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ID PMID Title PublicationDate abstract
22031680 [Pharmacological management of inflammatory rheumatic conditions]. 2011 Sep Inflammatory rheumatic disorders are related to different pathophysiological mechanisms and, hence, their therapeutic management varies according to the underlying disease. Crystal-induced arthritis is characterized by its almost specific responsiveness to colchicine. Regarding ankylosing spondylitis, non steroidal anti-inflammatory drugs (NSAIDs) and TNF blockers are the cornerstones of pharmacological intervention whereas oral corticosteroids at conventional doses are of little value, if any. Conversely, corticosteroids are the drug of choice to treat polymyalgia rheumatica. Furthermore, low-dose corticosteroids were shown to be more effective than NSAIDs in patients with rheumatoid arthritis (RA). However, the main goal being to achieve remission, disease-modifying antirheumatic drugs, either synthetic, especially methotrexate, and/or biologic, such as TNF inhibitors, have a major role in the management of RA. Finally, enhanced understanding of molecular pathogenesis of inflammatory disorders may help to find out how to best target available drugs to right individuals in the future.
22370803 [Off-label therapy of rheumatoid arthritis and spondyloarthritis]. 2012 Feb For rheumatoid arthritis (RA) and diseases of the spondyloarthritis group (SpA) a large number of approved medications are available. Nevertheless, in Germany even for these diseases several off-label risks exist for the rheumatologist prescribing antirheumatic drugs which have recently led to a series of recourses or threats of recourse. In RA as well as SpA first of all biologicals are the target of recourse imposed mainly by health insurances. In RA monotherapy (when labeled only in combination with methotrexate), combination with leflunomide (instead of methotrexate) and dose deviations are the most important causes. In SpA TNF inhibitors are labeled only for the definite diagnosis of ankylosing spondylitis (AS) and psoriatic arthritis (PsA) leaving aside patients with severe peripheral spondyloarthritis including enthesitis which does not exactly meet the diagnostic criteria of AS and PsA. The same applies to early AS not fulfilling the 1984 New York criteria which still lacks labeled use of TNF inhibitors. In these cases, however, based on successful randomized controlled trials and changed diagnostic criteria a label extension is expected in the near future. Until then it seems suitable to apply for permission for this treatment from insurers in each case.
21584420 Liver toxicity is rare in rheumatoid arthritis patients using combination therapy with lef 2011 Mar OBJECTIVE: Some studies have reported that adding leflunomide (LEF) to the treatment of rheumatoid arthritis (RA) in patients who do not respond to methotrexate (MTX) improved efficacy but increased the risk of liver toxicity. This study aimed at assessing the incidence of liver toxicity in patients with active RA using the LEF and MTX combination therapy in comparison with that of patients on MTX monotherapy. METHODS: Between February and September 2009, 97 consecutive patients followed up at the University Hospital of the Universidade Federal de Santa Catarina, Brazil, were enrolled. RA patients on MTX alone or using the LEF and MTX combination had their medical records systematically reviewed. The alanine/aspartate aminotransferase enzymes were retrospectively analyzed since the beginning of treatment with MTX or MTX plus LEF. Hepatotoxicity was defined as an increase of at least two-fold the upper limits of normal of the liver enzymes. RESULTS: 71 RA patients were included in the study: 36.6% were using 20-25 mg/week of MTX alone and 63.4% were using 20-25 mg/week of MTX plus 20 mg/day of LEF. Of the patients on the combination therapy, 11.1% had abnormal levels of liver enzymes versus 11.5% of the patients on monotherapy (P = 1.0). Abnormal aminotransferase levels have been seen with both MTX and LEF monotherapies in patients with RA. In our study, no difference was found between the percentages of aminotransferase elevations of patients being treated with MTX alone or in combination with LEF. CONCLUSION: The combination of MTX and LEF in RA patients is generally safe and well tolerated.
22444783 Systematic review of tocilizumab for rheumatoid arthritis: a new biologic agent targeting 2012 Apr BACKGROUND: Tocilizumab (TCZ), a humanized anti-interleukin-6 receptor monoclonal antibody, represents a new treatment strategy for patients with rheumatoid arthritis (RA) and is currently approved in the United States for RA patients who have failed to improve with at least one anti-tumor necrosis factor therapy. OBJECTIVE: The goal of this study was to summarize the efficacy and safety profile of TCZ. METHODS: A systematic literature review was conducted to identify English-language articles within PubMed and the Cochrane Library from January 1989 to August 2011 reporting results from Phase III TCZ double-blind, randomized controlled trials (RCTs), noncontrolled clinical trials, and open-label extensions with a duration ≥6 months. Study outcomes had to include at least one of the following: American College of Rheumatology (ACR) 20, 50, or 70 response rates; tender/swollen joint count; Health Assessment Questionnaire-Disability Index; radiographic outcomes and drug persistence. Phase II RCTs were included only if they contained relevant information not available in Phase III RCTs. Relevant studies were selected to evaluate TCZ's pharmacokinetics and pharmacodynamics. RESULTS: Ten published clinical trials (7 Phase III, 3 Phase II) for TCZ were retrieved (7833 articles initially identified) from PubMed and 31 from the Cochrane library. Compared with methotrexate (MTX) monotherapy, TCZ 8 mg/kg IV monotherapy had higher rates of ACR20 (P < 0.001), ACR50 (P = 0.002), and ACR70 (P < 0.001) scores at week 24. TCZ 8 mg/kg IV plus oral MTX had a higher ACR20 response rate than oral MTX plus placebo in patients with RA who failed to respond to MTX or anti-tumor necrosis factor therapy (P < 0.001). Patients receiving TCZ 8 mg/kg had less radiographic progression on the Genant-modified Sharp score (85% had no progression) than the control group (67% had no progression) (P < 0.001). The rate of serious infections was 4.7 events/100 patient-years of exposure in the TCZ groups. A greater frequency of neutropenia, thrombocytopenia, hyperlipidemia, and transaminitis was observed with TCZ compared with placebo. CONCLUSION: The short-term efficacy and safety profile of TCZ is promising. Additional long-term safety data are needed to better characterize the risk-benefit profile of this agent.
21708910 Changes in patient characteristics in anti-tumour necrosis factor clinical trials for rheu 2011 Sep OBJECTIVE: To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNFα) inhibitors in rheumatoid arthritis (RA) patients. METHODS: A systematic literature review was performed using predefined inclusion criteria to identify randomised, double-blind, controlled trials that evaluated TNFα inhibitors in adult RA patients. Entry criteria and baseline clinical characteristics were evaluated over time for methotrexate-experienced and methotrexate-naive study populations. Enrolment start date for each trial was the time metric. The anchor time was the study with the earliest identifiable enrolment start date. RESULTS: 44 primary publications (reporting the primary study endpoint) from 1993 to 2008 met the inclusion criteria. Enrolment start dates of August 1993 and May 1997 were identified as time anchors for the 37 methotrexate-experienced studies and the seven methotrexate-naive studies, respectively. In methotrexate-experienced trials, no significant change was observed over the years included in this study in any inclusion criteria (including swollen joint counts and C-reactive protein (CRP)), but a significant decrease over time was observed in the baseline swollen joint count, CRP and total Sharp or van der Heijde modified Sharp score, but not in baseline tender joint counts. In the methotrexate-naive studies, significant decreases over the years were observed in swollen joint and tender joint inclusion criteria, but not in baseline tender joint count, baseline CRP, CRP inclusion criteria or baseline total Sharp or van der Heijde modified Sharp score. CONCLUSION: Inclusion criteria and baseline characteristics of RA patients enrolled in studies of TNFα inhibitors have changed, with more recent trials enrolling cohorts with lower disease activity, especially in methotrexate-experienced trials.
23079125 The CIMESTRA study: intra-articular glucocorticosteroids and synthetic DMARDs in a treat-t 2012 Jul OBJECTIVES: Treatment of early rheumatoid arthritis (RA) include aiming at disease control with early use of methotrexate (MTX) in monotherapy or in combination with glucocorticoids or other disease-modifying drugs (DMARDs). The CIMESTRA study applied an aggressive treatment with DMARD and intra-articular injections of glucocorticoids (i.a. GC) to control disease activity. This paper reviews the results of the five years' study. METHODS: 160 patients with early RA (<6 months duration) were randomized to receive MTX 7.5-20 mg/week+cyclosporine (CYA) 2.5-4 mg/kg (combination) or MTX+placebo-CYA (monotherapy). At each visit (week 0, 2, 4, 6, 8, thereafter monthly up to 24 months) patients had steroid injections in all swollen joints. During year 2, CYA/placebo was withdrawn, and hydroxychlorochine added. Clinical responses were assessed by ACR20, 50 and 70, ACR and DAS remission. Radiographic progression by x-rays of hands and feet. RESULTS: At year 1 (year 5) treatment responses in mono/combination groups were: ACR20: 68% (85%) / 85% (94%), ACR50: 53% (74%) / 68% (88%), ACR70: 44% (63%) / 59% (72%). After year 1, no significant differences between groups were found. Remission rates were: ACR-remission: 28% (52%) / 35% (60%), DAS28-remission: 34% (76%) / 43% (80%). Radiographic progression in both groups was <1TSS unit/year. After 1 and 2 years, 62% and 56% of the injected joints had not relapsed (both groups). Cumulated i.a.GC dose <1mg prednisolone/day. 19% received biologics by 5 years, 16% no treatment (sustained ACR-remission). Baseline magnetic resonance imaging (MRI) bone oedema best predicted radiographic progression after 2 years. Treatments were well tolerated. CONCLUSIONS: MTX and i.a.GC in a treat-to-target strategy over 5 years halted radiographic progression and induced remission in the majority of patients. I.a. GC had in long-lasting effect and cumulated dosages were low.
21778909 Rheumatoid arthritis decision making: many information sources but not all rated as useful 2011 Aug BACKGROUND: Patients who make high-quality medical decisions are more likely to have better health outcomes. One of the central components to a high-quality decision is the well-informed manner in which it is made. However, there has been little research studying patient behaviors regarding how they seek information about treatments for rheumatoid arthritis (RA). METHODS: We conducted a pilot study surveying beneficiaries of a health plan who had 2 or more visits coded for RA. Of 799 invited subjects, 101 (13%) completed interviews. Participants answered a questionnaire regarding sources of RA treatment information and their usefulness, sociodemographic items, and scales regarding their attitudes toward providers and medicines. Outcomes of interest included the average number of sources described (range, 0-10) and the usefulness for each source (1 "not useful" and 4 "extremely useful"). RESULTS: Methotrexate was the most widely used medication reported. The mean (SD) number of information sources used was 5.0 (2.1). Participants rated the information they used with a mean (SD) score of 2.8 (0.7). We found no strong patient correlates of these outcomes when compared with the aforementioned domains. Of the 98% of the total sample who referred to a rheumatologist for information, 87% rated the source as extremely useful. The Internet was the most frequently used nonprovider source, with 63% of subjects reporting use, and a mean (SD) usefulness rating of 3.0 (1.03). CONCLUSIONS: In this pilot study, participants used many sources of information regarding treatment decisions for RA. Ninety-eight percent of the participants used rheumatologists as a source and found them extremely useful. Of the nonprovider sources, the Internet was most common, and 40% found it very useful.
21672203 Baseline characteristics and patient reported outcome data of patients prescribed etanerce 2011 Jun 14 BACKGROUND: The anti-TNF inhibitor, etanercept is administered as a once or twice weekly subcutaneous injection for the treatment of rheumatoid arthritis, psoriasis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis (JIA). Limited data from the patients' perspective are available on the use of biologics in the treatment of these chronic conditions and this evaluation was designed to collect data from patients who had been prescribed etanercept for the first time. This manuscript describes the self-reported baseline characteristics and health-related quality of life of patients prior to treatment. Follow-up data will be reported separately. METHODS: Patients throughout the United Kingdom prescribed etanercept were invited to participate in an evaluation of their condition and treatment using a data collection tool consisting of a web-based system supplemented by telephone reporting (PROBE). Outcome measures reported at baseline included demographic data, the condition being treated, previous treatment with biologic agents and current and previous medications. Questions modified from standard, validated quality of life questionnaires such as EQ-5D were incorporated and patients made a global assessment of the severity of their own illness using the CGI-S scale. RESULTS: A total of 344 patients/carers/parents participated in the evaluation at baseline, 290 (84%) by online questionnaire and 54 (16%) by telephone. Overall, the study population had a mean age of 53 years, was predominantly female (62%) and 20% had been previously treated with a biologic agent. A total of 191 (56%) patients were receiving treatment with etanercept for rheumatoid arthritis, 44 (13%) for psoriatic arthritis, 43 (13%) for ankylosing spondylitis, 35 (10%) for psoriasis, 9 (3%) for known juvenile idiopathic arthritis (JIA) and 22 (6%) for another condition/patient unsure/missing response. All patients were prescribed the 50 mg weekly dose of etanercept except for 1 patient with JIA (40 mg) dose and 2 patients with psoriasis (100 mg). Thirty-eight percent of patients with rheumatoid arthritis were not receiving treatment with methotrexate. CONCLUSIONS: The baseline characteristics and health-related quality of life of first time users of etanercept can be adequately described using self-reported patient data collected using an online questionnaire with a telephone option (PROBE).
21794814 [How does one manage patients with rheumatoid arthritis and positive serology to hepatitis 2011 May Chronic viral infections in rheumatic patients are a diagnostic and therapeutic challenge. Some of the disease-modifying antirheumatic drugs (DMARD) commonly used in rheumatoid arthritis, such as methotrexate and leflunomide, are hepatotoxic. With biological therapy, which is now widely used in patients refractory to these and other DMARD, some cases of reactivation of hepatitis B, even fulminant cases, have been reported, especially when employing TNF antagonists and rituximab, so their use must be carefully assessed and usually accompanied by antiviral therapy. However, there have not been reports of reactivation of hepatitis C after immunosuppressive therapy. In patients with HIV infection, administration of immunosuppressive therapy carries a high risk of opportunistic infections, although the new highly active antiviral therapy allows the use of some drugs in selected cases.
22341526 Interstitial lung disease related to rheumatoid arthritis: evolution after treatment. 2012 Mar OBJECTIVE: To describe the evolution of lung function in a cohort of rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) treated according to the medical judgment of attending physicians. METHODS: Retrospective cohort of RA patients with ILD, defined by a restrictive pattern in lung function tests and evidence of ILD in high resolution computed tomography (HRCT). Patients had an assessment of lung function including spirometry, diffusing capacity for carbon monoxide (DLCO), and HRCT. At a minimum of 4 months of follow up, a second assessment of lung function was done. All patients received a high dose of prednisone (1 mg/kg/day) scheme for 6 weeks with a reduction scheme ending with a dose of 10 mg/day of prednisone at about 6-8 months of follow up. Methotrexate was used in 18/40 (45%) patients and leflunomide or azathioprine or both were indicated in 22/40 (55%). RESULTS: Forty patients were identified. An indeterminate pattern with diffuse ground glass and reticulation images (50%) was the most prevalent pattern on HRCT scans. At a minimum of 4 months of follow up, an improvement in basal FVC values was observed (median (IQR)) 1.47 Lts. (0.99-1.91) vs 1.66 Lts. (1.37-2.1)), P<0.004. Patients with lower Kazerooni scores for fibrosis (<0.47) had a better improvement in the FVC values. CONCLUSIONS: Patients with RA and ILD may have an improvement in the FVC after a treatment with high doses of corticosteroids and disease modifying antirheumatic drugs (DMARDs).
21472474 Recurrent allergic bronchopulmonary aspergillosis in a patient with rheumatoid arthritis t 2011 Dec We report the case of a 68-year-old woman with Stage III and Class II rheumatoid arthritis (RA) that was resistant to prednisolone, methotrexate, and infliximab. After treatment with etanercept or tocilizumab, suspicious allergic bronchopulmonary aspergillosis (ABPA) repeatedly occurred and then rapidly improved after the withdrawal of each drug. We suspect that administration of etanercept and tocilizumab caused suspicious ABPA in this patient. The relevance to the pathogenesis of ABPA under these biological drugs is also discussed.
23138884 Nodular progression of lentigo malignant melanoma during a treatment with tocilizumab: cau 2013 Feb Tocilizumab is an anti-interleukin (IL)-6 receptor monoclonal antibody, used since 2010 for the treatment of severe rheumatoid arthritis (RA). It is known to induce infection, similarly to other biotherapies which modulate immune response and cytokines. Few cases of malignancy, however, have as yet been reported. We describe here the case of a patient with severe RA, previously treated with prednisolone, methotrexate, leflunomide, etanercept, and rituximab, who, after 8 months of treatment with tocilizumab, developed rapidly progressive nodular melanoma on a preexisting pigmented lesion on her left cheek. Recently, another case of nodular melanoma under tocilizumab has been published. The possible causative role of tocilizumab and other immunomodulatory agents in the development of this malignancy is discussed. Based on the present case, dermatologic screening is recommended before initiation of tocilizumab.
21624182 Understanding emerging treatment paradigms in rheumatoid arthritis. 2011 May 25 Treatment strategies for rheumatoid arthritis (RA) will continue to evolve as new drugs are developed, as new data become available, and as our potential to achieve greater and more consistent outcomes becomes more routine. Many patients will find both symptom relief and modest control of their disease with disease-modifying antirheumatic drugs (DMARDs), yet this course of therapy is clearly not effective in all patients. In fact, despite strong evidence that intensive treatment in the early stages of RA can slow or stop disease progression and may prevent disability, many patients continue to be managed in a stepwise manner and are treated with an ongoing monotherapy regimen with DMARDs. There is now a large body of evidence demonstrating the success of treating RA patients with anti-TNF therapy, usually in combination with methotrexate. As a result of the increased use of anti-TNF therapy, treatment paradigms have changed - and our practice is beginning to reflect this change. In the present review, we summarize the salient points of several recently proposed and emerging treatment paradigms with an emphasis on how these strategies may impact future practice.
22943199 Differential effects of infliximab on absolute circulating blood leucocyte counts of innat 2012 Oct Anti-tumour necrosis factor (TNF) biologics have revolutionized therapy of rheumatoid arthritis (RA). We compared the effects of infliximab on numbers of circulating leucocyte subsets in early RA (disease/symptom duration of ≤1 year) and late RA patients (>1 year). A control group consisted of early RA patients treated with a combination of methotrexate (MTX) and methylprednisolone. Blood samples were obtained at baseline (pre-therapy) from all RA patients, divided into three groups: (i) late RA receiving infliximab/MTX, (ii) early RA-infliximab/MTX, (iii) early RA-steroid/MTX, and also from follow-up patients at 2 and 14 weeks. Significant differences in absolute counts of monocytes and granulocytes were observed between healthy controls and RA patients. At baseline CD14(bright) monocytes and CD16(+) granulocytes were increased in both early RA and late RA patients. CD4(+) T cells, CD8(+) T cells and B cells were all increased at baseline in early RA, but not in late RA. At 2 weeks following infliximab treatment decreased granulocytes were observed in both early and late RA and decreased natural killer (NK) cells in late RA. CD16(+) granulocytes and NK cells were also decreased at 14 weeks post-infliximab in early RA. Biotinylated infliximab was used to detect membrane-associated TNF (mTNF)-expressing leucocytes in RA patients. CD16(+) granulocytes, NK cells and CD14(dim) monocytes all expressed higher levels of mTNF in RA patients. In summary infliximab is associated with decreased CD16(+) granulocyte and NK cell counts, possibly through binding of mTNF. Differential effects of infliximab between early and late RA suggest that pathogenic mechanisms change as disease progresses.
21449161 [Clostridium difficile-associated diarrhea: causes and relationship to reactive arthritis] 2011 Jan We present a patient treated with methotrexate (MTX] for rheumatoid arthritis, in whom clostridium difficile-associated colitis has developed, without preceding antibiotic treatment. Two weeks later, the patient was admitted with knee arthritis. Reactive arthritis was diagnosed and treated successfully with the naproxen. The article discusses risk factors for Clostridium difficile-associated diarrhea [CDAD] other than antibiotics, and the relation of this pathogen to the development of reactive arthritis. It seems to be the first report of the association of MTX treatment with CDAD.
22709496 Lack of adverse effect of anti-tumor necrosis factor-α biologics in treatment of rheumato 2012 Jun BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder affecting synovial joints and many other organs. Most patients seen in clinical settings have a progressive chronic disease, with radiographic damage, frequent work disability, incremental functional declines and increased mortality rates. The introduction of the biological drugs in treatment of RA has played an important role in prevention of destructive effects of the disease but may have serious adverse effects due to their powerful inhibition of the immune system. OBJECTIVES: To study the adverse effects (ADEs) of three different tumor necrosis factor α inhibitor (TNFi) drugs (infliximab, adalimumab and etanercept) in RA patients for 5 years in the south-west area of Saudi Arabia. METHODS: Two groups of RA patients were included in this study: The first group included 112 patients, representing the biologics group. These patients received biological therapy plus disease modifying anti-rheumatic drugs (DMARDs): 56 patients received infliximab (IFX), 36 patients received adalimumab (ADL) and 20 patients received etanercept (ETN). The second group also included 112 patients, representing the control group: RA patients treated only with the traditional DMARDs. ADEs were classified into mild and severe. RESULTS: The mild ADEs which had been recorded during 5 years of follow-up in patients receiving TNFi, were onycholysis (1.8%), positive tuberculin test (1.8%) and small vessel vasculitis (1.8%). Statistically, there were insignificant differences in the mild ADEs except for upper respiratory tract infection that was significantly higher in the control group. Severe ADEs included pneumonia (1.8%) and solid tumor (1.8%) and there were no significant differences between the biologics and control groups. Also there were no significant statistical differences for the ADEs, mild or severe, between the three biologics, infliximab, adalimumab and etanercept. Occurrence of ADEs did not correlate to methotrexate dose, steroid dose or rheumatoid factor positivity. CONCLUSIONS: Our results indicate that the use of TNFi therapy appeared to be as safe as traditional DMARDs in treatment of rheumatoid arthritis patients and long-term follow-up with careful examination is essential to pick up any abnormal ADEs.
21875874 Treatment strategies in patients with rheumatoid arthritis for whom methotrexate monothera 2011 Dec OBJECTIVES: To compare the effectiveness of adding synthetic disease-modifying antirheumatic drugs (sDMARDs) versus tumour necrosis factor α inhibitors (TNFi) to methotrexate (MTX) in patients with rheumatoid arthritis (RA) who were MTX inadequate responders (IR). Second, to examine outcomes in patients receiving MTX+TNFi for whom the MTX+sDMARD combination had also failed. METHODS: Patients with RA (disease duration ≤ 5 years, MTX IR and naïve to other DMARDs) starting treatment with MTX+TNFi or MTX+sDMARDs were included. From the latter group a subgroup of patients who went on to receive MTX+TNFi was identified. RESULTS: Patients receiving MTX+TNFi (n=98) and MTX+sDMARDs (n=129) had similar baseline disease activity when starting combination therapy (mean Disease Activity Score 28 (DAS28) = 4.90 and 4.96, respectively). Three- and 6-month effectiveness and 2-year drug survival were better for MTX+TNFi than for MTX+sDMARDs: mean DAS28 was -1.61 versus -0.85 after 3 months (p<0.001) and -1.91 versus -1.03 after 6 months (p=0.01); DAS28<2.6 was reached by 29.0% versus 11.6% after 3 and 34.5% versus 12.9% after 6 months. Effectiveness was somewhat better with triple therapy than other MTX+sDMARD combinations but was generally inferior compared with MTX+TNFi. For the patients who received MTX+TNFi as a third step after MTX+sDMARDs had failed (n=38) there was a tendency towards lower remission rates, worse disease activity states and inferior drug survival compared with patients who received MTX+TNFi directly after the failure of MTX. CONCLUSIONS: Effectiveness was better for MTX+TNFi than for MTX+sDMARDs. Patients who started MTX+TNFi after two synthetic DMARD regimens had failed had a tendency to less favourable disease states after 3 months than patients who switched directly from MTX to MTX+TNFi.
21983397 [Systemic autoimmune disorders and pregnancy]. 2011 Oct 23 The coincidence of systemic autoimmune diseases and pregnancy may modify the outcome of the disease and the pregnancy due to the background immunologic and hormonal processes. The great majority of patients with autoimmune diseases are young females in their reproductive years, willing to have babies. Consequently, we have to prepare for this special situation. Our concept on childbearing in autoimmune women has changed within the last 30 years. Earlier, systemic lupus erythematosus flared in about 50% of patients during pregnancy, but the flare rate has significantly decreased recently. This improvement can be attributed to increased attention to low diseases activity at the time of conception, which might reduce to the half of the risk for flare. Tight control of patients and appropriate use of corticosteroids also contribute to the better results. The adequate use of anti-thrombotic agents resulted in a significant amelioration of pregnancy outcome in antiphospholipid syndrome. The earlier use of methotrexate and the introduction of tumor necrosis factor-alpha inhibitors in the treatment of rheumatoid arthritis have changed the natural characteristics of the disease. The increase in remission rate indirectly has beneficial effect on the number of planned and carried out pregnancies. Authors review the connection between systemic autoimmune disorders and pregnancy as well as the possibilities of medical treatment of such diseases during pregnancy.
21930442 Liver stiffness correlates with methotrexate cumulative dose in patients with rheumatoid a 2012 Feb BACKGROUND: Liver stiffness values were recently proposed to identify patients with methotrexate-induced liver fibrosis. Aim of this study was to assess the clinical and laboratory determinants of the association between liver stiffness, measured by transient elastography, and methotrexate treatment in patients with rheumatoid arthritis in the absence of other factors contributing to liver damage and fibrosis. METHODS: 100 patients with rheumatoid arthritis, with a cumulative methotrexate dose ranging from 1530 to 13,000 mg over a mean period of 7.07±3.89 yrs, were retrospectively evaluated. RESULTS: The average liver stiffness value in the whole population was 4.93±1.8 kPa, excluding the presence of significant fibrosis. At univariate analysis, a significant correlation was found between liver stiffness and methotrexate cumulative dose, duration of treatment, alanine transaminases levels, body mass index, gamma glutamyl-transpeptidase and the presence of steatosis. At multivariate analysis, a significant association was detected only between liver stiffness and methotrexate cumulative dose. Out of 11 patients with liver stiffness >7.0 kPa, five were subjected to liver biopsy and mild or moderate perisinusoidal fibrosis was detected in two patients with a cumulative dose >4000 mg and liver stiffness >9 kPa. CONCLUSIONS: Chronic methotrexate treatment induces a progressive increase in liver stiffness corresponding to mild or moderate perisinusoidal fibrosis for values >9 kPa.
21452294 Atacicept in patients with rheumatoid arthritis and an inadequate response to methotrexate 2011 Jul OBJECTIVE: To assess the efficacy, safety, and biologic activity of atacicept in tumor necrosis factor antagonist-naive patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate. METHODS: In this phase II study, patients with active RA (n = 311) were randomized 1:1:1:1 to receive placebo, atacicept 150 mg weekly with or without a 4-week loading period (twice-weekly dosing), or open-label adalimumab 40 mg every other week, for 25 weeks. The primary end point was 20% improvement in disease severity according to the American College of Rheumatology criteria, assessed using the C-reactive protein level (ACR20-CRP), at week 26. Secondary end points included additional assessments of efficacy, biologic activity, and safety. RESULTS: The proportion of patients meeting the primary end point (ACR20-CRP response) did not differ significantly in the atacicept groups and the placebo group (46% in the placebo group, 45% in the atacicept loading group, and 58% in the atacicept nonloading group). In contrast, an ACR20-CRP response was observed in 71% of patients in the adalimumab group (P < 0.001 versus placebo). ACR50-CRP response rates were significantly higher in all active-treatment groups compared with placebo, but ACR70-CRP response rates were superior only in the adalimumab group. Atacicept treatment reduced the levels of serum IgG, IgA, and IgM rheumatoid factor and the levels of circulating mature B cells and plasma cells. The effects of treatment were similar with and without loading. Immunoglobulin levels returned toward baseline values during the treatment-free followup period (week 38). The most frequent adverse events associated with atacicept represented common illnesses. No serious infections occurred among patients treated with atacicept. CONCLUSION: The primary end point (ACR20-CRP response) was not met despite significant biologic effects of atacicept that were consistent with its proposed mechanism of action. Modest effects of atacicept were seen for some secondary efficacy end points. Treatment with atacicept raised no new safety concerns.