Pain in Rheumatoid Arthritis: Could JAK Inhibition be the Answer?

Mehta, Puja; Taylor, Peter

doi:10.31138/mjr.31.1.112

Cited by 4 publications

(5 citation statements)

References 46 publications

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“…Emerging evidence suggests that where pain is a predominant symptom in RA, there may be some advantages in swapping to a JAKi over cycling anti-TNFs 59 as JAKi appear to have beneficial effects on inflammatory and non-inflammatory pain in general. 60 Such findings are consistent with the overarching involvement of the JAK-signal transducer and activator of transcription pathway in mediating the action, expression, and regulation of multiple pro- and anti-inflammatory cytokines. 61 It is also possible that the use of an oral medication could reduce the perception of pain in patients who are needle phobic.…”

Section: Potential Selection Criteria For Treatment Following First-l...supporting

confidence: 75%

Managing inadequate response to initial anti-TNF therapy in rheumatoid arthritis: optimising treatment outcomes

Taylor

Matucci‐Cerinic

Alten

et al. 2022

Therapeutic Advances in Musculoskeletal

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Anti-tumour necrosis factors (anti-TNFs) are established as first-line biological therapy for rheumatoid arthritis (RA) with over two decades of accumulated clinical experience. Anti-TNFs have well established efficacy/safety profiles along with additional benefits on various comorbidities. However, up to 40% of patients may respond inadequately to an initial anti-TNF treatment because of primary non-response, loss of response, or intolerance. Following inadequate response (IR) to anti-TNF treatment, clinicians can consider switching to an alternative anti-TNF (cycling) or to another class of targeted drug with a different mechanism of action, such as Janus kinase inhibitors, interleukin-6 receptor blockers, B-cell depletion agents, and co-stimulation inhibitors (swapping). While European League Against Rheumatism recommendations for pharmacotherapeutic management of RA, published in 2020, are widely regarded as helpful guides to clinical practice, they do not provide any clear recommendations on therapeutic choices following an IR to first-line anti-TNF. This suggests that both cycling and swapping treatment strategies are of equal value, but that the treating physician must take the patient’s individual characteristics into account. This article considers which patient characteristics influence clinical decision-making processes, including the reason for treatment failure, previous therapies, comorbidities, extra-articular manifestations, pregnancy, patient preference and cost-effectiveness, and what evidence is available to support decisions made by the physician.

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Section: Potential Selection Criteria For Treatment Following First-l...supporting

confidence: 75%

Managing inadequate response to initial anti-TNF therapy in rheumatoid arthritis: optimising treatment outcomes

Taylor

Matucci‐Cerinic

Alten

et al. 2022

Therapeutic Advances in Musculoskeletal

Self Cite

View full text Add to dashboard Cite

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“…Among them, the early and sustained pain relief stands out, as has been noted with JAKis in RA as well, and merits further investigation. 67 The recent publication of the SELECT AXIS 2 trials of upadacitinib in patients refractory to bDMARDs and patients with nr-axSpA, completed the picture by demonstrating efficacy over the whole spectrum of axSpA.…”

Section: Discussionmentioning

confidence: 99%

JAK Inhibitors for the Treatment of Axial Spondyloarthritis

Klavdianou,

Papagoras,

Baraliakos

2023

MJR

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Axial spondyloarthritis (axSpA) is a chronic disease characterized by inflammation and new bone formation that causes pain and results in functional impairment and long-term disability. Biologic agents targeting TNFα or IL-17 have been the mainstay of treatment for patients with axSpA and an inadequate response to nonsteroidal anti-inflammatory drugs. However, a proportion of axSpA patients do not respond adequately to those drugs either, creating the need to target alternative disease pathways. Janus kinase (JAK) inhibitors (JAKis) are a group of targeted synthetic disease-modifying anti-rheumatic drugs that block the intracellular signalling pathway of several proinflammatory cytokines. Given their efficacy in the management of rheumatoid arthritis and that JAKs mediate the signalling of cytokines involved in the pathogenesis of axSpA as well, JAKis have been successfully tested in a number of clinical trials in axSpA, which has led to the approval of two compounds, tofacitinib and upadacitinib for the treatment of the disease. Data from new clinical trials, long-term extensions of completed trials, and real-life observational studies that continuously emerge will shape the efficacy and safety profile and ultimately the place of JAKis in the treatment of AxSpA.

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“…If data were missing, the number of patients with valid data is also presented. Given the escalation/initiation of anti-inflammatory treatment at baseline, this table presents frequencies for treatment categories until baseline (1) and the treatment prescribed at baseline (2) . *Adjunctive pain therapy includes any type of non-drug pain treatment documented from baseline but not until baseline.…”

Section: Das28 and Symptom-specific Prosmentioning

confidence: 99%

Predictors for severe persisting pain in rheumatoid arthritis are associated with pain origin and appraisal of pain

Baerwald,

Stemmler,

Gnüchtel

et al. 2024

Ann Rheum Dis

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ObjectivesTo determine the proportion of patients with rheumatoid arthritis (RA) with severe persisting pain and to identify predictive factors despite treatment-controlled disease activity.MethodsThis prospective multicentre study included outpatients with RA scheduled for escalation of anti-inflammatory treatment due to active disease and severe pain (Disease Activity Score 28 (DAS28)>3.2 and Visual Analogue Scale (VAS)>50). At week 24, patients were stratified into reference group (DAS28 improvement>1.2 or DAS28≤3.2 and VAS pain score<50), non-responders (DAS28 improvement≤1.2 and DAS28>3.2, regardless of VAS pain score) and persisting pain group (DAS28 improvement>1.2 or DAS28≤3.2 and VAS pain score≥50). The former two subgroups ended the study at week 24. The latter continued until week 48. Demographic data, DAS28-C reactive protein, VAS for pain, painDETECT Questionnaire (PD-Q) to identify neuropathic pain (NeP) and the Pain Catastrophising Scale were assessed and tested for relation to persisting pain.ResultsOf 567 patients, 337 (59.4%) were classified as reference group, 102 (18.0%) as non-responders and 128 (22.6%) as patients with persisting pain. 21 (8.8%) responders, 28 (35.0%) non-responders and 27 (26.5%) persisting pain patients tested positive for NeP at week 24. Pain catastrophising (p=0.002) and number of tender joints (p=0.004) were positively associated with persisting pain at week 24. Baseline PD-Q was not related to subsequent persisting pain.ConclusionsPersisting and non-nociceptive pain occur frequently in RA. Besides the potential involvement of NeP, pain catastrophising and a higher number of tender joints coincide with persisting pain.

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Pain in Rheumatoid Arthritis: Could JAK Inhibition be the Answer?

Cited by 4 publications

References 46 publications

Managing inadequate response to initial anti-TNF therapy in rheumatoid arthritis: optimising treatment outcomes

Managing inadequate response to initial anti-TNF therapy in rheumatoid arthritis: optimising treatment outcomes

JAK Inhibitors for the Treatment of Axial Spondyloarthritis

Predictors for severe persisting pain in rheumatoid arthritis are associated with pain origin and appraisal of pain

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