Gyógyszerészet – 2024. április

A cikksorozat befejező része sorra veszi azokat a terápiás lehetpségeket, amelyekben az emberi szervezet saját immunrendszerét használhatjuk ki az onkológiai, hematoonológiai és szisztémás gyulladásos kórképek kezelésére. Ide tartoznak az antigénfelismerő B- és T-sejt-receptorok, a sejtpusztító immunsejteket kontrolláló fiziológiás folyamatok, a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4 és a PD-1 receptor is (programmed cell death protein 1) és a tumor mikrokörnyezetét befolyásoló fehérjék. Az immunrendszer sejtjeit kiméra antigénreceptorral felszerelve új távlatok nyílnak az onkológiai és generalizált gyulladásos betegségek kezelésére, amelyek hosszan tartó remissziót, de akár a potenciális gyógyulás lehetőségét is magukban hordozzák.

Kulcsszavak: CTLA-4, ICI, PD-1, PD1L, CAR-T immunonkológia, sejtterápia, génterápia

Breakthroughs in cancer therapy: Immuncheckpoint inhibitors and live drugs (genetically modified cells)

The final part of this series of articles reviews the therapeutic possibilities of using the human body’s own immune system to treat oncological, haemato-oncological and systemic inflammatory diseases. These include antigen-recognizing B and T cell receptors, physiological processes controlling cell-destroying immune cells, CTLA-4 (Cytotoxic T-lymphocyte-associated protein 4 and PD-1 receptor (programmed cell death protein 1) and proteins that influence the tumour microenvironment. Equipping immune cells with chimeric antigen receptors opens up new perspectives for the treatment of oncological and generalised inflammatory diseases, which carry the potential for prolonged remission and even potential cure.

Keywords: CTLA-4, ICI, PD-1, PD1L, CAR-T immunoncology, cell therapy, gentherapy

Irodalom

1. Robert C. LAG-3 and PD-1 blockade raises the bar for melanoma. Nat Cancer 2, 1251-1253 (2021). https://doi.org/10.1038/s43018-021-00276-8 – 2. Mohsenzadegan M, Bavandpour P, Nowroozi MR, et al:. The Potential of T Cell Immunoglobulin and Mucin-Domain Containing-3 (Tim-3) in Designing Novel Immunotherapy for Bladder Cancer Endocr Metab Immune Disord Drug Targets 2021;21(12):2131-2146. https://doi.org/10.2174/1871530321666210310142141 – 3. Rousseau A, Parisi C, Barlesi, F.: Anti-TIGIT therapies for solid tumors: a systematic review. ESMO Open 2023; 8(2):101184. https://doi.org/10.1016/j.esmoop.2023.101184 – 4. Yum JE I, Hong Y-K.: Terminating Cancer by Blocking VISTA as a Novel Immunotherapy: Hasta la vista, baby. Front Oncol. 2021; 16:11:658488. https://doi.org/10.3389/fonc.2021.658488 – 5. Kuwana Y, Asakura Y, Utsunomiya N, et al.: Expression of chimeric receptor composed of immunoglobulin-derived V regions and T-cell receptor-derived C regions. Biochemical and Biophysical Research Communications. 1987. 149 (3): 960-968. https://doi.org/10.1016/0006-291X(87)90502-X – 6. Magnani, CF, Tettamanti, S, Alberti, G, et al:. Transposon-Based CAR T Cells in Acute Leukemias: Where Are We Going? 2020. Cells. 9(6): 1337. – 7. Müller F, Taubmann J, Bucci L, et al.: CD19 CAR T-Cell Therapy in Autoimmune Disease – A Case Series with Follow-up. 2024. N Engl J Med 390(8):687-700. https://doi.org/10.1056/NEJMoa2308917

A magyar lakosság 30%-a szenved valamilyen alvászavarban, melynek 80%-át az insomnia teszi ki. Az insomnia – klinikailag diagnosztizálható, kóros álmatlanság – lehet akut, időszakos vagy krónikus. A kórkép gyakran társul egyéb alvászavarokkal, valamint egyéb mentális (például depresszió különböző fajtái, szorongás) és szomatikus (például neurológiai) kórképekkel is. Leginkább az idősebb korosztályokban észlelhető, és gyakran – tévesen – normális öregedési jelenségnek tekintik.

Az insomnia diagnosztizálása az alapos klinikai anamnézisre támaszkodik a kiváltó tényezők, valamint a rossz alvást eredményező maladaptív viselkedések feltérképezése miatt. A krónikus insomnia jól kezelhető a nem gyógyszeres stratégiákkal. Az intermittáló és akut insomniával küzdő bete­gek terápiájában helyet kap a célzott farmakoterápia, melyben megtaláljuk a különböző hatástartamú benzodiazepineket, első generációs antihisztaminokat, valamint bizonyos antidepresszánsokat.

Mivel klinikai gyakorlatban minden területen találkozhatunk a kórképpel, nekünk, gyógyszerészeknek is fontos ismernünk a rendelkezésünkre álló terápiás lehetőségeket. A nem megfelelő kezelés nem várt következmények kialakulásával járhat (maladapció), a nem jól megválasztott farmakológiai kezelés pedig akár dependenciához is vezethet.

Kulcsszavak: insomnia, nemzetközi ajánlás, altatószerek

Hungarian implications in an international pathology A review of the 2023 Journal of Sleep Research therapeutic guideline for the treatment of insomnia

30% of the Hungarian population suffers from some form of sleep disorder, of which insomnia accounts for 80%. Insomnia – clinically diagnosable, abnormal insomnia – can be acute, intermittent or chronic. It is often associated with other sleep disorders, as well as other mental (e.g. various forms of depression, anxiety) and somatic (e.g. neurological) conditions. It is most common in older age groups and is often mistakenly considered a normal ageing phenomenon.

The diagnosis of insomnia relies on a thorough clinical history to identify the triggers and maladaptive behaviours that lead to poor sleep. Chronic insomnia is well managed with non-pharmacological strategies. Therapy for patients with intermittent and acute insomnia includes targeted pharmacotherapy with benzodiazepines of different duration, first-generation antihistamines and certain antidepressants.

As we encounter this pathology in all areas of clinical practice, it is important for us as pharmacists to be aware of the therapeutic options available to us. Inappropriate treatment can lead to unintended consequences (maladaptation) and inappropriate pharmacological treatment can lead to dependence.

Keywords: insomnia, international guideline, hypnotics

Irodalom

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Az atopiás dermatitis (ekcéma) száraz, viszkető és gyulladással járó bőrbetegség. Gyakoribb a kisgyermekeknél, de bármely életkorban előfordulhat. Az atopiás dermatitis krónikus betegség, amely hajlamos a fellángolásra. Prevalenciája (10-12% gyermekeknél és 0,9% felnőtteknél), a közelmúltban publikált terápiás ajánlás és az újonnan támogatásba kerülő gyógyszerek indokolják, hogy közleményben foglalkozzunk a kórképpel.

Kulcsszavak: atopiás dermatitis, lokális kalcineuringátlók, JAK-inhibitorok, PDE4-inhibitorok

Treatment options for atopic dermatitis in the light of recent international guidelines

Atopic dermatitis (eczema) is a dry, itchy and inflamed skin condition. It is more common in young children but can occur at any age. Atopic dermatitis is a chronic disease that is prone to flare-ups. Its prevalence (15-20% in children and 3-10% in adults), recently published therapeutic recommendations and newly reimbursed drugs justify addressing the disease in a publication.

Keywords: atopic dermatitis, topical calcineurin inhibitors, JAK inhibitors, PDE4 inhibitors

Irodalom

1. EL Simpson, M Gooderham, A Wollenberg: Efficacy and Safety of Lebrikizumab in Combination With Topical Corticosteroids in Adolescents and Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial (ADhere). JAMA Dermatol 2023 Feb 1;159(2):182-191. – 2. E Araviiskaia, C Pincelli, A Sparavigna, T Luger: The Role of a Novel Generation of Emollients, ‚Emollients Plus’, in Atopic Dermatitis. Clinical, Cosmetic and Investigational Dermatology 2022:15 2705-19. https://doi.org/10.2147/CCID.S389697 – 3. P M Elias, J S Wakefield, M Q Man: Moisturizers versus Current and Next-Generation Barrier Repair Therapy for the Management of Atopic Dermatitis. Skin Pharmacol Physiol. 2019;32(1):1-7. https://doi.org/10.1159/000493641 – 4. Vágvölgyi Á, Csoma Zs: Atópiás ekcéma. Gyermekorvos továbbképzés 2024: 22. évf. (5): 312-16. – 5. LM Pinto, A Chiricozzi, L Calabrese, és mtsai: Novel Therapeutic Strategies in the Topical Treatment of Atopic Dermatitis. Pharmaceutics. 2022 Dec; 14(12): 2767. https://doi.org/10.3390/pharmaceutics14122767 – 6. R Sidbury , A Alikhan , L Bercovitch és mtsai.: Guidelines of care for the management of atopic dermatitis in adults with topical therapies. J Am Acad Dermatol 2023 Jul;89(1):e1-e20. https://doi.org/10.1016/j.jaad.2022.12.029 – 7. A. Wollenberg, S. Barbarot, T. Bieber és mtsai.: Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatol Venereol 2018 May;32(5):657-682. – 8. A Wollenberg, M Kinberger, B Arents, N Aszodi és mtsai.: European guideline EuroGuiDerm) on atopic eczema – part II: non-systemic treatments and treatment recommendations for special AE patient populations. J Eur Acad Dermatol Venereol 2022, 36, 1904-1926. https://doi.org/10.1111/jdv.18429 – 9. A Blauvelt, H D Teixeira, E L Simpson és mtsai.: Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol 2021 Sep 1;157(9):1047-105. https://doi.org/10.1001/jamadermatol.2021.3023