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Photoacoustics Aug 2024Psoriasis is a chronic inflammatory skin disease, characterized by thick scaly plaques. It imposes a notable disease burden with varying levels of severity affecting the...
Psoriasis is a chronic inflammatory skin disease, characterized by thick scaly plaques. It imposes a notable disease burden with varying levels of severity affecting the quality of life significantly. Current disease severity assessment relies on semi-objective visual inspection based on the Psoriasis Area and Severity index (PASI) score that might not be sensitive to sub-clinical changes. Histology of psoriasis skin lesions necessitate invasive skin biopsies. This indicates an unmet need for a non-invasive, objective and quantitative approach to assess disease severity serially. Herein, we employ multispectral Raster-Scanning Optoacoustic Mesoscopy (ms-RSOM) derived structural and microvascular functional imaging metrics to examine the lesional and non-lesional skin in psoriasis subjects across different severities and also evaluate the treatment outcome in a subject with topical steroids and biologics, such as adalimumab. ms-RSOM derived structural metrics like epidermal thickness and total blood volume (TBV) and microvascular functional information such as oxygen saturation (sO) are evaluated by spectrally resolving the endogenous chromophores like melanin, oxy-, and deoxy-hemoglobin. Initial findings reveal an elevated sO and TBV with severity in lesional and non-lesional psoriasis skin, thus representing increasing inflammation. An increase in epidermal thickness is also noted with the degree of severity, corresponding to the inflammation and increased abnormal cell growth. As a marker to evaluate the treatment response, we observed a decrease in epidermal thickness, sO and TBV in a psoriasis patient post-treatment, which is consistent with the decrease in the PASI score from 4.1 to 1.9. We envision that ms-RSOM has a huge potential to be translated into routine clinical setting for the diagnosis of severity and assessment of treatment monitoring in psoriasis subjects.
PubMed: 38764522
DOI: 10.1016/j.pacs.2024.100611 -
Journal of Medical Case Reports May 2024Metastatic Crohn's disease is a rare disorder characterized by various granulomatous skin lesions that occur independently of gastrointestinal tract involvement.... (Review)
Review
BACKGROUND
Metastatic Crohn's disease is a rare disorder characterized by various granulomatous skin lesions that occur independently of gastrointestinal tract involvement. However, currently there is no standardized care or specific treatment. Therapeutic approaches include immunosuppressive agents, such as corticosteroids, azathioprine, and monoclonal antibodies targeting inflammatory cytokines like tumor necrosis factor (TNF).
CASE PRESENTATION
We present a case of a 29-year-old western European woman with significant blind ending abdominal subcutaneous fistulas and abscesses, who sought evaluation in the dermatology department. Histological examination revealed multiple epithelioid cell granulomas. There was no evidence of infectious or rheumatologic diseases such as sarcoidosis. The tentative diagnosis was metastatic Crohn's disease, which was not related to an intestinal manifestation of the disease. The patient responded to infliximab but had to discontinue it due to an allergic reaction. Subsequent adalimumab treatment failed to induce clinical remission; thus, therapy was switched to ustekinumab, resulting in a positive response. Written informed consent for publication of their clinical details and clinical images was obtained from the patient. For our study more than 1600 publications were screened for cases of metastatic Crohn's disease on PubMed database. 59 case reports with 171 patients were included in the analysis and evaluated for localization, diagnostic and therapeutic approaches, and complications and were summarized in this review.
CONCLUSION
The successful ustekinumab treatment of a patient with metastatic Crohn's disease underscores the potential of this minimally investigated therapeutic option, highlighting the need for future treatment guidelines given the increasing prevalence of such cases.
Topics: Humans; Crohn Disease; Female; Adult; Adalimumab; Ustekinumab; Infliximab; Cutaneous Fistula; Skin Neoplasms
PubMed: 38762485
DOI: 10.1186/s13256-024-04569-1 -
Northern Clinics of Istanbul 2024To investigate the effects of both the Fc fragment in tumor necrosis factor (TNF) inhibitors and rheumatoid factor (RF) titers on treatment survival, disease activity,...
OBJECTIVE
To investigate the effects of both the Fc fragment in tumor necrosis factor (TNF) inhibitors and rheumatoid factor (RF) titers on treatment survival, disease activity, and laboratory parameters in patients with rheumatoid arthritis (RA).
METHODS
In this retrospective cohort study, patients with RA who had started any anti-TNF therapy between January 2017 and March 2020 and who had stayed on this treatment for at least six months were included. The data of the patients were compared separately according to continuation or discontinuation of treatment and the presence or absence of Fc portion in the structure of anti-TNFs. Patients who were taking certolizumab pegol (CZP) without the Fc fragment were placed in the "without Fc group" (wo/Fc), while patients who were taking other drugs (adalimumab, etanercept, golimumab, and infliximab) were placed in the "with Fc group" (w/Fc).
RESULTS
Among the 221 RA patients whose data were available, 52 patients met the inclusion criteria and were included in the study. There was a significant difference in the DAS28-CRP score between wo/Fc group and w/Fc group in the third month of treatment (p=0.012). However, this difference did not persist at the sixth month of treatment (p=0.384). According to the cox-regression results, RF titers were determined to have a significant impact on the drug survival of anti-TNF agents when adjustments were made for the effects of other candidate predictors (Hazard ratio: 1.007 (1.002-1.012), p=0.009).
CONCLUSION
Our results suggest that compared to the Fc fragment, RF titers were the more important risk factor in survival of anti-TNF drugs.
PubMed: 38757098
DOI: 10.14744/nci.2023.01643 -
Mediterranean Journal of Rheumatology Mar 2024Janus kinases (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is involved in pathophysiologic cascade of a notable number of rheumatic diseases.... (Review)
Review
Janus kinases (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway is involved in pathophysiologic cascade of a notable number of rheumatic diseases. The development of JAK inhibitors has expanded treatment choices in rheumatoid arthritis (RA) with a sustained class-effect efficacy. Filgotinib is a novel selective inhibitor of JAK1 isoform licensed for use in RA and ulcerative colitis. In this review we aim to present an analysis of filgotinib's efficacy and drug-specific safety warnings. Patients with RA with or without concomitant conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) (naïve or experienced) and those who have failed biologic Disease-Modifying Antirheumatic Drugs (bDMARDs) were examined in randomised clinical trials. Filgotinib was also tested against placebo, methotrexate, or adalimumab. Long-term extension trials provide insights for up to four years of continuous filgotinib administration. Beneficial effects are depicted in both disease activity parameters and quality of life indexes in moderate or severe RA with a longitudinal efficacy. In head-to-head comparison with adalimumab, filgotinib 200 mg was non-inferior. Adverse effects alerts are marked by the elevated risk of infectious adverse effects with the exception of herpes zoster infection, which has a low incidence.
PubMed: 38756936
DOI: 10.31138/mjr.281123.fof -
JPGN Reports May 2024Approved options for advanced therapy in pediatric inflammatory bowel disease (IBD) are limited. Although Janus kinase (JAK) inhibitors are approved in adult IBD, their...
Approved options for advanced therapy in pediatric inflammatory bowel disease (IBD) are limited. Although Janus kinase (JAK) inhibitors are approved in adult IBD, their benefit in pediatric populations is not yet delineated. We present a 13-year-old female patient with ulcerative colitis (UC) refractory to numerous therapies and courses of prednisone that ultimately responded to a JAK inhibitor. Initial treatment consisted of 5-aminosalicylate and azathioprine. This was changed to adalimumab due to persistent symptoms. Repeat colonoscopy revealed pancolitis, thus she was transitioned to vedolizumab. She was hospitalized twice for uncontrolled symptoms on vedolizumab and subsequent scope showed continued pancolitis. As a result, she transitioned to ustekinumab without symptomatic relief after adjusting to monthly dosing. The family declined colectomy, opting to exhaust all medical therapies. Upadacitinib was started and her symptoms resolved within 1 week, and she remains in steroid-free remission. This case illustrates the possible role of JAK inhibitors in extensively refractory pediatric UC patients before colectomy.
PubMed: 38756133
DOI: 10.1002/jpr3.12067 -
Pilot and Feasibility Studies May 2024Pain management is a major unmet need in people with rheumatoid arthritis (RA). Although many patients are treated with disease modifying anti-rheumatic drugs (DMARDS),...
Assessing the effects of distinct biologic therapies on rheumatoid arthritis pain by nociceptive, neuropathic and nociplastic pain components: a randomised feasibility study.
BACKGROUND
Pain management is a major unmet need in people with rheumatoid arthritis (RA). Although many patients are treated with disease modifying anti-rheumatic drugs (DMARDS), including biologic therapies, many people with RA continue to experience significant pain. We aimed to determine whether performing a comprehensive pain evaluation is feasible in people with active RA receiving conventional DMARDs and biologic therapies.
METHODS
The BIORA-PAIN feasibility study was an open-label, randomised trial, which recruited participants suitable for treatment with biologic therapy. The primary feasibility outcomes were recruitment, randomisation and retention of eligible participants. All participants underwent pain assessment for nociceptive, neuropathic and nociplastic pain during the 12-month study period, with quarterly assessments for VAS (Visual Analogue Scale) pain, painDETECT and QST (quantitative sensory testing). This trial was registered in clinicaltrials.gov NCT04255134.
RESULTS
During the study period, 93 participants were screened of whom 25 were eligible: 13 were randomised to adalimumab and 12 to abatacept. Participant recruitment was lower than expected due to the COVID-19 pandemic. Pain assessments were practical in the clinical trial setting. An improvement was observed for VAS pain from baseline over 12 months, with a mean (SEM) of 3.7 (0.82) in the abatacept group and 2.3 (1.1) in the adalimumab group. There was a reduction in painDETECT and improvement in QST measures in both treatment groups during the study. Participant feedback included that some of the questionnaire-based pain assessments were lengthy and overlapped in their content. Adverse events were similar in both groups. There was one death due to COVID-19.
CONCLUSIONS
This first-ever feasibility study of a randomised controlled trial assessing distinct modalities of pain in RA met its progression criteria. This study demonstrates that it is feasible to recruit and assess participants with active RA for specific modalities of pain, including nociceptive, neuropathic and nociplastic elements. Our data suggests that it is possible to stratify people for RA based on pain features. The differences in pain outcomes between abatacept and adalimumab treated groups warrant further investigation.
TRIAL REGISTRATION
NCT04255134, Registered on Feb 5, 2020.
PubMed: 38755699
DOI: 10.1186/s40814-024-01505-4 -
Clinical Case Reports May 2024IgA pemphigus is usually treated by Dapsone. Recalcitrant cases may be treated by Colchicine, Sulfapyridine, or Acitretin. Some patients with recurrent severe disease...
KEY CLINICAL MESSAGE
IgA pemphigus is usually treated by Dapsone. Recalcitrant cases may be treated by Colchicine, Sulfapyridine, or Acitretin. Some patients with recurrent severe disease may not respond to the aforementioned medications. Our study highlights the role of TNFa inhibitor as an alternative modality in the treatment of recalcitrant IgA pemphigus.
ABSTRACT
IgA pemphigus is a rare autoimmune blistering disease characterized by a pruritic, annular, vesiculopustular eruption. In IgA pemphigus, there are IgA autoantibodies targeting the keratinocyte cell surface adhesion molecules, causing cell-to-cell dehiscence and a flaccid vesiculopustular eruption, mainly in the axilla and groin. Dapsone, despite being the drug of choice for treating IgA pemphigus, is not effective in clearing lesions in a minority of patients and such rare cases of recalcitrant IgA pemphigus need alternative modalities of treatment. Here, we report the successful treatment of a 50-year-old male patient with an adalimumab injection who had a poor response to dapsone.
PubMed: 38751960
DOI: 10.1002/ccr3.8807 -
Journal of Infection and Public Health Jun 2024The risk of infection including tuberculosis (TB) infection or reactivation during biological therapy with the current various clinical application is a major concern....
BACKGROUND
The risk of infection including tuberculosis (TB) infection or reactivation during biological therapy with the current various clinical application is a major concern. This risk may be higher in countries endemic to TB. Our aim of this study is to determine the risk of TB infection in patients receiving 3 biological treatments, Adalimumab, Etanercept and Tocilizumab.
METHODS
A retrospective cohort study extending over 2 years follow-up for all patients receiving Adalimumab, Etanercept and Tocilizumab for various clinical indications in a tertiary care center in Saudi Arabia.
RESULT
Over the period of 2015-2019, A total of 410 patients received Adalimumab, 271 received Etanercept and 58 patients received Tocilizumab. Rheumatoid arthritis was the most common indication for therapy in all groups and for Adalimumab the most common indication was inflammatory bowel disease, for Etanercept was psoriatic arthritis and for Tocilizumab was juvenile idiopathic arthritis. After a mean follow up period of 36 ± 8.9 months for patients receiving Adalimumab, 21.5 ± 8.4 months for patients receiving Etanercept and 21 ± 2.5 months for patients receiving Tocilizumab there were no reported cases of TB infection in all groups. Only one patient was diagnosed with latent TB 7 months later after starting Adalimumab and tow patients after starting Etanercept. The overall Interferon Gamma Release Assays (IGRA) positivity rate was 9.7%. There was significant association between IGRA positivity rate and patient age. The cutoff age in which IGRA positivity has significantly increased was 53.20 years.
CONCLUSION
In our study, patients receiving Etanercept, Adalimumab and Tocilizumab had no increased risk of TB infection. Only 0.3% of patients treated with Adalimumab and 0.9% of patients treated with Etanercept converted to a positive IGRA during therapy.
Topics: Humans; Saudi Arabia; Male; Female; Antibodies, Monoclonal, Humanized; Adalimumab; Etanercept; Retrospective Studies; Adult; Middle Aged; Tuberculosis; Arthritis, Rheumatoid; Antirheumatic Agents; Inflammatory Bowel Diseases; Arthritis, Juvenile; Arthritis, Psoriatic; Young Adult; Aged
PubMed: 38728834
DOI: 10.1016/j.jiph.2024.04.016 -
EClinicalMedicine Jun 2024Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to...
BACKGROUND
Disease extent in Ulcerative Colitis (UC) has prognostic implications for disease course. It is unclear whether the efficacy of medical therapies for moderate to severely active UC vary according to disease extent at enrollment.
METHODS
We analyzed patient level data from 11 Phase 2 and 3 clinical trials of advanced therapies in patients with moderate-to-severe UC to assess modifications of advanced therapy effects by disease extent. Primary outcome was clinical response and secondary outcomes were clinical remission, endoscopic response/remission and endoscopic improvement, and Mayo clinic subscore for both induction and maintenance studies. Binary and continuous outcomes were analyzed using the modified Poisson regression model and the mixed-effects model, respectively, adjusting for age, sex, disease duration, concomitant steroid use and prior anti-TNF use. Effect modifications with binary outcomes were quantified by ratios of risk ratio for left-sided to that for extensive colitis while effect modifications with the Mayo subscores were quantified by differences of the differences between mean scores of the left-sided and extensive colitis. Results were presented with point estimates and 95% confidence intervals as well as p-values.
FINDINGS
Eleven clinical trials enrolling 5450 UC patients (infliximab = 2, adalimumab = 2, golimumab = 2, vedolizumab = 2, tofacitinib = 3) were included. In induction trials, there was evidence to suggest effect modification by disease extent for clinical response with tofacitinib (the ratio of RRs 0.67, 95% CI [0.45, 0.99], p = 0.049) and clinical remission with infliximab (ratio of RRs 0.33, 95% CI [0.13, 0.85], p = 0.020) favoring patients with extensive colitis. There was no evidence to suggest effect modification for endoscopic improvement and clinical outcomes. There was evidence to suggest effect modification by disease extent for clinical remission with tofacitinib (ratio of RRs 0.44, 95% CI [0.22, 0.89], p = 0.020) favoring patients with extensive colitis. For symptom subscores from the Mayo Clinic score, tofacitinib was associated with a greater reduction in both stool frequency (difference of differences 0.37, 95% CI [0.08, 0.65], p = 0.012) and rectal bleeding scores (difference of differences 0.25, 95% CI [0.03, 0.47], p = 0.026) in patients with extensive colitis compared to left sided.
INTERPRETATION
These findings underscore the possibility of differential efficacy of medical therapies according to disease distribution. These results warrant further exploration in forthcoming trials to better inform treatment strategies and consideration of disease distribution as a baseline stratification factor in clinical trials.
FUNDING
This study did not receive any financial support.
PubMed: 38726222
DOI: 10.1016/j.eclinm.2024.102621 -
ACG Case Reports Journal May 2024A 46-year-old woman with fistulizing Crohn's disease in clinical remission in the setting of long-term adalimumab therapy presented to hospital and was ultimately...
A 46-year-old woman with fistulizing Crohn's disease in clinical remission in the setting of long-term adalimumab therapy presented to hospital and was ultimately diagnosed with anti--methyl-D (NMDA) receptor antibody-mediated autoimmune encephalitis (NMDAr-AE). Inflammatory central nervous system and antibody-mediated adverse effects have been found to be associated with anti-tumor necrosis factor agents, with 5 previous case reports noting cases of NMDAr-AE in patients on these medications. The current article reports this case, which is unique for the length of adalimumab therapy before this presentation, as well as a summary of literature regarding anti-tumor necrosis factors and NMDAr-AE.
PubMed: 38725477
DOI: 10.14309/crj.0000000000001360