Treatment Of Immune-mediated Inflammatory Diseases Research Articles

Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project

Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project

Safety, Pharmacokinetics, and Pharmacodynamics of Etrasimod: Single and Multiple Ascending Dose Studies in Healthy Adults.

Etrasimod is an investigational, once-daily, oral, selective sphingosine 1-phosphate receptor 1,4,5 modulator in development for immune-mediated inflammatory diseases (IMIDs). Here, we report the human safety, pharmacokinetics, and pharmacodynamics of etrasimod obtained from both a single ascending dose (SAD; 0.1-5mg) study and a multiple ascending dose (MAD; 0.35-3mg once daily) study. Overall, 99 healthy volunteers (SAD n = 40, MAD n = 59) completed the 2 studies. Evaluated single and multiple doses were well tolerated up to 3mg without severe adverse events (AEs). Gastrointestinal disorders were the most common etrasimod-related AEs. Over the evaluated single- and multiple-dose ranges, dose-proportional and marginally greater-than-dose-proportional etrasimod plasma exposure were observed, respectively. At steady state, etrasimod oral clearance and half-life mean values ranged from 1.0 to 1.2 L/h and 29.7 to 36.4 hours, respectively. Dose-dependent total peripheral lymphocyte reductions occurred following etrasimod single and multiple dosing. Etrasimod multiple dosing resulted in reductions from baseline in total lymphocyte counts ranging from 41.1% to 68.8% after 21 days. Lymphocyte counts returned to normal range within 7 days following treatment discontinuation. Heart rate lowering from pretreatment baseline on etrasimod dosing was typically mild, with mean reductions seen after the first dose of up to 19.5bpm (5mg dose). The favorable safety, pharmacokinetic, and pharmacodynamic properties of etrasimod in humans supported its further development and warranted its investigation for treatment of IMIDs.

On the Interdisciplinary Treatment and Management of Patients with Immune-Mediated Inflammatory Diseases. A Study on Patients' Personal Experiences and Perspectives.

Immune-mediated inflammatory diseases (eg, axial spondylitis, psoriasis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and hidradenitis suppurativa) are common diseases that exert an extensive effect on the health-related quality of life, particularly when multiple concomitant conditions are present. Previous reports indicate that the traditional siloed approach to care can lead to a lack of patient centricity and inefficient disease management. In this article, we aimed to evaluate an interdisciplinary program for the treatment of immune-mediated inflammatory diseases compared to routine clinical practice. This was a mixed-method study, combining qualitative and quantitative data. Patients with co-occurrence of ≥2 immune-mediated inflammatory diseases treated in an interdisciplinary clinic (n = 48) or traditional usual care (n = 17) answered open-ended questions about their care experiences. Two independent coders blinded to patients' treatment group coded three aspects of the narratives provided by the patients' responses: Themes, Emotional valence, and Personal growth (ie, redemption). Themes were analyzed descriptively to explore possible differences between patients assigned to the interdisciplinary clinic and patients assigned to the usual care setting. Group differences in patients' emotional experiences were assessed, and we examined potential group differences in positive personal growth. Our findings indicate that an interdisciplinary combined clinic approach provides benefits for patients with multiple inflammatory diseases towards the usual setup. Patients experienced benefits on a number of specific quality-of-life themes including acceptance, optimism, disease understanding, personal growth, and better disease control. The narratives of the patients in the interdisciplinary group were significantly more emotionally positive and included more positive personal growth compared to the usual care group. The findings indicate a patient-reported benefit, especially from the holistic approach and cross-specialty combined consultations in an interdisciplinary clinic compared to usual specialized healthcare, which was underscored by narratives highlighting an overall improved quality of life.

Effect of a 2-week interruption in methotrexate treatment on COVID-19 vaccine response in people with immune-mediated inflammatory diseases (VROOM study): a randomised, open label, superiority trial

Methotrexate is the first-line treatment for immune-mediated inflammatory diseases and reduces vaccine-induced immunity. We evaluated if a 2-week interruption of methotrexate treatment immediately after COVID-19 booster vaccination improved antibody response against the S1 receptor binding domain (S1-RBD) of the SARS-CoV-2 spike protein and live SARS-CoV-2 neutralisation compared with uninterrupted treatment in patients with immune-mediated inflammatory diseases. We did a multicentre, open-label, parallel-group, randomised, superiority trial in secondary-care rheumatology and dermatology clinics in 26 hospitals in the UK. Adults (aged ≥18 years) with immune-mediated inflammatory diseases taking methotrexate (≤25 mg per week) for at least 3 months, who had received two primary vaccine doses from the UK COVID-19 vaccination programme were eligible. Participants were randomly assigned (1:1) using a centralised validated computer program, to temporarily suspend methotrexate treatment for 2 weeks immediately after COVID-19 booster vaccination or continue treatment as usual. The primary outcome was S1-RBD antibody titres 4 weeks after COVID-19 booster vaccination and was assessed masked to group assignment. All randomly assigned patients were included in primary and safety analyses. This trial is registered with ISRCTN, ISRCTN11442263; following a pre-planned interim analysis, recruitment was stopped early. Between Sept 30, 2021, and March 7, 2022, we screened 685 individuals, of whom 383 were randomly assigned: to either suspend methotrexate (n=191; mean age 58·8 years [SD 12·5], 118 [62%] women and 73 [38%] men) or to continue methotrexate (n=192; mean age 59·3 years [11·9], 117 [61%] women and 75 [39%] men). At 4 weeks, the geometric mean S1-RBD antibody titre was 25 413 U/mL (95% CI 22 227-29 056) in the suspend methotrexate group and 12 326 U/mL (10 538-14 418) in the continue methotrexate group with a geometric mean ratio (GMR) of 2·08 (95% CI 1·59-2·70; p<0·0001). No intervention-related serious adverse events occurred. 2-week interruption of methotrexate treatment in people with immune-mediated inflammatory diseases enhanced antibody responses after COVID-19 booster vaccination that were sustained at 12 weeks and 26 weeks. There was a temporary increase in inflammatory disease flares, mostly self-managed. The choice to suspend methotrexate should be individualised based on disease status and vulnerability to severe outcomes from COVID-19. National Institute for Health and Care Research.

Type 1 interferons: A target for immune-mediated inflammatory diseases (IMIDs)

The improved understanding of the molecular basis of innate immunity have led to the identification of type I interferons (IFNs), particularly IFN-α, as central mediators in the pathogenesis of several Immune-mediated inflammatory diseases (IMIDs) such as systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myositis and Sjögren's syndrome. Here, we review the main data regarding the opportunity to target type I IFNs for the treatment of IMIDs. Type I IFNs and their downstream pathways can be targeted pharmacologically in several manners. One approach is to use monoclonal antibodies against IFNs or the IFN-receptors (IFNARs, such as with anifrolumab). The downstream signaling pathways of type I IFNs also contain several targets of interest in IMIDs, such as JAK1 and Tyk2. Of these, anifrolumab is licensed and JAK1/Tyk2 inhibitors are in phase III trials in SLE. Targeting IFN-Is for the treatment of SLE is already a reality and in the near future may prove useful in other IMIDs. IFN assays will find a role in routine clinical practice for the care of IMIDs as further validation work is completed and a greater range of targeted therapies becomes available.

Cardiovascular Risk Management in Patients Treated with JAK Inhibitors.

The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a critical role in the pathogenesis of many immune-mediated inflammatory diseases (IMIDs). Although Janus kinase inhibitors (JAKi) are an effective treatment for several IMIDs, they have come under scrutiny as a class due to a potential risk of venous thromboembolism (VTE) and cardiovascular (CV) events, specifically noted with the oral JAKi, tofacitinib, as reported in the ORAL Surveillance Trial of a high CV risk rheumatoid arthritis population. This trial resulted in a black box warning from the Food and Drug Administration and European Medicines Agency regarding risk of VTE and CV events that was extended across several types of JAKi (including topical ruxolitinib) when treating IMIDs, leading to considerable controversy. Included is an up-to-date review of the current and rapidly evolving literature on CV risk in patients with IMIDs on JAKi therapy, including identification of potential risk factors for future VTE and CV events on JAKi therapy. We suggest a comprehensive, multimodal, and systematic approach for evaluation of CV risk in patients considering taking JAKi and emphasize that cardiologists play an important role in risk stratification and mitigation for patients with high CV risk factors or on long-term JAKi therapies.

P85 Switching from adalimumab originator to biosimilar: a 3-year retrospective cohort analysis

Abstract Biological drugs have revolutionized the treatment of immune-mediated inflammatory diseases. Clinical experience and evidence suggest that biosimilars can be used as safely and effectively as their originator. However, patients’ perceptions of biosimilars are that they are inferior to the originator. Currently, few studies have assessed the tolerability and efficacy of switching from the adalimumab originator to a biosimilar in patients with well-controlled moderate-to-severe psoriasis. Our objective was to describe the clinical experience of switching patients from the adalimumab originator to a biosimilar and that of switching back to the originator for those intolerant to biosimilars. A single-centre, retrospective cohort study was conducted to identify patients with moderate-to-severe psoriasis who had switched from the adalimumab originator (Humira®) to a biosimilar (Amgevita® or Imraldi®) from 2018 to 2022. Patient data were obtained from a combination of patient records and databases, including the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) and the National High Tech Prescribing Hub. Patients were excluded from the study if their treatment duration on an adalimumab biosimilar was &amp;lt; 16 weeks or if they were being treated for an indication other than psoriasis. From 2018 to 2022, 100 patients who switched from the adalimumab originator to a biosimilar were identified. At week 16, 81 patients (81%) maintained their initial switch from the adalimumab originator to biosimilar. Nineteen (19%) patients who were switched to an adalimumab biosimilar were switched back to the originator secondary to adverse events. Maintenance or improvement in baseline Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) was observed in 91% and 90%, respectively, in patients who remained on a biosimilar. For those intolerant to biosimilars, maintenance or improvement in baseline PASI and DLQI was still observed although in fewer patients: 63% and 47%, respectively. Our study demonstrates that drug efficacy was recaptured and adverse events were ameliorated for all patients switched from an adalimumab biosimilar back to the originator. For patients who did not tolerate biosimilar switch, reasons for switching back to the originator mirrored those reported in the literature. All patients who switched back to the originator from a biosimilar recovered from loss of efficiency and the adverse events they had reported. Physicians should be confident in switching patients with well-controlled psoriasis to adalimumab biosimilars. For the small proportion of patients who experienced loss of efficacy or adverse events, all were recaptured by either switching to an alternative adalimumab biosimilar or switching back to the adalimumab originator.

P43 Patient tolerability of adalimumab biosimilar therapy in dermatology and rheumatology: real-world experience from a large tertiary centre

Abstract Adalimumab is widely used in the treatment of immune-mediated inflammatory diseases. It is the highest-spend drug in the National Health Service, costing more than £400 million annually. In 2018, adalimumab biosimilars became available, leading to substantial cost savings. However, patient tolerability of biosimilars remains underexplored. We evaluated the tolerability of adalimumab biosimilar therapy (Idacio®) in patients who were switched from Humira® in a large dermatology and rheumatology tertiary centre. We identified all patients issued with a prescription of Humira by dermatology [psoriasis and hidradenitis suppurativa (HS)] or rheumatology (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and Behçet disease) and analysed the number who switched to Idacio between January 2021 and March 2022. Patient electronic records were reviewed up to October 2022 to identify patients who switched back to the originator product and the documented reason for the switch. The primary outcome was the numbers of patients who were switched back from the biosimilar to the originator product. Of 769 patients issued with a prescription of Humira, 694 were switched to Idacio during the study period. Of these, 134 (19.3%) switched back to the originator product, 102 of whom (76.1%) remained on this during follow-up. The highest proportion of individuals switching back to the originator product was observed in the HS population (26.7%). The most common reasons for switching back were patient-reported loss of disease control (n = 63; 47.0%), injection pain (n = 51; 38.1%) or both (n = 10; 7.5%). The median time to switch back was 197 days (interquartile range 138–280). Of 694 patients prescribed Idacio, 32 (4.6%) were switched to an alternative biologic agent during the study period. Our experience with previous biosimilar switches within rheumatology and dermatology (etanercept, rituximab and infliximab) has resulted in few patients requiring a switch back to the originator. Our data indicate that around one in five patients in our study population switched back to the originator product. The higher proportion of patients citing injection pain may relate to the citrate excipient content or larger injection volume of the biosimilar Idacio. Loss of efficacy with time is well established with adalimumab, in part due to antidrug antibodies, and cannot be specifically attributed to the biosimilar. Switching may alter a patient’s confidence in the drug, which is particularly important when it may be a first-line therapy or the only approved biologic for a condition. Data on switch-back rates for other adalimumab biosimilars is required to understand how generalizable our findings are and the potential economic implications.

Venous and arterial thromboembolic risk of Janus kinase inhibitors: a systematic review with meta-analysis.

Preliminary data led licencing authorities to alert clinicians of an increased venous thrombotic risk associated to the use of Janus kinase (JAK) inhibitors (JAKi). We performed a systematic review to estimate the risk of venous and arterial thrombosis associated to JAKi for the treatment of immune-mediated inflammatory diseases (IMIDs). Randomized controlled trials (RCTs) on JAKi in patients with IMIDs were identified by the MEDLINE and EMBASE databases until October 2021. Risk of bias was assessed according to Cochrane criteria. The beta-binomial model was applied to calculate pooled odds ratio (OR) and corresponding 95% CI. The PROSPERO registration number is CRD42022324143. We have included one phase I, 21 phase II, three phase II-III and 36 phase III RCTs for a total of 19 443 patients in the JAKi group and 6354 in the control group. Thirty-one (unweighted rate 0.16%; 95% CI: 0.10, 0.21) events were reported in the JAKi group and 20 (unweighted rate 0.22%; 95% CI: 0.12, 0.32) in the control group in a mean follow-up of 16.8 weeks. IMID patients treated with JAKi did not have an increased thromboembolic risk compared with those treated with placebo (OR 0.82; 95% CI: 0.43, 1.56). No statistically different results were seen in subanalyses for each investigated IMID, drug and dosage. JAKi do not increase thromboembolic risk compared with placebo in IMID patients enrolled in selected RCTs.

Therapeutic drug monitoring of disease-modifying antirheumatic drugs in circulating leukocytes in immune-mediated inflammatory diseases.

The treatment of immune-mediated inflammatory diseases (IMIDs) is one of the main challenges of modern medicine. Although a number of disease-modifying antirheumatic drugs (DMARDs) are available, there is wide variability in clinical response to treatment among individuals. Therapeutic drug monitoring (TDM) has been proposed to optimize treatment; however, some patients still experience unsatisfactory outcomes, although the blood concentrations of drugs in these patients remain in the therapeutic range. One possible reason for this is that the conventional samples (e.g., whole blood or plasma) used in TDM may not accurately reflect drug concentrations or concentrations of their metabolites at the target site. Hence, more refined TDM approaches to guide clinical decisions related to dose optimization are necessary. Circulating leukocytes or white blood cells have a critical role in driving the inflammatory process. They are recruited to the site of injury, infection and inflammation, and the main target of small molecule DMARDs is within immune cells. Given this, assaying drug concentrations in leukocytes has been proposed to be of possible relevance to the interpretation of outcomes. This review focuses on the clinical implications and challenges of drug monitoring of DMARDs in peripheral blood leukocytes from therapeutic or toxicological perspectives in IMIDs.

Advances in the mechanisms and applications of inhibitory oligodeoxynucleotides against immune-mediated inflammatory diseases.

Inhibitory oligodeoxynucleotides (ODNs) are short single-stranded DNA, which capable of folding into complex structures, enabling them to bind to a large variety of targets. With appropriate modifications, the inhibitory oligodeoxynucleotides exhibited many features of long half-life time, simple production, low toxicity and immunogenicity. In recent years, inhibitory oligodeoxynucleotides have received considerable attention for their potential therapeutic applications in immune-mediated inflammatory diseases (IMIDs). Inhibitory oligodeoxynucleotides could be divided into three categories according to its mechanisms and targets, including antisense ODNs (AS-ODNs), DNA aptamers and immunosuppressive ODNs (iSup ODNs). As a synthetic tool with immunomodulatory activity, it can target RNAs or proteins in a specific way, resulting in the reduction, increase or recovery of protein expression, and then regulate the state of immune activation. More importantly, inhibitory oligodeoxynucleotides have been used to treat immune-mediated inflammatory diseases, including inflammatory disorders and autoimmune diseases. Several inhibitory oligodeoxynucleotide drugs have been developed and approved on the market already. These drugs vary in their chemical structures, action mechanisms and cellular targets, but all of them could be capable of inhibiting excessive inflammatory responses. This review summarized their chemical modifications, action mechanisms and applications of the three kinds of inhibitory oligodeoxynucleotidesin the precise treatment of immune-mediated inflammatory diseases.

Exploring the perspective of patients with immune-mediated inflammatory diseases and care providers on the use of immunomodulatory drugs in infections: an interview study.

Immunomodulatory agents are safe and effective as treatment for various immune-mediated inflammatory diseases (IMIDs), but are associated with a slightly increased infection risk. It is uncertain whether, in the event of an infection, continuation or temporary interruption of immunomodulatory agents leads to better outcomes. Owing to this uncertainty, it is of importance to explore the perspectives of health-care providers (HCPs) and patients on this topic. In this study, we set out to identify and provide an overview of reasons for both treatment strategies. Semi-structured interviews were conducted with HCPs involved in the pharmacological treatment of IMIDs and with IMID patients using one or more immunomodulatory agent. Purposive sampling was used to enrich data variation. Interviews were conducted until data saturation was reached and subsequently analysed using qualitative content analysis. In total, 13 HCPs and 19 IMID patients were interviewed. A wide range of reasons for both treatment strategies were identified, categorized into 10 overarching themes, including IMID characteristics, infection characteristics and the patient-HCP relationship. In this interview study, we identified various reasons for continuation or temporary interruption of immunomodulatory agents during infections for both IMID patients and HCPs. We found overlapping themes, such as IMID characteristics; however, the content and interpretation of these themes might differ between HCPs and patients. Both HCPs and patients mentioned that the decision for a treatment strategy is often about weighing benefits against risks (e.g. infection severity vs disease flare).

The biology of VSIG4: Implications for the treatment of immune-mediated inflammatory diseases and cancer

V-set and immunoglobulin domain containing 4 (VSIG4), a type I transmembrane receptor exclusively expressed in a subset of tissue-resident macrophages, plays a pivotal role in clearing C3-opsonized pathogens and their byproducts from the circulation. VSIG4 maintains immune homeostasis by suppressing the activation of complement pathways or T cells and inducing regulatory T-cell differentiation, thereby inhibiting the development of immune-mediated inflammatory diseases but enhancing cancer progression. Consequently, VSIG4 exhibits a potential therapeutic effect for immune-mediated inflammatory diseases, but also is regarded as a novel target of immune checkpoint inhibition in cancer therapy. Recently, soluble VSIG4, the extracellular domain of VSIG4, shed from the surface of macrophages, has been found to be a biomarker to define macrophage activation-related diseases. This review mainly summarizes recent new findings of VSIG4 in macrophage phagocytosis and immune homeostasis, and discusses its potential diagnostic and therapeutic usage in infection, inflammation, and cancer.

Overview of biosimilars for immune-mediated inflammatory diseases: summary of current evidence

Biosimilars offer the potential to deliver substantial cost savings in biologic therapy and to contribute to increased patient access to biologic treatments, both of which are particularly relevant for immune-mediated inflammatory diseases, given the number of patients affected by and receiving treatment for these conditions. For the United States to benefit from bringing biosimilar pipeline products to the market, legal and price-related barriers to competition must be addressed. In addition, education of prescribers, patients, payers, and providers is essential to increase uptake as biosimilars reach the market. This article discusses biosimilars currently available for the treatment of immune-mediated inflammatory diseases in the United States, reviews the main concepts related to regulatory approval of biosimilars by the FDA, and considers potential barriers to the uptake of biosimilars.

T-cell exhaustion in immune-mediated inflammatory diseases: New implications for immunotherapy.

Immune-mediated inflammatory diseases(IMIDs) are referred to as highly disabling chronic diseases affecting different organs and systems. Inappropriate or excessive immune responses with chronic inflammation are typical manifestations. Usually in patients with chronic infection and cancer, due to long-term exposure to persistent antigens and inflammation microenvironment, T-cells are continuously stimulated and gradually differentiate into an exhausted state. Exhausted T-cells gradually lose effector function and characteristics of memory T-cells. However, existing studies have found that exhausted T-cells are not only present in the infection and tumor environment, but also in autoimmunity, and are associated with better prognosis of IMIDs. This suggests new prospects for the application of this reversible process of T-cell exhaustion in the treatment of IMID. This review will focus on the research progress of T-cell exhaustion in several IMIDs and its potential application for diagnosis and treatment in IMIDs.

Impact of COVID-19 Pandemic on Initiation of Immunosuppressive Treatment in Immune-Mediated Inflammatory Diseases in Austria: A Nationwide Retrospective Study.

Objective: Conventional immunosuppressive and advanced targeted therapies, including biological medications and small molecules, are a mainstay in the treatment of immune-mediated inflammatory diseases (IMID). However, the COVID-19 pandemic caused concerns over these drugs’ safety regarding the risk and severity of SARS-CoV-2 infection. Thus, we aimed to assess the impact of the COVID-19 pandemic on the initiation of these treatments in 2020. Study Design and Setting: We conducted a population-based retrospective analysis of real-world data of the Austrian health insurance funds on the initiation of conventional immunosuppressive and advanced targeted therapies. The primary objective was to compare the initiation of these medications in the year 2020 with the period 2017 to 2019. Initiation rates of medication were calculated by comparing a certain unit of time with an average of the previous ones. Results: 95,573 patients were included. During the first lockdown in Austria in April 2020, there was a significant decrease in the initiations of conventional immunosuppressives and advanced targeted therapies compared to previous years (p < 0.0001). From May 2020 onwards, numbers rapidly re-achieved pre-lockdown levels despite higher SARS-CoV-2 infection rates and subsequent lockdown periods at the end of 2020. Independent from the impact of the COVID-19 pandemic, a continuous increase of starts of advanced targeted therapies and a continuous decrease of conventional immunosuppressants during the observation period were observed. Conclusions: In IMID patients, the COVID-19 pandemic led to a significant decrease of newly started conventional immunosuppressive and advanced targeted therapies only during the first lockdown in Austria.

34296 Introduction of BELCOMID: BELgian Cohort study of COVID-19 in Immune Mediated Inflammatory Diseases

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pandemic is turning into a significant wrinkle in the history of modern health care. It remains unclear what the exact risk and impact of COVID-19 is on patients with immune mediated inflammatory diseases (IMIDs). Targeted immune-modulating therapies (TIMT) for treatment of IMIDs could interfere with humoral immune response against COVID-19. To analyze exposure to SARS-CoV2 and to map the effect of TIMT on humoral immune response after COVID-19 infection or COVID-19 vaccination, a Belgian IMID-cohort was founded: all patients with IMIDs of the gut (Crohn’s disease, ulcerative colitis and indeterminate colitis), joints (rheumatoid arthritis, psoriatic arthritis and spondyloarthritis) and skin (psoriasis, hidradenitis suppurativa and atopic dermatitis) in clinical follow-up at the cooperating sites were invited to participate: 2165 patients were included. IMID disease course and SARS-CoV2 exposure were evaluated through questionnaires and seroprevalence of SARS-CoV2 IgG (Spike and Nucleocapsid antibodies). Baseline serum samples were obtained between December 17th, 2020 and February 28th, 2021, before COVID-19 vaccination. Sampling was repeated between July 1st, 2021 and September 30th, 2021. In this poster we present the levels of SARS-CoV2 IgG (Spike and Nucleocapsid antibodies) both at baseline and six months later (after COVID-19 vaccination). We report on the effect of four different treatment groups (JAKi/biologic treatment; conventional/immunomodulatory treatment; combination treatment; systemic steroid treatment) on the degree of COVID-19 humoral immunity after infection and/or vaccination. This poster aims to inform the dermatological community about the effect of commonly used drugs on the humoral immune response after COVID-19 infection and/or COVID-19 vaccination.

Sarcoidosis-like reaction secondary to adalimumab treatment in a patient with axial spondyloarthritis.

Anti-TNF agents, namely adalimumab, are safe drugs that represent an important arsenal in the treatment of immune-mediated inflammatory diseases. "Paradoxical effects" have been described with their use. A sarcoidosis "like" reaction induced by these agents is rare and is characterized by a systemic granulomatous reaction indistinguishable from sarcoidosis. We present a 55-year-old male patient, with axial spondyloarthritis, treated with with adalimumab. About 17 months under this therapy, he complained of dry cough and wheezing. Chest CT showed a peri-lymphatic and pericisural micronodular pattern and hilo-mediastinal lymph nodes, suggestive of sarcoidosis. Angiotensin converting enzyme was increased. Assuming the hypothesis of a sarcoidosis-like reaction secondary to adalimumab this therapy was discontinued with progressive improvement in the patient's complaints and in the radiological changes.

Janus kinase inhibitors in immunoinflammatory diseases: 10 years of clinical practice in rheumatology

Despite great advances in the diagnosis and treatment of Immune-mediated inflammatory diseases (IMIDs), which have led to a significant improvement in the prognosis in many patients, the central medical problems of this pathology – restoring the quality of life and reducing mortality to the population level – are far from being resolved. This served as a powerful stimulus for the study of new approaches to the pharmacotherapy of IMIDs, one of which is associated with the discovery of targets for small-molecule therapeutics that inhibit intracellular “signaling” molecules JAKs (Janus kinases). The current achievements, trends and recommendations regarding the use of JAK inhibitors in the treatment of IMIDs and also in the hyper-response phase of COVID-19 are reviewed.

Oral Conventional Synthetic Disease-Modifying Antirheumatic Drugs with Antineoplastic Potential: a Review.

There is an increasing trend of malignancy worldwide. Disease-modifying antirheumatic drugs (DMARDs) are the cornerstones for the treatment of immune-mediated inflammatory diseases (IMIDs), but risk of malignancy is a major concern for patients receiving DMARDs. In addition, many IMIDs already carry higher background risks of neoplasms. Recently, the black box warning of malignancies has been added for Janus kinase inhibitors. Also, the use of biologic DMARDs in patients with established malignancies is usually discouraged owing to exclusion of such patients in pivotal studies and, hence, lack of evidence. In contrast, some conventional synthetic DMARDs (csDMARDs) have been reported to show antineoplastic properties and can be beneficial for patients with cancer. Among the csDMARDs, chloroquine and hydroxychloroquine have been the most extensively studied, and methotrexate is an established chemotherapeutic agent. Even cyclosporine A, a well-known drug associated with cancer risk, can potentiate the effect of some chemotherapeutic agents. We review the possible mechanisms behind and clinical evidence of the antineoplastic activities of csDMARDs, including chloroquine and hydroxychloroquine, cyclosporine, leflunomide, mycophenolate mofetil, mycophenolic acid, methotrexate, sulfasalazine, and thiopurines. This knowledge may guide physicians in the choice of csDMARDs for patients with concurrent IMIDs and malignancies.