The interleukin-17 pathway in psoriasis and psoriatic arthritis: disease pathogenesis and possibilities of treatment.

Psoriasis and psoriatic arthritis (PsA) are pathophysiological enigmas among rheumatic diseases. Substantial clinical advances have been made with new therapy targeting different components of the IL-17 and IL-23 pathways. At the same time, an increase in research on the topic has provided new insights into the potential functional effects of treatments on cell types, pathways, and tissues of interest. Here we review our knowledge of all IL-17 family members, their relationships with the IL-23 pathway, and the outcomes of relevant clinical trials in which different strategies for targeting these molecules have been tested in the treatment of moderate to severe psoriasis and PsA.

The 'head-to-head' comparison of etanercept and infliximab in treating children with juvenile idiopathic arthritis.

OBJECTIVES: Our aim was to assess long-term efficacy and tolerability of etanercept and infliximab in patients with JIA. METHODS: This was an observational, retrospective study of 41 patients treated with anti-TNF therapy. We assessed clinical remission, flare, ACR improvement, improvement of DAS28, and JADAS. Some patients with polyarticular JIA were scored according to the modified SHARP criteria. RESULTS: Twenty-four weeks after beginning of therapy 35 patients (92.1%) achieved ACR 20, 33 patients (86.8%) ACR 30, 31 patients (81.6%) ACR 50, 28 patients (73.7%) ACR 70 and 20 patients (52.6%) ACR 90. In the same period 19 patients (50%) had good DAS28 response, 12 patients (31.6%) had moderate response, and 5 patients (13.2%) did not respond to therapy. Statistically significant difference was shown in the average value of JADAS-71 before the beginning and 24 weeks after introduction of anti-TNF therapy. Eleven patients had a flare in the study period (28.9%); five on etanercept (13.1%), three on infliximab (7.9%), and three flared on both of the medications (7.9%). After 12 months, fifteen patients fulfilled criteria for clinical remission on medications. Seven of them were on infliximab and eight on etanercept. Eleven patients have fulfilled criteria for clinical remission off of medications: three were taking etanercept, seven infliximab, and one was switched from etanercept to infliximab. CONCLUSIONS: In our patient cohort, both etanercept and infliximab performed well, since we found no significant difference in the duration, response, flare, resistance or adverse effects between both drugs, however long term remissions are rare.

The potential value of blood monitoring of biologic drugs used in the treatment of rheumatoid arthritis.

The advent of biological therapies has been a major therapeutic advance in rheumatology. Many patients now enjoy improved quality of life through better disease control. The number of therapies continues to grow both within drug class (including biosimilar drugs) and via new mechanisms. For the first time, nonbiological drugs such as small-molecule inhibitors (Janus kinase inhibitors) have shown clinical equivalence. However, clinical unmet need remains with up to a third of patients commenced on a biologic therapy having minimal or no response: (a) Generally, the first biologic used secures the best response, with likelihood of remission falling thereafter with successive therapies; (b) the success of strategy trials using biological therapies can be difficult to replicate in clinical practice due to a combination of patient factors and service limitations. Accordingly, ensuring optimization of initial treatment is an important consideration before switching to alternatives. Therapeutic drug monitoring (TDM) is the measurement of serum levels of a biologic drug with the aim of improving patient care. It is usually combined with detection of any antidrug antibodies that could neutralize the effect of the therapy. This technology has the potential to be a form of 'personalized medicine' by individualizing therapy, in particular, dosing and likelihood of sustained treatment response. It requires a clear relationship between drug dose, blood concentration and therapeutic effect. This paper will outline the technology behind TDM and unpack what we can learn from our colleagues in gastroenterology, where the adoption of TDM is at a more advanced stage than in rheumatology. It will explore and set out a number of clinical scenarios where rheumatologists might find TDM helpful in day-to-day practice. Finally, an outline is given of international developments, including regulatory body appraisals and guideline development.

[Thrombophilia, preeclampsia and other pregnancy complications]. / Trombofilija, preeklampsija i ostale komplikacije trudnoce.

The aim of this paper is to present the latest developments in therapy and prophylaxis of deep vein thrombosis and other pregnancy complications in women with inherited or acquired thrombophilia and in women with mechanical heart valves. The data presented in the paper have been extracted from the Current Contents database. It is well known that the hypercoagulable state in pregnant women, caused either by the physiological changes of pregnancy or by inherited thrombophilia, increases the risk of venous thromboembolism (VTE), pulmonary embolism (PE), preeclampsia, recurrent early and late fetal loss, intrauterine growth retardation (IUGR), placental abruption, and other less probable complications of pregnancy and its outcome. In women with mechanical heart valves, the risk of systemic embolism is also seen to increase during pregnancy. According to data analyzed, positive antiphospholipid antibodies (APLA) as well as anticardiolipin antibody and lupus anticoagulant (nonspecific inhibitor) positivity, homozygosity and heterozygosity for factor V Leiden mutation and heterozygosity for the prothrombin G20210A variant, MTHFR C677T variant homozygosity and hyperhomocysteinemia are in strong association with pregnancy complications and severe pregnancy outcome. The strongest association for late fetal loss was seen in women with protein S deficiency. In order to reduce such risks, anticoagulation therapy is administered throughout pregnancy. The antithrombotic agents available for the prevention and treatment of VTE during pregnancy and pregnancy complications include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) and aspirin. Vitamin K antagonists are contraindicated in pregnancy. Low-dose aspirin may have a role in the prevention of some pregnancy complications, although its safety in early pregnancy is uncertain. LMWH and UFH are quite safe and efficacious when properly selected, dosed and monitored. The efficacy and safety of LMWH have been demonstrated in the prevention and treatment of VTE in pregnancy. LMWH in association with aspirin administered throughout pregnancy have been shown to be associated with a lower risk of complications in women with APLA syndrome. Women at a high risk of preeclampsia are recommended to use low-dose aspirin throughout pregnancy. When there is a history of preeclampsia, the administration of anticoagulation therapy is not recommended as a prophylaxis in subsequent pregnancies, as the risk appears to be already decreased as compared with previous pregnancy. LMWH has probable advantages over UFH for the incidence of side effects. In pregnant women with mechanical heart valves, anticoagulant therapy during pregnancy should include assessment of additional risk factors for thromboembolism including valve type, position, and history of thromboembolism, and decision should also be strongly influenced by the patient's preferences. If the risk of thromboembolism in patients with mechanical heart valves is considered very high, and efficacy or safety of prophylaxis with UFH or LMWH is not satisfactory (older-generation prosthesis in the mitral position or history of thromboembolism), administration of vitamin K antagonists throughout pregnancy is recommended with replacement by UFH or LMWH close to delivery. It should be considered that limited effectiveness of UFH or LMWH in patients with mechanical heart valves might be due to inadequate dosing. The necessity of anticoagulation therapy in women with inherited or acquired thrombophilia is biologically plausible; nevertheless, optimum management in such cases remains unknown.