Current Therapeutic Options for the Treatment of Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease and an exclusion diagnosis that includes all forms of arthritis that persists for more than 6 weeks under the age of 16. Although there is not yet a cure for JIA, and recent advances in the therapeutic field have created a more hopeful present and future for the patients. In the past, therapies for JIA have depended on non-steroidal medication, conventional synthetic disease-modifying antirheumatic drugs and corticosteroids. However, over the last decades, the advent of biologic therapies in JIA contributed to the preservation of functional activity, control of pain, avoidance of joint damage, and extra-articular manifestations. Furthermore, over the last years, international institutions, such as the American College of Rheumatology, have released recommendations and guidelines for rheumatologists for optimal JIA management. All the above have revolutionized the treatment of JIA with promising outcomes. To this end, the relevant literature is reviewed and discussed appropriately.

Cardiovascular risk profile in patients with spondyloarthritis.

OBJECTIVES: The spondyloarthritides (SpA) are associated with an increased cardiovascular risk. We studied cardiovascular risk factors in patients with SpA. METHODS: The following risk factors were assessed in SpA patients and healthy controls: smoking, family history of premature ischemic heart disease, obesity, serum lipids, apolipoproteins, urate and carotid intima media thickness (IMT). RESULTS: Overall 150 patients (73 with ankylosing spondylitis [AS], 71 with psoriatic arthritis [PsA] and six with other SpA types) were included. Generally SpA patients were significantly more often smokers, while PsA patients had greater values of abdominal obesity. AS patients had significantly lower levels of triglyceride, HDL, ApoB, ApoE and Lp(a) and a higher atherogenic index (total cholesterol/HDL). PsA patients had significantly lower levels of HDL, ApoAI and ApoE, an elevated atherogenic index and higher serum urate. In multivariate analysis the atherogenic index was positively associated with SpA across all patient groups independently of smoking and other lipid parameters. Carotid IMT in SpA patients (0.71 mm) was higher than controls (0.63 mm, P=0.017), although after adjusting for smoking this ceased to be significant. Treatment of patients with previously untreated disease resulted in a small but significant decline in ApoB levels at 6 months (P=0.045), which, however, was no longer evident at 12 months. CONCLUSION: Spondyloarthritis patients are at a greater cardiovascular risk owing to the higher prevalence of smoking and a higher atherogenic index. PsA patients have more abdominal fat and higher urate levels. Immunosuppressive treatment of SpA produces minor and temporary effects on the lipid profile.

Fertility in male patients with seronegative spondyloarthropathies treated with infliximab.

OBJECTIVES: The majority of patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are affected during their peak reproductive years. Tumor necrosis factor (TNF)α plays a pivotal role in the pathogenesis of both diseases. Today, anti-TNFα blockers are an essential treatment for these patients. To identify male patients who achieved pregnancy development during their management with anti-TNFα blockers (infliximab). METHODS: We reviewed the data of 65 patients with AS and 30 patients with PsA who were followed-up in our rheumatology outpatients clinic and they were on infliximab therapy between January 2001 and December 2010. RESULTS: We identified overall seven male patients with AS and three male patients with PsA who had fathered 14 healthy infants. Moreover, we recognized one man with PsA who was on infliximab and on concomitant therapy with MTX at the time of conception, whose wife had to proceed to therapeutic abortion due to congenital abnormalities of the fetus (hydrocephalia), while she was on the first trimester of pregnancy. CONCLUSIONS: We described male patients with AS and PsA who demonstrated no fertility problems while they were on infliximab treatment. The data designated in this report provide some supportive evidence for the safe use of infliximab in male patients who are affected of those inflammatory diseases during their peak reproductive years.

Sustained clinical response in psoriatic arthritis patients treated with anti-TNF agents: a 5-year open-label observational cohort study.

OBJECTIVE: To investigate the efficacy, toxicity, and drug discontinuation in patients with psoriatic arthritis treated with anti-tumor necrosis factor agents. METHODS: Sixty-five patients with active disease were included in this open-label study. They had tender or swollen joint count ≥5, Psoriatic Arthritis Severity Index (PASI) score ≥10, and erythrocyte sedimentation rate ≥28 mm Hg/1st hour and/or C-reactive protein ≥10 mg/L. All were refractory to at least 2 disease-modifying antirheumatic drugs. Thirty were treated with infliximab, 25 with etanercept, and 10 with adalimumab. Infliximab (5 mg/kg body weight) was given intravenously at weeks 0, 2, 6, and every 8 weeks thereafter; etanercept was given subcutaneously (25 mg twice a week), while adalimumab was given subcutaneously (40 mg every other week) for a period of 5 years. Data concerning anti-tumor necrosis factor efficacy tolerability, adverse events, and drug discontinuation were recorded. The percentage of patients who achieved the Psoriatic Arthritis Response Criteria (PSARC), the improvement of PASI, the improvement according to the American College of Rheumatology (ACR) criteria, and the disease activity for 28 joint indices score (DAS-28) were recorded. RESULTS: After 5 years, PSARC was 60%, PASI 70 was 66.7%, PASI 90 was 63.3%, while ACR 50 was 56.7% for the patients treated with infliximab. Moreover, PsARC was 64%, PASI 70 and PASI 90 were 68%, while ACR 50 was 56% for those treated with etanercept. Furthermore, in the adalimumab group PsARC was 56%, PASI 70 and PASI 90 were 58% and 50%, respectively, while ACR 50 was 50%. Additionally, DAS-28 scores were significantly improved. Thirteen patients treated with infliximab, 6 with etanercept, and 5 patients with adalimumab were withdrawn. At the end of treatment, the survival of infliximab was 56.7%, for etanercept 76%, and for adalimumab 50%. CONCLUSION: All drugs were effective, safe, and well-tolerated. The clinical improvement was maintained through the 5 years with satisfying infliximab and adalimumab survival and high etanercept survival.

A case report of a psoriatic arthritis patient on hemodialysis treated with tumor necrosis factor blocking agent and a literature review.

This report seeks to describe the clinical efficacy and safety of infliximab in a patient with psoriatic arthritis on hemodialysis and to review the literature on the topic. We present a patient with psoriatic arthritis on hemodialysis treated with infliximab and we review the literature. Our case includes a patient with severe psoriasis and dactylitis with chronic renal failure requiring regular hemodialysis. At presentation the patient had a psoriasis area and severity index (PASI) score of 35.1 and dactylitis affecting the right thumb. Evaluation of laboratory parameters revealed a slight increase of erythrocyte sedimentation rate (21 mm/h) and a mild normocytic anemia (Hct 36.4). The rest of the laboratory and imaging tests were within normal limits. Infliximab was initiated at the loading dose of 5 mg/kg body weight at weeks 0, 2, 6, and every 8 weeks thereafter. On retreatment at week 14 the PASI score was measured to 3.4. After the conclusion of 6 months of treatment, the reduction of PASI score was sustained reaching the point of 0.8. In addition, dactylitis, as well as laboratory parameters, showed a striking improvement. On the other hand, during the same period of time, no changes of renal functions were noted and no complications were reported and the patient continued his hemodialysis on a regular basis. Our case is in accordance with other reports supporting that infliximab treatment in patients undergoing hemodialysis can be safe, well tolerated, and effective. However, larger trials are needed to prove its use in these patients.

Maintained clinical response of infliximab treatment in ankylosing spondylitis: a 6-year long-term study.

OBJECTIVES: To investigate the efficacy, safety and drug discontinuation in patients with ankylosing spondylitis treated with infliximab, as well as the drug survival over a period of 6 years. METHODS: Forty patients with ankylosing spondylitis treated with infliximab were included in this open label study. All patients fulfilled the New York revised criteria for ankylosing spondylitis. Infliximab was given intravenously (5 mg/kg/body weight) at weeks 0, 2, 6 and every 8 weeks thereafter for a period of 6 years. Data concerning infliximab efficacy, tolerability, adverse events and drug discontinuation, were recorded. Clinical improvement according to the Bath Ankylosing Spondylitis Disease Activity Index 50% and the Ankylosing Spondylitis Assessment Study Group 20% and 40% were also recorded. RESULTS: A significant improvement in the Bath Ankylosing Spondylitis Disease Activity Index and Ankylosing Spondylitis Assessment Study Group scores was noted in the first year which sustained through the sixth year of treatment. More specifically, after the sixth year of treatment, Bath Ankylosing Spondylitis Disease Activity Index 50% was achieved by 65% of patients (26/40), Ankylosing Spondylitis Assessment Study Group 20% by 72.5% (29/40) and Ankylosing Spondylitis Assessment Study Group 40% was reached by 70% (28/40) of patients. Clinical improvement was associated with the reduction of acute phase reactants, such as C-reactive protein levels. After the first and the second year of treatment, the survival rate of infliximab reached 95%, after the third year it was 80%, while after the fourth year it was 72.5%, which was maintained throughout the fifth and sixth year of therapy. Five patients were increased the dose of infliximab and three of them had shortened the interval infusion. Overall, 11 patients were withdrawn during the observational period, three because of adverse events, two because of lack of efficacy, while six were lost from follow-up. CONCLUSION: Infliximab was effective, safe and well-tolerated in patients with ankylosing spondylitis. The clinical response was maintained for a period of 6 years, with high infliximab survival rate, reaching the percentage of 72.5%.

Fertility and reproduction in male patients with ankylosing spondylitis treated with infliximab.

OBJECTIVE: To identify male patients who were treated with infliximab and had fathered healthy newborns during their management. METHODS: We reviewed medical records of men with ankylosing spondylitis (AS) who were followed up at the Rheumatology Outpatients clinic and were treated with infliximab during the period 2001-2007. RESULTS: We identified 4 patients with AS who had fathered 6 healthy children during infliximab treatment. One patient was also treated with small doses of methotrexate. CONCLUSION: Limited data are available concerning the effects of infliximab on semen quality. Our cases provide some evidence or reassurance for male patients treated with the anti-tumor necrosis factor-alpha agent. Further prospective studies are necessary, however, to guide clinicians in decision making.