Rheumatoid Arthritis: Di Franco M

Valesini G, Di Franco M, Spinelli FR, Scrivo R. · Dipartimento di Clinica e Terapia Medica, Reumatologia, Sapienza, Università di Roma, Policlinico Umberto I, 00161, Rome, Italy. · Rheumatol Int. · Pubmed #18807254 No free full text.

Abstract: The concept of remission in rheumatology is complicated by the lack of a single gold standard measurement, spontaneous remissions and the usage of several sets of remission criteria. Feasibility is reduced by traditional clinical practice, which does not include remission criteria monitoring. The "window of opportunity" to prevent joint damage with DMARD therapy lasts only a few months. The perspective of the physician and patient differ, as the former gives importance to signs of disease activity, whereas the latter to disability and quality of life. All patients with rheumatoid arthritis are candidates for combination DMARD-based therapy, which should be instituted without delay. Remission is important to prevent joint destruction, preserve adequate quality of life and prevent disability. The introduction of biological agents has made this objective feasible, but the failure rate is still high (about 50%), on account of lack of response, contraindications and intolerance.

Valesini G, Iannuccelli C, Marocchi E, Pascoli L, Scalzi V, Di Franco M. · Cattedra e UOC Reumatologia, Università di Roma La Sapienza, Policlinico Umberto I, 00161 Roma, Italy. · Autoimmun Rev. · Pubmed #17967723 No free full text.

Abstract: Tumor necrosis factor alpha (TNFalpha) is implicated in the pathogenesis of many chronic inflammatory diseases such as rheumatoid arthritis (RA), psoriasis and psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease, ulcerative colitis and uveitis. The availability of new pharmacological agents (infliximab, etanercept, adalimumab), able to selectively block the TNFalpha, has recently offered new opportunity for the treatment of these diseases. TNFalpha antagonists are different in the mechanism of action and are all effective agents in the treatment of RA and several chronic inflammatory diseases as a large number of controlled clinical trials have shown. Among biological effects of TNFalpha antagonists, the production of autoantibodies has been emphasized. This phenomenon is not correlated with the disease background, since anti-nuclear antibodies (ANA) and anti-double stranded-DNA antibodies (anti-dsDNA) induction is observed in RA as well as in spondyloarthritis (SpA) patients. Nonetheless, recent studies had reported a significant reduction in the serum titre of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (anti-CCP) during anti-TNFalpha therapy. The TNFalpha antagonists represent a significant advance in the therapy of active RA and other chronic inflammatory diseases. However, they have distinct biological, clinical, and pharmacological properties that must be considered when selecting a drug for therapy.

Scrivo R, Di Franco M, Spadaro A, Valesini G. · Dipartimento di Clinica e Terapia Medica, Sapienza Università di Roma, Policlinico Umberto I, Roma, Italy. · Ann N Y Acad Sci. · Pubmed #17893995 No free full text.

Abstract: Rheumatoid arthritis (RA) is represents the most common chronic inflammatory joint disease and is still a major medical challenge because of unsolved issues related to the etiologic and pathogenetic questions. Intensive research has been conducted over the last years that focused on the inappropriate activation of the immune system: although T cells have long been deemed to play a central role in the origin and propagation of joint inflammation, data accumulated so far have widened this perspective recognizing the contribution of other cells, as well as the major histocompatibility complex class II proteins and a composite set of costimulatory signals responsible for the production of proinflammatory cytokines and other soluble mediators implicated in tissue destruction typical of the disease. This paper will provide an insight into the immune system in RA, dissecting cellular and humoral aspects both in serum and in synovium of patients.

Giacomelli R, Cipriani P, Matucci Cerinic M, Fulminis A, Barattelli G, Pingiotti E, Di Franco M, Trotta A, Perricone R, Zazzeroni F, Alesse E, Tonietti G. · Clinica Medica, University of L'Aquila, Italy. · Clin Exp Rheumatol. · Pubmed #12102473 No free full text.

Abstract: OBJECTIVE: To evaluate the ability of two different combination therapies with prednisone (PDN), methotrexate (MTX) and cyclosporine (CSA) to modulate both TNFalpha transcription and production in early rheumatoid arthritis (RA). METHODS: 24 patients with early RA received a step-down bridge therapy with MTX and PDN (group A). Twelve patients out of the 24 randomly received also CSA (group B). Blood samples and peripheral blood mononuclear cells (PBMC) were collected at different times. TNFalpha levels were measured both in sera and in PBMC supernatants. TNFalpha mRNA was assessed by use of RT-PCR. RESULTS: 10 patients in group A and 9 in group B improved. At baseline, RA patients serum TNFalpha levels were increased compared to controls (p < 0.001) and did not correlate with clinical and serological parameters. These levels decreased within the first month of therapy in both groups, the lower levels being observed in the sera of CSA treated patients. After 30 days of therapy, TNFalpha levels in group B supernatants were significantly lower than those observed in group A, both after 24 and 48 hours of PHA stimulation (p < 0.03 and p < 0.05 respectively). TNFalpha mRNA levels never differed between patients and controls, independently of both the clinical picture and the assigned therapy. CONCLUSION: The addition of CSA to a treatment regimen of PDN + MTX lowers TNFalpha production in vitro without decreasing TNFalpha mRNA expression. This effect could help to induce early immunosoppressive and therapeutic effects during RA.

Conti F, Scrivo R, Spinelli FR, Truglia S, Magrini L, Di Franco M, Ceccarelli F, Valesini G. · , Dipartimento di Clinica e Terapia Medica, Sezione di Reumatologia, Sapienza Università di Roma, Policlinico Umberto I, Rome, Italy. · Clin Exp Rheumatol. · Pubmed #19604456 No free full text.

This publication has no abstract.

Sarzi-Puttini P, Atzeni F, Di Franco M, Lama N, Batticciotto A, Iannuccelli C, Dell'Acqua D, de Portu S, Riccieri V, Carrabba M, Buskila D, Doria A, Valesini G. · Rheumatology Unit, L. Sacco University Hospital, Milan, Italy. · Autoimmunity. · Pubmed #18176867 No free full text.

Abstract: OBJECTIVE: To investigate the prevalence of antipolymer antibody (APA) in patients with fibromyalgia (FM) and to examine its association with FM severity symptoms. METHODS: The study population consisted of 79 FM patients and 75 controls: 32 with psoriatic arthritis and 43 with rheumatoid arthritis APA levels were indirectly assayed using a commercial ELISA kit from Corgenix (Westmister, Colorado, USA). Optical density (OD) values were recorded on duplicates of each of the reference and patient samples. Among clinical variables we investigated pain, measured according to visual analog scales (VAS: 0-100), fatigue, stiffness, anxiety, depression, all measured by VAS (0-100), and health status measured by Fibromyalgia Impact Questionnaire (FIQ). RESULTS: Sixteen of the 79 FM patients (20.3%) and 12/78 controls (15.4%) were positive for APAs (P = 0.536). Following ROC analysis, area under curve (AUC) was 0.49 (95% CI: 0.40, 0.58). Focusing on FM patients, we observed a correlation between APA titre and pain (tau: - 0.221; P = 0.020) and fatigue (tau: - 0.205; P = 0.032) at univariate analysis. Binomial regression analysis, controlling for clinical and demographic variables, showed that pain (PPR: 0.923; P = 0.007) and fatigue (PPR: 0.948; P = 0.024) were significantly associated with APA test sensitivity. CONCLUSIONS: APA test exhibited a low sensitivity in FM patients and it did not distinguish this group of patients from the controls enrolled in this study. Interestingly, positive APA test prevalence increased with less severe pain or fatigue.

Pasqui F, Mastrodonato L, Ceccarelli F, Scrivo R, Magrini L, Riccieri V, Di Franco M, Gentili M, Valesini G, Spadaro A. · Cattedra di Reumatologia, Dip. di Clinica e Terapia Medica Applicata, Azienda Policlinico Umberto I, Università di Roma "La Sapienza", Roma, Italia. · Reumatismo. · Pubmed #17013435 links to  free full text

Abstract: OBJECTIVE: To assess the effect of occupational therapy (OT) in rheumatoid arthritis (RA) patients treated with anti-TNF-alpha drugs in a short-term open controlled prospective study. METHODS: 31 RA subjects [(M/F=5/26; mean age= 56 (range=28-73) years; mean disease duration= 165 (range =15-432) months], treated with anti- TNF-alpha drugs, were allocated to OT (n=15) or control (n=16) group. We evaluated at entry and 12 weeks the following outcome parameters including Health Assessment Questionnaire (HAQ), Short-Form Health Survey (SF-36), Global Health (GH), Ritchie index, number of swollen or tender joints, pain, patient and physician disease activity, Disease Activity Score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein CRP) and the correct adherence to items regarding activity daily living (ADL). RESULTS: At baseline, OT and control group had similar demographic and clinical features. After 12 weeks, the changes from baseline of main outcome parameters were not significantly different between the two groups. After 12 weeks, in 7 out of 11 items regarding ADL, the percentage of patients showing a correct adherence was significantly increased in OT group only. Moreover at the end of the study, the OT group showed a correct adherence to 8 out of 11 ADL items in an higher percentage of patients respect to the control group. CONCLUSION: Our study sustains that OT improves self-management but not main parameters of disease activity or functional capacity. Nevertheless educational intervention should be considered as a useful tool in conjunction with pharmacological treatment.

Scrivo R, Spadaro A, Riccieri V, Bombardieri M, Di Franco M, Celestino D, Valesini G. · Cattedra di Reumatologia, Dipartimento di Clinica e Terapia Medica Applicata, Azienda Policlinico Umberto I, Università di Roma "La Sapienza", Viale del Policlinico, 155 - 00161 Roma, Italia. · Reumatismo. · Pubmed #16380751 links to  free full text

Abstract: OBJECTIVE: P-selectin is an adhesion molecule expressed by activated endothelial cells and platelets favouring the leukocyte adherence to microvascular endothelium. A soluble form of this molecule has been described, whose serum levels were found to be elevated and correlate with disease activity in rheumatoid arthritis (RA) patients. Aim of this study was to determine soluble P-selectin levels in synovial fluid (SF) and serum from patients with psoriatic arthritis (PsA), where it has never been investigated, to define its involvement in PsA synovial damage. METHODS: we analysed, by ELISA, soluble P-selectin serum and SF levels in 100 patients presenting a knee joint effusion: 38 of them presented PsA, 40 RA and 22 osteoarthritis (OA). We examined the main clinical and laboratory parameters of these patients. Soluble P-selectin serum levels were also detected in 15 healthy subjects. RESULTS: soluble P-selectin SF levels were significantly higher in PsA and RA patients respect to OA subjects. Soluble P-selectin SF levels were lower than those found in serum and the SF/serum ratio was higher in PsA and RA patients respect to OA. Soluble P-selectin serum levels were not significantly different among patients and controls. No correlation was found between SF and serum levels of soluble P-selectin and the main clinical parameters. CONCLUSIONS: our study of soluble P-selectin in PsA reveals a prominent local role of this molecule, with no differences respect to RA. Histological findings may be of help in understanding the role of this adhesion molecule in PsA.

Di Franco M, Paradiso M, Mammarella A, Paoletti V, Labbadia G, Coppotelli L, Taccari E, Musca A. · Rheumatology Unit, University "La Sapienza". · Ann Rheum Dis. · Pubmed #10700433 links to  free full text

Abstract: OBJECTIVE: The aim of this study was to evaluate left ventricular filling in patients with rheumatoid arthritis (RA), analysing transmitral flow and pulmonary venous flow, with special regard to age and disease duration. METHODS: 32 patients affected by RA according to ARA criteria were selected, without evidence of cardiac disease, and compared with matched control subjects. All patients and the control group were submitted to M-mode, two dimensional, Doppler and colour Doppler (continuous and pulsed wave) echocardiography. The following diastolic parameters were evaluated: transmitralic flow (E/A ratio), pulmonary venous flow (S/D ratio), a-Pw, IVRT and DT. RESULTS: In RA patients left ventricular filling abnormalities were found characterised by a reduced E/A ratio (mean (SD) 1.16 (0.31) v. controls 1.37 (0.32); p = 0.02) and an increased S/D ratio (1.43 (0.40) v. controls 1.22 (0.29); p = 0.017). In the group of patients a relation was found between E/A ratio and disease duration (r= 0.40, p = 0.01 Spearman rank correlation). CONCLUSIONS: At present, it is concluded that RA patients, in absence of clinical evidence of heart disease, show diastolic dysfunction characterised by impaired E/A and S/D ratio. The relation between transmitral flow alteration and disease duration suggests a sub-clinical myocardial involvement.

Di Franco M, Spadaro A, Mauceri MT, Cortese A, Guerrisi R, Ciocci A. · Department of Medical Therapy, La Sapienza University, Roma, Italy. · Rev Rhum Engl Ed. · Pubmed #10380256 No free full text.

Abstract: OBJECTIVE: To evaluate the relationship between rheumatoid factor isotypes and articular damage detected by magnetic resonance imaging and plain radiography in early rheumatoid arthritis. METHODS: 20 consecutive patients with early active rheumatoid arthritis underwent determinations of serum IgM, IgA, and IgG rheumatoid factors by enzyme-linked immunosorbent assay (ELISA). Plain radiographs of the hands and wrists were obtained, and the wrist, metacarpophalangeal joints, and proximal interphalangeal (PIP) joints on the more severely affected side were investigated by magnetic resonance imaging before and after gadolinium-DTPA injection. RESULTS: IgM, IgA, and IgG rheumatoid factors were found in 13 (65%), 13 (65%), and 15 (75%) of patients, respectively. Sera from five patients (25%) contained no detectable rheumatoid factor isotypes. Correlations were found among the levels of the three rheumatoid factor isotypes. Levels of IgA, IgG, and IgM rheumatoid factor were significantly higher in patients with than without erosions on magnetic resonance imaging scans. No such difference was found when patients with and without erosions on plain radiographs were compared. Magnetic resonance imaging detected soft tissue lesions more frequently than plain radiography. Magnetic resonance imaging was also more likely than plain radiography to show bone erosions and bone cysts, but this difference was not statistically significant. CONCLUSIONS: Quantitative rheumatoid factor isotype assays and magnetic resonance imaging evaluation of erosions of the hand and wrist may be useful for investigating patients with early rheumatoid arthritis.