Rheumatoid Arthritis: Laganà B

Laganà B, Vinciguerra M, D'Amelio R. · Azienda Ospedaliera S. Andrea, University of Rome Sapienza II, Department of Immunology, Allergology and Rheumatology, Rome, Italy. · Clin Drug Investig. · Pubmed #19243211 No free full text.

Abstract: Rheumatoid arthritis (RA), characterized by progressive joint destruction, deformity, disability and impaired quality of life (QOL), is a prevalent autoimmune disease affecting 1% of adults in the US. The goal of therapy in patients with RA is to arrest the disease and to achieve remission by preventing or controlling joint damage, preventing loss of function and providing pain relief, thereby improving QOL. Non-biological disease-modifying antirheumatic drugs (DMARDs) have been the mainstay of early intervention in RA, of which methotrexate has been used most frequently. However, in the long term, patients treated with non-biological DMARDs (including methotrexate) may experience joint deterioration and subclinical inflammation even after clinical remission, emphasizing the need for alternative therapies. Several biological therapies, such as anti-tumour necrosis factor (TNF)-alpha agents, have been developed in the last decade and may be used either as monotherapy or in combination with non-biological DMARDs. Although anti-TNFalpha therapy is generally associated with an improvement in symptoms of RA, some patients may experience inadequate response to or may not tolerate these agents. The new biological agent abatacept, a recombinant protein consisting of the extracellular region of the human cytotoxic T-lymphocyte-associated antigen (CTLA)-4 receptor fused to the constant fragment (Fc) region of IgG1, binds to the CD80/CD86 molecules on antigen-presenting cells and modulates T-cell activation. Clinical trials have shown that abatacept is effective in reducing disease activity, structural joint damage and improving QOL in patients with RA who had inadequate response to prior methotrexate or anti-TNFalpha therapy. Pooled analysis of these trials showed that abatacept was also generally well tolerated in these patients. Thus, abatacept therapy may be an option for the treatment of RA in patients who have had an inadequate response to prior DMARD therapy.

Laganà B, Picchianti Diamanti A, Ferlito C, Germano V, Migliore A, Cremona A, Argento G, David V, Salemi S, D'Amelio R. · Department of Medical Sciences, Sapienza University of Rome, 2nd School of Medicine, S. Andrea University Hospital, Rome, Italy. · Int J Immunopathol Pharmacol. · Pubmed #19505397 No free full text.

Abstract: The aim of this preliminary study is to evaluate clinical and imaging response in twenty patients with early Rheumatoid Arthritits (eRA) treated with Etanercept (Etn) + Methotrexate (Mtx) and to investigate whether clinical and MRI remission may be maintained after biological therapy interruption. Assessment included: radiography, Visser score and anti-CCP antibodies at baseline; disease activity score in 44 joints (DAS44), rheumatoid factor (RF), Magnetic Resonance Imaging (MRI) of hands and wrists at baseline (T0), 12 (T1), and 24 months (T2). MRI was scored for synovitis, bone oedema and erosions (OMERACT study); patients who reached clinical and imaging remission at T1 were considered eligible for interrupting Etn. At T1 8/20 (40 percent) patients showed a total remission, DAS44 from 5 (T0) to 1.4 (T1); p<0.02, whereas the other 12/20 (60 percent) showed an improvement, without complete remission, DAS44 from 4.8 (T0) to 2.8 (T1); p<0.05. Etn was therefore interrupted in the first group of patients (group A), whereas it was continued in the other group (group B). At T2, group A maintained clinical remission and group B showed further not significant DAS44 reduction from T1. At T1, a significant reduction in synovitis, bone oedema and total score (p<0.01) was observed both in group A and in group B. At T2, group A showed an increase in all the MRI scores that was significant for the synovitis and total score, whereas group B exhibited a further not significant reduction. This preliminary study reports an excellent clinical and imaging response in eRA patients treated with Etn with total remission in 40 percent of them after a 1-year therapy period. However, it indicates that joint damage may progress, despite a sustained clinical remission, after Etn suspension.

del Porto F, Aloe L, Laganà B, Triaca V, Nofroni I, D'Amelio R. · Cattedra e U.O.C di Allergologia, Immunologia Clinica e Reumatologia, II Facoltà di Medicina e. Chirurgia, Università La Sapienza, Ospedale Sant'Andrea, Via di Grottarossa 1035-1039, 00189 Roma, Italy. · Ann N Y Acad Sci. · Pubmed #16855171 No free full text.

Abstract: Twenty consecutive rheumatoid arthritis (RA) patients (mean age 50.4 +/- 10.5 years; 17 females; mean disease duration 5.78 +/- 3.75 years) enrolled for tumor necrosis factor-alpha (TNF-alpha) blockers therapy (10 infliximab and 10 etanercept) were selected. Before starting therapy, 3 and 6 months thereafter all patients were evaluated for disease activity score (DAS), erythrocyte sedimentation rate (ESR), serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF). After 3 and 6 months a significant reduction in DAS, ESR, CRP, and IL-6 was observed, whereas no significant differences of NGF and BDNF serum levels were found. These preliminary results confirm that TNF-alpha blockers significantly improve disease activity and inflammation in RA; nevertheless further studies are needed to explain the mechanisms regulating NGF and BDNF release in RA patients treated with TNF-alpha blockers.

Migliore A, Bizzi E, Laganà B, Altomonte L, Zaccari G, Granata M, Canzoni M, Marasini B, Massarotti M, Massafra U, Ranieri M, Pilla R, Martin LS, Pezza M, Vacca F, Galluccio A. · UOS of Rheumatology, S. Pietro FBF Hospital, Research Center S. Pietro, Rome, Italy. · Int J Immunopathol Pharmacol. · Pubmed #19505394 No free full text.

Abstract: Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis are commonly thought of as inflammatory diseases that affect younger individuals. Although the initial presentation of these diseases is common in a patients twenties or thirties, they usually persist for the duration of the patients life. In addition, up to one-third of patients with RA have disease onset after 60 years of age. Anti-TNF-a therapies now have well-recognized safety profiles that have been demonstrated in the usual clinical trial populations for these diseases, but such populations under-represent patients > or =65 years of age. This retrospective study aims to determine the safety profiles for etanercept, infliximab and adalimumab in patients of 65 years or more, undergoing anti-TNF treatment for an active inflammatory disease such as rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis, or skin disease like psoriasis. Our data show that admitting elderly patients into anti-TNF therapeutic regimens is a safe option and that it grants these patients access to the best current therapeutic option, possibly leading to better disease outcome. Quality of life in elderly patients affected by arthritis or psoriasis, often reduced by comorbidities, is as important as quality of life in younger patients. Applying the recommended screening before using biological treatment helps to reduce adverse events related to the therapy, and the application of the same screening in elderly patients seems to lead to comparable results.

Luzi G, Laganà B, Salemi S, Di Rosa R. · II School of Medicine, Sapienza University of Rome, A.O. Sant'Andrea, Rome, Italy. · Clin Ter. · Pubmed #19452100 No free full text.

Abstract: OBJECTIVE: To evaluate the incidence of infections in subjects with rheumatoid arthritis (RA), treated with an anti-TNFalpha blocker during one year follow-up. The aim of the study was focused to evaluate the number of infectious episodes in two groups of patients treated with etanercept (ETN) plus methotrexate (MTX) or ETN plus MTX and glucocorticoid drugs (GCs/prednisone) for a 12 months period. MATERIALS AND METHODS: Sixty-nine out of 122 RA patients treated with an anti-TNFalpha drug (ETN) were included in an outpatient control system within the Immunology Department Sapienza-University of Rome-II; School of Medicine. RA patients were studied during the first year after ETN introduction. Particularly 20 RA patients have been included in a subgroup. For these 20 patients infections have been monitored for 2 years: 12 months before and 12 months after ETN treatment starting. RESULTS: According to drugs administration protocols, after a careful screening aiming to exclude latent tuberculosis infection, 20 patients have been treated with ETN (10 of them received treatment in association to MTX, while 10 were given a GCs therapy plus MTX). During the one-year ETN treatment period, 7 infections have been described in the group treated with ETN, MTX and GCs and no infection in the group treated with ETN and MTX. After analysing the infection number in the two groups of patients, in the year preceding biological treatment no significant change arose. CONCLUSIONS: The risk of infections in subjects treated with the biological drug ETN is well known. Our data show that after one year therapy the [ETN+MTX+GCs] group is marked by a greater frequency of infectious episodes compared to the subjects treated with ETN plus MTX. Therefore, the additional infectious risk appears to be related to steroid therapy itself, though infections were not serious.

Del Porto F, Laganà B, Lai S, Nofroni I, Tinti F, Vitale M, Podestà E, Mitterhofer AP, D'Amelio R. · Università La Sapienza, II Facoltà di Medicina e Chirurgia, Azienda Ospedaliera Sant'Andrea, Dipartimento di Scienze Mediche, Via di Grottarossa, Rome, Italy. · Rheumatology (Oxford). · Pubmed #17449484 links to  free full text

Abstract: OBJECTIVES: To determine whether tumour necrosis factor (TNF)-alpha blockers may reduce carotid intima-media thickness (cIMT) in patients with active rheumatoid arthritis (RA) steadily responsive to such therapy. METHODS: From 287 consecutive RA patients attending our out-patient clinic and diagnosed on the basis of the American College of Rheumatology (ACR) criteria, 49 without traditional cardiovascular risk factors and meeting the requirements for TNF-alpha blockers therapy were selected. Among them, 39 actually started TNF-alpha blockers, but only 30, who reached at least a response on the ACR 20% improvement criteria at 14 weeks, maintained during the whole year of treatment, were finally considered (group A). The remaining 10/49, homogeneous for age, sex, traditional cardiovascular risk factors, socioeconomic status, disease activity and duration, who did not consent to TNF-alpha-blocker administration, were used as controls (group B). Disease activity score in 44 joints (DAS44), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were evaluated before starting the study, and 3, 6, 12 months thereafter; cIMT was measured by ultrasound before and 12 months thereafter only. RESULTS: Patients in group A showed a very significant cIMT reduction (P < 0.0001 and P < 0.0001, on the right and left side, respectively), preceded by an early and lasting significant decrease in DAS44, ESR and CRP. Moreover, a significant correlation was found between cIMT and DAS44 (r = 0.435, P < 0.05). CONCLUSIONS: These results demonstrate that TNF-alpha blockade is associated with cIMT reduction in RA patients steadily responsive to therapy, probably by lowering inflammation.

Del Porto F, Laganà B, Biselli R, Donatelli I, Campitelli L, Nisini R, Cardelli P, Rossi F, D'Amelio R. · Università La Sapienza, II Facoltà di Medicina e Chirurgia, Ospedale Sant'Andrea, Cattedra ed U.O.C. di Allergologia ed Immunologia Clinica, Rome, Italy. · Vaccine. · Pubmed #16466833 No free full text.

Abstract: OBJECTIVE: To evaluate immunological safety and immunogenicity of influenza vaccine administration in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). PATIENTS AND METHODS: Twenty-four patients with low and/or stable disease activity 14 with SLE (mean age 43.42+/-12.18 years; 13 women) and 10 with RA (mean age 51+/-14.57 years; 9 women), diagnosed on the basis of the American College of Rheumatology criteria, have been immunized with trivalent split influenza vaccine without adjuvant. Further 24 non-vaccinated patients, 14 with SLE and 10 with RA, and 10 vaccinated healthy subjects, all age- and sex-matched, were used as controls. The patients underwent clinical and laboratory (specific anti-influenzavirus antibodies, auto-antibodies, peripheral blood lymphocyte subpopulations) evaluation before and 30 days after vaccination; auto-antibodies were also assessed at 90 days and disease activity at 90 and 180 days. RESULTS: The specific antibody response towards the three used antigens (A/New Caledonia/20/99, A/Moscow/10/99, and B/Shangdong/7/97) significantly increased in both patients and healthy controls, without any significant difference between them. No significant difference could instead be observed on the clinical activity, auto-antibodies, and peripheral blood lymphocyte subpopulations before and after vaccination, and between patients and controls. CONCLUSIONS: Trivalent split influenza vaccine without adjuvant seems to be safe and immunogenic in patients with SLE and RA, provided that only patients with low and/or stable disease activity are selected.

Laganà B, Picchianti Diamanti A, Germano V, Argento G, Ferlito C, D Amelio R. · No affiliation provided · J Biol Regul Homeost Agents. · Pubmed #19036231 No free full text.

Abstract: This case report describes an excellent clinical and radiological response in an eRA patient treated with Etanercept; however, it indicates that joint damage may progress, despite a sustained clinical remission, after Etanercept suspension.