Chlormethine Gel in Combination With Other Therapies for Treatment of Mycosis Fungoides: A Review With Patient Cases

Topical chlormethine gel has been approved as monotherapy for treatment of adult patients with mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma. In clinical practice, chlormethine gel is often combined with other skin-directed or systemic therapies to optimize response and target recalcitrant lesions. Positive outcomes with combination regimens using chlormethine gel and topical corticosteroids, phototherapy, retinoids, methotrexate, or interferon-α have been reported in literature. However, there are no treatment guidelines on the use of combination regimens with chlormethine gel. To provide real-world evidence and guidance on the use of chlormethine gel combination regimens, several cases of patients treated with chlormethine gel combined with phototherapy (n = 5), retinoids (n = 16), or mogamulizumab (n = 3) are presented. These different combination regimens showed promising results. Most patients had a complete or partial response following treatment and the combinations were well-tolerated over extended treatment periods. Patients receiving chlormethine gel with retinoids had long-term periods of remission, even after treatment discontinuation. Durations of response of up to 3 years were observed in these patients. This long-term disease control may be the result of disease-modifying effects of chlormethine. Previous studies have shown targeted reductions in malignant T-cell clones in patients treated with chlormethine gel as well as improved post-treatment responses. Further research is needed to determine the effectiveness and safety of combination treatment regimens with chlormethine gel and to assess the impact chlormethine gel has on disease control

Effectiveness and tolerability of chlormethine gel for the management of mycosis fungoides: a multicenter real-life evaluation

BackgroundTopical chlormethine (CL) is recommended as a first-line treatment for early-stage mycosis fungoides (MF) and in 2017, the European Medicines Agency approved the CL gel formulation to treat adult patients. More recently, to increase patient compliance and adherence, clinicians have developed flexible protocols that allow the concomitant use of CL gel with topical corticosteroids in daily practice regimens. Therefore, sharing real-life data on CL gel use and side effects management may help improve the use of this agent.ObjectivesTo expand knowledge about the actual use of CL gel in patients with MF, the present study assessed the improvement of MF skin lesions after CL gel treatment and provided information on the management of cutaneous adverse events (AEs) in a real-life setting.MethodsThis was an Italian retrospective study conducted among six dermatology referral centers. Patients ≥18 years affected by MF and in treatment with CL gel (160 µ/g), alone or in combination according to routine clinical practice, between December 2019 and December 2021 were considered. The study’s primary aim was to evaluate the effectiveness of CL gel in terms of overall response rate (ORR) after 3 months of treatment.ResultsA total of 79 patients (61% male) with different stages of MF (84% early stage) were included. CL gel was prescribed mainly in association with topical corticosteroids (66% of patients). ORR after 3 months of treatment was 42%, with no differences between early- and advanced-stage MF. Response rates improved over time up to 97% after 18 months of treatment. Overall, 66 AEs were reported in 67% of patients; most were hyperpigmentation (45%) and irritant contact dermatitis (37%). Six AEs led to treatment discontinuation, and five out of six (83%) patients who reported these events resumed treatment after interruption. No AEs were classified as severe.ConclusionsOur observations support the use of CL gel in patients with early- and advanced-stage MF, making it a valuable treatment option

Autoimmune bullous dermatoses in cancer patients treated by immunotherapy: a literature review and Italian multicentric experience

Cutaneous immune-related adverse events are frequently associated with immune checkpoint inhibitors (ICIs) administration in cancer patients. In fact, these monoclonal antibodies bind the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/ligand 1 leading to a non-specific activation of the immune system against both tumoral cells and self-antigens. The skin is the most frequently affected organ system appearing involved especially by inflammatory manifestations such as maculopapular, lichenoid, psoriatic, and eczematous eruptions. Although less common, ICI-induced autoimmune blistering diseases have also been reported, with an estimated overall incidence of less than 5%. Bullous pemphigoid-like eruption is the predominant phenotype, while lichen planus pemphigoides, pemphigus vulgaris, and mucous membrane pemphigoid have been described anecdotally. Overall, they have a wide range of clinical presentations and often overlap with each other leading to a delayed diagnosis. Achieving adequate control of skin toxicity in these cases often requires immunosuppressive systemic therapies and/or interruption of ICI treatment, presenting a therapeutic challenge in the context of cancer management. In this study, we present a case series from Italy based on a multicenter, retrospective, observational study, which included 45 patients treated with ICIs who developed ICI-induced bullous pemphigoid. In addition, we performed a comprehensive review to identify the cases reported in the literature on ICI-induced autoimmune bullous diseases. Several theories seeking their underlying pathogenesis have been reported and this work aims to better understand what is known so far on this issue

Effects of TNF-α inhibition on pre-clinical enthesitis: observational study on 49 psoriatic patients

Background Enthesitis is a hallmark of psoriatic arthritis (PsA) and echographic ultrasounds (US) represent a support for diagnosis of pre-clinical signs of enthesitis in asymptomatic patients at high risk for advanced forms. Early treatment with anti-TNFα could prevent permanent damage contrasting the degenerative course of the disease. Objectives To evaluate the effects of adalimumab on echographic and preclinical enthesitis signs in patients affected by plaque psoriasis. Methods 49 psoriatic patients undergoing adalimumab treatment for plaque-type psoriasis were subjected to echographic screening for identifying pre-clinical signs of enthesitis. Patients underwent clinical and ultrasonographic examination of hands, elbows and knees before starting adalimumab and after 24 and 48 weeks of treatment. Results We observed a reduction of the total number of echographic abnormalities and a significant decrease of the thickness of quadriceps tendons at week 24 and week 48. Furthermore, there was no evidence of significant articular damage progression during the entire study duration. Conclusions Entheseal ultrasonography may be used for preclinical diagnosis of PsA. Our study demonstrates that early detection and management with adalimumab leads to a block of articular damage progression. On quadriceps tendon, adalimumab has shown to be effective with a significant thickening reduction at week 24 and 4

Long-term treatment with adalimumab in psoriatic arthritis: serum adalimumab concentration, immunogenicity and the link with clinical response

Objectives: An observational study to evaluate the relationship between serum concentrations of adalimumab and disease activity in patients receiving long-term adalimumab treatment for psoriatic arthritis. Methods: Serum adalimumab and adalimumab antidrug antibodies were quantified by enzyme linked immunosorbent assay. Disease activity was assessed using Disease Activity Score (44 joint measures). Serum C-reactive protein was quantified using standard methods. Results: A total of 30 patients were recruited. There were significant inverse correlations between serum adalimumab concentration and serum C-reactive protein (CRP) concentration [r = −0.43], the number of tender joints (r = −0.4), and Disease Activity Score (DAS44)-CRP (r = −0.36). Mean serum adalimumab levels were significantly higher in patients with DAS44-CRP <1.6 than in patients with DAS44-CRP ≥1.6. Conclusions: Serum adalimumab could be an important tool that may improve the management of psoriatic arthritis in patients responding to long-term treatment

Use of biological drugs in patients with psoriasis and psoriatic arthritis in Italy: Results from the PSONG survey

This Italian multicenter retrospective study compared the drug survival and efficacy of different anti-TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsA patients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 was analyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug survival rate and probability of maintaining PASI response were evaluated. The impact of dependent variables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients were included, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumab followed by etanercept and infliximab in PsO and PsA patients. The probability of maintaining PASI response was significantly higher for adalimumab followed by infliximab. For PsO patients, the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 8.1; 95% CI: 4.2\ue2\u80\u9315.6, p <.001) or infliximab (OR: 6.6; 95% CI: 2.6\ue2\u80\u9316.3, p <.001) vs. adalimumab. Likewise, for PsA patients the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 2.3; 95% CI: 1.4\ue2\u80\u933.8, p =.01) or infliximab (OR: 2.2; 95% CI: 1.1\ue2\u80\u934.1, p =.018) vs. adalimumab. Adalimumab could be the best therapeutic option over other anti-TNF agents for the treatment of PsO and PsA patients

PsA-Disk, a novel visual instrument to evaluate psoriatic arthritis in psoriatic patients: an Italian derma-rheuma multicentre study

BACKGROUND: Consensus among dermatologists and rheumatologists in the diagnosis and assessment of musculoskeletal diseases in psoriasis (PsO) patients is needed. This study assesses characteristics of musculoskeletal pain in patients with PsO for the presence of psoriatic arthritis (PsA) and evaluation of a novel 16-item visual instrument (PsA-Disk). METHODS: Data were collected from eight dermatological/rheumatological centres across Italy. Patients with PsO completed PEST (Psoriasis Epidemiology Screening Tool) and PsA-Disk questionnaires during the first visit. A rheumatological visit was performed to confirm the presence of PsA. Both validity and reliability of PsA-Disk were assessed. RESULTS: A total of 573 patients with PsO were examined at the first visit, and 120 (21%) were diagnosed with PsA. Patients with PsA compared with patients with PsO (n = 119) presented statistically significant differences for: nail involvement, PEST score \u2a7e3, higher erythrocyte sedimentation rate (ESR), Nail Psoriasis Severity Index (NAPSI)-feet, NAPSI-(hands + feet) and PsA-Disk scores (73.9\u2009\ub1\u200932.1 versus 58.1\u2009\ub1\u200939.8, p\u2009&lt;\u20090.001). Patients with PsA with knee arthritis had higher PsA-Disk scores (98.4\u2009\ub1\u200926 versus 71.5\u2009\ub1\u200931.9, p\u2009=\u20090.006) that were also correlated with number of swollen (r\u2009=\u20090.2, p &lt; 0.05) and tender joints (r = 0.24, p = 0.021), patient (r = 0.4, p &lt; 0.001) and physician-pain-visual analogue scale (VAS; r = 0.33, p &lt; 0.001), patient global assessment (PGA)-VAS (r = 0.23, p = 0.025), physician-health assessment questionnaire (HAQ; r = 0.38, p = 0.011), Disease Activity Score (DAS)-44 (r = 0.25, p = 0.023) and Disease Activity in Psoriatic Arthritis (DAPSA; r = 0.31, p = 0.005). The instrument had excellent reliability in terms of internal consistency (Cronbach's alpha = 0.90) and stability (intraclass correlation = 0.98). Moderate agreement between PsA-Disk and PEST (Cohen's kappa = 0.46) was observed, while construct validity appeared appropriate [PsA + patients: PsA-Disk score (interquartile range; IQR) =71 (50-96); PsA-patients: PsA-Disk score (IQR)=50 (20-90); p &lt; 0.001]. CONCLUSION: PsA-Disk may be considered a valid novel instrument aiding both dermatologists and rheumatologists in the rapid detection and assessment of musculoskeletal disease characteristics