EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update.

OBJECTIVE: New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA. METHODS: Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined. RESULTS: The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed. CONCLUSION: These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.

Long-term outcomes with HLX01 (HanliKang®), a rituximab biosimilar, in previously untreated patients with diffuse large B-cell lymphoma: 5-year follow-up results of the phase 3 HLX01-NHL03 study.

HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2-76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9-87.5%) and 75.4% (95% CI: 68.9-82.6%)( HR: 0.75, 95% CI 0.47-1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4-84.6%) and 73.0% (95% CI: 66.3-80.3%) (HR: 0.84, 95% CI 0.54-1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

Quality of life assessment in diffuse large B-cell lymphoma (DLBCL) in REFLECT: a prospective, non-interventional, multicenter, German study, assessing Sandoz rituximab in combination with CHOP.

Health-related quality of life (HRQoL) data are important indicators of health status in patients with lymphoma. The objective of this analysis was to assess the impact of treatment with Sandoz rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on HRQoL in treatment-naïve adult patients with diffuse large B-cell lymphoma (DLBCL) included in the prospective, real-world REFLECT study. REFLECT is the first prospective study to assess HRQoL in patients with DLBCL treated with a rituximab biosimilar. HRQoL was assessed via the patient-reported European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire at baseline, mid-treatment (month 3), end of treatment (month 6), and follow-up (months 9 and 12). Subgroup analyses were performed to evaluate the influence of baseline characteristics on HRQoL, and associations between baseline HRQoL and treatment response. HRQoL was assessed in 169 patients. Mean global health status score remained stable from baseline (54.8) to mid-treatment (month 3; 54.7), before steadily improving through to end of treatment (month 6; 61.4), and follow-up month 9 (64.9) and month 12 (68.8). Similar trends were observed across most functional and symptom subscales. Higher cognitive, physical, or role functioning, and less appetite loss, diarrhea, fatigue, or pain at baseline, were all associated with an improved likelihood of reaching a complete versus partial response at the end of treatment. Overall, these findings confirm the HRQoL benefits of R-CHOP therapy in treatment-naïve adult patients with DLBCL, and suggest that baseline HRQoL may be predictive of treatment response.

Impact of Excipient Extraction and Buffer Exchange on Recombinant Monoclonal Antibody Stability.

The foundation of a biosimilar manufacturer's regulatory filing is the demonstration of analytical and functional similarity between the biosimilar product and the pertinent originator product. The excipients in the formulation may interfere with characterization using typical analytical and functional techniques during this biosimilarity exercise. Consequently, the producers of biosimilar products resort to buffer exchange to isolate the biotherapeutic protein from the drug product formulation. However, the impact that this isolation has on the product stability is not completely known. This study aims to elucidate the extent to which mAb isolation via ultrafiltration-diafiltration-based buffer exchange impacts mAb stability. It has been demonstrated that repeated extraction cycles do result in significant changes in higher-order structure (red-shift of 5.0 nm in fluorescence maxima of buffer exchanged samples) of the mAb and also an increase in formation of basic variants from 19.1 to 26.7% and from 32.3 to 36.9% in extracted innovator and biosimilar Tmab samples, respectively. It was also observed that under certain conditions of tertiary structure disruptions, Tmab could be restabilized depending on formulation composition. Thus, mAb isolation through extraction with buffer exchange impacts the product stability. Based on the observations reported in this paper, we recommend that biosimilar manufacturers take into consideration these effects of excipients on protein stability when performing biosimilarity assessments.

Immunogenicity, efficacy, and safety of biosimilar insulin glargine (Gan & Lee glargine) compared with originator insulin glargine (Lantus®) in patients with type 2 diabetes after 26 weeks' treatment: A randomized open label study.

AIM: To evaluate the equivalence of immunogenicity, safety and efficacy of Gan & Lee (GL) Glargine (Basalin®; Gan & Lee Pharmaceutical) with that of the reference product (Lantus®) in adult participants with type 2 diabetes mellitus. METHODS: This was a phase 3, multicenter, open-label, equivalence trial conducted across 57 sites. In total, 567 participants with type 2 diabetes mellitus were randomized in a 1:1 ratio to undergo treatment with either GL Glargine or Lantus® for 26 weeks. The primary endpoint was the proportion of participants in each treatment arm who manifested treatment-induced anti-insulin antibodies (AIA). Secondary endpoints included efficacy and safety metrics, changes in glycated haemoglobin levels, and a comparative assessment of adverse events. Results were analysed using an equivalence test comparing the limits of the 90% confidence interval (CI) for treatment-induced AIA development to the prespecified margins. RESULTS: The percentages of participants positive for treatment-induced glycated haemoglobin by week 26 were similar between the GL Glargine (19.2%) and Lantus® (21.3%) treatment groups, with a treatment difference of -2.1 percentage points and a 90% CI (-7.6%, 3.5%) (predefined similarity margins: -10.7%, 10.7%). The difference in glycated haemoglobin was -0.08% (90% CI, -0.23, 0.06). The overall percentage of participants with any treatment-emergent adverse events was similar between the GL Glargine (80.1%) and Lantus® (81.6%) treatment groups. CONCLUSIONS: GL Glargine was similar to Lantus® in terms of immunogenicity, efficacy, and safety, based on the current study.

Pharmacokinetic similarity of switching SAR341402 insulin aspart biosimilar and NovoLog insulin aspart versus continuous use of NovoLog in adults with type 1 diabetes: The GEMELLI X trial.

AIM: To assess whether multiple switches between SAR341402 biosimilar insulin aspart (SAR-Asp) and the insulin aspart reference product (NovoLog; NN-Asp) leads to equivalent pharmacokinetic (PK) exposure compared with continuous use of NN-Asp in adults with type 1 diabetes (T1D). MATERIALS AND METHODS: This multicentre, open-label, phase 3 study randomized (1:1) 210 subjects with T1D treated with once-daily insulin glargine U100 as basal insulin to four 4-week periods of alternating multiple daily injections of SAR-Asp and NN-Asp (NN-Asp for the first 4 weeks, SAR-Asp in the last 4 weeks; switching group) versus 16 weeks of continuous NN-Asp (non-switching group). At week 16, a single dose (0.15 U/kg) of SAR-Asp in the switching group (n = 95) or NN-Asp in the non-switching group (n = 105) was given in the morning before breakfast. Primary PK endpoints were area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax ) of SAR-Asp versus NN-Asp after the single dose at week 16. RESULTS: The extent of PK exposure was similar between the two treatments (SAR-Asp in the switching group and NN-Asp in the non-switching group) at week 16, with point estimates of treatment ratios close to 1. The 90% confidence intervals for AUC treatment ratios were contained within 0.8-1.25. For Cmax in the primary analysis set, the upper confidence limit was 1.32. This was because of the profiles of three participants with implausible high values. A prespecified sensitivity analysis excluding implausible values showed results contained within 0.8-1.25. CONCLUSIONS: PK exposure of SAR-Asp (switching group) and reference NN-Asp (non-switching group) were similar, supporting interchangeability between these two insulin aspart products.

A randomized, double-blind, phase III study assessing clinical similarity of SB17 (proposed ustekinumab biosimilar) to reference ustekinumab in subjects with moderate-to-severe plaque psoriasis.

BACKGROUND: Ustekinumab (UST) is a safe and effective treatment for moderate-to-severe psoriasis. OBJECTIVES: To compare efficacy, safety, pharmacokinetics (PK), and immunogenicity of the proposed UST biosimilar SB17 with reference UST in subjects with moderate-to-severe plaque psoriasis. METHODS: In this randomized double-blind study, subjects were randomized to receive 45 mg of SB17 or UST subcutaneously at week 0, 4, and every 12 weeks. The primary endpoint was the percent change from baseline in Psoriasis Area and Severity Index at week 12 with an equivalence margin of [-15%, 15%]. Other secondary efficacy, safety, PK, and immunogenicity endpoints were measured through week 28. RESULTS: Two hundred forty-nine subjects were randomized to SB17, 254 to UST. Adjusted difference of Psoriasis Area and Severity Index change from baseline at week 12 of -0.6% (95% confidence interval; -3.780, 2.579) was within the equivalence margin. Physician's Global Assessment and Dermatology Life Quality Index were also comparable. Overall treatment-emergent adverse events were comparable (SB17: 48.2%, UST: 48.8%). The overall incidence of antidrug antibodies up to Week 28 was 13.3% with SB17 and 39.4% with UST. LIMITATIONS: Data were only through week 28. CONCLUSION: SB17 was clinically biosimilar to UST up to week 28.

Population pharmacokinetic, pharmacodynamic and efficacy modeling of SB12 (proposed eculizumab biosimilar) and reference eculizumab.

PURPOSE: To describe, compare similarity of pharmacokinetic (PK), pharmacodynamic (PD) and efficacy of SB12 and reference eculizumab (ECU) and find clinically significant covariate relationships. METHODS: The PK, PD (terminal complement activity) and efficacy (LDH) data of SB12 and ECU were obtained from 289 subjects from phase I and phase III studies. One- and two-compartment PK models with first-order elimination were evaluated for SB12 and ECU. For PD and efficacy, both direct and indirect models were tested. The impact of covariates on PK, PD and efficacy parameters was assessed. Relationship between PK/PD and PD/efficacy was characterized. This modeling was performed using NONMEM version 7.4 (Icon Development Solutions, Ellicott City, MD, USA). RESULTS: The two-compartment model adequately described the PK of SB12 and ECU, and the subject's weight was chosen as a clinically significant covariate affecting drugs' clearance and central volume of distribution. Treatment group was not a significant covariate affecting clearance. The direct response model using inhibitory sigmoid Emax and sigmoid Emax relationship well described the PK/PD relationship and PD/efficacy relationship of SB12 and ECU, respectively. Through this modeling, the relationships between PK, PD and efficacy were characterized. There were no differences in PK, PD and efficacy parameters between SB12 and ECU in pooled populations of healthy subjects and paroxysmal nocturnal haemoglobinuria (PNH) patients. CONCLUSION: The population modeling showed PK, PD and efficacy similarities between SB12 and ECU in pooled population of healthy subjects and PNH patients, supporting the totality of evidence on biosimilarity for SB12.

Achieving white blood cell equity: are the safety profiles of biosimilar and reference pegfilgrastims comparable?

Biosimilars can provide choices for patients and may provide cost savings; however, their uptake has been slow in the USA, in part due to limited knowledge. To provide additional confidence in US pegfilgrastim biosimilars, this narrative review compared the safety profiles of biosimilar pegfilgrastims, currently approved or filed for approval in the USA, with the EU- and US-approved reference pegfilgrastims. Headache and bone pain were common to biosimilars and reference products and occurred at a similar incidence. Clinical trial data on the safety profiles of biosimilar pegfilgrastims and reference products have demonstrated similarity and comparability, with no unexpected safety outcomes. Overall, the safety profiles of biosimilar pegfilgrastims and reference pegfilgrastims demonstrated a high degree of similarity and comparability.

Pegfilgrastim is a biologic drug (one made in living cells such as bacteria) that is given to some patients being treated for cancer. Pegfilgrastim is prescribed to reduce a patient's risk of infection due to a weakened immune system caused by various chemotherapy treatment plans. A biosimilar is a type of biologic medicine that is highly similar to a US FDA-approved reference biologic, and is often cheaper, making it more widely available to patients. As of March 2023, there are eight pegfilgrastim biosimilars (six approved and two awaiting approval by the FDA). This review compared the side effects for the reference pegfilgrastim with the biosimilar pegfilgrastims. The side effects in general and the side effects from treatment were similar for the reference pegfilgrastim and for the biosimilar pegfilgrastims, with the most common side effects being headache and bone pain. Serious side effects such as allergic reactions or problems with the spleen were very low and were also similar between the reference pegfilgrastim and the biosimilar pegfilgrastims. These results show that the safety of the biosimilar pegfilgrastims was similar to the reference pegfilgrastim, with no unexpected side effects. With comparable safety to their reference product, biosimilars have the potential to improve patient access to more affordable treatment options.

Real-world clinical scenarios during introduction of trastuzumab biosimilar for HER2-positive breast cancer in the European Union.

Aim: Trastuzumab-anns is an intravenously administered biosimilar to trastuzumab approved by the EMA and US FDA for treatment of HER2+ early and metastatic breast cancer as well as metastatic gastric cancer. Lack of real-world characterization of biosimilar use has hindered uptake. Methods: This observational chart review characterizes 488 patients who received trastuzumab-anns in EU clinical practice settings. Results: Approximately 2/3rds of patients initiated trastuzumab-anns in adjuvant and neoadjuvant settings and most were naive new starters (70%). 30% were switchers from another trastuzumab, among whom 48% switched from trastuzumab iv. reference product. Common reasons for trastuzumab-anns discontinuation were a switch to another biosimilar product (34.8%, n = 85) or to trastuzumab reference product (15.6%, n = 38). Conclusion: Trastuzumab-anns was widely used in various treatment settings for HER2+ breast cancer.

Some patients have a type of breast cancer caused by abnormal amounts of a normal growth factor receptor. This growth factor receptor, known as human epidermal growth factor receptor-2 (HER-2), plays a role in normal life changes that occur in breast tissue, including during pregnancy. HER-2 exists on the surface of breast cells and sends a signal inside cells for growth and proliferation. Sometimes an abnormal amount of HER-2 appears on breast cell surfaces, which causes HER-2 to promote excessive growth and proliferation and leads to HER2+ breast cancer. HER2+ breast cancer can be treated with trastuzumab, a medicine that specifically blocks HER-2 signals, and stops cancer cell growth. Trastuzumab has greatly improved outcomes for women worldwide with HER2+ breast cancer but trastuzumab is not always available due, in part, to its high cost. Biosimilars are medicines that are highly similar, but not identical, to the brand name (original) product and have been shown in clinical trials to result in no meaningful difference in efficacy and safety compared with the original product. Trastuzumab-anns is an intravenously administered biosimilar to trastuzumab. Biosimilars are as effective and safe as original products, although more cost-effective, such that physicians and patients can benefit from more information about their use in the real world. This study provided information about trastuzumab-anns use from clinical oncology practices in seven European countries. The study provides real world evidence that trastuzumab-anns is used widely across different patients with HER2+ breast cancer, including those with metastatic disease.

Explainable AI for CHO cell culture media optimization and prediction of critical quality attribute.

Cell culture media play a critical role in cell growth and propagation by providing a substrate; media components can also modulate the critical quality attributes (CQAs). However, the inherent complexity of the cell culture media makes unraveling the impact of the various media components on cell growth and CQAs non-trivial. In this study, we demonstrate an end-to-end machine learning framework for media component selection and prediction of CQAs. The preliminary dataset for feature selection was generated by performing CHO-GS (-/-) cell culture in media formulations with varying metal ion concentrations. Acidic and basic charge variant composition of the innovator product (24.97 ± 0.54% acidic and 11.41 ± 1.44% basic) was chosen as the target variable to evaluate the media formulations. Pearson's correlation coefficient and random forest-based techniques were used for feature ranking and feature selection for the prediction of acidic and basic charge variants. Furthermore, a global interpretation analysis using SHapley Additive exPlanations was utilized to select optimal features by evaluating the contributions of each feature in the extracted vectors. Finally, the medium combinations were predicted by employing fifteen different regression models and utilizing a grid search and random search cross-validation for hyperparameter optimization. Experimental results demonstrate that Fe and Zn significantly impact the charge variant profile. This study aims to offer insights that are pertinent to both innovators seeking to establish a complete pipeline for media development and optimization and biosimilar-based manufacturers who strive to demonstrate the analytical and functional biosimilarity of their products to the innovator. KEY POINTS: • Developed a framework for optimizing media components and prediction of CQA. • SHAP enhances global interpretability, aiding informed decision-making. • Fifteen regression models were employed to predict medium combinations.

Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Glargine (Gan & Lee Glargine) Compared With Originator Insulin Glargine (Lantus) in Patients With Type 1 Diabetes After 26 Weeks Treatment.

OBJECTIVE: To compare the immunogenicity, safety, and efficacy of Gan & Lee insulin glargine (GL Glargine) with that of the originator insulin glargine (Lantus) in patients with type 1 diabetes mellitus (T1DM). METHODS: This was a phase 3, multicenter, randomized, open-label, equivalence study. Five hundred seventy-six subjects with T1DM were randomized 1:1 to receive either GL Glargine or Lantus treatment for 26 weeks. The primary end point was the percentage of subjects in each treatment group who developed treatment-induced anti-insulin antibody after baseline and up to visit week 26, which was evaluated using a country-adjusted logistic regression model. The study also compared the changes in glycated hemoglobin, and adverse events including hypoglycemia. RESULTS: The percentage of subjects positive for treatment-induced anti-insulin antibody by Week 26 was 25.8% in the GL Glargine treatment group and 25.3% in the Lantus treatment group, with a 90% confidence interval (-5.4, 6.5) of the difference in proportions that fell completely between the similarity margins (-11.3, 11.3). The least squares mean difference between treatment groups for changes in glycated hemoglobin was -0.08 (90% confidence interval: -0.23, 0.06), and the other immunogenicity and safety profiles were comparable. CONCLUSION: GL Glargine demonstrated similar immunogenicity, efficacy, and safety compared to Lantus over 26 weeks in patients with T1DM.

The current status of the biosimilars landscape in China.

Biosimilars have played a significant role in alleviating healthcare burdens and enhancing patient access to high-quality biologic-based pharmaceutical therapies. The World Health Organization (WHO), as well as various national governments and regulatory agencies, have established corresponding regulations and guidelines to encourage the development of biosimilars. China, as a populous nation with a substantial demand for biologic therapies, has made substantial investments in the research and development (R&D) of a number of biosimilars, making it the global leader in terms of the number of biosimilar varieties developed and the companies involved. This article summarizes the landscape of biosimilar R&D and registration in China, the development of regulatory science for biosimilars (including guidelines) in China, the challenges faced in biosimilar development in China, and a discussion of and suggestions for tailoring or even waiving comparative clinical efficacy studies.

Utility of real-world evidence in biosimilar development.

Biosimilar development refers to the process of creating a biologic drug that is similar to an existing approved biologic drug, also known as a reference drug. Due to the complex nature of biologics drugs and the inherent variability in their manufacturing process biosimilars are not identical but highly similar to the reference drug in terms of quality, safety, and efficacy. Efficacy and safety trials for biosimilars involve large numbers of patients to confirm comparable clinical performance of the biosimilar and the reference product in appropriately sensitive clinical indications and for appropriate sensitive endpoints. The objective of a biosimilar clinical data is to address slight differences observed at previous steps and to confirm comparable clinical performance of the biosimilar and the reference product. In recent years with advances in big data computing, there has been increasing interest to incorporate the totality of information from different data sources (e.g. Real World data and published literature) in design and conduct of clinical trial to support regulatory objectives. The biosimilar development is an ideal framework for utilization of Real-World Evidence in design of trials as potentially large amount of data are available for the reference dug. Hence there may be an opportunity to use RWD in establishing, improving or validating equivalence margins (EQM) for biosimilar designs, specifically in the case there is no historical published data in the intended sensitive population. In this article, we propose a variation of matching method that seems promising to identify the matched set from a real-world data for which the effect size of targeted endpoint would be comparable to historical data. We believe this is a reasonable approach because in design stage, we can view covariates and secondary endpoints as data feature that can be used in a matching method. This approach was illustrated through a case study which indicated the estimate of the primary endpoint is within 1% of published results and thus RWD may be used to justify or estimate the equivalence margin. To ensure consistent results we recommend using this approach in different indications and endpoint scenarios. Thus utilization of RWD/RWE can provide an important opportunity to increase access to biologic therapies, reducing cost by repurposing existing data.

Evaluation of cost and infusion-related reactions among intravenous trastuzumab, subcutaneous trastuzumab, and trastuzumab biosimilars at an academic medical center.

INTRODUCTION: Trastuzumab is a vital treatment option for human epidermal growth factor 2 positive breast cancer. Since 2017, there have been 5 trastuzumab biosimilars approved for use. Despite hypotheses of infusion-related reactions among intravenous trastuzumab, subcutaneous trastuzumab, and trastuzumab biosimilars, there is minimal available literature comparing these agents. This evaluation will compare the rate of infusion-related reactions among these agents, evaluate our institution's utilization, and compare acquisition costs to determine if there is a potential cost savings by utilizing specific agents as our formulary preferred medication. METHODS: We retrospectively analyzed medical records to identify the incidence of infusion-related reaction after administration of intravenous or subcutaneous trastuzumab or trastuzumab biosimilars. Additionally, we conducted a cost analysis to identify potential cost savings by switching to an alternative institutional preferred agent. Infusion chair time was calculated to identify chair time savings with subcutaneous administration. RESULTS: There were 183 patients included in this study. Seven patients (3.8%) experienced an infusion-related reaction. The most utilized agent within our cohort was intravenous trastuzumab. During our study period, 181 patients received intravenous infusions, which could allow for substantial infusion chair savings by switching to trastuzumab/hyaluronidase, the subcutaneous formulation. Beyond the chair time, direct drug cost savings were also identified when comparing the costs of each of the evaluated medications. CONCLUSION: Subcutaneous trastuzumab or trastuzumab biosimilars do not pose a greater risk of infusion-related reactions compared to intravenous trastuzumab and may offer more affordable treatment options for breast cancer patients who qualify for trastuzumab therapy.

Biologics for inherited disorders of keratinisation: A systematic review.

BACKGROUND/OBJECTIVES: Recent literature highlights the potential of biologics in the management of inherited disorders of keratinisation. In this study, we conducted a systematic review of existing literature on treatment outcomes of inherited keratinisation disorders treated with biologics. METHODS: Eligible records were retrieved through searches of the electronic databases MEDLINE, Embase, PubMed and Scopus. Databases were searched from inception to July 2023 for eligible records. A snowballing method was employed to search the references of the retrieved records for the identification of potentially relevant articles. RESULTS: One hundred and four eligible studies consisting of a total of 166 patients with an inherited disorder of keratinisation were included. Patients had a median age of 19 years (range: 0.5 to 70 years). The most common disorders were Netherton syndrome (n = 63; 38%), autosomal recessive congenital ichthyoses (n = 27; 16%), CARD14-associated papulosquamous eruptions (n = 17; 10%) and familial pityriasis rubra pilaris (PRP) (n = 15; 9%).Of the 207 times biologics were employed, the three most frequently employed biologics were secukinumab (n = 47; 23%), dupilumab (n = 44; 21%) and ustekinumab (n = 37; 18%). Complete remission was observed in 10 (5%) instances, partial remission in 129 (62%), no or limited response to biologic therapy in 68 (32%) cases, and results are still pending in one case. A total of 33 adverse events were reported. CONCLUSIONS: Whilst biologics may be considered in cases of inherited keratinisation disorders recalcitrant to standard therapy, definitive conclusions are prohibited by the low-level of evidence and substantial heterogeneity in methodology across the included studies. Establishment of consensus definitions, and randomised clinical trials may help ascertain the efficacy and safety of biologic therapy in this context and establish the best agent and dosing protocol for each disorder.

Evaluation of bevacizumab biosimilar on wound healing complications in patients with colorectal cancer undergoing endoscopic mucosal resection: A systematic review and meta-analysis in anorectal medicine.

Complications related to wound healing pose substantial obstacle in the management of colorectal cancer (CRC), specifically in the field of anorectal medicine. Biosimilars of bevacizumab have emerged as crucial therapeutic agents in the management of these complications. With the particular emphasis on effects of Bevacizumab Biosimilar Plus on wound healing among patients diagnosed with CRC, this review underscores the potential of this anorectal medication to improve patient outcomes and was aimed to assess the safety and efficacy of Bevacizumab Biosimilar Plus in relation to complications associated with wound healing in patients with CRC. The assessment centers on its therapeutic potential and safety profile within the domain of anorectal medicine. In accordance with the PRISMA guidelines, a comprehensive literature search was performed, resulting in the identification of 19 pertinent studies out of an initial 918. Priority was given to assessing the safety and adverse effects of Bevacizumab Biosimilar Plus in conjunction with its effectiveness in wound healing. The extracted data comprised the following: study design, patient demographics, comprehensive treatment regimens, wound healing-specific outcomes and adverse effects. The evaluation of study quality was conducted utilizing the instruments provided by the Cochrane Collaboration and the Newcastle-Ottawa Scale (NOS). Bevacizumab Biosimilar Plus demonstrates efficacy in the management of wound healing complications among patients with CRC, with a safety and efficacy profile similar to that of the original Bevacizumab, according to the analysis. Notably, several studies reported improved rates of wound healing in relation to the biosimilar. The safety profiles exhibited similarities to the anticipated anti-VEGF agent effects. In wound management, the biosimilar also demonstrated advantages in terms of prolonged efficacy. In addition, analyses of cost-effectiveness suggested that the use of biosimilars could result in cost reductions. Bevacizumab Biosimilar Plus exhibited potential as an anorectal medication for the effective management of wound healing complications in patients with CRC. This has substantial ramifications for improving the quality of patient care, encompassing the affordability and effectiveness of treatments.

Investigation of treatment continuity, usefulness, and nocebo effect in switching from the original etanercept to its biosimilar in patients with rheumatoid arthritis: A JET observational study in Japanese clinical practice.

OBJECTIVES: To assess the usefulness and onset of nocebo effects after switching from the original etanercept (ETN) to a biosimilar (BS) in routine clinical practice at rheumatology clinics in Japan (13 sites). METHODS: A total of 165 patients (87.0% women, age = 57.88 ± 15.07 years, and disease duration = 10.32 ± 7.71 years), whose low disease activity was maintained with the original ETN for ≥12 weeks, and who agreed to switch treatment to its BS, were included. The end-points were disease activity score 28 (DAS28)-C-reactive protein and DAS28-erythrocyte sedimentation rate. RESULTS: No significant difference was observed between the changes in DAS28-C-reactive protein and DAS28-erythrocyte sedimentation rate >12 weeks before switching and >12 weeks after switching (P = 0.132 and 0.334, respectively). The treatment continuation rate during the 52 weeks after switching to BS was 97.3%. During this period, BS was discontinued in only four patients, and no nocebo effects were suspected in these four patients. CONCLUSION: Switching from ETN to BS was effective even in routine clinical practice at rheumatology clinics in Japan, and no nocebo effects were observed. Sufficient explanations to patients by rheumatologists and the additional payment for drug costs between patients at hospital visits effectively improved the continuation rate without any nocebo effect.

Comparison of safety and effectiveness between etanercept biosimilar LBEC0101 and reference in patients with rheumatoid arthritis in real-world data using the KURAMA cohort.

OBJECTIVES: Biosimilars are anticipated to be widely used in the treatment of rheumatoid arthritis (RA), owing to their cost efficiency; LBEC0101 was the first etanercept (ETN) biosimilar approved in Japan. However, there are limited real-world data comparing its safety and effectiveness with those of a reference product. METHODS: This study used data from the Kyoto University Rheumatoid Arthritis Management Alliance cohort, including patients with RA who received ETN therapy-ETN reference product (ETN-RP) or LBEC0101-between 2015 and 2021. Serum ETN levels were measured using liquid chromatography-tandem mass spectrometry. RESULTS: The 1-year continuation rates of ETN-RP and LBEC0101 were 58.7% and 74.4%, respectively. Effectiveness of treatment was evaluated in 18 patients; both products significantly reduced the 28-joint RA disease activity score and erythrocyte sedimentation rate (DAS28-ESR). Moreover, to determine equivalence, we analysed 11 patients who switched from ETN-RP to LBEC0101; the DAS28-ESR and serum ETN levels before and after switching were not significantly different. CONCLUSIONS: This real-world cohort study confirmed that the biosimilar of ETN, LBEC0101, was comparable to the reference product in terms of continuation rate, effectiveness at initiation of introduction, and effect persistence before and after switching in clinical practice.

Potential for biosimilars in rheumatology in Africa.

Biosimilars are products which are highly similar to a reference biologic product (RBP). In Africa, regulatory frameworks for biosimilar approval are still in development in many countries and few biosimilars for rheumatic diseases are currently available. The use of biosimilar medicines in Africa provides an important opportunity to treat more rheumatology patients with biologic drugs. This editorial aims to shed a light on the potential benefits, challenges and current efforts, regarding the use of biosimilars in Africa in Rheumatology.