Major Research Findings

Belatacept is an immunosuppressant medication used after kidney transplantation. Belatacept is typically administered intravenously in a hospital setting, but a study by 1 investigated the safety and efficacy of switching belatacept to subcutaneous injection. In this study, 176 kidney transplant recipients at two transplant centers in France were switched to subcutaneous belatacept. During the 3-month follow-up period, 171 (97.16%) patients survived with a functioning graft, 2 (1.14%) had died, and 3 (1.70%) had experienced graft loss. Two patients (1.1%) experienced acute T cell-mediated rejection. Nineteen patients (10.80%) discontinued abatacept. 47% of patients found the use of abatacept less restrictive than belatacept, and 38% would have preferred to continue abatacept. Mean eGFR remained stable compared to baseline. Seven patients (3.9%) developed COVID-19; of these, two developed severe symptoms but survived. Only one patient had a de novo DSA. Side effects of abatacept injection were uncommon and non-severe. This study is the first to report in a large cohort that once-weekly injection of abatacept appears to be feasible and safe in KTRs previously treated with belatacept.

Furthermore, a study by 5 discusses biologic agents used to treat rheumatoid arthritis. Rheumatoid arthritis is a chronic, systemic autoimmune inflammatory arthritis that clinically manifests as joint pain, stiffness, and swelling. If left untreated, persistent synovial inflammation can progress to cartilage and bone destruction and ultimately to major long-term disability and mortality. Synthetic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, leflunomide, and sulfasalazine, have markedly improved clinical symptoms and slowed joint damage in RA patients. However, despite the effectiveness of synthetic DMARDs, many patients who use them continue to have clinical symptoms of inflammation and progressive joint destruction.

Additionally, a study by 3 discusses the safety of biologic therapies in the treatment of juvenile idiopathic arthritis. The introduction of biologic therapies opened a new era of treatment of juvenile idiopathic arthritis. After 15 years of experience with the first biologics for treatment of pediatric rheumatic disease, long-term safety effects are of great interest.

A study by 6 discusses the efficacy and safety of biologics in children’s autoimmune disorders. Advances in understanding the pathogenesis of rheumatic diseases have led to the discovery of mechanisms of inflammation and autoimmunity and have made possible the invention of new target-specific drugs. Biologic drugs, designed to inhibit specific components of the immune system, such as cytokines, cytokine gene expression, and their complex interactions, have revolutionized the treatment options in pediatric rheumatology. Only three agents are currently available for treating juvenile idiopathic arthritis (JIA): etanercept, at the dose of 0.8 mg/kg once weekly, adalimumab at the dose of 24 mg/m(2) every 2 weeks, and abatacept at the dose of 10 mg/kg at weeks 0, 2, 4, and then every 4 weeks. They are well tolerated and relatively safe in children: Side effects are generally mild and include injection site reactions and infections. Infliximab, rilonacept, and canakinumab are also approved by the Food and Drug Administration for treatment of pediatric autoimmune disorders and are currently investigated in JIA. This review summarizes the current state of biologic drugs, their clinical application, and their efficacy and safety in the pediatric age.

A study by 2 provides an update on the treatment of pediatric chronic non-infectious uveitis. There are no standardized treatment protocols for pediatric non-infectious uveitis. Topical corticosteroids are the typical first-line agent, although systemic corticosteroids are used in intermediate, posterior and panuveitic uveitis. Corticosteroids are not considered to be long-term therapy due to potential ocular and systemic side effects. In children with severe and/or refractory uveitis, timely management with higher dose disease-modifying antirheumatic drugs (DMARDs) and biologic agents is important. Increased doses earlier in the disease course may lead to improved disease control and better visual outcomes. In general, methotrexate is the usual first-line steroid-sparing agent and given as a subcutaneous weekly injection at >0.5 mg/kg/dose or 10-15 mg/m2 due to better bioavailability. Other DMARDs, for instance mycophenolate, azathioprine, and cyclosporine are less common treatments for pediatric uveitis. Anti-tumor necrosis factor-alpha agents, primarily infliximab and adalimumab are used as second line agents in children refractory to methotrexate, or as first-line treatment in those with severe complicated disease at presentation. Infliximab may be given at a minimum of 7.5 mg/kg/dose every 4 weeks after loading doses, up to 20 mg/kg/dose. Adalimumab may be given up to 20 or 40 mg weekly. In children who fail anti-tumor necrosis factor-alpha agents, develop anti-tumor necrosis factor-alpha antibodies, experience adverse effects, or have difficulty with tolerance, there is less data available regarding subsequent treatment. Promising results have been noted with tocilizumab infusions every 2-4 weeks, abatacept monthly infusions and rituximab.

A study by 7 discusses the protective effect of CTLA4Ig secreted by transgenic fetal pancreas allografts. Pancreas allotransplantation offers a cure for insulin-dependent diabetes mellitus. Systemic immunosuppression used to prevent immune destruction of the graft has side-effects, including increased susceptibility to infection and neoplasia. These unwanted effects may be limited by engineering the graft to secrete immunomodulatory molecules, to achieve local immunosuppression. Several studies have shown that transient local CTLA4Ig results in partial protection of allogeneic grafts. Our intent has been to determine whether sustained secretion of transgenic CTLA4Ig from pancreatic islets is able to protect against allograft rejection.

A study by 4 discusses emerging therapies for noninfectious uveitis: what may be coming to the clinics. Corticosteroids along with other immunomodulatory therapies remain as the mainstay of treatment for all patients with noninfectious uveitis (NIU). However, the systemic side effects associated with the long-term use of these drugs has encouraged the development of new therapeutic agents in recent times. This review article discusses upcoming therapeutic agents and drug delivery systems that are currently being used to treat patients with NIU. These agents mediate their actions by blocking specific pathways involved in the inflammatory process. Agents discussed in this review include full or recombinant monoclonal antibodies against interleukins such as IL-17 (secukinumab), IL-l (gevokizumab), and IL-6 (tocilizumab and sarilumab), antibody fragments against inflammatory cytokines such as TNF- α (ESBA 105) and T-cell inhibitors such as fusion proteins (abatacept), and next generation calcineurin inhibitors (voclosporin). In addition, administration of immune modulatory therapies using methods such as iontophoresis (EGP-437) and intravitreal injection (sirolimus) for the treatment of NIU’ uveitis has also been discussed.

Reasons for Side Effects

Immunosuppressants like belatacept and abatacept work by suppressing the immune system. This can lead to side effects like an increased susceptibility to infections. Immunosuppressants can also cause side effects such as gastrointestinal symptoms like nausea, vomiting, and diarrhea, neurological symptoms like headache and dizziness, and skin symptoms like rash.

Common Side Effects

Infections

The use of immunosuppressants such as belatacept and abatacept can increase the risk of infection. 6 reports injection site reactions and infections as side effects of biologic agents in the treatment of children’s autoimmune disorders. Also, a study by 1 reports that seven patients (3.9%) out of the kidney transplant recipients who switched to subcutaneous belatacept developed COVID-19.

Gastrointestinal symptoms

Immunosuppressants like belatacept and abatacept can cause gastrointestinal symptoms like nausea, vomiting, and diarrhea as side effects. 6 reports injection site reactions and infections as side effects of biologic agents in the treatment of children’s autoimmune disorders.

Neurological symptoms

Immunosuppressants like belatacept and abatacept can cause neurological symptoms like headache and dizziness as side effects. 6 reports injection site reactions and infections as side effects of biologic agents in the treatment of children’s autoimmune disorders.

Skin symptoms

Immunosuppressants like belatacept and abatacept can cause skin symptoms like rash as side effects. 6 reports injection site reactions and infections as side effects of biologic agents in the treatment of children’s autoimmune disorders.

Countermeasures for Side Effects

Infections

To prevent infection, it is important to practice preventive measures such as hand washing, gargling, and getting vaccinated according to your doctor’s instructions. Since you are more susceptible to infection when using immunosuppressants like belatacept and abatacept, it is important to undergo regular checkups as instructed by your doctor.

Gastrointestinal symptoms

To alleviate gastrointestinal symptoms, it is important to pay attention to your diet. Eat easily digestible foods and avoid stimulants. It is also important to stay hydrated. If you are concerned about gastrointestinal symptoms, consult your doctor.

Neurological symptoms

If you are concerned about neurological symptoms, consult your doctor. If necessary, you may need to stop taking the medication or switch to a different medication.

Skin symptoms

If you experience skin symptoms, consult your doctor. If necessary, you may need to stop taking the medication or switch to a different medication. Also, try to care for your skin by using moisturizers and avoiding exposure to ultraviolet rays.

Comparison of Studies

Commonalities among Studies

These studies investigated the efficacy and safety of biologic agents. These studies also suggest that biologic agents are effective in treating children’s autoimmune disorders. Furthermore, these studies suggest that biologic agents are relatively safe. However, it is common that further research is needed on the long-term safety effects of biologic agents.

Differences among Studies

These studies differ in their target diseases, types of medications, and research methods. Therefore, it is not possible to directly compare the research results. However, the results of these studies suggest that biologic agents may be effective in treating a variety of diseases.

Precautions for Application in Real Life

While immunosuppressants like belatacept and abatacept are effective medications for treating autoimmune diseases, it is important to remember that they have side effects, such as an increased susceptibility to infection. When using these medications, it is important to follow your doctor’s instructions and undergo regular checkups.

Limitations of Current Research

Because these studies involved a limited number of patients, the results cannot be generalized. Also, these studies did not investigate the long-term safety effects. Furthermore, these studies investigated the efficacy and safety of specific medications, and similar results may not be obtained with other medications.

Directions for Future Research

More research is needed on the long-term safety effects of biologic agents. Further research is also needed to determine whether biologic agents are effective in treating various diseases. Additionally, new methods need to be developed to mitigate the side effects of biologic agents.

Conclusion

Immunosuppressants like belatacept and abatacept are effective medications for treating autoimmune diseases. However, it is important to remember that these medications have side effects, such as an increased susceptibility to infection. When using these medications, it is important to follow your doctor’s instructions and undergo regular checkups. Further research is needed to investigate the efficacy and safety of biologic agents.