<p>Crohns sjukdom är en kronisk inflammatorisk tarmsjukdom som kan drabba hela mag- tarmkanalen och karakteriseras av återkommande skov eller kontinuerliga besvär. Symptomen beror på lokaliseringen av sjukdomen, inflammationsgrad och komplikationer. Målen vid farmakabehandling vid Crohns sjukdom är bland annat erhållande av klinisk remission och bevarande av remission. Biologiska läkemedel för behandling av Crohns sjukdom introducerades under slutet av 1990-talet och till dem hör TNF-α-hämmare. Det proinflammatoriska cytokinet TNF-α spelar troligtvis en central roll i patogenesen vid Crohns sjukdom. När konventionell behandling som exempelvis glukokortikoider och immunmodulerande farmaka inte är tillräcklig kan behandling med TNF-α-hämmare bli aktuell. TNF-α-hämmaren adalimumab godkändes i Sverige för behandling av Crohns sjukdom i juni 2007.</p><p>Syftet med denna studie var att undersöka adalimumabs effekt avseende klinisk remission vid Crohns sjukdom, både vad beträffar att uppnå klinisk remission och bevarande av remission. Sekundär frågeställning var uppkomst av eventuella allvarliga infektiösa tillstånd vid adalimumabbehandling.</p><p>Metoden för studien har varit en litteraturstudie där fem vetenskapliga artiklar har studerats. Tre av studierna var RCT-studier och två var öppna studier.</p><p>I två studier var skillnaden signifikant högre vad gäller klinisk remission i vecka 56 i adalimumabgrupperna jämfört med placebogruppen. I en studie påvisades remission i signifikant högre grad i adalimumabgruppen än i placebogruppen vecka 4. I en annan studie visades signifikant större remissionsgrad vecka 52 jämfört med vecka 0 med adalimumabbehandling. En studie visade på erhållande av remission hos patienter med luminal sjukdom och hos patienter med fistulerande sjukdom med adalimumabbehandling. I tre av studierna hade man inga fall av allvarliga infektioner. I en studie rapporterades ett fåtal fall av allvarliga infektioner i placebogruppen men inga i adalimumabgruppen. I en studie rapporterades 7 fall av allvarliga infektioner i adalimumabgrupperna och 9 fall i placebogruppen under den blindade studien.</p><p>Sammanfattningsvis visade studierna att behandling med adalimumab kan inducera och bevara remission vid Crohns sjukdom upp till 56 veckor. Dessutom visade studierna på låg biverkningsprofil gällande allvarliga infektioner.</p>

No description available.

La polyarthrite rhumatoïde est une maladie auto-immune caractérisée par une inflammation chronique qui entraîne la destruction progressive des articulations et des os. Les dommages articulaires observés dans cette pathologie sont causés principalement par les ostéoclastes, des cellules spécialisées dans la résorption de la matrice osseuse. Ce processus de résorption dépend de la capacité à générer des ostéoclastes, de leur activité individuelle et de leur survie. De plus, certaines cytokines inflammatoires peuvent avoir un effet sur la différenciation et l'activité des ostéoclastes. Parmi celles-ci, on retrouve notamment le TNF-?, un médiateur pathologique majeur dans la polyarthrite rhumatoïde. En effet, celui-ci peut agir de façon directe sur la résorption osseuse en stimulant l'ostéoclastogénèse, ou de façon indirecte en augmentant l'expression du RANKL par les ostéoblastes. Subséquemment à ces découvertes, plusieurs agents anti-TNF-? ont été développés pour traiter la polyarthrite rhumatoïde. Ces agents s'avèrent être très efficaces pour réduire les dommages articulaires chez les patients atteints de la maladie. Cependant, leurs mécanismes exacts ainsi que leurs effets sur la biologie des ostéoclastes humains sont encore mal définis. Ainsi, l'objectif principal de cette étude est d'étudier l'effet d'une thérapie anti-TNF-? sur le nombre de précurseurs ostéoclastiques dans le sang périphérique de patients atteints de la polyarthrite rhumatoïde, sur le nombre d'ostéoclastes générés in vitro ainsi que leur activité avant et pendant le traitement avec l'adalimumab, un agent anti-TNF-?. Pour ce faire, 25 patients atteints de cette maladie et ayant reçu une prescription d'adalimumab ont été recrutés pour participer à trois visites consécutives, soit les visites d'inclusion (avant traitement) ainsi que les visites 3 mois et 6 mois après le début du traitement. Pour chaque visite, le nombre de précurseurs ostéoclastiques, le nombre d'ostéoclastes et la résorption osseuse générés in vitro ont été évalués. Les mêmes paramètres ont également été vérifiés pour les cellules incubées en présence d'adalimumab exogène. L'activité de la maladie et le statut fonctionnel du patient, mesurés respectivement avec le Disease Activity Score 28 et le Health Assessment Questionnaire ont été évalués à chaque visite de la présente étude. La collecte de ces données a permis de conclure que le traitement avec l'adalimumab pendant 6 mois n'a pas d'impact statistiquement significatif sur le nombre de précurseurs ostéoclastiques, l'ostéoclastogénèse et la résorption osseuse in vitro , même si nous pouvons observer une tendance vers une diminution pour les deux derniers paramètres. En ce qui concerne les résultats cliniques, l'adalimumab a un effet statistiquement significatif sur le score DAS28 et le questionnaire HAQ, tous deux ayant diminué 6 mois après l'initiation du traitement.

Crohns sjukdom är en kronisk inflammatorisk tarmsjukdom som kan drabba hela mag- tarmkanalen och karakteriseras av återkommande skov eller kontinuerliga besvär. Symptomen beror på lokaliseringen av sjukdomen, inflammationsgrad och komplikationer. Målen vid farmakabehandling vid Crohns sjukdom är bland annat erhållande av klinisk remission och bevarande av remission. Biologiska läkemedel för behandling av Crohns sjukdom introducerades under slutet av 1990-talet och till dem hör TNF-α-hämmare. Det proinflammatoriska cytokinet TNF-α spelar troligtvis en central roll i patogenesen vid Crohns sjukdom. När konventionell behandling som exempelvis glukokortikoider och immunmodulerande farmaka inte är tillräcklig kan behandling med TNF-α-hämmare bli aktuell. TNF-α-hämmaren adalimumab godkändes i Sverige för behandling av Crohns sjukdom i juni 2007. Syftet med denna studie var att undersöka adalimumabs effekt avseende klinisk remission vid Crohns sjukdom, både vad beträffar att uppnå klinisk remission och bevarande av remission. Sekundär frågeställning var uppkomst av eventuella allvarliga infektiösa tillstånd vid adalimumabbehandling. Metoden för studien har varit en litteraturstudie där fem vetenskapliga artiklar har studerats. Tre av studierna var RCT-studier och två var öppna studier. I två studier var skillnaden signifikant högre vad gäller klinisk remission i vecka 56 i adalimumabgrupperna jämfört med placebogruppen. I en studie påvisades remission i signifikant högre grad i adalimumabgruppen än i placebogruppen vecka 4. I en annan studie visades signifikant större remissionsgrad vecka 52 jämfört med vecka 0 med adalimumabbehandling. En studie visade på erhållande av remission hos patienter med luminal sjukdom och hos patienter med fistulerande sjukdom med adalimumabbehandling. I tre av studierna hade man inga fall av allvarliga infektioner. I en studie rapporterades ett fåtal fall av allvarliga infektioner i placebogruppen men inga i adalimumabgruppen. I en studie rapporterades 7 fall av allvarliga infektioner i adalimumabgrupperna och 9 fall i placebogruppen under den blindade studien. Sammanfattningsvis visade studierna att behandling med adalimumab kan inducera och bevara remission vid Crohns sjukdom upp till 56 veckor. Dessutom visade studierna på låg biverkningsprofil gällande allvarliga infektioner.

Newer biological treatment strategies have been developed in the last decade with some promising outcomes. Their safety, however, has been questioned lately with multiple reports of increased risk for malignancies and infectious complications. These reports render their use suboptimal. We report a 44-year-old woman receiving adalimumab (Humira®) for advanced juvenile rheumatoid arthritis who then developed acute myelogenic leukemia.

Ankyloserande spondylit (AS) är en kronisk inflammatorisk sjukdom som drabbar axialskelettet. Inflammationen som uppstår tros bero på ett överskott av tumörnekrosfaktor (TNF) i kroppen som gör att inflammation och smärta förekommer utan någon direkt anledning. Ungefär 0,5% av befolkningen har AS och det är mer vanligt att män drabbas. Även barn kan drabbas av AS. Adalimumab är en humaniserad monoklonal antikropp och hämmare av cytokinet TNF. Hämmas TNF minskar inflammationen och smärtan i kroppen och progressionen av AS begränsas. Adalimumab ges subkutant via injektion i dosen 40 mg varannan vecka. Syftet med detta litteraturarbete var att undersöka huruvida adalimumab är ett effektivt och säkert läkemedel att använda vid behandling av AS. Artiklarna som undersökts i detta arbete hittades via sökningar i databasen Pubmed och då användes sökorden ”ankylosing spondylitis adalimumab” och ”ankylosing spondylitis adalimumab safety”. Utav resultaten som erhölls från de fem studierna kan det konstateras att adalimumab har god effekt vid behandling av AS jämfört med placebo. De allra flesta värdena som sågs var statistiskt signifikanta. Liknande biverkningar såg från alla studier men de som förekom var av mild grad. Slutsatsen av detta litteraturarbete är att adalimumab är ett effektivt läkemedel att använda vid behandling av AS. Det minskar symtomen och bromsar upp progressionen av AS. Adalimumab är även ett säkert läkemedel då de vanligaste biverkningarna som förekommer är av mild grad. / Ankylosing spondylitis (AS) is chronic inflammatory disease that affects the axial skeleton causing pain and stiffness. The inflammation occurs due to an excess of tumor necrosis factor (TNF) in the body which causes an inflammation without any direct cause. Approximately 0.5% of the population has AS and it´s more common that men suffer from this disease. Children can also be affected by this disease. Adalimumab is a humanized monoclonal antibody and inhibitor of the TNF cytokine. If TNF is inhibited the inflammation and the pain in the body will be reduced and the progression of AS will be limited. Adalimumab is given subcutaneously via injection at a dose of 40 mg every other week.  The intention with this literature work was to investigate whether adalimumab is an effective and safe drug to use in the treatment of AS. The articles examined in this work were found through searches in the database Pubmed where the words “ankylosing spondylitis adalimumab” were used. This resulted in 32 articles and four of them were selected. Since the four articles found during the first search were very similar, the searchword “safety” was added to broaden the information about adalimumab and look more at side effects adalimumab might possibly give. By adding “safety” the fifth article was found. The results from these five articles in this literature work shows that adalimumab has god effect in the treatment of AS compared with placebo. A majority of the values seen was statistically significant. Similar side effects were seen from all studies but the reported side effects were mild. The conclusion of this literature study is that adalimumab is an effective drug to use in the treatment of AS. It reduces the symptoms and slows the progression of AS. Adalimumab is also a safe drug since the most common side effects that occurs are mild.

Reumatoid artrit (RA) är en typ av reumatisk sjukdom där uttalad inflammation uppstår i flertalet leder tillsammans med smärta och stelhet. Inflammationen uppkommer som resultat av en autoimmun reaktion. I Sverige har ungefär 1 % av befolkningen RA och sjukdomen är 2–3 gånger vanligare hos kvinnor än hos män. Adalimumab (Humiraâ) är en TNF-hämmare som används vid behandling av RA. Humira är en humaniserad monoklonal antikropp som binder till TNF och neutraliserar de effekter som TNF utövar och reducerar på så vis symtom samt bromsar progressionen av RA. Under 2018 beräknas Humira utsättas för konkurrens av biosimilarer, vilka innehåller en version av den verksamma substansen som finns i det biologiska referensläkemedlet. För att en biosimilar ska godkännas krävs det att de bland annat har jämförbar effekt och säkerhet som referensläkemedlet. Syftet med denna litteraturstudie var att undersöka om biosimilarer till adalimumab är lika effektiva och säkra vid behandling av RA som det biologiska referensläkemedlet Humira. De fem artiklar som analyserats i denna litteraturstudie hittades via sökning i databasen PubMed med sökorden “rheumatoid arthritis”, “adalimumab” och “biosimilar”. Totalt gav detta 38 träffar varav 5 artiklar valdes ut. Enligt de resultat som sågs i denna litteraturstudie kan det konstateras att de fem biosimilarer som undersökts hade likvärdig effekt som referensläkemedlet adalimumab (Humiraâ) vid behandling av RA. Fyra av fem studier visade även att immunogenicitet mellan biosimilar och Humira var likvärdig. Liknande biverkningar förekom i båda behandlingsgrupper och behandling med en biosimilar gav inte fler eller allvarligare biverkningar än behandling med Humira. Lansering av biosimilar till adalimumab kommer troligtvis leda till lägre behandlingskostnader och därmed till att fler patienter kan få möjlighet till behandling. / Rheumatoid arthritis (RA) is a type of rheumatic disease where pronounced inflammation occurs in several joints along with pain and stiffness. The inflammation occurs as a result of an autoimmune reaction. In Sweden, approximately 1% of the population has RA and the disease is 2-3 times more common among women than men. One of the proinflammatory cytokines that plays a major role in RA is tumor necrosis factor (TNF). TNF is produced primarily by macrophages in the synovial membrane and has been shown to regulate release of other cytokines like IL-1 and IL-6. TNF also contributes to the release of metalloproteases from fibroblasts, reduced synthesis of proteoglycan from chondrocytes and to monocytes differentiate into osteoclasts. In this way, TNF contributes to joint destruction. Adalimumab (Humiraâ) is a TNF-inhibitor used in the treatment of RA. Humira is a humanized monoclonal antibody that binds to TNF and neutralizes the effects that TNF exerts and thus reduces symptoms and inhibits the progression of RA. In 2018, Humira is expected to be exposed to biosimilars competition. Biosimilars contains a version of the active substance in the biological reference drug and in order for a biosimilar to be approved it is necessary that they have comparable effect and safety as the reference drug. The purpose of this literature study was to investigate whether biosimilars to adalimumab are as effective and safe in the treatment of RA as the biological reference drug Humira. The five articles analyzed in this literature study were found through a search in the PubMed database with the words "rheumatoid arthritis", "adalimumab" and "biosimilar". In total, this resulted in 38 hits, of which 5 were selected. According to the results seen in this literature study, it can be noted that the five biosimilars investigated had similar effect as the reference drug adalimumab (Humira) in the treatment of RA. Four out of five studies also showed that the immunogenicity between the biosimilar and Humira was similar. Similar side effects occurred in both treatment groups and treatment with a biosimilar did not give more or more serious side effects than treatment with Humira. The launch of biosimilar adalimumab is likely to result in lower treatment costs and cost savings, as a result of the price competition that may occur between biosimilar adalimumab and the reference drug Humira. How much the cost will fall is hard to predict, but if there is a 58% reduction previously seen with other launched biosimilars, it can result in a cost saving of SEK 635 million. However, the amount of price reduction remains to be seen.

Introdução: recentemente, foi descrita a ação do abatacepte (ABA) na redução nos níveis de imunoglobulinas (Ig) plasmáticas em pacientes com artrite reumatoide (AR). No entanto, a possível associação destes resultados com infecções não foi avaliada até o presente momento. Objetivos: comparar os níveis totais de Igs, suas frações (IgG, IgM, IgA) e das cadeias leves (kappa e lambda) em pacientes com AR em uso de ABA vs. agentes anti-TNF semestralmente, durante 24 meses de uso, e correlacioná-los com a presença de infecções. Método: dezoito pacientes consecutivos com AR tratados abatacepte (ABA-AR) foram comparados com 18 pacientes com AR tratados com anti-TNF (aTNF-AR). Dados clínicos, laboratoriais e dosagens de imunoglobulinas total, suas frações (IgG, IgM, IgA) e das cadeias leves (kappa e lambda) foram obtidos a cada seis meses até o tempo total de 24 meses. Foi feito screening sistemático para presença de infecções. Os critérios de exclusão foram: uso prévio de abatacepte/rituximabe e hipogamablobulinemia basal (< 0,7 g/dL). Resultados: no baseline, as medianas da idade (55 vs. 53 anos, P = 0,92), porcentagem de gênero feminino (78 vs. 78%, P = 1,0), comorbidades (28 vs. 28%, P = 1,0), DAS-28 (5,73 vs. 5,67, P = 0,93), HAQ (1,5 vs. 1,13, P = 0,1), VHS (21,5 vs. 22 mm/1ahora, P = 0,49), PCR (15,5 vs. 12 mg/dL, P = 0,43) e contagem de linfócitos (2.200 vs. 1.800/mm3, P = 0,18) foram semelhantes entre os grupos ABA-AR e aTNF-AR, assim como as medianas da gamaglobulina total (1,4 vs. 1,35 g/dL, P = 0,74), IgG (1.168 vs. 1.079 mg/dL, P = 0,46), IgM (107 vs. 113mg/dL, P = 0,38), IgA (333 vs. 322 mg/dL, P = 0,71), kappa (342 vs. 249 mg/dL, P = 0,39) e lambda (170 vs. 150 mg/dL, P = 0,20). No grupo ABA-AR, após seis meses de uso, houve uma queda dos níveis séricos de gamaglobulina total (1,4 vs. 1,05 g/dL, P < 0,001), IgG (1.168 vs. 997 mg/dL, P < 0,001), IgA (333 vs. 278 mg/dL, P < 0,001), kappa (342 vs. 257 mg/dL, P < 0,001) e lambda (170 vs. 144 mg/dL, P < 0,001). Esses níveis permaneceram estáveis dos seis meses até os 24 meses de tratamento (P > 0,05). Em contraste, no grupo aTNF-AR, não houve alteração nos níveis séricos da gamaglobulina total, suas frações e cadeias leves (P > 0,05) em nenhum momento. A variação negativa da gamaglobulina total, IgG, IgM, IgA, kappa e lambda no grupo ABA-AR foi diferente do grupo aTNF-AR (P < 0,05) em todas as avaliações. No entanto, a frequência de infecções foi semelhante entre os grupos (77,8 vs. 88,9%, P = 0,66) e não se associou às variações da gamaglobulina total, de suas frações ou das cadeias leves em nenhum dos dois grupos. Não houve infecções graves durante o período do estudo. Conclusão: o presente estudo demonstra que o abatacepte, mas não os aTNFs, induz uma queda nos níveis de imunoglobulina total, suas frações e cadeias leves nos primeiros seis meses de uso, com estabilidade nos níveis até 24 meses. No entanto, essa queda não está relacionada ao aumento da frequência de infecções nesse grupo de pacientes / Objective: to evaluate the influence of abatacept on gamma-globulin levels in comparison to anti-TNF treatment and correlate these effects with infections frequency in rheumatoid arthritis (RA) patients. Methods: eighteen consecutive RA patients undergoing abatacept (ABA-RA) were compared to 18 patients treated with anti-TNF (aTNF-RA) agents with similar ages. Clinical and laboratory data, total, specific (IgG, IgM, IgA) gamma-globulin and free light chains (FLC) levels were assessed before and every six months during biologic treatment, up to 24 months. Systematic clinical screening protocol for infection was performed. Exclusion criteria were previous abatacept/rituximab treatments and low gamma-globulin level ( < 0.7 g/dL). Results: at baseline, median age (55 vs. 53 years, P = 0.92), female gender (78 vs. 78%, P = 1.0), co morbities (28 vs. 28%, P = 1), DAS-28 (5.73 vs. 5.67, P = 0.93), HAQ (1.5 vs. 1.13, P = 0.1), ESR (21.5 vs. 22mm/1sth, P = 0.49), CRP (15.5 vs. 12mg/dL, P = 0.43) and lymphocyte count (2,200 vs. 1,800/mm3, P = 0.18) were comparable in ABA-RA and aTNF-RA. Medians of gamma-globulin (1.4 vs. 1.35g/dL, P = 0.74), IgG (1,168 vs. 1,079mg/dL, P = 0.46), IgM (107 vs. 113mg/dL, P = 0.38), IgA (333 vs. 322mg/dL, P = 0.71), kappa (342 vs. 249mg/dL, P = 0.39), lambda (170 vs. 150mg/dL, P = 0.20) were also alike. In ABA-RA, total gamma-globulin (1.4 vs. 1.05 g/dL, P < 0.001), IgG (1,168 vs. 997 mg/dL, P < 0.001), IgA (333 vs. 278 mg/dL, P < 0.001), kappa (341.5 vs. 257 mg/dL, P < 0.001), lambda (169.5 vs. 144.3 mg/dL, P < 0.001) levels decreased after six months in comparison to baseline values and persisted stable up to 24 months (P > 0.05). In contrast, in aTNF-RA no decrease in total, specific gamma-globulin levels or FLC was seen (P > 0.05). The negative variation of gamma-globulin, IgG, IgM, IgA, kappa and lambda levels in ABA-RA was different from aTNF-RA (P < 0.05) at all evaluations. However, the infection rates (77.8 vs. 88.9%, P = 0.66) were similar and not associated to variations in total or specific gamma-globulin levels in any group. No severe infection was observed. Conclusion: these comparative data demonstrate that ABA, but not the aTNF, induces a non-progressive and mild, but significant reduction in gamma-globulin levels. We further demonstrated that this alteration is not clinically relevant since it is not associated with increased infection rate

Introdução: recentemente, foi descrita a ação do abatacepte (ABA) na redução nos níveis de imunoglobulinas (Ig) plasmáticas em pacientes com artrite reumatoide (AR). No entanto, a possível associação destes resultados com infecções não foi avaliada até o presente momento. Objetivos: comparar os níveis totais de Igs, suas frações (IgG, IgM, IgA) e das cadeias leves (kappa e lambda) em pacientes com AR em uso de ABA vs. agentes anti-TNF semestralmente, durante 24 meses de uso, e correlacioná-los com a presença de infecções. Método: dezoito pacientes consecutivos com AR tratados abatacepte (ABA-AR) foram comparados com 18 pacientes com AR tratados com anti-TNF (aTNF-AR). Dados clínicos, laboratoriais e dosagens de imunoglobulinas total, suas frações (IgG, IgM, IgA) e das cadeias leves (kappa e lambda) foram obtidos a cada seis meses até o tempo total de 24 meses. Foi feito screening sistemático para presença de infecções. Os critérios de exclusão foram: uso prévio de abatacepte/rituximabe e hipogamablobulinemia basal (< 0,7 g/dL). Resultados: no baseline, as medianas da idade (55 vs. 53 anos, P = 0,92), porcentagem de gênero feminino (78 vs. 78%, P = 1,0), comorbidades (28 vs. 28%, P = 1,0), DAS-28 (5,73 vs. 5,67, P = 0,93), HAQ (1,5 vs. 1,13, P = 0,1), VHS (21,5 vs. 22 mm/1ahora, P = 0,49), PCR (15,5 vs. 12 mg/dL, P = 0,43) e contagem de linfócitos (2.200 vs. 1.800/mm3, P = 0,18) foram semelhantes entre os grupos ABA-AR e aTNF-AR, assim como as medianas da gamaglobulina total (1,4 vs. 1,35 g/dL, P = 0,74), IgG (1.168 vs. 1.079 mg/dL, P = 0,46), IgM (107 vs. 113mg/dL, P = 0,38), IgA (333 vs. 322 mg/dL, P = 0,71), kappa (342 vs. 249 mg/dL, P = 0,39) e lambda (170 vs. 150 mg/dL, P = 0,20). No grupo ABA-AR, após seis meses de uso, houve uma queda dos níveis séricos de gamaglobulina total (1,4 vs. 1,05 g/dL, P < 0,001), IgG (1.168 vs. 997 mg/dL, P < 0,001), IgA (333 vs. 278 mg/dL, P < 0,001), kappa (342 vs. 257 mg/dL, P < 0,001) e lambda (170 vs. 144 mg/dL, P < 0,001). Esses níveis permaneceram estáveis dos seis meses até os 24 meses de tratamento (P > 0,05). Em contraste, no grupo aTNF-AR, não houve alteração nos níveis séricos da gamaglobulina total, suas frações e cadeias leves (P > 0,05) em nenhum momento. A variação negativa da gamaglobulina total, IgG, IgM, IgA, kappa e lambda no grupo ABA-AR foi diferente do grupo aTNF-AR (P < 0,05) em todas as avaliações. No entanto, a frequência de infecções foi semelhante entre os grupos (77,8 vs. 88,9%, P = 0,66) e não se associou às variações da gamaglobulina total, de suas frações ou das cadeias leves em nenhum dos dois grupos. Não houve infecções graves durante o período do estudo. Conclusão: o presente estudo demonstra que o abatacepte, mas não os aTNFs, induz uma queda nos níveis de imunoglobulina total, suas frações e cadeias leves nos primeiros seis meses de uso, com estabilidade nos níveis até 24 meses. No entanto, essa queda não está relacionada ao aumento da frequência de infecções nesse grupo de pacientes / Objective: to evaluate the influence of abatacept on gamma-globulin levels in comparison to anti-TNF treatment and correlate these effects with infections frequency in rheumatoid arthritis (RA) patients. Methods: eighteen consecutive RA patients undergoing abatacept (ABA-RA) were compared to 18 patients treated with anti-TNF (aTNF-RA) agents with similar ages. Clinical and laboratory data, total, specific (IgG, IgM, IgA) gamma-globulin and free light chains (FLC) levels were assessed before and every six months during biologic treatment, up to 24 months. Systematic clinical screening protocol for infection was performed. Exclusion criteria were previous abatacept/rituximab treatments and low gamma-globulin level ( < 0.7 g/dL). Results: at baseline, median age (55 vs. 53 years, P = 0.92), female gender (78 vs. 78%, P = 1.0), co morbities (28 vs. 28%, P = 1), DAS-28 (5.73 vs. 5.67, P = 0.93), HAQ (1.5 vs. 1.13, P = 0.1), ESR (21.5 vs. 22mm/1sth, P = 0.49), CRP (15.5 vs. 12mg/dL, P = 0.43) and lymphocyte count (2,200 vs. 1,800/mm3, P = 0.18) were comparable in ABA-RA and aTNF-RA. Medians of gamma-globulin (1.4 vs. 1.35g/dL, P = 0.74), IgG (1,168 vs. 1,079mg/dL, P = 0.46), IgM (107 vs. 113mg/dL, P = 0.38), IgA (333 vs. 322mg/dL, P = 0.71), kappa (342 vs. 249mg/dL, P = 0.39), lambda (170 vs. 150mg/dL, P = 0.20) were also alike. In ABA-RA, total gamma-globulin (1.4 vs. 1.05 g/dL, P < 0.001), IgG (1,168 vs. 997 mg/dL, P < 0.001), IgA (333 vs. 278 mg/dL, P < 0.001), kappa (341.5 vs. 257 mg/dL, P < 0.001), lambda (169.5 vs. 144.3 mg/dL, P < 0.001) levels decreased after six months in comparison to baseline values and persisted stable up to 24 months (P > 0.05). In contrast, in aTNF-RA no decrease in total, specific gamma-globulin levels or FLC was seen (P > 0.05). The negative variation of gamma-globulin, IgG, IgM, IgA, kappa and lambda levels in ABA-RA was different from aTNF-RA (P < 0.05) at all evaluations. However, the infection rates (77.8 vs. 88.9%, P = 0.66) were similar and not associated to variations in total or specific gamma-globulin levels in any group. No severe infection was observed. Conclusion: these comparative data demonstrate that ABA, but not the aTNF, induces a non-progressive and mild, but significant reduction in gamma-globulin levels. We further demonstrated that this alteration is not clinically relevant since it is not associated with increased infection rate

Σκοπός της παρούσας διατριβής ήταν η μελέτη της ασφάλειας και της αποτελεσματικότητας των αντι-TNFα βιολογικών παραγόντων, ινφλιξιμάβης και αδαλιμουμάβης, στους ασθενείς με ιδιοπαθή φλεγμονώδη νοσήματα του εντέρου (ΙΦΝΕ) στο Πανεπιστημιακό Γενικό Νοσοκομείο Πατρών. Προσπαθήσαμε να εντοπίσουμε τυχόν συσχετίσεις μεταξύ ομάδων ασθενών και εμφάνισης παρενεργειών ή κλινικής ανταπόκρισης. Μέθοδοι: Από τον Μάιο του 2013 ως τον Μάιο του 2014 καταγράφηκαν τα στοιχεία 63 ασθενών με μοναδικά κριτήρια εισαγωγής τη διάγνωσή τους με ΙΦΝΕ (νόσο του Crohn, ελκώδη κολίτιδα ή αδιευκρίνιστη κολίτιδα) και τη θεραπεία τους με ινφλιξιμάβη ή αδαλιμουμάβη. Κριτήριο αποτελεσματικότητας ήταν η κλινική ύφεση ή έξαρση της νόσου. Κριτήριο ασφαλείας ήταν η εμφάνιση ή όχι παρενεργειών. Αποτελέσματα: Το 65,1% των ασθενών (41/63) λάμβανε ινφλιξιμάβη. Μόλις το 20,6% των ασθενών (13/63) απαίτησε τροποποίηση του βιολογικού παράγοντα (αύξηση δόσης ή συχνότητας χορήγησης). Το 11,1% των ασθενών (7/63) διέκοψαν οριστικά τη θεραπεία εξαιτίας μη ανταπόκρισης ή απώλειας ανταπόκρισης και το 3,2% (2/63) εξαιτίας παρενεργειών. Το 7,9% των ασθενών (5/63) αναγκάστηκαν να διακόψουν παροδικά (λιγότερο από 1 έτος) τη θεραπεία λόγω μη ανταπόκρισης ή απώλειας ανταπόκρισης και το 9,5% (6/63) εξαιτίας παρενεργειών. Το 61,1% των ασθενών (33/54) που είχαν λάβει έστω και μια φορά ινφλιξιμάβη και το 38,1% των ασθενών (8/21) που είχαν λάβει έστω και μία φορά αδαλιμουμάβη εμφάνισε παρενέργειες. Οι πιο συχνές παρενέργειες ήταν οι λοιμώξεις (12/59, 20,3%) και οι αρθραλγίες (12/59, 20,3%) στους ασθενείς που λάμβαναν ινφλιξιμάβη, και οι λοιμώξεις (4/10, 40%) και η κεφαλαλγία (4/10, 40%) σε όσους λάμβαναν αδαλιμουμάβη. Το 69,8% των ασθενών (44/63) βρίσκονταν σε ύφεση. Συμπεράσματα: Η δράση των βιολογικών παραγόντων είναι στατιστικά σημαντικά καλύτερη στη νόσο του Crohn παρά στην ελκώδη κολίτιδα (81,4% vs 18,6%, αντίστοιχα βρίσκονταν σε κλινική ύφεση, p < 0,005). Για όσο περισσότερο χρόνο οι ασθενείς λαμβάνουν τους βιολογικούς παράγοντες και όσο νωρίτερα στην πορεία της νόσου τους ξεκινά η λήψη τους, τόσο καλύτερα ανταποκρίνονται. Κανένας θάνατος δεν παρουσιάστηκε. Οι παρενέργειες που αποτέλεσαν αιτία διακοπής (παροδικής ή οριστικής) εμφανίστηκαν μόνο σε ασθενείς που λάμβαναν ινφλιξιμάβη. Η αδαλιμουμάβη φαίνεται να έχει λιγότερες και λιγότερο σοβαρές παρενέργειες. Περαιτέρω μελέτες σε περισσότερους ασθενείς ή σε μεγαλύτερο βάθος χρόνου (περισσότερο από ένα έτος) είναι απαραίτητες για την εξαγωγή πιο ασφαλών συμπερασμάτων. / The aim of this work was to study the safety and efficacy of anti-TNFα biologic agents, infliximab and adalimumab, in patients suffering from inflammatory bowel disorders (IBD) at Patras University Hospital. We tried to associate clinical response or the occurrence of side-effects with several patient groups. Methods: From May 2013 to May 2014, 63 patients were recorded with the only inclusion criteria being their diagnosis with IBD (Crohn’s disease, ulcerative colitis or indeterminate colitis) and the treatment with infliximab or adalimumab. The efficacy was evaluated based on the presence of clinical remission or active disease. The safety was evaluated based on the presence or absence of side-effects. Results: 65.1% of all patients (41/63) received infliximab infusions. Only 20.6% of patients (13/63) required any adjustment to their biologic agent (dose increase or increased dose frequency). 11.1% of patients (7/63) permanently stopped treatment due to lack or loss of response and 3.2% (2/63) due to side-effects. 7.9% of patients (5/63) transiently stopped treatment (up to 1 year) due to lack or loss of response and 9.5% (6/63) due to side-effects. 61.1% of patients (33/54) who had been treated at least once with infliximab presented side-effects. 38.1% of patients (8/21) who had been treated at least once with adalimumab presented side-effects. The most common side-effects recorded in the group of patients that were treated with infliximab were infections (12/59, 20.3%) and arthralgias (12/59, 20.3%). The most common side-effects recorded in the group of patients that were treated with adalimumab were infections (4/10, 40%) and headache (4/10, 40%). 69.8 of patients (44/63) were in clinical remission. Conclusions: The efficacy of biologic agents is statistically significant better in Crohn’s disease than in ulcerative colitis (81.4% Vs 18.6% respectively were in clinical remission, p < 0.005). The longer the patients were being treated with the biologic agents and the sooner these agents were introduced in the course of the disease the better the clinical response was. No death was observed. The side-effects that led to treatment cessation (either permanent or transient) were only associated with the treatment with infliximab. The treatment with adalimumab seems to be associated with both fewer and less serious side-effects. Studies recording more patients and for a longer period of time (more than one year) need to be conducted in order to draw more clear conclusions.