Successful Certolizumab Pegol Treatment of Chronic Anterior Uveitis Associated with Psoriasis Vulgaris

This report presents details on a 45-year-old male Japanese patient with chronic and refractory anterior uveitis associated with psoriasis vulgaris who was administered certolizumab pegol (CZP), which is an anti-tumor necrosis factor alpha (TNF-α) monoclonal antibody. Although CZP has only been formally approved for rheumatoid arthritis treatment in Japan, a clinical trial allowed us to assess CZP effectiveness in this patient. The grade 3+ anterior chamber inflammation (for both the cells and flare) observed at baseline improved to grade 0 at 3 months post-treatment. Dermatologically, the psoriasis area severity index (PASI) score was 25.4, while the body surface area (BSA) was 88% at baseline. At 3 months after treatment, the scores improved to 2.8 for PASI and less than 1% for BSA. After the treatment, remission has lasted for at least 9 months. No adverse events were seen during the CZP treatment. These findings suggest that CZP could be an effective therapeutic alternative in some refractory anterior uveitis patients with psoriasis vulgaris

Monitoring Sleep and Scratch Improves Quality of Life in Patients with Atopic Dermatitis

Atopic dermatitis itch may cause sleep disturbance and impair quality of life. For patients finding topical therapy difficult to continue, it is important to control itch and reduce scratching. This study developed algorithms to measure nocturnal sleep and scratch, using an actigraph device worn on the back of the hand, and assessed smartphone application feedback to improve adherence with therapy. In the first trial, actigraph measurements in 5 participants who wore the device were highly correlated with measurements by a sleep-monitoring device beneath the mattress. Total actigraph-measured scratching duration for each hour of sleep was highly correlated with measurements by a person rating infrared video-recording of the sleepers. In the second trial, 40 patients with atopic dermatitis were randomly allocated into an intervention group that used the actigraph and smartphone application, and a control group that did not. Both groups were instructed to use the same moisturizer. Dermatology Life Quality Index scores decreased significantly from baseline and were lower than those in the control group at week 8. It is suggested that the device and associated smartphone application reinforced therapy adherence, moisturizer use, and contributed to improved quality of life in patients with atopic dermatitis

Bimekizumab in patients with psoriatic arthritis, naive to biologic treatment: a randomised, double-blind, placebo-controlled, phase 3 trial (BE OPTIMAL)

Background: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17A and IL-17F. We assessed the efficacy and safety of bimekizumab in patients with active psoriatic arthritis who were naive to biologic disease-modifying antirheumatic drugs (DMARDs). Methods: BE OPTIMAL was a 52-week, phase 3, multicentre, randomised, double-blind, placebo-controlled, active reference (adalimumab) trial done at 135 sites (hospitals, clinics, doctors' offices, and research centres) in 14 countries. Eligible patients were 18 years or older with a documented diagnosis of adult-onset psoriatic arthritis that met the Classification Criteria for Psoriatic Arthritis for at least 6 months before screening. Participants were randomly assigned with an interactive-voice and web-response system on the basis of a predetermined randomisation schedule (3:2:1, stratified by region and bone erosion number at baseline) to bimekizumab 160 mg every 4 weeks, placebo every 2 weeks, or the reference group (adalimumab 40 mg every 2 weeks), all administered subcutaneously. At week 16, patients randomly assigned to placebo switched to bimekizumab 160 mg every 4 weeks. The primary endpoint was the proportion of patients reaching 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 (non-responder imputation). Efficacy analyses included all patients who were randomly assigned (intention-to-treat population); the safety analysis set comprised patients who received one or more doses of treatment. Data are presented to week 24 (preplanned analysis). This trial is registered at ClinicalTrials.gov, NCT03895203. Findings: Between April 3, 2019, and Oct 25, 2021, 1163 patients were screened and 852 were randomly assigned to bimekizumab (n=431), placebo (n=281), and reference (adalimumab; n=140) groups. At week 16, significantly more patients receiving bimekizumab (189 [44%] of 431) reached ACR50 response versus placebo (28 [10%] of 281; odds ratio 7·1 [95% CI 4·6–10·9], p<0·0001; adalimumab 64 [46%] of 140). All secondary hierarchical endpoints were met. Treatment-emergent adverse events up to week 16 were reported in 258 [60%] of 431 patients receiving bimekizumab, 139 [49%] of 281 patients receiving placebo, and 83 [59%] of 140 patients receiving adalimumab. No deaths occurred. Interpretation: Bimekizumab treatment had superior improvements in joint, skin, and radiographic efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis who were naive to biologic DMARDs. The safety profile of bimekizumab, including the occurrence of fungal infections, was consistent with previous phase 3 studies in patients with plaque psoriasis, and with IL-17A inhibitors. Funding: UCB Pharma

Bimekizumab in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α inhibitors: a randomised, double-blind, placebo-controlled, phase 3 trial (BE COMPLETE)

Background: Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F and IL-17A. This study compared the efficacy and safety of bimekizumab with placebo over 16 weeks in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor-α (TNFα) inhibitors. Methods: BE COMPLETE was a phase 3, multicentre, randomised, double-blind, placebo-controlled trial conducted across 92 sites (including hospitals, clinics, and research centres) in 11 countries (Australia, Canada, Czech Republic, Germany, Hungary, Italy, Japan, Poland, Russia, the UK, and the USA). Eligible patients were aged 18 years or older with adult-onset psoriatic arthritis (meeting the Classification Criteria for Psoriatic Arthritis for at least 6 months before screening) with a history of inadequate response or intolerance to treatment with one or two TNFα inhibitors for either psoriatic arthritis or psoriasis. We stratified patients with active psoriatic arthritis by region and previous TNFα inhibitor use. Patients were randomly assigned (2:1) to receive subcutaneous bimekizumab 160 mg every 4 weeks or placebo by an interactive-voice and web-response system on the basis of a predetermined randomisation schedule. The primary endpoint was the proportion of patients with 50% or greater improvement in American College of Rheumatology criteria (ACR50) at week 16 (non-responder imputation). Efficacy analyses were done in the randomised population. The safety analysis set comprised patients who received one or more doses of study treatment. This trial was registered at ClinicalTrials.gov, NCT03896581, and is completed. Findings: Between March 28, 2019, and Feb 14, 2022, 556 patients were screened and 400 patients were randomly assigned to bimekizumab 160 mg every 4 weeks (n=267) or placebo (n=133). The primary and all hierarchical secondary endpoints were met at week 16. 116 (43%) of 267 patients receiving bimekizumab reached ACR50, compared with nine (7%) of 133 patients receiving placebo (adjusted odds ratio [OR] 11·1 [95% CI 5·4–23·0], p<0·0001). 121 (69%) of 176 patients with psoriasis affecting at least 3% body surface area at baseline who received bimekizumab reached 90% or greater improvement in the Psoriasis Area and Severity Index (PASI90), compared with six (7%) of 88 patients who received placebo (adjusted OR 30·2 [12·4–73·9], p<0·0001). Treatment-emergent adverse events up to week 16 were reported in 108 (40%) of 267 patients receiving bimekizumab and 44 (33%) of 132 patients receiving placebo. There were no new safety signals and no deaths. Interpretation: Bimekizumab treatment led to superior improvements in joint and skin efficacy outcomes at week 16 compared with placebo in patients with psoriatic arthritis and inadequate response or intolerance to TNFα inhibitors. The safety profile of bimekizumab was consistent with previous phase 3 studies in patients with plaque psoriasis, and studies of IL-17A inhibitors. Funding: UCB Pharma

A case of varicella due to primary varicella zoster virus infection followed by respiratory disease on the background of an immunocompromised condition

Key Clinical Message We encountered an immunocompromised patient with severe respiratory disease immediately after the onset of varicella. Varicella zoster virus infection may be associated with more severe immunosuppressive condition

Clinical Significance of Serum Galectin-9 and Soluble CD155 Levels in Patients with Systemic Sclerosis

Signaling through coinhibitory receptors downregulates the immune response to prevent excessive immune activation and maintain optimal immunity and tolerance. The aim of this study was to examine the levels of the soluble forms of coinhibitory receptors and their ligands, namely, galectin-9 (the ligand of T-cell immunoglobulin and mucin domain 3) and CD155 (the ligand of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain), and their association with clinical features in patients with systemic sclerosis (SSc). The serum levels of galectin-9 and soluble sCD155 were examined by enzyme-linked immunosorbent assays in patients with SSc, and the results were evaluated with respect to clinical features. Patients with SSc exhibited raised serum levels of galectin-9, but not sCD155. Serum galectin-9 levels were raised not only in patients with diffuse cutaneous SSc but also in patients with limited cutaneous SSc. Furthermore, serum galectin-9 levels correlated positively with the erythrocyte sedimentation rate. In addition, increased serum galectin-9 levels tended to be associated with higher mortality and serious organ involvement. These results suggest that galectin-9, but not CD155, may be involved in the pathogenesis of SSc. In addition, the measurement of serum galectin-9 levels could be used to predict serious organ involvement and high mortality in patients with SSc

Case of carbon-ion radiation recall mucositis associated with anti-programmed cell death 1 treatment for paranasal sinuses melanoma.

Since the treatment for mucosal melanoma often accompanies surgical difficulty, carbon-ion radiotherapy in combination with immune check point inhibitors (ICI) against programmed cell death 1(PD-1) and/or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a favorable choice. Radiation recall henomenon (RRP) is represented by an inflammatory reaction within previously irradiated fields,such as mucositis, dermatitis, and pneumonitis, in association with theadministration of chemotherapeutic agents.1 Here, we report a case of carbon-ion radiation recall mucositis associated with nivolumab and pembrolizumab for melanoma located in the paranasal sinuses. A 71-year-old Japanese woman was referred to us because of cheek pain and bloody rhinorrhea. Computed tomography revealed a tumor in the left paranasal sinuses without metastasis.Histopathological examinations showed that atypical cells proliferated in the mucosa (Figure 1a). The tumor cells were positive for Melan-A and HMB-45 (Figure 1b), consistent with mucosal melanoma. As thetumor was unresectable, it was treated with carbon-ion radiotherapy(Figure 1c), and local resolution was achieved. However, bilateral adrenalmetastases were observed 1 year later without local recurrence,and then nivolumab as anti-PD-1 antibody was administrated. At 1 week after the first administration of nivolumab, the patient complained of left oral pain. Physical examination revealed erythema and swelling on the left upper lip (Figure 1d), and erosive ulcers on the left side of the palatal, buccal, and nasal mucosa (Figure 1e), although histopathological examination was not performed in accordance with the patient’s wishes. The symptoms were resolved by discontinuation of nivolumab. Despite the change from nivolumab to pembrolizumab as another anti-PD-1 antibody, mucositis recurred 1 week after the administration of pembrolizumab (Figure 1f). We diagnosed the patientas radiation recall mucositis associated with anti-PD-1 therapy, since:(i) the irradiated fields were exclusively affected; and (ii) the symptomsappeared only when anti-PD-1 antibodies were administrated,in disagreement with radiomucocitis (Figure 1g). Pembrolizumab was intermittently administrated on the occasion of the improvement of mucositis, and the volume of adrenal metastases decreased. Radiation recall phenomenon has been reported to occur in relation with antineoplastic drugs including anthracyclines, alkylating agents, antimetabolites, nucleoside analog, and taxanes.1 However,RRP induced by anti-PD-1 antibodies has rarely been reported,2as well as that induced by carbon-ionradiation. Although the mechanisms of radiation recall mucositis/dermatitis are still controversial,several mechanisms have been suggested including DNArepair impairment, radiation-impaired epithelial function of stem cells, and increasing sensitivity to antineoplastic drugs.3 Carbon-ion radiation elicits local immune responses through a greater cell-killing effect by high density of energy deposition per unit length than conventional radiation.4,5 ICI elicits intensive immune responses through PD-1 and/or CTLA-4 blockade. Therefore, the combination may lead to higher risk of RRP. To our knowledge, this is the first report of the carbon-ion radiation recall mucositis associated with anti-PD-1 therapy. Since mucositis potentiallyserves as a limiting factor for ICI therapy, careful attention to RRP is required after administration of ICI as well as cytotoxic antineoplastic agents in combination with carbon-ion radiotherapy