Bakgrund Astma är en kronisk sjukdom som försvårar lungfunktion och påverkar individer hela livet. Orsakerna för astma är olika mellan olika individer, men sjukdomen har liknande symtom. Nyligen visades Thymic Stromal Lymphopoietin ”TSLP” ha viktig roll vid initiering av inflammationen i lungorna som leder till astmaattack hos patienterna. Biologiska läkemedel, som tezepelumab, avbryter specifikt i initieringen av inflammation som påbörjas vid en exponering hos astmatiker. Tezepelumab är en monoklonal antikropp för behandling vid svår astma. Syfte Syfte med studien var att undersöka om det nya läkemedlet på marknaden var en effektiv behandling för astmapatienter som har lidit av svår och okontrollerad astma. Metod En litteraturstudie genomfördes genom en sökning i databasen PubMed. Det används några nyckelord som tex Astma, Tezepelumab, TSLP och monoklonal antikropp, Det genomfördes ett urval och analysering av studier från PubMed. Resultat De fem studierna visade positiva behandlingseffekt av tezepelumab av okontrollerad astma trots behandlingen med Långverkande beta-2 stimulerare ”LABAs” och Inhaled Corticosteroids”CISs”. Studierna visade att anti TSLP behandling med tezepelumab förbättrade symtomen och livskvalitet hos patienterna.Andelen av astmaanfall reducerades under behandlingens period med tezepelumab. Nivåer av inflammationsmarkörer minskade och patienternas livskvalitet förbättrades. Tezepelumab har lång halveringstid vilket möjliggör dosering endast en gång var fjärde vecka.Tezepelumab visade inga oväntade negativa eller allvarliga livshotande biverkningar, den visade inte ens reaktioner på huden vid injektionsstället eller urtikaria. Slutsats Tezepelumab är en effektiv och säker behandling för svår, okontrollerad astma hos vuxna. / Asthma is one of the most common and chronic diseases in the world. Asthma patients suffer from symptoms related to the respiratory system or the lungs. Symptoms include coughing, increased sputum secretion, shortness of breath, and inflammation in the airways, which may lead to an asthmatic crisis that leads to an emergency admission to the hospital. Asthma treatment was for many years limited to reducing symptoms by means of long-acting beta-agonists, “LABA” or corticosteroid inhalers, “CSI” or both. Still, this treatment was not sufficient for many patients with uncontrolled asthma. With the research development and increased knowledge about  the immune system, the role of the cytokine thymic stromal lymphopoietin (TSLP) in activating TH-cells and other cytokines that cause inflammation has been defined. This increased knowledge has resulted in the development of a new drug which is an antibody against TSLP intended to inactivate TSLP, thereby reducing the symptoms of inflammation in asthma patients.  This study is based on a selection of randomized controlled trials designed to study the effectiveness of the medicine in asthma patients in reducing the frequency of exacerbations of asthma and reducing the vital signs that cause inflammation. Asthma patients in studies Ⅰ- Ⅳ were selected and randomly distributed in groups to take three doses of tezepelumab or a placebo. The results were effective in favor of tezepelumab because it reduced the average of asthma attacks during a year compared to placebo patients, reduced IL-7, IL-5, and reduced eosinophil and FeNO, which usually cause inflammation. Tezepelumab also improved lung function. These results led to an improved quality of patients’ life. When studying the pharmacokinetics, the results indicated that tezepelumab was influential in the body, as it was associated with its target (TSLP) and performed its expected function. The serum half-life t1/2 is four weeks. The studies were similar in terms of several factors, and the results were also similar, which means that the newly developed medicine could bind successfully to TSLP and exert a relatively long-term effect, which reduces the inflammation caused by asthma exacerbation. In conclusion, the chosen studies demonstrate that Tezepelumab has positive results on severe and uncontrolled asthma with no serious side effects.

Chronic spontaneous urticaria (CSU) is defined as itchy hives with or without angioedema with a burning sensation that last for six weeks or longer and have no apparent external trigger. The disease occurs in about 1 % of the population. The itching and burning symptoms affect the patient’s quality of life in a negative way which makes a treatment highly needed. The first-line medication for the treatment of CSU is non-sedating H1-antihistamines in recommended doses and the second line of treatment is an increased dose of H1-antihistamines, up to four-fold the approved doses. However, many patients do not response to these therapies whereas a third-line treatment, an add-on therapy with omalizumab, is necessary. Omalizumab is a monoclonal anti-IgE-antibody that binds to free IgE and prevents them to attach to FcεRI-receptors on inflammatory cells like mast cells. This leads to a lower activation of mast cells and less histamine gets released. The definite mechanism of action of CSU-symptoms relief is still unclear but it is thought to be due to decreased levels of IgE and FcεRI-receptors. The symptoms of CSU can be scored using weekly itch severity score (ISS7) which scores the pruritus, weekly hive severity score (HSS7) which scores the number of hives and weekly urticaria activity score (UAS7) that scores both pruritus and number of hives together. The aim of this literature review was to evaluate the efficacy and safety of omalizumab in patients diagnosed with CSU. A search on PubMed was conducted with the search terms "omalizumab" AND "chronic spontaneous urticaria" and "omalizumab" AND "chronic idiopathic urticaria". The articles were limited to randomized, controlled and double-blinded trials that were published 2010 or later. A total of five studies were included for further analysis; MYSTIQUE, ASTERIA II, ASTERIA I, POLARIS and GLACIAL. The studies showed that omalizumab 300 mg and 150 mg reduced the symptoms of CSU significantly compared with placebo, whereas 300 mg had the best efficacy in decreasing the values of ISS7, HSS7 and UAS7. The patients went from having severe urticaria to mild urticaria after treatment with omalizumab. The degree of itching improved from severe itching to mild itching. The side effects were mild to moderate, the most common were nasopharyngitis, headache, arthralgia and upper respiratory tract infection. Omalizumab showed to be effective and safe as an add-on therapy for the treatment of patients with chronic spontaneous urticaria who did not respond adequately to treatment with H1-antihistamines.

Biologiska läkemedel har under det senaste århundradet utökats, och under de senaste 25 åren så har proportionen av godkända biologiska läkemedel har ökat för behandlingen av sjukdomar, vaccin, och diagnostik. Det finns flera olika mekanismer för protein aggregering, och en av dessa är seeding, vilket innebär aggregering inducerat av tillsatta aggregat eller förekomsten av strukturförändringar i proteinet. I detta examensarbete har två terapeutiska proteiner, Somatropin och en monoklonal antikropp, studerats i form av aggregering. Denna studie har utförts genom att värma en del av proteinlösningen för att bilda aggregat och strukturförändrat protein, och sedan blanda detta med nativt protein till olika volymprocent. Dessa lösningar förvarades i olika temperaturer, 4°C, RT och 40°C för att undersöka temperaturberoendet. Med Dynamic Light Scattering (DLS) mättes storleksfördelningen och medelstorleken på proteinet, vilket visade att de seedade proverna ökade i medelstorlek med tiden. Detta indikerar att seedingen inducerade aggregering med tiden. / Biological pharmaceuticals have expanded their use over the last decade, and during the recent 25 years, the proportion of approved biologics has increased for the treatment of diseases, vaccines, and diagnostics. There are several aggregation mechanisms, and one is seeding, i.e., aggregation induced by pre-formed aggregates or the presence of conformational changed proteins. In this master thesis, two therapeutic proteins, Somatropin and one monoclonal antibody have been studied in terms of aggregation. The study has been performed by heating a part of a protein solution to induce aggregation and mixing this with native protein in different volume percentages. These were stored in different temperatures, 4°C, RT, and 40°C, to investigate the temperature dependence. With Dynamic light scattering (DLS), the size distribution and the average-sized particles were measured. This showed that there was a growth of average size in the seeded samples with time. This indicates that the seeding induced aggregation with time.