Anti-inflammatory Disease Modifying Research Articles

A simplified model to understand the targeted disease-modifying anti-inflammatory drugs

This review presents a simplified model to understand better how disease-modifying anti-inflammatory drugs (DMAIDs) work in immune-mediated inflammatory diseases (IMIDs) with a focus on rheumatology, dermatology, and gastroenterology. In this model, IMIDs are listed on a spectrum from autoinflammatory to autoimmune characterised by the involvement of either mostly the innate or the adaptive immune system. DMAIDs specifically target these immune components and have shown efficacy in distinct IMIDs. DMAID classes include TNF blockers, IL-1 blockers, IL-6 receptor blockers, IL-17 blockers, IL-23 blockers, and janus kinase inhibitors.

The use of biological and targeted synthetic basic anti-inflammatory drugs in elderly patients with rheumatoid arthritis: for or against

Due to the global aging of the population and increasing life expectancy, the population of elderly patients with rheumatoid arthritis is growing, both due to patients with onset after 60 years of age (EORA), and elderly patients in whom the disease started at a young age. Treatment of such patients is associated with a number of difficulties, which is associated with the characteristics of the aging of the immune system and the body as a whole, and the burden of comorbid conditions. Elderly patients, unlike young ones, have a higher risk of developing adverse events when prescribed both basic and biological drugs. These features lead to a more “gentle” treatment strategy for elderly patients, limited use of adequate doses of basic drugs and a low number of prescriptions of biological drugs among doctors. This article provides current data on the safety and effectiveness of the use of biological and targeted synthetic disease-modifying anti-inflammatory drugs in elderly patients with rheumatoid arthritis.

Tofacitinib in the treatment of rheumatoid arthritis: real-life practice and randomized clinical trial data

The article justifies the need for a large arsenal of drugs to treat perennial rheumatoid arthritis. The authors present randomized controlled trial data showing high efficacy of tofacitinib at different doses as monotherapy, or in combination with methotrexate, or other conventional synthetic disease-modifying anti-inflammatory drugs in suppressing the activity and progression of the disease in various groups of patients, both non-responders to methotrexate, and non-responders to tumour necrosis factor-alpha inhibitors. Extension-phase data of randomized clinical trials demonstrated sustained efficacy of tofacitinib for up to 9.5 years. The authors presented the real-world evidence confirming high efficiency of the drug and noted the rapidity of onset of the effect and its high analgesic activity. The safety issues of tofacitinib with an emphasis on the cardiovascular safety of the drug, taking into account updates to the latest 2022 EULAR Recommendations on the need to consider risk factors for the development of cardiovascular adverse events when planning therapy with Janus kinase inhibitors are discussed. It is reported that slightly increased risk of such adverse events during use of tofacitinib, as compared with inhibitors of tumour necrosis factor alpha, was observed in elderly patients who have at least one risk factor for the development of cardiovascular events. Tofacitinib safety data were obtained from meta-analyses, systematic reviews, national registries, open observational studies, as well as outcomes of the use of the drug in real clinical practice. The launch of a domestic generic of the original drug was noted in the Russian Federation.

Autoimmune disorders and thyroid function in patients with rheumatoid arthritis after biological treatment

Rheumatoid arthritis (RA) and autoimmune diseases of the thyroid gland (AITD) often occur together. As autoimmune diseases, they share common pathological pathways, reflecting the fact that the treatment of the underlying disease can influence the course of thyroid disorders. The pharmacotherapy of RA is based on the supply of disease-modifying anti-inflammatory drugs with an increasing focus on biologics. This article aims to review the available literature describing the effects of biological treatments on thyroid function. The use of biological drugs may have the potential benefit of regulating the level of anti-thyroid antibodies. On the other hand, tumour necrosis factor-alpha (TNF-a) inhibitors are not indifferent to thyroid function and may increase the incidence of subacute thyroiditis. The coexistence of AITD and RA prompts consideration of the need for routine thyroid screening in RA patients and for RA screening in patients with thyroid disease who report joint problems.

The Impact of Rheumatoid Arthritis on Bone Loss: Links to Osteoporosis and Osteopenia.

Rheumatoid arthritis (RA) is an autoimmune chronic connective tissue disease that produces persistent systemic inflammation, with joint inflammation leading to function loss and joint destruction. Low bone mass causes skeletal bone loss, commonly referred to as osteopenia or osteoporosis. We conducted this literature review to examine the relationship between RA and osteoporosis and the variables contributing to this connection. We used articles from the US National Library of Medicine (PubMed), Google Scholar, Science Direct to access the required information. Eventually, our results concluded that RA could result in local periarticular and generalized bone loss. Many risk factors contribute to this association, such as chronic joints inflammation, glucocorticoid use, genetics, and estrogen hormone effects. Still, it is not clear yet whether this is due to a consequence of treatment, immobility, or the activity of the disease. There are many recommendations by the American College of Rheumatology for RA patients during the disease course to reduce the risk of osteoporosis development, which include early starts of disease-modifying anti-inflammatory drugs (DMARDs), doing a dual-energy x-ray (DXA) or quantitative ultrasound (QUS) for identifying a patient at risk of osteoporosis, taking vitamin D, calcium, and bisphosphonates. Further prospective studies and clinical trials are essential to provide a solid evidence-based recommendation that will help to prevent bone loss in RA patients.

The Diagnosis and Treatment of Adult Patients with SAPHO Syndrome: Controversies Revealed in a Multidisciplinary International Survey of Physicians

IntroductionThis study aimed to investigate the current practice in the diagnosis and treatment of SAPHO syndrome among the international rheumatology and dermatology communities.MethodsWe conducted an electronic survey among the members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the Japan Spondyloarthritis, and Israeli Societies of Rheumatology.ResultsA total of 78 physicians participated in the survey: rheumatologists (83%, n = 65), dermatologists (11.5%, n = 9), and orthopedics (3.8%, n = 3). SAPHO was considered a subtype of spondyloarthritis by 48.7% (n = 38), a subtype of psoriatic arthritis by 19.2% (n = 15), a separate entity by 25.6% (n = 20), and a subtype of reactive arthritis by 6.4% (n = 5). Palmoplantar pustulosis was the most prevalent cutaneous manifestation (n = 44, 56.4%) and anterior chest pain—the most prevalent osteoarticular manifestation (n = 66, 84.6%). The majority (84.6%, n = 66) voted for the update of the present diagnostic criteria by Khan 1994. Magnetic resonance imaging was considered the preferred imaging modality for the diagnosis of SAPHO by 41% (n = 32). Conduction of bone biopsy for diagnosis of non-infectious osteitis was supported only by 10.3% (n = 8). Patient-reported outcomes were considered the most appropriate measure for the assessment of disease activity by 47.4% (n = 37). The treatment approach was overall similar among the rheumatology and dermatology communities, including non-steroidal anti-inflammatory drugs, bisphosphonates, conventional disease-modifying anti-inflammatory drugs, and biologics.ConclusionsOur study underlines the controversy on diagnosis and treatment of SAPHO syndrome among specialists in rheumatology and dermatology and emphasizes an unmet need for update and validation of diagnostic criteria and treatment approach.

Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis (SAPHO): An Interesting Clinical Syndrome

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare disorder that classically involves the musculoskeletal system, i.e. bone, joint and skin. The exact pathogenesis of this syndrome is unknown. However, autoimmunity, infections, immune malfunction and genetic factors are attributed to its pathophysiology. Bone and joint involvements are the hallmark of SAPHO syndrome and not necessarily require cutaneous involvement at the time of diagnosis. X-ray of the affected joints could show osteitis with sclerosis. Anterior chest wall involvement particularly ''bullhead appearance'' seen on bone scan is a striking feature of the syndrome. Erythrocyte sedimentation rate (ESR) is usually elevated amongst the majority of patients. Diagnosis of SAPHO is always challenging and often delayed because of a multitude of symptoms. The mainstay of treatment is control of pain and inflammation with both non-steroidal anti-inflammatory drugs (NSAIDs) and rescue courses of systemic steroids. If failed to control symptoms with first-line agents and in those with severe disease, disease-modifying anti-inflammatory drugs (DMARDs) may be needed eventually. Despite a chronic inflammatory condition, it remains stable in the majority of cases. Here in this case report, we reiterate the importance of early recognition, timely diagnosis and prompt treatment initiation.

Values and Correlations between C-Reactive Protein and Apolipoprotein B after Treatment with Methotrexate at Patients with Rheumatoid Arthritis.

BACKGROUND:Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD). Lipid changes related to inflammation have been described in RA. Methotrexate (MTX) treatment is effective in controlling inflammation and decreasing the CRP (C-reactive protein) values.AIM:To examine the disease activity, CRP and Apo B values in the detection of new patients with active and untreated RA, and impact of MTX therapy on their levels after 6 months and one year of treatment, and the correlation between their values in this period.METHODS:80 patients with active and newly discovered RA patients who meet the American Rheumatology Association (ARA) 1987 revised criteria were treated with disease-modifying anti-inflammatory drugs (DMARDs) according to the protocol for treatment.RESULTS:After a year of therapy RA patients achieved significant decrease in the DAS28 (disease activity score) (p < 0.01 and p < 0.001), and CRP values (p < 0.001). Levels of Apo B values at the 12 months were nonsignificantly higher compared to the results obtained at the beginning of the study (p < 0.001). After 6 and 12 months there was a weak nonsignificant negative correlation about the values of CRP and Apo B at baseline and after 12 months (r = –0.15 and r = -0.12 p > 0.05).CONCLUSION:Use of MTX therapy at RA patients had a reduced effect on disease activity and inflammation, but the nonsignificance effect on the values of Apo B lipoproteins.

Radioisotope synovectomy in the treatment of patients with rheumatoid arthritis

In a number of cases, systemic therapy for rheumatoid arthritis (RA), including disease-modifying anti-rheumatic drugs, biological agents, glucocorticoids (GCs), and nonsteroidal anti-inflammatory drugs, fails to completely suppress joint inflammatory changes in the patients. Therefore, local methods are widely used in the combination therapy of RA. Intra-articular injection of hyaluronic acid (HA) is a highly local treatment modality. HA can be used as initial therapy when it is necessary to achieve rapid clinical improvement, or at a later stage of the disease, in exacerbation of arthritis. However, in some patients the effect of intra-articular HA can be short-lasting, and a favorable result can be obtained with local radiotherapy. It is based on powerful irradiation of the inflamed synovium, which is provided by intra-articular injection of radioactive isotope colloids. In Russia, RA was successfully treated with colloidal Au-198, but its production was ceased in the 1990s, and agents for radioisotope synovectomy have been long unavailable. Tungsten-188/Rhenium-188generator has been recently designed in Russia, which allows Rhenium-188 to be obtained in clinics. Preclinical trials have shown that intra-articular injection ensures good fixation of the drug in the knee joint with its insignificant accumulation in the liver and other non-target organs and tissues. Introduction of this drug into routine clinical practice can markedly improve the efficiency of treatment in patients with chronic arthritis.

Searching for Novel Janus Kinase-2 Inhibitors Using a Combination of Pharmacophore Modeling, 3D-QSAR Studies and Virtual Screening.

The Janus kinases (JAKs) play a pivotal role in cytokine receptor signaling pathways via activation of downstream signal transducers and activators of transcription (STAT) pathway. Intracellular pathways that include JAKs are critical to immune cell activation and pro-inflammatory cytokine production. Selective inhibitors of JAKs are potentially disease-modifying anti-inflammatory drugs for the treatment of rheumatoid arthritis (RA). Each of the four members of the JAK family plays an individual role in the oncogenesis of the immune system, and therefore, the development of potent and specific inhibitors for each member is needed. Although there is a high sequence homology and structural identity of JAK1 and JAK2, such as a very similar binding mode of inhibitors at the ATPbinding site of enzymes, obvious differences surrounding the JAK1 and JAK2 ATP-binding sites provide a platform for the rational design of JAK2- and JAK1-specific inhibitors. In the present study, a dataset of 33 compounds characterized by a common scaffold of 2-amino-[1,2,4]triazolo[1,5-&#945;]pyridine with well-defined in vitro activity values was computationally explored. Most of the compounds included in the dataset had higher ligand efficiency against JAK2 than JAK1. To improve further the selectivity of these triazolopyridines, Common Pharmacophore Hypotheses (CPHs) were generated and 3D-QSAR studies were carried out on them, in order to comprehend on the molecular features responsible for their selectivity. The proposed computational approach was applied in order to perform an in silico database virtual screening study with the aim to discover novel potent and selective JAK2 inhibitors.

The Use of Tocilizumab in 40 Patients With Polyarticular Juvenile Idiopathic Arthritis: the Results of a Retrospective Study

The issue of a therapy of children with juvenile idiopathic arthritis (JIA) with intolerance or insufficient effectiveness of methotrexate remains actual. Objective: Our aim was to study the efficacy and safety of tocilizumab in patients with polyarticular JIA. Methods. In a retrospective study, we studied the results of the use of tocilizumab in patients with active polyarticular JIA ( 5 active joints) resistant to prior therapy with methotrexate or a combination of methotrexate with other nonbiologic disease-modifying antiinflammatory drugs. Results. The data of 40 children (83% girls) with the onset median of polyarticular JIA of 4.8 (2.9, 8.1) years and the interval between the disease onset and the initiation of tocilizumab therapy of 5.7 (1.8, 8.5) years was analyzed. Tocilizumab was used as an intravenous infusion of 8 mg/kg (with a weight 30 kg) or 10 mg/kg (with a weight < 30 kg) every 4 weeks. The duration of tocilizumab monotherapy in 5 (13%) children was 1,109 days (452; 1,542). The stages of inactive disease (according to the criteria of C. Wallace, 2004) in 6 months of tocilizumab therapy reached 6 (15%) patients, in 42 months — 32 (80%) patients. In 3 patients, tocilizumab was canceled due to persistent remission. After 6 months of treatment, there was a marked decrease in erythrocyte sedimentation rate, C-reactive protein concentration, number of leukocytes and platelets (in all cases, p < 0.001) to normal values, which persisted throughout the whole period of drug administration. Predictors for achieving inactive disease were the initial (at the onset of tocilizumab therapy) number of peripheral blood leukocytes < 9.0X109/l [relative risk (RR) 1.92; 95% confidence interval (CI) 0.9–4.6)] and the absence of prior biological therapy (RR 1.92, 95% CI 0.9–4.6). The most frequent side effects of tocilizumab therapy were transient hypercholesterolemia (in 13), hypertriglyceridemia (in 4), transient grade II neutropenia (in 1). Conclusion. The long-term efficacy and relative safety of tocilizumab in children with polyarticular JIA have been showed.

Is Obesity in Psoriatic Arthritis Associated With a Poorer Therapeutic Response and More Adverse Effects of Treatment With an Anchor Drug?

ObjectivesTo assess the association between obesity, control of inflammatory activity and increased adverse effects in psoriatic arthritis (PsA) with disease-modifying anti-inflammatory drugs (DMARD). MethodsA systematic literature review was performed using MEDLINE and EMBASE databases following the guidelines of the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) consensus statement. Studies were selected if they included patients with PsA, obesity was studied as a predictive factor, and the outcome was adverse effects, including efficacy failure. Quality was assessed using an ad hoc risk of bias tool. A qualitative analysis was carried out by type of study and study population, quality and specific results. ResultsWe found 1043 articles, discarding most of them on the basis of title and abstract. Ten articles were studied in detail and finally excluded three. The majority concluded, with statistically significant results, that in patients with PsA and treated with TNFα inhibitors (TNFαi), obesity is associated with poorer chances of achieving and maintaining a minimal disease activity, higher treatment discontinuation rates, and lower skin response. Regarding conventional synthetic DMARD, a trend toward a moderate increase in transaminases with methotrexate (MTX) was observed in obese patients with PsA. ConclusionsObesity is a negative predictor of clinical response in patients with PsA being treated with TNFαi. Except MTX hepatotoxicity, no other adverse effects, either with TNFαi or other drugs, were found in relation to obesity in PsA.

Hand pains in women and men in early rheumatoid arthritis, a one year follow-up after diagnosis. The Swedish TIRA project

Purpose This research analysed general pain intensity, hand pain at rest and hand pain during activity in women and men in early rheumatoid arhtritis (RA). Method Out of the 454 patients that were recruited into the Swedish early RA project “TIRA” the 373 patients (67% women) that remained at 12 months follow-up are reported here. Disease activity 28 joint score (DAS-28), disability (Health Assessment Questionnaire = HAQ) and pain (VAS) were recorded at inclusion and after 3 (M3), 6 (M6) and 12 (M12) months. General pain, hand pain during rest, hand pain during test of grip force as assessed by Grippit™, prescribed disease-modifying anti-inflammatory drugs (DMARDs) and hand dominance were recorded. Results DAS-28 and HAQ scores were high at inclusion and improved thereafter in both women and men. There were no significant differences between sexes at inclusion but women had higher DAS-28 and HAQ at all follow-ups. Women were more often prescribed DMARDs than were men. In both women and men all pain types were significantly lower at follow-up compared to at inclusion and women reported higher pain than men at follow-ups. The pain types differed significantly from each other at inclusion into TIRA, general pain was highest and hand pain during rest was lowest. There were no significant differences in hand pain related to hand dominance or between right and left hands. Conclusions Disease activity, disability and pain were high at inclusion and reduced over the first year. Despite more DMARDs prescribed in women than in men, women were more affected than were men. General pain was highest and not surprisingly hand pain during active grip testing was higher than hand pain during rest that was lowest in both sexes. Although our cohort was well controlled, it was evident that hand pain remains a problem. This has implications for rehabilitation and suggests potential ongoing activity limitations that should continue to receive attention from a multi-professional team.Implications for RehabilitationGeneral pain and hand pain remain a problem in RA despite today’s early intervention and effective disease control with new era biologics.The extent of hand pain evidenced in our work gives a more detailed and comprehensive account of pain status.Higher hand pain during active grip testing than that during rest indicates a potential relationship to ongoing activity limitation.Hand pain assessment can help guiding multi-professional interventions directed to reduce hand pain and thereby probably reduce activity limitations.

¿Se asocia la obesidad en la artritis psoriásica a una menor respuesta terapéutica y más efectos adversos con el tratamiento de fondo?

ObjectivesTo assess the association between obesity, control of inflammatory activity and increased adverse effects in psoriatic arthritis (PsA) with disease-modifying anti-inflammatory drugs (DMARD). MethodsA systematic literature review was performed using MEDLINE and EMBASE databases following the guidelines of the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) consensus statement. Studies were selected if they included patients with PsA, obesity was studied as a predictive factor, and the outcome was adverse effects, including efficacy failure. Quality was assessed using an ad hoc risk of bias tool. A qualitative analysis was carried out by type of study and study population, quality and specific results. ResultsWe found 1043 articles, discarding most of them on the basis of title and abstract. Ten articles were studied in detail and finally excluded three. The majority concluded, with statistically significant results, that in patients with PsA and treated with TNFα inhibitors (TNFαi), obesity is associated with poorer chances of achieving and maintaining a minimal disease activity, higher treatment discontinuation rates, and lower skin response. Regarding conventional synthetic DMARD, a trend toward a moderate increase in transaminases with methotrexate (MTX) was observed in obese patients with PsA. ConclusionsObesity is a negative predictor of clinical response in patients with PsA being treated with TNFαi. Except MTX hepatotoxicity, no other adverse effects, either with TNFαi or other drugs, were found in relation to obesity in PsA.

RESULTS OF USTEKINUMAB TREATMENT IN PATIENTS WITH PSORIATIC ARTHRITIS IN THE RUSSIAN FEDERATION ACCORDING TO THE DATA OF PSUMMIT 1 AND PSUMMIT 2

Psoriatic arthritis (PsA) is a chronic inflammatory disease of the joints, vertebral column, and entesises, which is associated with psoriasis. T helper type 17 cells (Th-17) play a leading role in the development of inflammation in psoriasis and PsA so different biologicals affecting interleukins (IL) 17 and 23 are being intensively investigated. Randomized, placebo-controlled Phase III PSUMMIT 1 (NCT01009086, EudraCT 2009-012264-14) and PSUMMIT 2 (NCT01077362, EudraCT 2009-012265-60) studies were undertaken to evaluate the efficiency and tolerability of ustekinumab (UST) treatment in PsA patients. Subject s and methods. The PSUMMIT 1 study covered 152 Russian patients with active PsA (≥5 tender and ≥5 swollen joints; C-reactive protein ≥3 mg/l) who were randomly (using the dynamic centralized randomization method on the basis of an interactive vocal response algorithm) divided into three groups (at a 1:1:1 ratio): 1) subcutaneous UST 45 mg; 2) UST 90 mg; 3) placebo (PL) at baseline, 4 weeks later, and then every 12 weeks). After 16 weeks the patients showing a less than 5% reduction in the number of tender and swollen joints were given UST 45 mg (if they belonged to the PL group) or 90 mg (if they were in the UST 45-mg group). The PL-receiving patients were given UST 45 mg at weeks 24 and 28 and then every 12 weeks. The treatment duration was 2 years. A therapeutic response was estimated by theAmericanCollege of Rheumatology (ACR) response criteria. The PSUMMIT 2 study enrolled 40 Russian patients who had previously received or were currently receiving disease-modifying anti-rheumatic drugs and/or nonsteroidal anti-inflammatory drugs and tumor necrosis factor-α inhibitors. The patients were randomized to the groups of those receiving UST 45 mg or 90 mg or PL at baseline and at week 4, then once every 12 weeks. The last dose of UST was given at week 40. The follow-up lasted until week 60. Result s and discussion. In the PSUMMIT 1 study, 24-week administration of UST 45 mg and 90 mg significantly more frequently ensured a 20% improvement according to the ACR criteria than that of PL (39.2; 44.0, and 15.7%, respectively; p < 0.01); the therapeutic response persisted until week52. In the PSUMMIT 2, following 24 weeks, the UST 45-mg and 90-mg groups considerably more often showed a 20% improvement according to the ACR criteria than the PL group (64.3, 57.1, and 16.7%, respectively; p < 0.01); the therapeutic response persisted until week 52. Among 150 Russian patients taking UST, on the average, for 45.1 weeks in the PSUMMIT 1 study, 62 (41.3%) were observed to have adverse events (AE) that were serious in 6 (4.0%). Among 40 PsA patients who participated in the PSUMMIT 2 study inRussia, AEs were seen in a total of 25 (62.5%) patients, serious AEs being absent. Conclusion. The results of the PSUMMIT 1 and PSUMMIT studies in the Russian population indicated that UST treatment contributed to a significant reduction of PS symptoms and exhibited a good tolerability. DOI: http://dx.doi.org/10.14412/1995-4484-2015-125-133

Abstract 255: Addition of biologic therapy to traditional disease-modifying anti-inflammatory drugs and the risk of cancer in patients with rheumatoid arthritis: a nationwide cohort study

Abstract Background: Rheumatoid arthritis (RA) is associated with certain types of cancer. The add-on effect of biologics on cancer occurrence in long-term RA remains unknown. We aimed to investigate the relative risk of cancer development among RA patients combining biologics with traditional disease-modifying anti-rheumatic drugs (DMARDs). Methods: We conducted a nationwide cohort study between March 2003 and December 2010 using the Taiwan National Health Insurance Research Database (NHIRD). A total of 42,263 patients with RA who received long term DMARDs were identified. The risk of newly diagnosed cancer was compared between patients taking biologics in addition to DMARDs (biologics cohort, N=4,119) and four-fold propensity score-matched control patients taking nonbiologic DMARDs only (biologics-naive cohort, N=16,476). Cumulative incidences and hazard ratios (HR) were calculated after adjusting for competing mortality. Multivariate analyses were performed using Cox proportional hazards model. Results: The incidence rates of cancer among biologics and biologics-naive cohorts were 2.09 (95% confidence interval [CI] 1.31-2.86) and 3.25 (95% CI 2.76-3.74) per 1000 person-years, respectively (p=0.03). On modified Cox proportional hazards analysis, the risk of cancer was significantly reduced in subjects in biologics cohort (adjusted HR 0.61, 95% CI 0.40-0.94, p=0.025) in comparison with subjects in biologics-naive cohort, after adjusting for age, gender, disease duration, major co-morbidities, and prior use of DMARDs and corticosteroids. The effect of biologics was consistent across all multivariate stratified analyses; and the association between biologics use and cancer risk was independent of dosage of concomitant use of non-biological DMARDs. Conclusion: RA patients taking biologics plus long term traditional DMARDs therapy are associated with a lower risk of cancer when compared with RA patients taking traditional DMARDs alone. Citation Format: Yi-Ju Chen, Chun-Ying Wu, Der-Yuan Chen, Jui-Lung Shen, Hsiu J. Ho, Han-Nan Liu, Yun-Ting Chang, Ken-Nan Kuo. Addition of biologic therapy to traditional disease-modifying anti-inflammatory drugs and the risk of cancer in patients with rheumatoid arthritis: a nationwide cohort study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 255. doi:10.1158/1538-7445.AM2014-255

The prediction and long-term maintenance of low disease activity during therapy with disease modifying anti-inflammatory drugs for rheumatoid arthritis

Therapy with biological agents (biologics) over the past few years has become an important part of the strategy of medical treatment of patients with rheumatoid arthritis who respond insufficiently to the disease modifying anti-inflammatory drugs. The possibility to predict response to biologics is of special importance. Factors associated with good response to TNF-inhibitors are very different: age, liver and kidney function, body mass index, concomitant therapy, immunogenicity, the presence of ACPA and the rheumatoid factor, the cytokine profile, genetics, smoking, previous therapy by biologics etc. Another factor that significantly affects the long-term prognosis of biologic therapy is the primary response to treatment. Inhibitors of TNF-α as a whole is characterized by the development of the most marked clinical response within the first 12–24 weeks of treatment that can sustain for 12 months or more. Certolizumab pegol is characterized by rapid development of marked clinical response to treatment against disease activity and function with maintaining consistent improvement over the years, and the prognosis can be determined in most patients by the response to therapy in the first 12 weeks. We present a clinical case.

SAT0576-HPR Hand Pains and General Pain in Women and Men in Early RA, a One Year Follow Up after Diagnosis in the Tira-2 Cohort

BackgroundPain in Rheumatoid arthritis (RA) is more prevalent in women than men. Hand involvement in RA is associated with hand pain, low grip force and reduced grip ability. Hand pain...

Possible reasons for the inefficacy of genetically engineered biological agents in rheumatoid arthritis and ways of its prevention

Genetically engineered biological agents (GEBAs) have held a firm place in the treatment of rheumatoid arthritis (RA). Patients are selected for this treatment in accordance with international and Russian guidelines. The question as to whether GEBAs should be added to therapy with disease-modifying anti-inflammatory drugs (DMAIDs) is raised after there is an inadequate response to therapy with two DMAIDs, one of which should be methotrexate. Tumor necrosis factor-α (TNF-α) inhibitors as a first-line drug are indicated only in high RA activity. There are few predictors of the efficacy of GEBAs. It is noted that in accordance with the principles of the Treatment to Target program, RA is treated under control of monthly estimated scores in patients with high/moderate disease activity; if there is no remission (with low disease activity being an alternative aim) after three months it is decided whether to correct therapy. In routine practice, when the effect of GEBAs, which is observed in many patients in the first week of treatment, appears, physicians often begin to discontinue symptomatic drugs and at times to decrease the dose or withdraw DMAIDs, which may result in the progression of symptoms of arthritis and which may be misinterpreted as the inadequate or none effect of GEBAs. There are objective reasons for the possible inefficacy of GEBAs. The valid predictor for a response to inhibitors of TNF-α is its baseline expression by synovial membrane cells. It is also important to take into account the nature of previous GEBA therapy. All GEBAs are noted to be highly effective when applying a weighed approach to selecting and managing patients; in so doing, rapid discontinuation of symptomatic therapy should be avoided.

Golimumab for the treatment of psoriatic arthritis

This paper presents a summary of the evidence review group (ERG) report into the use of golimumab for the treatment of psoriatic arthritis (PsA). The main clinical effectiveness data were derived from a single phase III randomised controlled trial (RCT: GO-REVEAL) that compared golimumab with placebo for treating patients with active and progressive PsA who were symptomatic despite the use of previous disease-modifying antirheumatic drugs or non-steroidal anti-inflammatory drugs. The 14-week data showed that, compared with placebo, golimumab 50 mg significantly improved joint disease response as measured by American College of Rheumatology (ACR) 20 [relative risk (RR) 5.73, 95% confidence interval (CI) 3.24 to 10.56] and Psoriatic Arthritis Response Criteria (PsARC) (RR 3.45, 95% CI 2.49 to 4.87), and skin disease response as measured by the Psoriasis Area and Severity Index (PASI) 75 (RR 15.95, 95% CI 4.62 to 59.11). The 24-week absolute data showed that these treatment benefits were maintained. There was a significant improvement in patients' functional status as measured by the Health Assessment Questionnaire (HAQ) change from baseline at 24 weeks (-0.33, p < 0.001). The open-label extension data showed that these beneficial effects were also maintained at 52 and 104 weeks. However, PASI 50 and PASI 90 at 14 weeks, and all of the PASI outcomes at 24 weeks, were not performed on the basis of intention-to-treat analysis. Furthermore, analyses of the 24-week data were less robust, failing to adjust for treatment contamination due to patient crossover at week 16. The manufacturer conducted a mixed treatment comparison (MTC) analysis. The ERG considered the assumption of exchangeability between the trials for the purpose of the MTC analysis to be acceptable, and the statistical approach in the MTC analysis to be reliable. Regarding the safety evaluation of golimumab, the manufacturer failed to provide longer-term data or to consider adverse event data of golimumab from controlled studies in other conditions, such as rheumatoid arthritis and ankylosing spondylitis. Although the adverse effect profile of golimumab appears similar to other anti-tumour necrosis factor (TNF) agents, the longer-term safety profile of golimumab remains uncertain. The manufacturer's submission presented a decision model to compare etanercept, infliximab, golimumab and adalimumab versus palliative care for patients with PsA. In the base-case model, 73% of the cohort of patients were assumed to have significant psoriasis (> 3% of body surface area). Estimates of the effectiveness of anti-TNF agents in terms of PsARC, HAQ change and PASI change were obtained from an MTC analysis of RCT data. The manufacturer failed to calculate incremental cost-effectiveness ratios (ICERs) correctly by comparing golimumab with palliative care instead of the most cost-effective alternative (etanercept). Despite the manufacturer's claim that golimumab is a cost-effective treatment option, the manufacturer's own model showed that golimumab is not cost-effective compared with other biologics when the ICERs are correctly calculated. None of the sensitivity analyses carried out by the manufacturer or the ERG regarding uncertainty in the estimates of clinical effectiveness, the acquisition and administration cost of drugs, the cost of treating psoriasis and the utility functions estimated to generate health outcomes changed this conclusion. However, a key area in determining the cost-effectiveness of anti-TNF agents is whether they should be treated as a class. If all anti-TNF agents are considered equally effective then etanercept, adalimumab and golimumab have very nearly equal costs and equal quality-adjusted life-years (QALYs), and all have an ICER of about £ 15,000 per QALY versus palliative care, whereas infliximab with a higher acquisition cost is dominated by the other biologics.