OBJECTIVES: The GO-BACK study was designed to evaluate the efficacy and safety of golimumab (GLM) treatment withdrawal in adults with non-radiographic axial spondyloarthritis (nr-axSpA) who demonstrate inactive disease during a 10-month open-label (OL) GLM run-in. METHODS: Eligible participants received OL GLM in period 1. In period 2, participants who achieved inactive disease were randomized 1:1:1 to receive double-blind (DB) treatment with monthly placebo (PBO, treatment withdrawal) or continued GLM treatment given monthly (GLM QMT) or every 2 months (GLM Q2MT). Participants who did not have a disease flare continued DB treatment for ∼12 months. Participants with a disease flare discontinued DB treatment and resumed monthly OL GLM. Primary endpoint compared the proportion of participants without a disease flare in the continued GLM treatment groups (QMT or Q2MT) vs PBO in a multiplicity-controlled, step-down fashion. Safety follow-up continued for ∼3 months after last treatment. RESULTS: A total of 188 patients, out of the 323 enrolled, were eligible for participation in period 2. Both GLM QMT and GLM Q2MT were superior to treatment withdrawal (PBO) in preventing disease flare (P < 0.001), with a treatment-difference vs PBO of 50.4% and 34.4% for the GLM QMT and GLM Q2MT groups, respectively. The time-to-first flare was significantly longer (log-rank P < 0.0001) with GLM treatment compared with PBO. Of 53 participants (in Q2MT or PBO) who had a confirmed disease flare, 51 (96.2%) attained a clinical response within 3 months of restarting OL GLM. Adverse events were consistent with the known GLM safety profile. CONCLUSION: Among participants with active nr-axSpA who attained inactive disease after 10 months of GLM treatment, continued GLM treatment is well tolerated and provides superior protection against disease flares compared with GLM withdrawal. (EudraCT: 2015-004020-65, registered on 30 March 2022; NCT: 03253796, registered on 18 August 2017.).

• Klíčová slova
• efficacy, golimumab, non-radiographic axial spondyloarthritis, reduced dosing, safety, withdrawal,
• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé MeSH
• non-radiografická axiální spondyloartritida * MeSH
• opakovaná terapie MeSH
• syndrom vzplanutí nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• golimumab MeSH Prohlížeč

GO-MORE (NCT00975130) was a large open-label, multinational, multicenter, prospective phase 3 trial evaluating add-on therapy with golimumab in biologic-naïve patients with active rheumatoid arthritis (RA). The objective of this post hoc analysis was to examine regional differences in baseline disease activity and remission rates following golimumab treatment for RA. This was a planned, descriptive post hoc analysis of data from the GO-MORE trial. Baseline disease activity and remission were defined as moderate or severe based on EULAR criteria. This analysis included 3280 participants from the GO-MORE trial. All participants included in this analysis had high or moderate disease activity at baseline. At baseline, high disease activity was least common in Europe (71.0%), Canada (77.0%), and the Middle East (78.2%) and most common in Latin America (90.7%), South Africa (91.5%), and Asia (92.5%). Month 6 remission rates were highest in South Africa (29.1%), Europe (27.9%), and the Middle East (27.3%) and lowest in Canada (19.7%), Latin America (17.2%), and Asia (15.0%). Higher rates of remission in each geographical region generally corresponded with lower baseline disease activity. We suspect that access to care and implementation of the treat-to-target strategy were the most important determinants, but this apparent relationship needs to be confirmed in further studies that include a statistical analysis of prognostic indicators.

• Klíčová slova
• Antirheumatic agents, Clinical trial, Geographic locations, Golimumab, Rheumatoid arthritis,
• MeSH
• antirevmatika terapeutické užití   MeSH
• dospělí MeSH
• indukce remise MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monoklonální protilátky terapeutické užití   MeSH
• prospektivní studie MeSH
• revmatoidní artritida farmakoterapie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antirevmatika MeSH
• golimumab MeSH Prohlížeč
• methotrexát MeSH
• monoklonální protilátky MeSH

OBJECTIVE: This 24-week, phase IIb, double-blind study was undertaken to evaluate the efficacy and safety of mavrilimumab (a monoclonal antibody to granulocyte-macrophage colony-stimulating factor receptor α) and golimumab (a monoclonal antibody to tumor necrosis factor [anti-TNF]) in patients with rheumatoid arthritis (RA) who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) (referred to as DMARD-IR) and/or inadequate response to other anti-TNF agents (referred to as anti-TNF-IR). METHODS: Patients with active RA and a history of DMARD-IR (≥1 failed regimen) or DMARD-IR (≥1 failed regimen) and anti-TNF-IR (1-2 failed regimens) were randomized 1:1 to receive either mavrilimumab 100 mg subcutaneously every other week or golimumab 50 mg subcutaneously every 4 weeks alternating with placebo every 4 weeks, administered concomitantly with methotrexate. The primary end points were the American College of Rheumatology 20% improvement (ACR20), 50% improvement, and 70% improvement response rates at week 24, percentage of patients achieving a Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) of <2.6 at week 24, percentage of patients with a score improvement of >0.22 on the Health Assessment Questionnaire (HAQ) disability index (DI) at week 24, and safety/tolerability measures. This study was not powered to formally compare the 2 treatments. RESULTS: At week 24, differences in the ACR20, ACR50, and ACR70 response rates between the mavrilimumab treatment group (n = 70) and golimumab treatment group (n = 68) were as follows: in all patients, -3.5% (90% confidence interval [90% CI] -16.8, 9.8), -8.6% (90% CI -22.0, 4.8), and -9.8% (90% CI -21.1, 1.4), respectively; in the anti-TNF-IR group, 11.1% (90% CI -7.8, 29.9), -8.7% (90% CI -28.1, 10.7), and -0.7% (90% CI -18.0, 16.7), respectively. Differences in the percentage of patients achieving a DAS28-CRP of <2.6 at week 24 between the mavrilimumab and golimumab groups were -11.6% (90% CI -23.2, 0.0) in all patients, and -4.0% (90% CI -20.9, 12.9) in the anti-TNF-IR group. The percentage of patients achieving a >0.22 improvement in the HAQ DI score at week 24 was similar between the treatment groups. Treatment-emergent adverse events were reported in 51.4% of mavrilimumab-treated patients and 42.6% of golimumab-treated patients. No deaths were reported, and no specific safety signals were identified. CONCLUSION: The findings of this study demonstrate the clinical efficacy of both treatments, mavrilimumab at a dosage of 100 mg every other week and golimumab at a dosage of 50 mg every 4 weeks, in patients with RA. Both regimens were well-tolerated in patients who had shown an inadequate response to DMARDs and/or other anti-TNF agents.

• MeSH
• antirevmatika škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monoklonální protilátky škodlivé účinky   terapeutické užití   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antirevmatika MeSH
• golimumab MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH
• mavrilimumab MeSH Prohlížeč
• methotrexát MeSH
• monoklonální protilátky MeSH
• TNF-alfa MeSH

OBJECTIVE: To create a tool to predict probability of remission and low disease activity (LDA) in patients with RA being considered for anti-TNF treatment in clinical practice. METHODS: We analysed data from GO-MORE, an open-label, multinational, prospective study in biologic-naïve patients with active RA (DAS28-ESR ⩾3.2) despite DMARD therapy. Patients received 50 mg s.c. golimumab (GLM) once monthly for 6 months. In secondary analyses, regression models were used to determine the best set of baseline factors to predict remission (DAS28-ESR <2.6) at month 6 and LDA (DAS28-ESR ⩽3.2) at month 1. RESULTS: In 3280 efficacy-evaluable patients, of 12 factors included in initial regression models predicting remission or LDA, six were retained in final multivariable models. Greater likelihood of LDA and remission was associated with being male; younger age; lower HAQ, ESR (or CRP) and tender joint count (or swollen joint count) scores; and absence of comorbidities. In models predicting 1-, 3- and 6-month LDA or remission, area under the receiver operating curve was 0.648-0.809 (R(2) = 0.0397-0.1078). The models also predicted 6-month HAQ and EuroQoL-5-dimension scores. A series of matrices were developed to easily show predicted rates of remission and LDA. CONCLUSION: A matrix tool was developed to show predicted GLM treatment outcomes in patients with RA, based on a combination of six baseline characteristics. The tool could help provide practical guidance in selection of candidates for anti-TNF therapy.

• Klíčová slova
• biologic, predictors of response, remission, rheumatoid arthritis, tumour necrosis factor,
• MeSH
• antirevmatika terapeutické užití   MeSH
• chronická nemoc MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• prediktivní hodnota testů MeSH
• prospektivní studie MeSH
• regresní analýza MeSH
• revmatoidní artritida farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antirevmatika MeSH
• golimumab MeSH Prohlížeč
• monoklonální protilátky MeSH

The original publication contains two areas which require correcting. None of these errors change the results or conclusions of the article, but the authors wish to highlight the areas of change to the reader.

• Publikační typ
• časopisecké články MeSH
• tisková chyba MeSH

In human, autoimmune uveitis is a leading cause of visual disability and ranks with diabetic retinopathy as a major source of blind registrations in developed countries. Since most cases of non-infectious uveitis are considered to be autoimmune or at least immune-mediated, the management of such patients has rested on appropriate immunosuppression. Some patients, however, despite maximal immunotherapy, fail to respond or are seriously intolerant of the drug therapies. Since its establishment 20 years ago, the model of experimental autoimmune uveoretinitis has served as a useful template for novel therapeutic approaches. The aim of our study was to compare the efficacy of mycophenolate mofetil and cyclophosphamide and golimumab treatment in the mouse model of experimental autoimmune uveitis. The intensity of intraocular inflammation was evaluated histologically in the treatment and control groups. Experimental autoimmune uveitis has been induced in mouse strain C57BL/6 by subcutaneous application of interphotoreceptor retinoid binding protein in complete Freund's adjuvant and pertussis toxin. The treatment was commenced on the day of uveitis induction. Cyclophosphamide was applied intraperitoneally in a single dose (100 mg/kg), mycophenolate mofetil intraperitoneally daily (30 mg/kg or 50 mg/kg), golimumab subcutaneously weekly (70 mg/kg). Sham intraperitoneal injection of a placebo (aqua pro injectione) and untreated mice with experimental autoimmune uveitis served as controls. The results show statistically significant suppression of experimental uveitis both with mycophenolate mofetil and with cyclophosphamide, and thus support its use in human medicine.

• MeSH
• antiflogistika nesteroidní terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• kyselina mykofenolová analogy a deriváty   terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• monoklonální protilátky terapeutické užití   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• uveitida farmakoterapie   MeSH
• zánět farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• antiflogistika nesteroidní MeSH
• cyklofosfamid MeSH
• golimumab MeSH Prohlížeč
• kyselina mykofenolová MeSH
• monoklonální protilátky MeSH

Conventional DMARDs such as MTX are the mainstay of treatment for patients with RA. However, failure to achieve adequate disease control in many patients, even with combination therapy, has spurred the development of agents that target various immune mediators involved in the disease process. In the past decade, biologic agents have proved viable as alternative or add-on therapy to DMARDs in patients whose disease is inadequately controlled. Well-controlled clinical trials have evaluated the effects of these agents not only on disease activity, but also on inhibition of structural change and improvement in physical function. This article reviews phase 3 clinical trial results on biologic agents that inhibit T- and B-cell activation (abatacept and rituximab, respectively), inflammatory cytokines such as TNF-α (adalimumab, etanercept, infliximab, golimumab and certolizumab) and IL-6 (tocilizumab). Although data comparing the efficacy of the various biologic agents are limited, the availability of biologic therapies with differing mechanisms of action expands therapeutic options for patients whose disease is inadequately controlled with DMARDs and allows for greater individualization of treatment.

• MeSH
• antirevmatika terapeutické užití   MeSH
• B-lymfocyty účinky léků   MeSH
• cytokiny účinky léků   MeSH
• imunosupresiva terapeutické užití   MeSH
• klinické zkoušky, fáze III jako téma MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• revmatoidní artritida farmakoterapie   MeSH
• T-lymfocyty účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antirevmatika MeSH
• cytokiny MeSH
• imunosupresiva MeSH

Administration of biological therapy (BT) in rheumatoid arthritis (RA) patients is often associated with hematological complications, which result in switching among therapies. Thus, there is an instant need for suitable screening parameters that will help to individualize the therapy and minimize the onset of adverse effects. We analyzed the hematological profile of 99 RA patients receiving TNFα (Adalimumab - ADA, Golimumab - GOL, Etanercept - ETA) or IL-6 receptor (Tocilizumab - TCZ) inhibitors in order to find possible indicators to improve personalization of RA therapy. BTs significantly affect the levels of observed hematological parameters. In contrast to TNF-α inhibitors, TCZ normalized almost all monitored hematological parameters to values of healthy donors. Only GOL from the TNF-α inhibitors studied, was able to normalize neutrophil counts, as well as platelet indicators. Importantly, effects on the blood parameters (e.g. lymphocytes or platelet count) differ even within the same therapeutic group (anti-TNFα). Variable effects of individual biological agents in RA treatment point to importance to evaluate the patient's hematological profile to improve the selection of suitable BT. It will help to personalize the administration of BT and prevent unnecessary switching from an effective therapy just because of provocation of avoidable hematological complications.

• Klíčová slova
• IL-6, TNFalpha, biological therapy, hematologic parameters, rheumatoid arthritis,
• Publikační typ
• časopisecké články MeSH

UNLABELLED: The biological treatment which is the most effective type of therapy for inflammatory rheumatic diseases, has become part of a standard clinical rheumatology practice in recent years. Thousands of patients in the Czech Republic with rheumatoid arthritis, different forms of spondyloarthritides and with psoriatic arthritis are now successfully treated in this way. The following medications are registered in the Czech Republic for the treatment of rheumatic diseases: infliximab, adalimumab, golimumab, certolizumab pegol, etanercept, abatacept, rituximab, tocilizumab and belimumab, newly also secukinumab. This effective therapy also entails a new spectrum of adverse effects, different to those of the synthetic disease modifying antirheumatic drugs. The most frequent problems include a higher incidence of infections including exacerbation of latent tuberculosis, further we can meet hematological, gastroenterological and immunological abnormalities some of which, luckily of rare occurrence, may have a very serious character. The cardiovascular risk is rather reduced during long-term therapy, however in patients with chronic heart failure the anti-TNF therapy may lead to its worsening. All physicians caring for patients with inflammatory rheumatic diseases should have the basic knowledge of the range of the adverse effects. KEY WORDS: abatacept - adalimumab - ankylosing spondylitis - biological treatment - certolizumab pegol - goli-mumab - TNFα inhibitors - infliximab - adverse effects - psoriatic arthritis - rheumatoid arthritis - rituximab - secukinumab - tocilizumab.

• MeSH
• antirevmatika terapeutické užití   MeSH
• kardiovaskulární nemoci etiologie   prevence a kontrola   MeSH
• lidé MeSH
• revmatoidní artritida komplikace   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antirevmatika MeSH

Advances in the current knowledge of pathogenetic mechanisms of rheumatoid arthritis have contributed to the development of biological therapy, and translated research findings into clinical practice. TNF-alpha (infliximab, etanercept, adalimumab), IL-1 (anakinra) and IL-6 (tocilizumab) inhibitors, a B-cell depleting agent (rituximab) and a drug blocking T-cell costimulation (abatacept) have been approved for rheumatoid arthritis. The progress in manufacturing biotechnology has contributed to the development of several other prospective agents that may form the basis for the therapy of rheumatoid arthritis in the near future. New or modified TNF-alpha inhibitors (golimumab, certolizumab pegol), new monoclonal antibodies against other cytokines (e.g. IL-1, IL-6, IL-12, IL-15, IL-17, IL-23), and other agents targeting B-cell depletion (e.g. ocrelizumab, ofatumumab) are in various stages of development. Many pharmaceutical companies have focused on developing small molecule inhibitors with possible peroral administration, which are considered promising drugs for rheumatoid arthritis. In most cases, these small molecules inhibit cellular kinases (e.g. p38, JAK or Syk) that mediate the signaling and transcription of proinflammatory genes. In this review, we describe the cytokine inhibitors and modulators of the immune response currently in ongoing clinical trials, the results of which may further expand the spectrum of efficient therapies for chronic autoimmune diseases.

• MeSH
• biologická terapie * trendy   MeSH
• cytokiny imunologie   MeSH
• diferenciační antigeny imunologie   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• lidé MeSH
• lymfocytární deplece MeSH
• malá interferující RNA genetika   MeSH
• mezibuněčná komunikace účinky léků   imunologie   MeSH
• monoklonální protilátky MeSH
• revmatoidní artritida genetika   imunologie   terapie   MeSH
• RNA interference MeSH
• signální transdukce účinky léků   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH
• diferenciační antigeny MeSH
• inhibitory proteinkinas MeSH
• malá interferující RNA MeSH
• monoklonální protilátky MeSH