Summary New treatment strategies have substantially changed the course of rheumatoid arthritis. Many patients can achieve remission if the disease is recognised early and is treated promptly and ...continuously; however, some individuals do not respond adequately to treatment. Rapid diagnosis and a treat-to-target approach with tight monitoring and control, can increase the likelihood of remission in patients with rheumatoid arthritis. In this Series paper, we describe new insights into the management of rheumatoid arthritis with targeted therapy approaches using classic and novel medications, and outline the potential effects of precision medicine in this challenging disease. Articles are included that investigate the treat-to-target approach, which includes adding or de-escalating treatment. Rheumatoid arthritis treatment is impeded by delayed diagnosis, problematic access to specialists, and difficulties adhering to treat-to-target principles. Clinical management goals in rheumatoid arthritis include enabling rapid access to optimum diagnosis and care and the well informed use of multiple treatments approved for this disease.
Current and future status of JAK inhibitors McLornan, Donal P; Pope, Janet E; Gotlib, Jason ...
The Lancet (British edition),
08/2021, Letnik:
398, Številka:
10302
Journal Article
Recenzirano
An enhanced understanding of the importance of Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signalling in multiple disease states has led to an increasing ...applicability of therapeutic intervention with JAK inhibitors. These agents have revolutionised treatments for a heterogeneous group of disorders, such as myeloproliferative neoplasms, rheumatoid arthritis, inflammatory bowel disease, and multiple immune-driven dermatological diseases, exemplifying rapid bench-to-bedside translation. In this Therapeutics paper, we summarise the currently available data concerning the successes and safety of an array of JAK inhibitors and hypothesise on how these fields could develop.
•CRP is a valuable marker and regulator of systemic inflammation in RA.•CRP levels appear to be associated with common comorbidities of RA.•CRP appears to play a direct role in bone destruction and ...disease progression in RA.•Pentameric and monomeric isoforms of CRP have different effects.•Stratification by CRP level in clinical trials may provide valuable information.
C-reactive protein (CRP) is routinely assessed as a marker of systemic inflammation in rheumatoid arthritis (RA). However, it is also an immune regulator that plays an important role in inflammatory pathways associated with RA and promotes atherogenic effects. Comorbidities linked to systemic inflammation are common in RA, and CRP has been associated with the risk for cardiovascular disease, diabetes, metabolic syndrome, pulmonary diseases, and depression. The relationship between systemic inflammation, CRP, and comorbidities in RA is complex, and it is challenging to determine how changing CRP levels may affect the risk or progression of these comorbidities. We review the biological role of CRP in RA and its implications for disease activity and treatment response. We also discuss the impact of treatment on CRP levels and whether reducing systemic inflammation and inhibiting CRP-mediated inflammatory pathways may have an impact on conditions commonly comorbid with RA.
Fatigue in rheumatoid arthritis is highly prevalent. It is correlated only weakly with disease activity but more so with pain, mood, personality features, poor sleep, obesity and comorbidities. ...Fatigue can be measured by many standardised questionnaires and more easily with a Visual Analogue Scale or numeric rating scale. Most patients with RA have some fatigue, and at least one in six have severe fatigue. Chronic pain and depressed mood are also common in RA patients with significant fatigue. It affects function and quality of life and is worse on average in women. Evidence-based treatment for fatigue includes treatment of underlying disease activity (with on average modest improvement of fatigue), exercise programmes and supervised self-management programmes with cognitive-behavioural therapy, mindfulness and reinforcement (such as reminders). The specific programmes for exercise and behavioural interventions are not standardised. Some medications cause fatigue such as methotrexate. More research is needed to understand fatigue and how to treat this common complex symptom in RA that can be the worst symptom for some patients.
Objective
There is a lack of agreement regarding treatment for many aspects of systemic sclerosis (SSc). We undertook this study to generate SSc treatment algorithms endorsed by a high percentage of ...SSc experts.
Methods
Experts from the Scleroderma Clinical Trials Consortium and the Canadian Scleroderma Research group (n = 170) were asked whether they agreed with SSc algorithms from 2012. Two consensus rounds refined agreement; 62, 54, and 48 experts (36%, 32%, and 28%, respectively) completed the first, second, and third surveys, respectively.
Results
For treatment of scleroderma renal crisis, 81% of experts agreed (first‐, second‐, and third‐line treatments were angiotensin‐converting enzyme inhibitors, then adding calcium‐channel blockers CCBs, then adding angiotensin receptor blockers ARBs, respectively). For pulmonary arterial hypertension (PAH), 81% of experts agreed (for mild PAH, treatments were phosphodiesterase 5 PDE5 inhibitors, then endothelin receptor antagonists plus PDE5 inhibitors, then prostanoids, respectively; for severe PAH, prostanoids were first‐line treatment). For mild Raynaud's phenomenon (RP), 79% of experts agreed (treatments were CCBs, then adding PDE5 inhibitors, then ARBs or switching to another CCB, respectively; after the third line of treatment, mild RP was deemed severe). For severe RP, the first‐ through fourth‐line treatments were CCBs, then adding PDE5 inhibitors or prostanoids, then adding PDE5 inhibitors (if not added as second‐line treatment) or prostanoids (if not added as second‐line treatment), then switching to another CCB, respectively. For active treatment of digital ulcers, 66% of experts agreed (first‐ and second‐line treatments were CCBs and PDE5 inhibitors, respectively). For interstitial lung disease, 69% of experts agreed (for induction therapy, treatments were mycophenolate mofetil MMF, intravenous cyclophosphamide IV CYC, and rituximab, respectively; for maintenance, first‐line treatment was MMF). For skin involvement, 71% of experts agreed (for a modified Rodnan skin thickness score MRSS of 24, first‐ and second‐line treatments were methotrexate MTX and MMF, respectively; for an MRSS of 32, first‐ through fourth‐line treatments were MMF, MTX, IV CYC, and hematopoietic stem cell transplantation, respectively). For inflammatory arthritis, 79% of experts agreed (first‐ through fourth‐line treatments were MTX, low‐dose glucocorticoids, hydroxychloroquine, and rituximab or tocilizumab, respectively). Algorithms for cardiac and gastrointestinal involvement had ≥75% agreement.
Conclusion
Total agreement for SSc algorithms was considerable. These algorithms may guide treatment.
Scleroderma epidemiology update Calderon, Leonardo Martin; Pope, Janet E
Current opinion in rheumatology,
03/2021, Letnik:
33, Številka:
2
Journal Article
Systemic sclerosis (scleroderma, SSc) is a rare multisystem autoimmune disease characterized by autoantibodies, vasculopathy, and fibrosis of the skin and internal organs. This review aims to provide ...an overview and summary of the recent epidemiological studies in systemic sclerosis.
Global trends of scleroderma demonstrate greater prevalence of SSc in European, North, and South American patients compared with East Asian patients. However, the greatest prevalence (47 in 100 000), was found among the indigenous peoples in Canada. Phenotypical differences exist depending on the age of presentation with greater internal organ involvement and disease acceleration present in older patients. Sex differences include greater severity of disease expression, relative prevalence of diffuse cutaneous SSc, and organ involvement in males versus females. New studies conflict with previous data reporting greater proportion of pulmonary arterial hypertension in females. Furthermore, the effect of low median household income is demonstrated as a factor increasing risk of death in SSc patients.
Understanding the epidemiological factors in SSc enables patient care through patient classification, prognostication, and monitoring. Future research may emphasize enrichment of SSc patients in randomized trials who are more likely to progress or be treatment responsive, focused screening, and personalized patient care through the creation and validation of new SSc criteria and subsets.
Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease with multi-organ involvement, fibrosis and vasculopathy. Treatment in SSc, including early diffuse cutaneous SSc (dcSSc) and ...the use of organ-specific therapies, has improved, as evident from randomized clinical trials. Treatments for early dcSSc include immunosuppressive agents such as mycophenolate mofetil, methotrexate, cyclophosphamide, rituximab and tocilizumab. Patients with rapidly progressive early dcSSc might be eligible for autologous haematopoietic stem cell transplantation, which can improve survival. Morbidity from interstitial lung disease and pulmonary arterial hypertension is improving with the use of proven therapies. Mycophenolate mofetil has surpassed cyclophosphamide as the initial treatment for SSc-interstitial lung disease. Nintedanib and possibly perfinidone can be considered in SSc pulmonary fibrosis. Pulmonary arterial hypertension is frequently treated with initial combination therapy (for example, with phosphodiesterase 5 inhibitors and endothelin receptor antagonists) and, if necessary, the addition of a prostacyclin analogue. Raynaud phenomenon and digital ulcers are treated with dihydropyridine calcium channel blockers (especially nifedipine), then phosphodiesterase 5 inhibitors or intravenous iloprost. Bosentan can reduce the development of new digital ulcers. Trial data for other manifestations are mostly lacking. Research is needed to develop targeted and highly effective treatments, best practices for organ-specific screening and early intervention, and sensitive outcome measurements.
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