Initial experience with golimumab in clinical practice for ulcerative colitis

Background: Golimumab is a TNF-blocking agent indicated as a second-line therapy in ulcerative colitis. Purpose: To research the effectiveness and safety of golimumab in patients with ulcerative colitis in clinical practice. Methods: Retrospective study of the effectiveness and safety of golimumab in patients with ulcerative colitis. All patients received golimumab 200 mg subcutaneously at week 0, and golimumab 100 mg subcutaneously at week 2. After the induction treatment, each patient received 50 mg sc. every 4 weeks in patients with body weight less than 80 kg, and 100 mg every 4 weeks in patients with body weight greater than or equal to 80 kg. Results: Study of a group of 23 ulcerative colitis patients, 7 of whom were naive to any anti-TNF therapy, and 16 patients who had previously been treated with an anti-TNF agent other than golimumab (non-naive patients). The average treatment time with golimumab was 14.3 weeks. Globally, withdrawal of corticosteroids was observed in 74% of cases. Clinical response was observed in 85.5% of patients who had not received biological treatment previously, and in patients who had previously received biological treatment the response rate was 75%. Conclusions: In this short study, golimumab seems to be an alternative treatment in naive and non-naive anti-TNF ulcerative colitis patients. It is also a safe therapy, given that there were no adverse effects in the patients studied.

Perspectivas Futuras no Tratamento da Psoríase. Novidades em Terapêutica Biológica

A psoríase é uma doença crónica,inflamatória, imuno-mediada. É uma doença associada a uma elevada carga psicológica e financeira, assim como uma diminuição significativa da qualidade de vida dos doentes. O conhecimento actual da fisiopatologia subjacente permitiu nos últimos anos novos e encorajadores desenvolvimentos terapêuticos. Estes fármacos têm como alvo elementos precisos da cascata imunológica e a sua introdução na última década constituiu um avanço significativo na abordagem da psoríase moderada a grave refractária. Neste artigo pretende-se fazer uma revisão dos mais recentes avanços no conhecimento da imunopatogénese da psoríase e com base nestes, os novos fármacos biológicos que têm sido desenvolvidos. Os fármacos biológicos para o tratamento da psoríase e/ou artrite psoriática são definidos pelo seu modo de acção e são classificados nas seguintes categorias: moduladores de acção das células T, inibidores do factor de necrose tumoral alfa (anti-TNFα) e inibidores das interleucinas (IL) 12 e IL-23. Neste artigo são abordados para além dos inibidores do TNFα, golimumab e certolizumab, os fármacos ustecinumab, briacinumab, tasocitinib, sipilizumab e abatacept.

Safety and Efficacy of the Newer Biological Therapeutics in the Treatment of Rheumatoid Arthritis

Biological therapies have been a major advance in RA treatment. However, remission or response is not achieved in all patients. Therefore, new drugs seem necessary. Most recent trials have focused in the development of three different groups of molecules: those against commercialized targets but minimizing side effects or improving administration, others molecules against new targets, and a third group including small molecules. Some of them have been shown to be clinically efficacious and safe in RA patients, including: two new anti-TNF therapies (golimumab and certolizumab pegol), three anti-CD (ocrelizumab, ofatumumab and a SMIP), subcutaneous abatacept, anti-IL17 therapy, tasocitinib and fostamatinib disodium. Therefore, a wide spectrum of new RA therapeutics are promising, but more studies are necessary to confirm these results.

Two cases of Takayasu's arteritis occurring under anti-TNF therapy.

Takayasu's arteritis is a granulomatous, large vessel vasculitis that affects the aorta, its major branches and the pulmonary arteries. Compelling evidence exists to support the notion that Takayasu's arteritis is a T-cell mediated process and that tumor necrosis factor alpha (TNFa) is an important factor in the pathogenesis of this disease. Moreover, encouraging results from recent studies support the use of anti-TNFa therapy for relapsing or resistant cases of Takayasu's arteritis. Here, however, we describe the case of two patients: one with seropositive rheumatoid arthritis, the other with HLA-B27 negative spondylarthropathy, who developed Takayasu's arteritis during treatment with TNFa inhibitors (adalimumab and golimumab respectively). This is the first report of Takayasu's arteritis in rheumatic patients under TNFa blocking agents which suggests the presence of different pathogenetic mechanism in a subgroup of patients with Takayasu's arteritis, as well as a potential role of TNFa blockers as triggers of this disease in some cases.

Off-label uses of anti-TNF therapy in three frequent disorders: Behçet's disease, sarcoidosis, and noninfectious uveitis.

Tumoral necrosis factor α plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab) has turned into the most important tool in the management of a variety of disorders, such as rheumatoid arthritis, spondyloarthropatties, inflammatory bowel disease, and psoriasis. Nonetheless, theoretically, some other autoimmune disorders may benefit from these agents. Our aim is to review these off-label uses of anti-TNF blockers in three common conditions: Behçet's disease, sarcoidosis, and noninfectious uveitis. Due to the insufficient number of adequate clinical trials and consequently to their lower prevalence compared to other immune disorders, this review is mainly based on case reports and case series.

Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study.

AIMS: TNF-α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm birth and reduced birth weight after first trimester exposure to TNF-α inhibitors. METHODS: Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational cohort study and compared with outcomes of a non-exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services. RESULTS: In total, 495 exposed and 1532 comparison pregnancies were contributed from nine countries. The risk of major birth defects was increased in the exposed (5.0%) compared with the non-exposed group (1.5%; adjusted odds ratio (ORadj ) 2.2, 95% CI 1.0, 4.8). The risk of preterm birth was increased (17.6%; ORadj 1.69, 95% CI 1.1, 2.5), but not the risk of spontaneous abortion (16.2%; adjusted hazard ratio [HRadj ] 1.06, 95% CI 0.7, 1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non-exposed cohort (P = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated. CONCLUSIONS: TNF-α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF-α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs.

Tratamiento de Artritis reumatoide con antagonistas del factor de necrosis tumoral alfa y su asociación con el desarrollo de melanoma cutáneo: revisión sistemática de la literatura y meta-análisis.

Introducción: El tratamiento con antagonistas del factor de necrosis tumoral alfa (anti TNF) ha impactado el pronóstico y la calidad de vida de los pacientes con artritis reumatoide (AR) positivamente, sin embargo, se interroga un incremento en el riesgo de desarrollar melanoma. Objetivo: Conocer la asociación entre el uso de anti TNF y el desarrollo de melanoma maligno en pacientes con AR. Metodología: Se realizó una búsqueda sistemática en MEDLINE, EMBASE, COCHRANE LIBRARY y LILACS para ensayos clínicos, estudios observacionales, revisiones y meta-análisis en pacientes adultos con diagnóstico de AR y manejo con anti TNF (Certolizumab pegol, Adalimumab, Etanercept, Infliximab y Golimumab). Resultados: 37 estudios clínicos cumplieron los criterios de inclusión para el meta-análisis, con una población de 16567 pacientes. El análisis de heterogeneidad no fue significativo (p=1), no se encontró diferencia en el riesgo entre los grupos comparados DR -0.00 (IC 95% -0.001; -0.001). Un análisis adicional de los estudios en los que se reportó al menos 1 caso de melanoma (4222 pacientes) tampoco mostró diferencia en el riesgo DR -0.00 (IC 95% -0.004 ; -0.003). Conclusión: En la evidencia disponible a la fecha no encontramos asociación significativa entre el tratamiento con anti TNF en pacientes con diagnóstico de AR y el desarrollo de melanoma cutáneo.

Systematic review and analysis of evidences on clinical efficacy and cost-effectiveness of biological drugs for the treatment of Ankylosing Spondylitis

Technology: Infliximab and comparator biological such as adalimumab, etanercept, golimumab. Conditions: Ankylosing spondylitis (AS) Issue: Infliximab is registered to be used in patients with AS. The aim of the Report is to evaluate the clinical efficacy and safety of infliximab and comparator biologicals for the treatment of adult AS. Methods: Systematic literature review and analysis as well as meta-analysis (direct and indirect comparison) of published randomised controlled clinical trials (RCT) were performed, all relevant health economics literature were identified ad analysed. Results: Clinical efficacy of biological therapies is based on good clinical evidences regarding to all clinical efficacy endpoints (ASAS20, ASAS40, ASAS 5/6, and BASDAI 50% response). Altogether, 22 trials are included in our meta-analysis, 12 infliximab, 3 adalimumab studies, 6 etanercept and 1 golimumab. Efficacy of biological treatments for the treatment of AS has been established by clinical scientific evidences, significant improvement at all outcomes considered was confirmed. According to the results of indirect comparison, there were no significant difference between biological treatments and placebo in terms of safety and tolerability endpoints. We found no significant difference between the clinical efficacy and safety of infliximab, adalimumab, etanercept and golimumab therapies. Cost-utility analysis of adalimumab and/or infliximab, etanercept and golimumab treatment for AS were performed in the UK, Canada, The Netherlands, Germany, Spain and France. There are no cost-utility studies from Eastern Central Europe. Implications for decision making: Efficacy of infliximab and comparator biologicals for the treatment of Ankylosing Spondylitis (AS) was proved by clinical evidence, significant improvement at all outcomes considered was confirmed. We found no significant differences in efficacy and safety of different biological treatments. Health economics results suggest that biological therapies are cost-effective alternatives for the treatment of AS in group of developed high income countries. There is a lack of health economics results in Central-Eastern European countries however these data are more and more required by governments and funders as part of the company economic dossiers.

Comparative efficacy and safety of biosimilar infliximab and other biological treatments in ankylosing spondylitis: systematic literature review and meta-analysis.

OBJECTIVES: To compare the efficacy and safety of infliximab-biosimilar with other biological drugs for the treatment of active ankylosing spondylitis (AS). METHODS: Systematic literature review for randomized controlled trials (RCTs) with adalimumab, etanercept, golimumab, infliximab and infliximab-biosimilar in AS was performed and indirect meta-analysis (Bayesian mixed treatment comparison) was carried out. The proportion of patients reaching 20 % improvement by the assessment of Spondyloarthritis International Society response criteria (ASAS20) at weeks 12 and 24 was used as efficacy endpoints, and the occurrence of serious adverse events at week 24 was applied to compare the safety of the biologicals. RESULTS: Altogether, 13 RCTs, identified by the systematic literature search, were included in the analysis. Results on the ASAS20 efficacy endpoint were reported for week 12 in 12 RCTs involving 2,395 patients, and for week 24 in 5 RCTs comprising 1,337 patients. All the five biological agents proved to be significantly superior to placebo. Infliximab showed the highest odds ratio (OR) of 7.2 (95 % CI 3.68-13.19) compared to placebo, followed by infliximab-biosimilar with OR 6.25 (95 % CI 2.55-13.14), both assessed at week 24. No significant difference was found between infliximab-biosimilar and other biological treatments regarding their efficacy and safety. CONCLUSIONS: This is the first study which includes a biosimilar drug in the meta-analysis of biological treatments in AS. The results have proven the similar efficacy and safety profile of infliximab-biosimilar treatment compared to other biologicals.

Efficacy and safety of infliximab-biosimilar compared to other biological drugs in rheumatoid arthritis: a mixed treatment comparison.

OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and safety of infliximab-biosimilar and other available biologicals for the treatment of rheumatoid arthritis (RA), namely abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab and tocilizumab. METHODS: A systematic literature review of MEDLINE database until August 2013 was carried out to identify relevant randomized controlled trials (RCTs). Bayesian mixed treatment comparison method was applied for the pairwise comparison of treatments. Improvement rates by the American College of Rheumatology criteria (ACR20 and ACR50) at week 24 were used as efficacy endpoints, and the occurrence of serious adverse events was considered to assess the safety of the biologicals. RESULTS: Thirty-six RCTs were included in the meta-analysis. All the biological agents proved to be superior to placebo. For ACR20 response, certolizumab pegol showed the highest odds ratio (OR) compared to placebo, OR 7.69 [95 % CI 3.69-14.26], followed by abatacept OR 3.7 [95 % CI 2.17-6.06], tocilizumab OR 3.69 [95 % CI 1.87-6.62] and infliximab-biosimilar OR 3.47 [95 % CI 0.85-9.7]. For ACR50 response, certolizumab pegol showed the highest OR compared to placebo OR 8.46 [3.74-16.82], followed by tocilizumab OR 5.57 [95 % CI 2.77-10.09], and infliximab-biosimilar OR 4.06 [95 % CI 1.01-11.54]. Regarding the occurrence of serious adverse events, the results show no statistically significant difference between infliximab-biosimilar and placebo, OR 1.87 [95 % CI 0.74-3.84]. No significant difference regarding efficacy and safety was found between infliximab-biosimilar and the other biological treatments. CONCLUSION: This is the first indirect meta-analysis in RA that compares the efficacy and safety of biosimilar-infliximab to the other biologicals indicated in RA. We found no significant difference between infliximab-biosimilar and other biological agents in terms of clinical efficacy and safety.