Evaluation of Th9 lymphocytes in peripheral blood of rheumatoid arthritis patients and correlation with anti-tumor necrosis factor therapy: results from an in vitro pivotal study.

The aim of this study was to determine the prevalence of T helper 9 (Th9) lymphocytes in rheumatoid arthritis (RA) patients and to identify a possible association between the percentage of Th9 and the discontinuation of a biological treatment with an anti-tumor necrosis factor (TNF) (infliximab). We collected peripheral blood mononuclear cells (PBMCs) from 55 consecutive RA outpatients and 10 healthy controls. Among RA patients, 15 were not receiving any immunosuppressive drug, 20 were successfully treated with infliximab and 20 discontinued infliximab because of adverse events or inefficacy and were treated with other biological agents. PBMCs were cultured with/without infliximab 50 mg/L for 18 h, and the percentage of Th9 cells was assessed by means of flow cytometry. Th9 lymphocytes were identified as interferon gamma, interleukin (IL)4-, IL17-, IL9-secreting cluster of differentiation 4 (CD4)+ T cells. Cytometric analysis revealed no significant decrease in the percentage of Th9 cells after infliximab exposure in any of the groups, although it was lower in healthy controls than RA patients either before and after the infliximab stimulation assay. Th9 cells are IL-9-secreting T helper lymphocytes whose role in RA is still poorly known. IL-9 levels are increased in RA patients, in whom this cytokine plays a crucial role. Th9 cells are the major producers of IL-9, and their prevalence is higher in RA patients than in healthy subjects; however our experiment in vitro does not demonstrate an association between Th9 lymphocytes and the response to infliximab. Further studies are required to evaluate the real involvement of Th9 population in the immunogenicity of anti-TNF agents.

Oral type II collagen in the treatment of rheumatoid arthritis. A six-month double blind placebo-controlled study.

OBJECTIVE: To evaluate the efficacy of oral chicken type II collagen (CII) in the treatment of rheumatoid arthritis (RA). METHODS: Sixty patients with clinically active RA of long duration (mean 7.2 +/- 5.5 years) were treated for 6 months with oral chicken CII at 0.25 mg/day (n = 31) or with placebo (n = 29) in a double-blind randomized study. RESULTS: The response rate to treatment of the collagen-treated group, based on the ACR 20% criteria, was higher than that of the control group but this difference was not statistically significant at any time. Intention-to-treat (ITT) analysis did not show statistically significant improvement in any of the several secondary outcome measures over the 6 months of the study in the collagen-treated patients in comparison with the placebo-treated group. However, in 2 collagen-treated patients we observed a clinical remission according to the criteria of the American Rheumatism Association. CONCLUSION: Our study seems to show that the oral treatment of RA patients with chicken CII is ineffective and results in only small and inconsistent benefits. Furthermore, our results raise the possibility that in a sub-group of patients oral collagen administration, usually considered devoid of harmful effects, may actually induce disease flares.

Multiple intra-articular treatment of rheumatoid arthritis: a randomized prospective study comparing rifamycin SV with pefloxacin.

In a randomized, prospective study the efficacy and tolerability of extensive multiple intra-articular administrations of two antibiotics, rifamycin SV and pefloxacin, were evaluated in 40 patients with classical or definite rheumatoid arthritis. Total weekly doses of 525 mg rifamycin or 560 mg pefloxacin were given for 10 weeks, and 12 months after treatment all clinical indices, erythrocyte sedimentation rate and C-reactive protein improved significantly in the rifamycin group. Some of the treatment indices (morning stiffness, severity of pain by visual analogue scale, grip strength and Ritchie's index) were already improved when the treatment ended, whereas others (erythrocyte sedimentation rate, C-reactive protein, number of painful and swollen joints) improved progressively during the follow-up. In the pefloxacin treatment group all indices except C-reactive protein and severity of pain determined using a visual analogue scale were significantly improved 12 months after treatment. Comparison of the two treatments showed a significant difference in erythrocyte sedimentation rate (P less than 0.047), Ritchie's index (P less than 0.036) and C-reactive protein (P less than 0.028) in favour of rifamycin.

Prevention of appearance of radiological lesions in early rheumatoid arthritis: a randomized, single-blind study comparing intra-articular rifamycin with auranofin.

In a prospective, randomized, single-blind study of 116 patients with early rheumatoid arthritis (mean disease duration 7 months), therapeutic activity of intra-articular rifamycin SV (525 mg/week) infiltration into each peripheral joint over 10 weeks was compared with that of 3 mg auranofin given orally twice daily. The incidence of side-effects was lower in rifamycin-treated patients. At the end of follow-up, the clinical variables and erythrocyte sedimentation rate showed a significant and persistent improvement both in 16 patients who continued the auranofin treatment regularly and in 55 treated with rifamycin who had completed the therapeutic cycle 62.5 months before; the latex test decreased only in the rifamycin group. In patients treated with auranofin or who changed to other commonly used antirheumatic agents, 57% of those with an initially negative radiological picture developed new radiological lesions in at least one of the small joints compared with 9% in the rifamycin group. Although the number of patients treated with rifamycin was small and the follow-up relatively short, the results of the study indicated that treatment with intra-articular rifamycin SV may prevent the appearance of radiological lesions in patients with early rheumatoid arthritis and normal radiographs initially.