscopic POR at 6-12 months was 41%. The non-randomised comparison of anti-TNFs and vedolizumab has provided controversial results. One placebo-controlled RCT confirmed that vedolizumab is quite effective in preventing POR in CD patients with increased risk of recurrence. Seven studies (including 162 patients) evaluated ustekinumab, with a mean endoscopic POR at 6-12 months of 41%. The comparative efficacy of ustekinumab and anti-TNFs is still unclear. Ustekinumab and vedolizumab seem to be equally effective, although the experience is very limited. In conclusion, to date, anti-TNFs are the most effective agents in preventing and treating POR in CD. Anti-TNFs remain an effective option to prevent POR also in patients with anti-TNF failure before surgery. Vedolizumab seems to be quite effective in the prevention of POR in patients with increased risk of recurrence. Ustekinumab is probably also effective in the postoperative setting, although the comparative efficacy with anti-TNFs or vedolizumab is still unclear.
Topics: Humans; Crohn Disease; Ustekinumab; Biological Factors; Antibodies, Monoclonal, Humanized; Tumor Necrosis Factor-alpha; Treatment Outcome; Retrospective Studies
PubMed: 37505446
DOI: 10.1007/s40265-023-01916-2 -
Dermatology and Therapy Nov 2023Deucravacitinib, a newly approved oral medication for the treatment of patients with moderate to severe plaque psoriasis, demonstrated efficacy versus apremilast and...
INTRODUCTION
Deucravacitinib, a newly approved oral medication for the treatment of patients with moderate to severe plaque psoriasis, demonstrated efficacy versus apremilast and placebo in two phase 3 randomized controlled trials (RCTs). A systematic review and network meta-analysis (NMA) indirectly compared deucravacitinib with other relevant systemic biologic/nonbiologic treatments.
METHODS
Online databases were searched for RCTs published through October 2021. Eligible studies were head-to-head comparisons between systemic therapies and/or placebo reporting 50%, 75%, 90%, or 100% improvement in Psoriasis Area and Severity Index (PASI) from baseline in adults with moderate to severe plaque psoriasis. Comparisons included tumor necrosis factor inhibitors, interleukin (IL)-17, IL-23, and IL 12/23 inhibitors, and systemic nonbiologics. A multinomial Bayesian NMA was used to derive estimates of the relative efficacy of deucravacitinib and other systemic therapies. Response probabilities for each treatment and corresponding 95% credible intervals (CrIs) for achieving a PASI response were calculated over short-, mid-, and long-term follow-up (weeks 10-16, 24-28, and 44-60).
RESULTS
The NMA included 47 RCTs. Deucravacitinib showed the highest PASI 75 response rates among nonbiologic systemic therapies across time points. Deucravacitinib PASI 75 response rate (95% CrI) over short-term follow-up was 54.1% (46.5-61.6), within the range of first-generation biologics (etanercept, 39.7% [31.6-48.3]; infliximab, 79.0% [74.0-83.5]). At mid-term follow-up, deucravacitinib PASI 75 increased to 63.3% (58.0-68.4). At long-term follow-up, deucravacitinib PASI 75 was 65.9% (58.0-73.4), comparable to first-generation biologics adalimumab (62.8%; 55.3-69.6) and ustekinumab (68.0%; 64.6-71.5).
CONCLUSIONS
Patients receiving deucravacitinib were more likely to achieve PASI 75 response versus apremilast and methotrexate across all time points. The long-term PASI 75 response rate for deucravacitinib was similar to those of adalimumab and ustekinumab. The approval of deucravacitinib offers patients the choice of an oral therapy with long-term efficacy similar to that of some biologics.
PubMed: 37801281
DOI: 10.1007/s13555-023-01034-7