AB0135 A VERY EARLY CLINICAL RESPONSE TO TOFACITINIB IS ASSOCIATED WITH LOW RHEUMATOID ARTHRITIS ACTIVITY AFTER 3 AND 6 MONTHS

Background:JAK inhibitors block intracellular signaling pathways responsible for the synthesis of cytokines and mediators involved in the development of chronic pain and central sensitization (CS). This determines a very rapid clinical response to JAK inhibitors. However, it is not clear how the significant pain reduction in the first weeks of therapy is associated with the achievement of low rheumatoid arthritis (RA) activity.Objectives:to assess the relationship between the early clinical response to tofacitinib and the decrease in RA activity after 3 and 6 months.Methods:Study group included 88 patients with RA, their age was 53±11,5, 79.3% of women, 89.8% of RF “+”, DAS28 5.2±1.2, receiving DMARDs (methotrexate 59.5% and leflunomide 19.8%), who were administered with tofacitinib 5 mg 2 times a day due to inefficacy or intolerance of biological DMARDs. There were assessed the pain severity using Brief pain inventory (BPI) questionnaire, the presence of neuropathic pain component (NPC) using PainDETECT questionnaire and signs of CS using Central Sensitisation Inventory (CSI) questionnaire at early time after tofacitinib administration, RA activity using DAS28 after 3 and 6 months.Results:The mean pain severity at baseline was 5.3±2.0 according to the visual analogue scale (VAS 0-10), 51.1% of patients had signs of central sensitization (CSI ≥ 40), 15.9% had NPC (PainDETECT ≥18). 7 days after tofacitinib intake there was statistically reliable reduction of pain severity – up to 4.1±1.8 (р<0.05) and CS – CSI from 40.4±13.5 to 36.5±12.5 (р=0.01). After 28 days, the effect was higher: the pain level (VAS) was 2.8±1.6 (p=0.000), PainDETECT decreased from 11.8±5.6 to 6.8±3.1 (p=0.000), CSI – to 31.6±13.9 (p=0.000). DAS28 after 3 and 6 months was 3.7±1.3 and 3.6±1.2. The number of patients with pain decrease of ≥50% after 28 days of therapy was 59.9%. Low RA activity after 3 months. (DAS28 ≤3.2) was achieved in 64.4% of patients. There was a clear correlation between the number of patients with significant pain reduction at 28 days and the number of patients with low RA activity after 3 and 6 months (rS=0.548, p=0.000; rS=0.790, p=0.000). Six patients withdrew from the study due to inefficacy or social reasons. There were no serious adverse reactions.Conclusion:The application of JAK inhibitor tofacitinib allows to reach a fast analgesic effect and reduce CS signs. An early clinical response to tofacitinib (pain relief) predicts a decrease in RA activity after 3 and 6 months of the therapy.Limitation: Open-label observatory study.Disclosure of Interests:None declared

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Evaluation of the effectiveness of Tofacitinib in rheumatoid arthritis in real clinical practice: The relationship between pain relief in the first 4 weeks and disease activity after 3–6 months

Rheumatology Science and Practice ◽

10.47360/1995-4484-2021-394-400 ◽

2021 ◽

Vol 59 (4) ◽

pp. 394-400

Author(s):

A. E. Karateev ◽

E. Yu. Pogozheva ◽

V. N. Amirjanova ◽

E. S. Filatova ◽

A. M. Lila ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Pain Relief ◽

Clinical Response ◽

Central Sensitization ◽

Analgesic Effect ◽

Intracellular Signaling ◽

Pain Reduction ◽

Jak Inhibitor ◽

Number Of Patients ◽

The Relationship

The JAK inhibitor tofacitinib (TOFA) blocks the intracellular signaling pathway that activates the synthesis of cytokines and mediators involved in the development of pain and central sensitization (CS), which determines the rapid analgesic effect. However, it is not clear how pain reduction is associated with achieving low activity in rheumatoid arthritis (RA).The aim of the study was to assess the relationship between the early clinical response to tofacitinib and a decrease in rheumatoid arthritis activity after 3 and 6 months.Material and methods. The study group consisted of 88 RA patients (age – 53±11.5 years; 79.3% of women) who received basic anti-inflammatory drugs (59.5% – methotrexate, 19.8% – leflunomide) and who were prescribed TOFA in a dose 10 mg/day. Seropositivity for rheumatoid factor was 89.8%; the value of the DAS28 index is 5.2±1.2. The severity of pain was assessed using the Brief Pain Inventory questionnaire, the neuropathic component of pain (NCP) – using the PainDETECT questionnaire, signs of CS – using the Central Sensitization Inventory (CSI) questionnaire in the early stages after the administration of TOFA, RA activity – using the DAS28-CRP index after 3 and 6 months.Results. The mean severity of pain at baseline was 5.3±2.0 on the visual analogue scale (VAS); 51.1% of patients had signs of CS (CSI>40), 15.9% had NCP (PainDETECT>18). 7 days after the start of therapy, there was a significant decrease in pain – to 4.1±1.8 according to VAS (p<0.05) and CS – 40.4±13.5 to 36.5±12.5 according to CSI (p=0.01). After 28 days, the effect was even more significant: the level of pain according to the VAS was 2.8±1.6 (p=0.000), the NCP decreased from 11.8±5.6 to 6.8±3.1 (p=0.000), CS – up to 31.6±13.9 (p=0.000). The value of the DAS28-CRP index after 3 and 6 months was 3.7±1.3 and 3.6±1.2, respectively. The number of patients with pain relief ≥50% after 28 days was 59.9%, low RA activity after 3 months. (DAS28-CRP≤3.2) was acieved in 64.4% of patients. There was a clear correlation between the number of patients with a pain reduction of ≥50% at 28 days and the number of patients who achieved low RA activity at 3 and 6 months. (rS=0.548, p=0.000 and rS=0.790, p=0.000). 6 patients dropped out of the study due to inefficiency or social reasons. No serious adverse reactions were noted.Conclusions. The use of the JAK inhibitor TOFA allows achieving a quick analgesic effect and reducing the signs of CS. An early clinical response to TOFA (pain relief) predicts a decrease in RA activity after 3 and 6 months of therapy.

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THU0206 А VERY EARLY (7-28 DAYS) RESPONSE ON JAK INHIBITOR TOFACITINIB IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS: EFFECT ON PAIN AND CENTRAL SENSITIZATION.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4029 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 327.3-327

Author(s):

A. Karateev ◽

E. Filatova ◽

E. Pogozheva ◽

V. Amirdzhanova ◽

E. Nasonov ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Central Sensitization ◽

Early Time ◽

National Registry ◽

Genetically Engineered ◽

Pain Severity ◽

Signal Pathways ◽

Jak Inhibitor ◽

Jak Inhibitors ◽

Biological Drugs

Background:The presence of central sensitization (CS) significantly burdens the course of rheumatoid arthritis (RA). JAK inhibitors block intracellular signal pathways including the ones responsible for synthesis of mediators and cytokines causing pain and CS. The application of JAK inhibitors is supposed to relieve pain and reduce CS severity promptly.Objectives:To evaluate JAK inhibitor effect on pain and signs of CS in patients with active RA 7 and 28 days after the start of therapy.Methods:Study group included 39 patients with RA, their age was 50.9±11.1, 79.5% of women, 89.7% of RF “+”, DAS28 5.8±0.6, receiving DMARDs (methotrexate 82.0% and leflunomide 18.0%), who were administered with tofacitinib 5 mg 2 times a day due to inefficiency or intolerance of genetically engineered biological drugs. There were assessed the pain severity using Brief pain inventory (BPI) questionnaire, the presence of neuropathic pain component (NPC) using PainDETECT questionnaire and signs of CS using Central Sensitisation Inventory (CSI) questionnaire at early time after tofacitinib administration.Results:Patients initially experienced a severe pain – 5.72±2.21 according to the visual analogue scale (VAS), 53.8% had signs of central sensitization (CSI ≥ 40), 17.9% had NPC (PainDETECT ≥18). 7 days after tofacitinib intake there was statistically reliable reduction of pain severity – up to 4.37±2.2 (р=0.01), pain decrease of 29.4±17.9% (BPI), NCP – PainDETECT from 12.9±5.5 to 10.6±5.6 (р=0.047) and CS – CSI from 43.1±12.8 to 35.9±11.2 (р=0.01). The effect had increased after 28 days: pain level (VAS) was 2.84±1.57 (р=0.000), pain decrease of 43.6±29.6% (BPI), PainDETECT 29.8±12.4 (р=0.000), CSI 26.4±13.9 (р=0.000).During this period there were no serious adverse reactions.Conclusion:The application of JAK inhibitor tofacitinib allows to reach a fast analgesic effect, also due to impact on CS and NCP.Source: National Registry patients with RADisclosure of Interests: :Andrey Karateev: None declared, Ekaterina Filatova: None declared, Elena Pogozheva: None declared, Vera Amirdzhanova: None declared, Evgeny Nasonov: None declared, Alexander Lila: None declared, V Mazurov: None declared, N Lapkina: None declared, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Tatiana Salnikova: None declared, Ruzana Samigullina: None declared, Diana Chakieva: None declared, Irina Marusenko: None declared, Olga Semagina: None declared, Marina Semchenkova: None declared

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Clinical significance of Janus kinase inhibitors in the therapy of rheumatoid arthritis: achievements and prospects

Modern Rheumatology Journal ◽

10.14412/1996-7012-2019-4-116-123 ◽

2019 ◽

Vol 13 (4) ◽

pp. 116-123 ◽

Cited By ~ 1

Author(s):

V. I. Mazurov ◽

I. B. Belyaeva

Keyword(s):

Rheumatoid Arthritis ◽

Molecular Weight ◽

Intracellular Signaling ◽

Kinase Inhibitors ◽

Janus Kinase ◽

Jak Inhibitors ◽

Janus Kinase Inhibitors ◽

Expected Effect ◽

Signaling Systems ◽

Disease Modifying

Significant successes in the use of biological agents (BA) have been achieved in the treatment of rheumatoid arthritis (RA); nonetheless, about 36% of patients cannot respond to therapy or achieve the expected effect. A new area in the treatment of RA is the use of Janus kinase (JAK) inhibitors, targeted synthetic disease-modifying anti-rheumatic drugs (chemical molecules with a molecular weight <1 kDa for oral administration) that inhibit the activity of intracellular signaling systems. The authors consider the clinical achievements and prospects, which open the use of JAK inhibitors in the treatment of RA.

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POS0674 DIRECT COMPARISON OF EFFECTIVENESS AND SAFETY OF TOFACITINIB AND BARICITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL-WORLD SETTINGS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3469 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 581.3-581

Author(s):

N. Iwamoto ◽

T. Suzuki ◽

A. Okada ◽

K. Fujikawa ◽

T. Aramaki ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Propensity Score ◽

Disease Activity ◽

Clinical Response ◽

Treatment Response ◽

Real World ◽

Jak Inhibitors ◽

Low Disease Activity ◽

Real World Setting ◽

Significant Difference

Background:Tofacitinib is a non-selective first-generation JAK inhibitor and baricitinib was approved for the treatment of Rheumatoid arthritis several years after approve of tofacitinib. Randomized controlled trials have shown good treatment response for RA in these two drugs. However, the evaluation of these two drugs in real-world setting have been rarely reported, moreover, until now, no published data of a direct comparison among JAK inhibitors in RA have been available.Objectives:To compare the efficacy and safety of the JAK inhibitors tofacitinib and baricitinib in patients with rheumatoid arthritis (RA) by using propensity score matching in a real-world setting.Methods:A total of 242 patients with RA who were treated with tofacitinib (n=161) or baricitinib (n=81) were enrolled. To avoid confounding, we performed propensity score matching based on multiple baseline characteristic variables, and then 80 baricitinib-treated patients and 57 tofacitinib-treated patients were extracted for the direct comparison. A mixed effect model with a repeated measures analysis of variance (ANOVA) was performed to ascertain whether there were significant differences in clinical efficacy between the two treatment groups during the treatment period.Finally, We evaluated the predictive factor of clinical responses by performing univariate and multivariable logistic regression analyses.Results:The mean delta disease activity scores (DAS)28-ESR from baseline to 6 months were −1.60 (tofacitinib) and −1.46 (baricitinib). The remission rate defined by the DAS28-ESR at 24 weeks were 21.1% (tofacitinib) and 25.0% (baricitinib). There was no significant difference in the clinical response between the baricitinib-treated and tofacitinib-treated groups. Although there was no significant difference, the concomitant use of methotrexate (MTX) showed better clinical efficacy in the cases of baricitinib treatment as compared with in the case of tofacitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response differed. The concomitant use of oral steroid was independently associated with the achievement of DAS-low disease activity in both groups, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used and the DAS28-ESR at the time of initiation were associated with DAS-low disease activity.Conclusion:This study indicate that tofacitinib and baricitinib had comparable efficacies and safety profiles in a real-world setting. However, the influence of clinical characteristics on the treatment response differed between these two drugs. Direct comparison between two JAK inhibitors provide useful information to optimal use of JAK inhibitors in real-world settings.Disclosure of Interests:None declared

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Recommendations of the Brazilian Society of Rheumatology for the use of JAK inhibitors in the management of rheumatoid arthritis

Advances in Rheumatology ◽

10.1186/s42358-021-00228-x ◽

2021 ◽

Vol 61 (1) ◽

Author(s):

Karina Rossi Bonfiglioli ◽

Licia Maria Henrique da Mota ◽

Ana Cristina de Medeiros Ribeiro ◽

Adriana Maria Kakehasi ◽

Ieda Maria Magalhães Laurindo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Intracellular Signaling ◽

Treatment Algorithm ◽

Efficacy And Safety ◽

Jak Inhibitors ◽

Janus Kinases ◽

Low Disease Activity ◽

Brazilian Society ◽

Systemic Inflammatory Disease

AbstractRheumatoid arthritis (RA) is a chronic and autoimmune systemic inflammatory disease that can cause irreversible joint deformities, with increased morbidity and mortality and a significant impact on the quality of life of the affected individual. The main objective of RA treatment is to achieve sustained clinical remission or low disease activity. However, up to 40% of patients do not respond to available treatments, including bDMARDs. New therapeutic targets for RA are emerging, such as Janus kinases (JAKs). These are essential for intracellular signaling (via JAK-STAT) in response to many cytokines involved in RA immunopathogenesis. JAK inhibitors (JAKi) have established themselves as a highly effective treatment, gaining increasing space in the therapeutic arsenal for the treatment of RA. The current recommendations aim to present a review of the main aspects related to the efficacy and safety of JAKis in RA patients, and to update the recommendations and treatment algorithm proposed by the Brazilian Society of Rheumatology in 2017.

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SAT0153 GENDER DOES NOT INFLUENCE CLINICAL RESPONSE TO JAK INHIBITORS IN RHEUMATOID ARTHRITIS: AN ITALIAN MULTICENTRE ANALYSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5978 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1016.2-1017

Author(s):

F. R. Spinelli ◽

M. S. Chimenti ◽

M. Vadacca ◽

C. Iannuccelli ◽

P. Conigliaro ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Clinical Response ◽

Social Impact ◽

Disease Duration ◽

Female Gender ◽

Clinical Feature ◽

Jak Inhibitors ◽

Low Disease Activity ◽

Men And Women

Background:Gender medicine aims at describing how diseases differ between men and women in terms of epidemiology, clinical feature, therapeutic approach, treatment response and prognosis, psychological and social impact. Rheumatoid Arthritis (RA) affects women 2-3 times more than men. Female gender seems to be independently associated to a more refractory disease and a worst response to conventional synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs) and biological DMARDs. Male patients achieve remission more often than females probably due to the higher number of tender joints reported by the latter.Objectives:In the light of the effect of Janus kinases inhibitors (JAKi) on pain, the objective of the study was to investigate whether gender might affect the achievement of remission or low disease activity in RA patients treated with baricitinib and tofacitinib.Methods:We performed a multicentric, prospective study on consecutive patients starting one of the two available JAKi: baricitinib and tofacitinib. Demographic and clinical data were recorded in a dedicate database and included: gender, age, disease duration, serological status (Rheumatoid Factor – RF; anti-citrullinated peptide antibodies, ACPA) number of previous csDMARDs and bDMARDs, number of tender joints (TJ) and swollen joints (SJ), C reactive protein (CRP); patient global assessment (PGA) and pain were recorded on a 0-100 mm visual-analogue scale (VAS). Disease activity score (DAS) 28 was calculated at baseline and at two follow-up visits (after 3-4 months and after 6-8 months). Data were expressed as mean±standard deviation or median (interquartile range) according to variables’ distribution. Continuous variables were compared by Mann Whitney test while dichotomous ones by Chi-squared test; p value < 0.05 were considered statistically significant.Results:We enrolled 182 RA patients (149 F:33 M) with similar age (F 58±12 vs M 60±10) and disease duration (F 143±101 vs M 147±105 months). Females and males were previously treated with the same number of csDMARDs [2(2)] but female have previously received numerically more bDMARDs [2(3) vs 1(2)]. At the 3 timepoints females and males showed similar number of TJ, SJ, similar values of CRP, PGA and pain. We did not observe any difference in percentage of males and females achieving remission or low disease activity according to gender (figure 1A) nor in terms of reduction of TJ, SJ and PGA; only pain decreased significantly more in male than in female patients at both timepoints (figure 1B).Conclusion:In RA patients treated with JAK inhibitors, even if the effect of JAKi on pain seems to be more relevant in male than in female, gender seems not to influence the overall clinical response, allowing men and women the same probability of reaching the therapeutic targetReferences:Disclosure of Interests:Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Maria Sole Chimenti: None declared, Marta Vadacca: None declared, Cristina Iannuccelli: None declared, Paola Conigliaro: None declared, Silvia Laura Bosello: None declared, Fulvia Ceccarelli: None declared, Cristina Garufi: None declared, Giulia Raffone: None declared, Paola Di Noi: None declared, Dario Bruno: None declared, Antonella Afeltra: None declared, Roberto Perricone: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB

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