scholarly journals Clinical significance of the direct analgesic effect of targeted medications in patients with rheumatoid arthritis

2020 ◽  
Vol 4 (8) ◽  
pp. 483-486
Author(s):  
E.V. Zhilyaev ◽  
◽  
G.V. Lukina ◽  
E.N. Koltsova ◽  
E.I. Shmidt ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Significance ◽  
Analgesic Effect ◽  
Genetically Engineered ◽  
Tender Joint Count ◽  
Confounding Factors ◽  
Subjective Indicators ◽  
Anti Inflammatory ◽  
Objective Indicators ◽  
Selection Of

Aim: to evaluate the possibility of clinically significant analgesic effect of tofacitinib in patients with rheumatoid arthritis (RA) under the conditions of actual clinical practice. Patients and Methods: data of patients with RA from the Moscow Unified Register of Arthritis (MERA) were analyzed. The subjective indica-tors included tender joint count (TJC), the HAQ (Health Assessment Questionnaire) Functional Capacity Index, the RAPID3 (Routine Assess-ment of Patient Index Data 3) Disease Activity Index. Swollen joint count (SJC) and the level of C-reactive protein (CRP) were analyzed as objective indicators of inflammatory activity. The estimation was conducted of the quotient obtained when subjective indicators were divided by objective indicators in all possible combinations for various targeted medications used in the studied group of patients. Given the observa-tional nature of the study, the search was carried out for confounding factors for all of these quotients. The calculated indices were compared during treatment with various targeted medications, adjusted for detected confounding factors. The process of selecting confounding factors was carried out in 2 stages — preliminary selection of indicators that have a significant one-factor association with the dependent variable, and subsequent reverse stepwise selection of variables within the framework of a generalized linear model.Results: the analysis included 944 episodes of treatment in 832 patients. The duration of episodes was 1312±1006 days. In particular, 93 epi-sodes of tofacitinib treatment were analyzed (average duration — 836±453 days). When the analysis was adjusted for the detected confound-ing factors, it was found that the indicators of TJC/(SJC+1), HAQ/(SJC+1) and RAPID3/(SJC+1) during tofacitinib therapy were significantly lower than the average values obtained with target medications. There were no significant differences between the medications in relation to the studied subjective indicators and the level of CRP.Conclusions: the severity of subjective perceptions and functional disorders in patients treated with tofacitinib may be less with the same severity of arthritis objective indicators compared to genetically engineered anti-inflammatory drugs.KEYWORDS: targeted medication, genetically engineered anti-inflammatory drug, tofacitinib, rheumatoid arthritis, real clinical practice.FOR CITATION: Zhilyaev E.V., Lukina G.V., Koltsova E.N. et al. Clinical significance of the direct analgesic effect of targeted medications in patients with rheumatoid arthritis. Russian Medical Review. 2020;4(8):483–486. DOI: 10.32364/2587-6821-2020-4-8-483-486.

scholarly journals SAT0161 THE ANALGESIC EFFECT OF TOFACITINIB MAY HAVE CLINICAL SIGNIFICANCE IN PATIENTS WITH RHEUMATOID ARTHRITIS. DATA FROM THE MOSCOW UNIFIED REGISTER OF ARTHRITIS (MUAR)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1021.2-1021
Author(s):  
E. Zhilyaev ◽  
G. Lukina ◽  
E. Koltsova ◽  
E. Shmidt ◽  
K. Lytkina
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Significance ◽  
Analgesic Effect ◽  
Activity Index ◽  
Theoretical Data ◽  
Disease Activity Index ◽  
Subjective Indicators ◽  
Ability Index ◽  
Subjective Estimates ◽  
Objective Indicators

Background:Some theoretical data suggest that the JAK-kinase blocker tofacitinib (TOFA) may have a direct analgesic effect.Objectives:to evaluate the clinical significance of the analgesic effect in patients with rheumatoid arthritis (RA) in real clinical practice.Methods:Hypothesis being tested: the analgesic effect of TOFA may be manifested by a decrease in the ratio of subjective to objective indicators of arthritis activity.Data from RA patients receiving biologics (bDMARD) and/or TOFA and included in the MUAR register were analyzed. The tender joints count (TJC), the HAQ-DI functional ability index, and the RAPID3 disease activity index were considered as subjective estimates. The swollen joints count (SJC) and the level of CRP were treated as objective indicators. The estimation of quotients from the division of subjective indicators into objective ones in all combinations is made.Taking into account the observational nature of the study, we searched for confounders for each of these ratios. Comparison of the calculated indices during the treatment with various targeted DMARDs (tDMARDs) was made with an adjustment for the detected confounders.Results:the analysis included 944 treatment episodes in 832 patients, including 93 episodes of TOFA treatment. The average age was 55.3 ± 12.4 years, women - 698 (83.9%), seropositive for RF -672 (80.8%). The analysis of the adjusted values showed that the ratios of the TJC, HAQ-DI and RAPID3 to the SJC during the treatment with TOFA was significantly lower than with tDMARDs on average. There were no significant differences in the ratios of objective indicators to the CRP level (Table).Table.Ratios of objective and subjective indicators during the treatment with tofacitinib and with tDMARDs therapy in generalConclusion:the severity of subjective feelings and functional disorders in RA patients receiving TOFA may be less with the same level of objective signs of arthritis compared with bDMARDs.Disclosure of Interests:Evgeniy Zhilyaev Speakers bureau: Novartis, UCB, Pfizer, Biocad, Abbvie, MSD, Roche, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Ekaterina Koltsova: None declared, Evgeniya Shmidt Speakers bureau: MSD, Novartis, Pfizer, Karine Lytkina Speakers bureau: Novartis, Eli Lilly, Pfizer, UCB, Abbvie, Biocad, MSD, Jonson&Jonson

scholarly journals AB1080 OPTICAL SPECTRAL TRANSMISSION IMAGING SCORES DECREASE AFTER ONE MONTH OF BIOLOGICAL THERAPY, ESPECIALLY IN RHEUMATOID ARTHRITIS PATIENTS WHO RESPOND TO THERAPY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1829.2-1829
Author(s):  
A. Blanken ◽  
C. J. Van der Laken ◽  
M. Nurmohamed
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Response To Therapy ◽  
Tender Joint Count ◽  
Imaging Method ◽  
Spectral Transmission ◽  
Transmission Imaging ◽  
Before And After ◽  
Anti Inflammatory ◽  
Inflammatory Changes

Background:Optical spectral transmission imaging (OST) is a new imaging method that measures inflammation in the hands of rheumatoid arthritis (RA) patients. OST might be used to assess disease activity instead of disease activity score 28 (DAS28) or ultrasonography (US). The advantage of OST is that it is fast and not operator dependent. Up to now OST has only been investigated cross-sectionally and it is unknown if and to what extent OST can detect inflammatory changes due to anti-inflammatory treatment for RA.Objectives:To compare OST measurements before and after 1 month of biological treatment for RA and to compare these OST changes with changes on US and disease activity.Methods:The HandScan device from Hemics, the Netherlands, was used to measure OST scores for 13 RA patients before and after 1 month of anti-inflammatory therapy. Treatment included tumor necrosis factor inhibitor (n=10), tocilizumab (n=2) and tofacitinib (n=1). OST scores range from 0-66 (one score for both hands) and are based on bilateral wrist, MCP and PIP joints. US was performed in the same joints as OST and semi-quantitatively scored on a scale of 0-3 for grey-scale (GS) synovitis and power Doppler (PD) signal. Joint scores of GS synovitis or PD were summed, resulting is a total GS synovitis score and a total PD score, both also ranging from 0-66. Furthermore, tender joint count 28 (TJC28), swollen joint count 28 (SJC28), DAS28, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined. Response to therapy was defined as achieving the minimal clinically interesting improvement of DAS28 (DAS28 difference after 1 month > -1) as proposed by Ward et al. [1]Results:Baseline OST was 17.73 ± 6.10 and this significantly decreased to 16.01 ± 6.68 (difference -1.71, 95%CI 0.05-3.38, p=0.045) after 1 month of therapy. This decrease was only present in patients who responded to therapy (n=8; OST decreased from 17.24 ± 5.98 to 14.26 ± 5.65, p=0.01) and not in non-responders (n=5; OST increased from 18.52 ± 6.90 to 18.83 ± 7.87, p=0.03).In the total group, also DAS28 (difference -1.59, 95%CI 0.74-2.45, p=0.002), SJC28 (difference 4.62, 95%CI 1.50-7.73, p=0.007), ESR (Wilcoxon Rank p=0.008) and CRP (Wilcoxon Rank p=0.03) significantly decreased after 1 month of therapy, but TJC28 did not (difference 2.62, 95%CI -2.7-7.91, p=0.30).OST change after 1 month of therapy significantly correlated with TCJ28 change (table 1). For GS synovitis the correlation coefficient nearly reached statistical significance. Changes in all other disease activity parameters were not correlated with OST change.Table 1.Correlation of change in OST measurement with change in disease activity after 1 months of anti-inflammatory therapySpearman rp-valueTotal GS synovitis0.540.06Total PD0.220.47DAS280.350.25SJC280.290.33TJC280.630.02ESR-0.420.15CRP-0.230.45Conclusion:OST scores significantly decreased after 1 month of anti-inflammatory therapy and only in the RA group that responded well to this therapy. This indicates that OST is capable of detecting therapy induced inflammatory changes in the hands of RA patients. Larger studies are needed to further assess the monitoring value of OST for therapy efficacy in RA patients.References:[1]Ward et al. 2015 Clinically important changes in individual and composite measures of rheumatoid arthritis activity: thresholds applicable in clinical trials. Ann Rheum Dis 74(9): p. 1691-6.Disclosure of Interests:Annelies Blanken: None declared, C.J. van der Laken: None declared, Michael Nurmohamed Grant/research support from: Not related to this research, Consultant of: Not related to this research, Speakers bureau: Not related to this research

scholarly journals Amlodipine modulation of analgesic effect of non-steroidal anti-inflammatory drugs in rheumatoid arthritis, comorbid with arterial hypertension

2020 ◽  
Vol 11 (4) ◽  
pp. 557-562
Author(s):  
N. M. Seredynska ◽  
V. I. Kornienko ◽  
D. V. Kibkalo ◽  
O. S. Suvorova ◽  
O. M. Marchenko ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Arterial Hypertension ◽  
Analgesic Activity ◽  
Analgesic Effect ◽  
Adjuvant Arthritis ◽  
Pain Sensitivity ◽  
Acute Period ◽  
Combined Use ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

 With the interaction of drugs belonging to different pharmacotherapeutic groups – nonsteroidal anti-inflammatory and antihypertensive – against the background of comorbid arterial hypertension with rheumatoid arthritis, the activity and safety of drugs may change with their combined use. Changes in the analgesic activity of nonsteroidal anti-inflammatory drugs, different in their selectivity to the types of cyclooxygenase (diclofenac, nimesulide and celecoxib), under the conditions of their long-term combined use with amlodipine in different periods of inflammation against the background of hypertension should be studied. Using the model of adjuvant arthritis comorbid with hypertension, in experiments on nonlinear mature white rats, the threshold of pain sensitivity has been determined by means of the “tail flick” test. Hypertension was caused by salt load with 1% sodium chloride solution for drinking with free access to it. Adjuvant arthritis was induced by the introduction of complete Freund’s adjuvant into the plantar aponeurosis of the hind limb of each animal with the established arterial hypertension. Against the background of arterial hypertension and comorbid pathology, there was an increase in the threshold of pain sensitivity observed in rats, which indicated the development of hypoalgesia. When combined, amlodipine enhanced the analgesic activity of diclofenac during 60 days of observation, slightly heightened the analgesic effect of nimesulide – up to 42 days, the effect of Celecoxib – in the acute period and the period of manifestation of adjuvant arthritis against the background of hypertension. The antinociceptive effect of diclofenac with amlodipine and celecoxib with amlodipine exceeded the analgesic effect of the combined nimesulide with amlodipine use against the background of comorbid pathology. The results obtained can be taken into account under the conditions of prescribing drugs belonging to the studied pharmacotherapeutic groups. It is likely that the use of diclofenac for analgesia against the background of comorbid conditions is only appropriate in the acute period of rheumatoid arthritis. The use of nimesulide to achieve an analgesic effect in the recurrence of rheumatoid arthritis against the background of hypertension is appropriate in the acute period and in the period of the inflammatory process attenuation. A highly selective coxib group cyclooxygenase-2 inhibitor, celecoxib, can reduce pain during the acute period of arthritis and during the manifestation of an inflammatory reaction that has developed against the background of arterial hypertension.

Potential Effect of Anti-Inflammatory Treatment on Reducing the Cardiovascular Risk in Rheumatoid Arthritis

2012 ◽  
Vol 10 (5) ◽  
pp. 639-646 ◽  
Author(s):  
Cecilia Chighizola ◽  
Tommaso Schioppo ◽  
Francesca Ingegnoli ◽  
Pier Luigi Meroni
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Risk ◽  
Potential Effect ◽  
Anti Inflammatory

Evaluation of Serum Calprotectin Level and Disease Activity in Patients with Rheumatoid Arthritis

2019 ◽  
Vol 15 (4) ◽  
pp. 316-320
Author(s):  
Mir Amir Aghdashi ◽  
Seyedmostafa Seyedmardani ◽  
Sholeh Ghasemi ◽  
Zohre Khodamoradi
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Arthritis ◽  
Unknown Etiology ◽  
Tender Joint Count ◽  
Serum Samples ◽  
Tender Joint ◽  
Cross Sectional ◽  
Calprotectin Level ◽  
Remission Phase

Background: Rheumatoid Arthritis (RA) is the most common type of chronic inflammatory arthritis with unknown etiology marked by a symmetric, peripheral polyarthritis. Calprotectin also can be used as a biomarker of disease activity in inflammatory arthritis and other autoimmune diseases. Objective: In this study, we evaluated the association between serum calprotectin level and severity of RA activity. Methods: A cross-sectional study was conducted on 44 RA patients with disease flare-up. Serum samples were obtained from all patients to measure calprotectin, ESR, CRP prior to starting the treatment and after treatment period in the remission phase. Based on Disease Activity Score 28 (DAS28), disease activity was calculated. Results: Of 44 RA patients, 9(20.5%) were male and 35(79.5%) were female. The mean age of our cases was 53±1.6 years. Seventeen (38.6%) patients had moderate DAS28 and 27(61.4%) had high DAS28. The average level of calprotectin in the flare-up phase was 347.12±203.60 ng/ml and 188.04±23.58 ng/ml in the remission phase. We did not find any significant association between calprotectin and tender joint count (TJC; P=0.22), swollen joint count (SJC; P=0.87), and general health (GH; P=0.59), whereas significant associations were found between the calprotectin level and ESR (p=0.001) and DAS28 (p=0.02). The average calprotectin level in moderate DAS28 (275.21±217.96 ng/ml) was significantly lower than that in high DAS28 (392.4±183.88 ng/ml) (p=0.05). Conclusion: We showed that the serum level of calprotectin can be a useful and reliable biomarker in RA activity and its severity. It also can predict treatment response.

Helenalin: An Anti-Inflammatory and Anti-Neoplastic Agent: A Review

2020 ◽  
Vol 16 (8) ◽  
pp. 1134-1146
Author(s):  
Priyanka Kriplani ◽  
Kumar Guarve ◽  
Uttam S. Baghel
Keyword(s):  
Rheumatoid Arthritis ◽  
Adverse Effects ◽  
Chronic Conditions ◽  
Review Article ◽  
Google Scholar ◽  
Medical Community ◽  
Inflammatory Agent ◽  
Skin Cancers ◽  
Medicinal Properties ◽  
Anti Inflammatory

Objective: Helenalin is a natural anti-inflammatory agent that is proving its efficacy to treat various medical conditions. Though many plants are proving their effectiveness but their mechanisms are still not well understood. The objective of the review is to summarize various mechanisms of helenalin to treat inflammatory disorders and cancers, adverse effects, and avenues of further research. Methods: Structured research was carried out including Pub med, Science direct Medline, Research Gate and Google Scholar to find all articles published on helenalin. Various keywords used were “helenalin”, “Arnica”, “cancer”, “anti-inflammatory”, “cardiovascular”, “IBD”, “pharmacokinetics” etc. The aim of the review was to find out the problem prevailing in the data published to date which will help the researchers to investigate the molecule clinically. Results: Seventy articles are included in the review. Helenalin is found to cure chronic conditions like rheumatoid arthritis, ulcers and malignancies like stomach, colon, breast, larynx, lung and skin cancers via multiple mechanisms. These diseases do not proceed via a unilateral pathway. So, it can be a useful molecule to treat numerous diseases. Conclusion: This review article will help us to systemically analyze the wealth of information concerning the medicinal properties of helenalin and to recognize the gaps which have vetoed its pervasive application in the medical community.

scholarly journals Distinct Roles of Vav Family Members in Adaptive and Innate Immune Models of Arthritis

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 695
Author(s):  
Javier Conde ◽  
Isabel Fernández-Pisonero ◽  
Myriam Cuadrado ◽  
Antonio Abad ◽  
Javier Robles-Valero ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Family Members ◽  
Experimental Models ◽  
Innate Immune ◽  
Main Role ◽  
Zymosan A ◽  
Proliferation And Differentiation ◽  
Signal Transduction Proteins ◽  
Selection Of

Genetic evidence suggests that three members of the VAV family (VAV1, VAV2 and VAV3) of signal transduction proteins could play important roles in rheumatoid arthritis. However, it is not known currently whether the inhibition of these proteins protects against this disease and, if so, the number of family members that must be eliminated to get a therapeutic impact. To address this issue, we have used a collection of single and compound Vav family knockout mice in experimental models for antigen-dependent (methylated bovine serum albumin injections) and neutrophil-dependent (Zymosan A injections) rheumatoid arthritis in mice. We show here that the specific elimination of Vav1 is sufficient to block the development of antigen-induced arthritis. This protection is likely associated with the roles of this Vav family member in the development and selection of immature T cells within the thymus as well as in the subsequent proliferation and differentiation of effector T cells. By contrast, we have found that depletion of Vav2 reduces the number of neutrophils present in the joints of Zymosan A-treated mice. Despite this, the elimination of Vav2 does not protect against the joint degeneration triggered by this experimental model. These findings indicate that Vav1 is the most important pharmacological target within this family, although its main role is limited to the protection against antigen-induced rheumatoid arthritis. They also indicate that the three Vav family proteins do not play redundant roles in these pathobiological processes.

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