Vain harvojen lääkkeiden turvallisuudesta raskauden aikana on riittävästi tietoa, jotta riskiä voidaan arvioida luotettavasti. Raskaana olevat eivät ole mukana kliinisissä lääketutkimuksissa, ja myyntiluvan myöntämisen jälkeen tietoa kertyy hajanaisesti. Lisäksi tiedon tulkinta on usein haastavaa.

Inflammatory bowel disease (IBD) is a globally increasing chronic disease, for which the pathogenesis still is unclear. The most common subtypes of IBD are Crohn’s disease (CD) and ulcerative colitis (UC). It is widely known that, in addition to the genetics, an altered immune response against the gut microbiome plays an important role in the development of the disease. For the IBD patients, to whom conventional medication is not sufficient, the TNF-α blocker infliximab, is given. However, about one third of the patients receiving infliximab treatment, do not respond to the drug, or lose response over time. Since there to this day are no reliable diagnostic markers available, the finding of such is of great importance. The goal of this study was to investigate possible markers for drug response in the gut mycobiota composition of IBD patients. The gut mycobiota composition of 72 IBD patients receiving infliximab was studied by MiSeq sequencing of fungal DNA from fecal samples, collected during one year. The sequencing data was analyzed using the mare package in R. In addition, anti-Saccharomyces cerevisiae antibody (ASCA) concentrations were measured from baseline serum samples by ELISA. Finally, calprotectin concentrations were measured from baseline and twelve weeks post infliximab serum samples by ELISA to study whether serum samples could be used instead of fecal samples for measuring calprotectin values. Results show an increase of the Candida and Spiromyces genera in the gut mycobiota of non-responding patients at baseline. At all timepoints, the Spiromyces genus was observed at a higher abundance, compared to the group of patients responding well or partially to the medication. Interestingly, the increase of Candida was seen only in Crohn’s disease patients, when looking at the composition at all timepoints. ASCA values did not differ between the response groups. The serum calprotectin values did not correlate with fecal calprotectin, and serum calprotectin can thus not be used as a marker of gut inflammation. In conclusion, the gut mycobiota can offer predictive markers for drug response prediction to infliximab in IBD patients, which can with further studies offer a clinical diagnostic tool for prediction of drug response.

Background Juvenile Idiopathic Arthritis (JIA) may cause significant impairment in health-related quality of life (HrQoL), despite effective therapies. The aim of this study was to assess HrQoL during first-year treatment in patients with new-onset polyarticular JIA, and to compare treatment strategies. Methods In ACUTE-JIA Study, 60 patients with new-onset JIA were randomized to receive either infliximab with methotrexate (IFX+MTX); a triple therapy of methotrexate, hydroxychloroquine, and sulfasalazine (Triple); or methotrexate monotherapy (MTX). Efficacy was measured with American College of Rheumatology pediatric (ACRp) score, and juvenile arthritis disease activity score (JADAS). HrQoL was evaluated with Child Health Questionnaire (CHQ), which includes physical and psychosocial summary scores (PhS and PsS). Linear mixed models were utilized to compare groups over time. Results In the whole group of 60 patients, mean physical summary score (PhS) improved from 26.2 (SD 8.7) at week 0 to 49.7 (SD 13.2) at week 54 (p=0.046). Mean improvement of PhS was 20.3 (95% CI -15.5 to 56.2); 22.6 (-19.5 to 64.7); and 26.6 (-12.1 to 65.3) in IFX+MTX, Triple, and MTX, respectively. Changes in psychosocial summary score (PsS) were smaller: from 51.0 (SD 8.5) to 54.7 (6.3) (p=0.019) in all patients. No differences between the three treatment groups were detected in either of the measures. In multivariate analyses, Child Health Assessment Questionnaire (CHAQ), pain VAS, and time spent in inactive disease contributed to improvement in PhS; gender and CHAQ to PsS. Conclusions HrQol improved during the first year on therapy for JIA irrespective of the treatment strategy. The timing of change in the different dimensions of HrQoL varied; improvement occurred earlier in physical than psychosocial domains of HrQol.

Lähtökohdat : Tavoitteena oli tarkastella TNF-α:n salpaaja infliksimabin aloitushoidon aikaansaamaa vastetta tulehduksellista suolistosairautta sairastavilla lapsilla. Menetelmät : Tutkimuksessa oli mukana 20 Crohnin tautia, 5 haavaista koliittia ja 5 välimuotoista koliittia sairastavaa lasta. Kuuden viikon aloitushoidon aikana potilaat saivat kolme infliksimabi-infuusiota. Hoitovastetta mitattiin ulosteen kalprotektiinin avulla. Tulokset : Kalprotektiinin mediaani hoitojakson alussa oli 908 µg/g, kahden viikon kuluttua mediaani oli laskenut merkitsevästi tasolle 295 µg/g (p = 0,005). Kuuden viikon jälkeen mediaani oli 256 µg/g, eikä ero kahden viikon arvoon ollut tilastollisesti merkitsevä. Vain Crohnin tautia sairastavilla kalprotektiinin mediaani laski tilastollisesti merkitsevästi (p = 0,0057). Potilaista 87 % jatkoi ylläpitohoitoon infliksimabilla. Päätelmät : Infliksimabi laski osalla potilaista tehokkaasti kalprotektiinitasoa jo kahden viikon jälkeen hoidon aloittamisesta. Crohnin tautia sairastaville saatiin parempi vaste kuin haavaisessa tai välimuotoisessa koliitissa.

• Kroo­ninen tuleh­duk­sel­linen suolis­to­tauti (inflam­ma­tory bo­wel di­sease, IBD) on yleensä lap­silla aggres­sii­vi­sempi kuin aikui­silla, ja tau­din var­hainen totea­minen on tär­keää nor­maalin kas­vun ja kehi­tyksen turvaa­mi­seksi. • Lapsi­po­ti­laiden hoi­dossa on tär­keää myös moniu­lot­teinen hoi­to, jo­ka si­sältää ravit­se­muksen, lääke­hoidon ja hen­kisen hoi­don se­kä tau­din kompli­kaa­tioiden hy­vän hoi­don. • Paran­tavaa lääke­hoitoa ei ole, vaan lääki­tyksen tarkoi­tuk­sena on rau­hoittaa tuleh­dusta, es­tää pahe­ne­mis­vai­heita ja hel­pottaa tau­din oi­reita. • Biolo­giset lääk­keet ovat mullis­taneet vai­kean tuleh­duk­sel­lisen suolis­to­taudin hoi­don, ja uu­sia lääk­keitä ­ke­hi­tetään jatku­vasti. • Edelleen tar­vitaan myös kirur­gista hoi­toa.

Background: Clinical use of biosimilar infliximab (CT-P13) in inflammatory bowel diseases (IBDs) is based on extrapolation of indication from clinical studies performed in rheumatological diseases. Only few data exist of behaviour of infliximab trough levels (TLs) and anti-drug antibodies (ADAs) during switching.Aim: The objective of this study was to evaluate changes in TLs, ADA formation and disease activity after switching from originator infliximab to biosimilar one.Methods: All our IBD patients receiving maintenance infliximab therapy were switched to biosimilar infliximab. TLs and ADAs were measured before the last originator infusion and before the third biosimilar infusion. Laboratory values, disease activity indices (partial Mayo score and Harvey-Bradshaw index) and demographic data were collected from patient records.Results: A total of 62 patients were included in the final analysis (32 Crohn's disease, 30 ulcerative colitis (UC) or IBD-unclassified). No significant changes in median TLs before (5.5mg/l) and after switching (5.5mg/l, p=.05) occurred in the entire study group or in the Crohn's disease (CD) subgroup (5.75 and 6.5mg/l, p=.68). However, in the subgroup of ulcerative colitis, the change in median TL was significantly different (from 5.2 to 4.25mg/l, p=.019). Two patients developed ADAs after switching. No changes in disease activity were detected during switching and no safety concerns occurred.Conclusions: Switching from originator to biosimilar infliximab resulted in statistically significant differences in infliximab TLs in patients with UC but not in patients with Crohn's disease. The clinical significance for this difference is doubtful and in neither group changes in disease activity occurred.