Terapia biológica em artrite reumatoide: novas perspectivas no controle e remissão / Biological therapy in rheumatoide arthritis: new perspectives in control and remission

O tratamento das doenças autoimunes sofreu grande avanço nos últimos anos. A artrite reumatoide, de etiologia desconhecida, porém com uma desregulação do sistema imunológico relacionada à sua eclosão e evolução, é hoje passível de tratamento, visando à remissão tanto clínica quanto das lesões estruturais. Além dos anti-inflamatórios e analgésicos utilizados para alívio dos sintomas, várias outras drogas, rotuladas de modificadoras do curso da doença (DMCDs), que visam controlar este distúrbio imunológico expresso pela atividade de diversos mediadores inflamatórios, estão contribuindo para a melhoria da qualidade de vida e do prognóstico dos pacientes.

Autoimmune diseases, as rheumatoid arthritis (RA) had a strong development in their treatment last years. Over the past years, the knowledge about the pathophysiological mechanism of RA has advanced dramatically, with the development of new classes of drugs and the implementation of different strategies of treatment and follow-up. Beside this new drugs, the associated use of the anti-inflammatory drugs, corticoids, sintetic or traditionals disease-modifying antirheumatic drugs allow control or suppress the disease activity giving a better quality of life and prognosis to the patients.

Effect of age at disease onset in the clinical profile of spondyloarthritis: a study of 1424 Brazilian patients.

OBJECTIVES: To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients. METHODS: A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 ± 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 151 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%). RESULTS: Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low back pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups. CONCLUSIONS: There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset ≤ 40 years and another favouring the peripheral manifestations in those with later disease onset.

Double-blind crossover study of acarbose in type 1 diabetic patients.

The addition of acarbose to insulin treatment was evaluated in 14 Type 1 (insulin-dependent) diabetic patients assessed conventionally (blood glucose profile and HbA1c measurement) and with an artificial B-cell. Their metabolic control was poor, fasting blood glucose 10.7 +/- 0.3 (+/- SE) mmol l-1, mean daily blood glucose 9.7 +/- 0.3 mmol l-1, and HbA1c 9.6 +/- 0.2% (normal range 5.0-6.1%). They were of normal body weight (body mass index 22.5 +/- 0.3 kg m-2), and were C-peptide deficient (fasting 0.08 +/- 0.02 nmol l-1). In addition to their usual insulin therapy (46.9 +/- 3.5 U day-1 in three pre-meal injections), they received 100 mg acarbose or placebo three times a day for 6 weeks in a randomized double-blind crossover design. On the last day of either acarbose or placebo treatment, the usual insulin therapy was discontinued and an artificial B-cell was used for insulin delivery, programmed for euglycaemia. Placebo or acarbose was continued before meals. Acarbose reduced mean daily blood glucose concentrations (8.5 +/- 0.3 vs 9.7 +/- 0.3 mmol l-1, p = 0.002) and HbA1c levels (8.3 +/- 0.1 vs 9.6 +/- 0.2%, p less than 0.001). A significant reduction in insulin requirement after meals was found with the artificial B-cell, 25.1 +/- 2.5 (first treatment acarbose) and 24.1 +/- 2.9 U (first treatment placebo) with acarbose and 40.0 +/- 2.5 and 35.6 +/- 2.9 U with placebo (p less than 0.001). These results suggest that acarbose could usefully be administered to Type 1 diabetic patients to ameliorate glucose control and reduce insulin requirement.

The effect of ciprofloxacin on oral contraceptive steroid treatments.

The effect of ciprofloxacin, a new broad-spectrum quinolone derivative, on concomitant oral contraceptive steroids has been studied in a double-blind cross-over placebo-controlled randomized trial. Ten healthy women using long-term oral contraceptive steroids received either ciprofloxacin 500 mg BID or placebo during two consecutive cycles. Therapy was continued for seven days from the first day of contraceptive treatment. FSH, LH and oestradiol blood levels were repeatedly determined to monitor contraceptive steroid efficacy. A seven-day treatment with ciprofloxacin did not affect steroid treatment outcome and appears to be safe in women using this contraceptive method.

PIP: In Italy, health care personnel at the General Hospital in Busto Arsizio randomly assigned 10 healthy women, 22-33 years old, using combined oral contraceptives (OCs) over a long time to either the group receiving 500 mg oral ciprofloxacin twice a day for 7 days for 2 consecutive cycles or to the placebo group. They monitored the women daily and took blood samples on days 7, 9, 14, and 16 of the 2 consecutive cycles. Researchers wanted to determine the interaction between OCs and ciprofloxacin. The volunteers had not taken any drug, other than OCs, in the month before the study. The various OCs consisted of .02-.04 mg ethinyl estradiol and .05-15 mg levonorgestrel, .15 mg desogestrel, or .075 gestodene. None of the women experienced breakthrough bleeding. Ciprofloxacin did not change serum levels of luteinizing hormone, follicle-stimulating hormone, or estradiol (p .05). In fact, the levels for both the ciprofloxacin group and the placebo group were below those levels which signal ovulation. The researchers could not determine the effect of ciprofloxacin on entero-hepatic recirculation of estradiol. These results suggested that ciprofloxacin does not reduce the contraceptive effect of OCs and, therefore, can be safely used to treat infections in women using OCs.

[1% bifonazole lotion in the therapy of otomycosis]. / Bifonazolo lozione 1% nella terapia delle otomicosi.

Twenty-five patients suffering from otomycosis were treated once daily with bifonazole lotion 1% for a period of 4-15 days (means +/- DS 9.5 +/- 2.6 days). Two days before the end of the treatment complete resolution of the clinical picture in 23/23 patients was observed. Direct mycological and cultural examinations undertaken during the same control visit showed complete eradication of the responsible fungi in all 23 patients. Two-four weeks after the end of therapy a further control visit was carried out, during which 2/21 cases with clinical and mycological relapses were seen; both patients had chronic otitis. Tolerability of bifonazole was satisfactory in all cases but one, who interrupted treatment because of pain and local hyperemia where the lotion had been applied. In some patients suffering from chronic otitis application of the lotion caused slight and short-lasting pain and burning of the ear.

[Ciprofloxacin in urinary infections: analysis of the Italian data pool]. / Ciprofloxacin nelle infezioni urinarie: analisi del data-pool italiano.

Efficacy and safety of oral ciprofloxacin (500-1000 mg/die) were evaluated in 231 patients with bacteriologically documented infections of the urinary tract. The clinical resolution rate was 89.6% with eradication of the aetiological organism in 90.1% of cases. Superinfection, both bacterial or fungal, as well as side-effects were minimal. It is concluded that ciprofloxacin represents an effective and safe therapy in urinary tract infections.

Effects of orally administered activated charcoal on ciprofloxacin pharmacokinetics in healthy volunteers.

Ciprofloxacin is a broad-spectrum antibiotic orally active against both gram-positive and gram-negative bacteria. Recent literature indicates that orally administered activated charcoal can alter the bioavailability of many drugs and in vitro studies have demonstrated an interaction with ciprofloxacin. To evaluate in vivo the effects of activated charcoal on ciprofloxacin pharmacokinetics, six healthy volunteers received, according to a cross-over design, either ciprofloxacin 500 mg alone or concomitantly 1 g activated charcoal. The coadministration of the latter drug did not influence any of the considered pharmacokinetic parameters. Activated charcoal at a clinically effective dose, therapeutically used in gaseousness, does not alter ciprofloxacin pharmacokinetics.

Ciprofloxacin in elderly patients with underlying chronic diseases.

Age is not as important in predisposing to infections as are the associated problems peculiar to certain age groups. Factors such as the advanced age of the patients combined with the presence of chronic disease reduce their resistance to infection. This study comprises 212 elderly patients (aged 65-98 years) who were treated with 500-1000 mg/day ciprofloxacin for 1-18 days. Despite the high incidence of associated chronic diseases, microbiology showed that infections were eradicated in 88.5%. Clinical resolution occurred in 75.5% of patients and clinical failure occurred in 6.1%. Treatment was well tolerated, with clinical side-effects reported in only seven patients. Ciprofloxacin may be considered an effective and safe antimicrobial agent for the treatment of infections in the elderly.

Treatment of infections in non-neutropenic patients with cancer, AIDS, or renal transplant using ciprofloxacin.

Infective complications not only remain the major factor in preventing a large proportion of cancer patients from achieving a complete remission, but also greatly influence the outcome of immunosuppressed transplant recipients and are a prominent problem in subjects affected by AIDS. We report the results of 73 patients, 54 males and 19 females with a mean age of 61.4 +/- 15.1 years affected by solid cancer (64 pts), AIDS (6 pts) or with kidney transplant (3 pts), treated with ciprofloxacin 250 mg bid (21 pts) or 500 mg bid (52 pts) for respiratory tract infections (41 cases), urinary tract infections (22), septicemia (5) or other infections (5). The mean course of therapy was 9.6 +/- 5.7 days and led to a complete resolution of symptoms in 66 (90.4%) patients, improvement in 6 (8.2%), while the clinical picture was unaffected in 1 (1.4%). Candida superinfection occurred in one case and only four patients experienced side effects. Ciprofloxacin results to be an effective antibacterial agent in a high risk population.

In vitro influence of charcoal on ciprofloxacin activity.

The effect of charcoal-containing media on ciprofloxacin (BAY o 9867) has been evaluated. The minimal inhibitory concentrations of ciprofloxacin are increased by the presence of charcoal, thus a correction factor has to be calculated to know the real efficacy of the drug, especially in life-threatening infections such as pneumonia due to Legionella spp.

Efficacy and safety of ciprofloxacin in the treatment of UTIs and RTIs in patients affected by liver diseases.

The clinical efficacy and the safety of ciprofloxacin was studied in 92 patients (aged 26 to 83 years; mean 57.5 years) affected by urinary tract infections (UTI) and respiratory tract infections (RTI) suffering also with various liver diseases. Ciprofloxacin was given orally at different dose regimens: 500 mg b.i.d. (22 cases), 250 mg b.i.d. (20 cases), 500 mg s.i.d. (20 cases) for the treatment of UTIs; 500 mg b.i.d. (ten cases) and 250 mg b.i.d. (20 cases) for the treatment of RTIs. The doses were not correlated to the severity of the infections. Patients were treated for five to 15 days. All the bacteria isolated from sputum or urine before treatment were sensitive to ciprofloxacin (MIC range less than or equal to 0.015 mg/l to 8 mg/l). The clinical and bacteriological responses were favourable in a high percentage of patients both for RTIs and UTIs, irrespective of the dose. Side effects were infrequent (7%) and mild (nausea, gastralgia, oral candidosis), never requiring the interruption of the treatment. No change in the blood chemistry tests was observed at any dose.

Results of clinical trials with ciprofloxacin in Italy.

The Authors report about the results of 23 clinical trials carried out in Italy with oral formulations of BAY o 9867 (ciprofloxacin) in the treatment of infections in various sites of the body. Altogether 644 patients were evaluated for therapeutic efficacy; positive clinical results were obtained in 95 to 100% of the treated patients, according to the site of the infection. The bacteriological examinations performed on 575 cases show eradication in 89.22%, eradication with relapse or reinfection in 2.26%, and persistence in 6.09%. Adverse reactions were observed in 38 out of 646 patients (5.89%); none of them, however, were severe or irreversible.