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Medscape
21-05-2025
- Health
- Medscape
Rheumatology Guideline Updates Take New Life Course Approach
MANCHESTER, England — The latest guidelines on systemic sclerosis (SSc), axial spondyloarthritis (axSpA), and systemic lupus erythematosus (SLE) from the British Society for Rheumatology (BSR) have been updated and, where appropriate, now consider the full life course of these rheumatologic diseases, experts said at BSR 2025 Annual Meeting. BSR Clinical Guidelines Program Manager Lindsay Turner told Medscape Medical News that the approach was 'really valuable because often it's hard to get evidence in a pediatric population. The updates now mean that recommendations relevant to that population are included.' BSR guidelines are generally updated every 5 years, unless evidence becomes available that warrants a 'mini update,' Turner said. But that time schedule can get stretched out over longer periods, as occurred with the SSc guideline update, as Christopher Denton, MBChB, PhD, professor of experimental rheumatology at UCL Medical School in London, England, told Medscape Medical News . 'Obviously, COVID got in the way for 2 years,' he said. 'And of course, the process itself takes at least 2 years. So I think inevitably that even if you start to do the update, it's going to be about 7-8 years.' SSc Guideline Highlights Denton, who is also head of the Centre for Rheumatology at the Royal Free Hospital, London, England, presented highlights only of the updated SSc guideline at the conference because these have already been published. Christopher Denton, MBChB, PhD One of the key recommendations he highlighted is to use nailfold capillaroscopy during the diagnosis of SSc, as this is as important as antinuclear antibody testing, taking the history, and a physical examination. Moreover, all patients diagnosed with SSc should have a baseline assessment done regardless of what treatment plan is being considered and that should include bloodwork, ECGs, echocardiograms, pulmonary function tests, and a high-resolution CT (HRCT). Discussing the HRCT recommendation, Denton said: 'I think it does reflect the importance of knowing as early as possible whether there is interstitial lung disease present and also to help you follow patients noninvasively over time.' Another 'cornerstone' of the updated guidance is being vigilant and looking out for potential complications, such as malignancy. As for treatment, 'the general recommendation, or preference, was that mycophenolate mofetil is the drug that seems to be the most effective for diffuse cutaneous disease and for interstitial lung disease and limited skin involvement,' Denton said. The guideline also tries to make it clear when autologous hematopoietic stem cell transplantation (AHSCT) may or may not be suitable based on current evidence and states that this approach must be delivered within an experienced specialized center. As such, the recommendation is that AHSCT may be considered an option for diffuse cutaneous SSc, where the benefit is felt to outweigh any risks. However, if there is severe internal organ disease, then this approach may not be appropriate and careful evaluation is required. Also, while AHSCT may be considered an option for children and young people who have severe or refractory disease, regardless of whether they have diffuse cutaneous or limited disease, it is not for adults who have later-stage diffuse cutaneous or limited disease because there is not enough evidence currently to support its use, Denton said. AxSpA Guideline Highlights As for the updated axSpA guideline on management using biologic and targeted synthetic disease-modifying antirheumatic drugs, Sizheng Steven Zhao, MBChB, PhD, clinical senior lecturer and honorary consultant in rheumatology at The University of Manchester, Manchester, England, said there were three key points. Sizheng Steven Zhao, MBChB, PhD First, be open to re-evaluating the diagnosis, Zhao said: 'Getting the diagnosis right can be challenging. Be humble. Be open with your patients about the uncertainty around diagnosis and be willing to revisit that. Re-look at the [MRI] images if treatment response doesn't make sense.' Second, 'start recording the ASDAS [Ankylosing Spondylitis Disease Activity Score],' Zhao said, in addition to recording disease activity using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Recording the BASDAI is a requirement of the National Institute for Health and Care Excellence, but using ASDAS is 'where the future is. That's where we're moving toward,' Zhao said. He indicated that this should not be too difficult to incorporate into routine practice given that rheumatologists are already using scores such as the DAS in 28 joints for rheumatoid arthritis. Third, do not rule out using certain drug classes. 'Although we're blessed with three classes of drug, we only still have three classes of drug for a condition that needs many decades of treatment. Don't reflexively rule out a mechanism of action,' Zhao said. Specifically, he mentioned not ruling out the use of interleukin 17 inhibitors in a patient who had uveitis or inflammatory bowel disease (IBD). Work with ophthalmologists and gastroenterologists on a case-by-case basis to see if that drug class could still be suitable, Zhao said. Three overarching principles have been added to the guidance, which consider the goals for treatment, shared care decision-making, and the need for a multidisciplinary approach. Zhao urged his audience to read these and the full guideline, which was published in April. There were 'a lot of nuances,' put into the writing of overarching principles and the 15 recommendations, he said. The recommendations have been grouped into three broad areas: General, which covers starting, monitoring, and switching treatments; extra-musculoskeletal manifestations (EMMs), which includes uveitis, psoriasis, and IBD; and treatment strategy, which encompasses the treat-to-target approach, tapering, and treatment withdrawal. The BSR guideline is unique in its discussion of EMMs, Zhao said. This is not done in the American or European guidelines to the same extent: 'We spent that much time thinking about this because, quite frankly, all the therapies have similar efficacy across musculoskeletal features. It is the EMMs that influence which one we choose.' Zhao emphasized that physical therapy was not to be ignored and that pharmacologic treatments were there to 'enable our patients to continue physical activity, not instead of physical therapy.' SLE Guideline Highlights The updated BSR guideline for the management and treatment of SLE is just a few weeks away from publication, said Md Yuzaiful Md Yusof, MBChB, PhD, consultant rheumatologist and senior research fellow at the University of Leeds and Leeds Teaching Hospitals NHS Trust, both in Leeds, England. Md Yuzaiful Md Yusof, MBChB, PhD The updated guideline covers a much broader scope than its previous iteration, as it now includes recommendations for the management of children and adolescents, as well as adults. Literature searches were done from inception rather than from where the last guideline left off, 'particularly for the pediatric field,' Md Yusof said. Detailed guidance on the management of lupus nephritis has been included, and other new features of the guideline were the inclusion of cutaneous lupus, nonpharmacologic care, and the delivery of care, Md Yusof said. Of course, he added, 'we can't do it all,' and areas not covered were neonatal lupus, contraception and reproductive health, treatment during pregnancy and breastfeeding, complications and comorbidities, and detailed management of thrombosis and antiphospholipid syndrome. However, other national guidelines should already cover these topics. The guideline included 102 recommendations. 'I know it sounds a bit alarming, but they're quite logical and self-explanatory,' Md Yusof said. Overall, 96 of these are shown in a single infographic which is intended to act as a 'cheat code,' he added. The recommendations concern diagnosis, assessment and monitoring, management, and the delivery of care. In terms of diagnosis, timing is key, Md Yusof said. When primary care physicians have a strong suspicion of SLE, they should be looking to refer to secondary or tertiary care within 3 weeks, he said. Treat-to-target is one of the key recommendations regarding assessment and monitoring. The primary treatment goal is to meet the 2021 Definition of Remission in SLE criteria, Md Yusof said. And if that is not possible, the target should be to reach the Lupus Low Disease Activity State. As for management, there is guidance on what rheumatologists could prescribe for cutaneous disease without consulting a dermatologist, such as non-facial topical glucocorticoids and non-facial topical calcineurin inhibitors. The of use of the British Isles Lupus Assessment Group (BILAG)-2004 index and SLE Disease Activity Index 2000 to guide management choices was recommended, with the addition of Easy-BILAG, Md Yusof said. 'We recommend all people with mild lupus to be on hydroxychloroquine at a dose of 5 mg/kg of actual body weight per day,' he said. Glucocorticoids could be used as bridging therapy to settle disease flare but not for routine long-term maintenance. For moderate to severe disease activity, methotrexate or immunosuppression with mycophenolate mofetil, azathioprine, cyclosporin, or tacrolimus is recommended to be started early if there is no organ- or life-threatening disease. Biologics and trials are then advocated for more moderate to severe disease, where there is no renal involvement or if glucocorticoids could not be withdrawn. Trials, belimumab, rituximab, or anifrolumab are recommended for more severe disease activity. Regarding lupus nephritis, all patients should be managed jointly between rheumatology and renal services. 'Timely biopsy is really key, and also identifying poor prognostic markers from the outset,' Md Yusof said. A key message regarding glucocorticoid use is to put an end date on the prescription and 'to make sure you have a tapering plan.' Detailed advice is provided in the guideline on how to taper appropriately. The recommendation on induction treatment for lupus nephritis is the most up-to-date available, with combination therapy recommended over single-agent mycophenolate mofetil. 'Whichever combination that you use for remission induction, you carry on for the maintenance,' Md Yusof added. He concluded that the British guidelines were 'definitely more directive and also more up-to-date' than other available guidelines. Turner reported having no relevant financial relationships. Denton reported receiving research and grant funding and consultancy and speaker fees from or acting as a clinical trial investigator and serving on a steering committee for more than 20 companies. Zhao reported receiving consultancy or speaker fees from AbbVie, Alfasigma, Novartis, and UCB. He also acknowledged receiving financial support for attending conferences from Alfasigma, Eli Lilly & Company, Novartis, and UCB. Md Yusof reported acting as an advisory board member, consultant, or speaker for Alumis, Aurinia, GlaxoSmithKline, Novartis, Roche, UCB, and Vifor.
Medscape
06-05-2025
- Health
- Medscape
Does Immunosuppression Prevent PAH in Systemic Sclerosis?
MANCHESTER, England — Use of immunosuppressive drugs within 5 years of the onset of systemic sclerosis (SSc) did not lower patients' risk for developing pulmonary arterial hypertension (PAH) but was associated with a significantly lower likelihood of death in patients with the complication, researchers reported at the British Society for Rheumatology (BSR) 2025 Annual Meeting. Senior author for the study, Christopher Denton, MD, PhD, professor of experimental rheumatology at UCL Medical School and head of the Centre for Rheumatology at the Royal Free Hospital, London, England, told Medscape Medical News , 'Pulmonary hypertension is one of the complications of scleroderma that has been thought traditionally not to be so inflammatory or immunologically driven. But we got an interesting signal, which was that patients who were on hydroxychloroquine seem to have a lower frequency of developing pulmonary hypertension' than those who were not using immunosuppressants. Christopher Denton, MD, PhD Denton noted that, generally speaking, hydroxychloroquine was thought to be 'quite a benign drug,' so the result begs the question as to whether it could be beneficial to give to people with SSc who may be at risk for developing PAH. 'It does suggest that maybe immunomodulation could be helpful, although hydroxychloroquine does lots of other things as well as immunomodulation,' and this was a small study, Denton cautioned. A 'Dreadful Complication' Stefano Rodolfi, MD, who presented the study's findings and works as a clinical research fellow at the Royal Free Hospital, said that PAH was 'one of the most dreadful complications' of SSc that affects an estimated 8%-13% of patients during the disease course. The 3-year survival rate is around 50%, he said. Stefano Rodolfi, MD It is 'a complication whose proposed pathophysiological mechanism is thought to start with an initial vascular injury to the pulmonary vasculature, leading to an aberrant fibroproliferatory repair process, progressive obliterative pulmonary vasculopathy, ultimately resulting in an increase in the mean pulmonary arterial pressures, increasing pulmonary vascular resistances, and right ventricular dysfunction,' Rodolfi explained. 'However, we have evidence for a role of immune dysfunction in the pathogenesis and pathophysiology,' he said. There are data showing that various autoantibodies are present, such as antibodies against the endothelin-1 receptor, angiotensin II receptor, and fibroblasts. There are also data suggesting a proinflammatory cytokine profile and the presence of activated monocytes in patients with SSc-PAH. 'Furthermore, we have indirect evidence on the role of immunosuppression in this complication,' Rodolfi added. Thus, one might expect that immunosuppression would be part of the management approach for SSc-PAH, but its 'treatment mirrors the same approach of the idiopathic counterpart of PAH, being based on a combination of vasodilatory and antiproliferative agents.' Study Overview Rodolfi explained that a retrospective analysis of 629 'well-characterized' patients with SSc was performed to answer two key questions: First, can early immune suppression prevent the development of PAH? Second, does immunosuppression alter survival in SSc-PAH? PAH was defined using the Venice definition of precapillary pulmonary hypertension: Mean pulmonary artery pressure ≥ 25 mm Hg, pulmonary vascular resistance > 3 Wood units, and a pulmonary wedge pressure ≤ 15 mm Hg. Rodolfi noted that this was a prior definition. After excluding patients with interstitial lung disease (ILD) that extended ≥ 20% on a high-resolution CT scan or who had a forced vital capacity < 70%, there were 607 patients available for analysis. Of these, 320 had received immunosuppression through their disease course, and 287 had not. Early Immunosuppression and Development of SSc-PAH For the first part of the analysis, patients were divided into three groups: Those who had received immunosuppression 'early,' ie, within the first 5 years of their SSc diagnosis (n = 206); those who had received immunosuppression 'late,' receiving it after 5 years of their SSc diagnosis (n = 144); and those who received no immunosuppression (n = 287). Immunosuppression was defined as treatment with glucocorticoids (prednisone equivalent ≥ 10 mg/d for ≥ 6 months) or conventional synthetic or biologic disease-modifying antirheumatic drugs. Over a median follow-up of 21 years, 77 patients developed PAH: 11 (5.3%) in the early immunosuppression group, 21 (14.6%) in the late suppression group, and 45 (15.7%) in the no suppression group. The difference between those with early immunosuppression and those without any use of immunosuppression was significant ( P < .001). However, after adjusting for potential confounding factors, such as male sex, diffuse cutaneous onset of SSc, ILD, scleroderma renal crisis, severe cardiac involvement, and presence of specific autoantibodies, there was no difference between the groups in terms of the time to developing PAH. Time to PAH was 'superimposable' across the three groups (10.5 vs 11 vs 11 years, respectively; P = .581), 'so we can conclude that early immune suppression did not significantly impact on the development of PAH,' Rodolfi reported. However, when analyzing the potential effects of individual immunosuppressive agents, treatment with mycophenolate mofetil (MMF) was associated with significantly reduced odds (odds ratio [OR], 0.12; P = .048) of developing PAH vs not using MMF. Other notable findings were that the presence of ILD, even if 'mild,' was associated with the development of PAH (OR, 3.01; P = .006). Other factors associated with increased risk for SSc-PAH were scleroderma renal crisis (OR, 6.54; P = .035) and the presence of anticentromere antibodies (OR, 2.94; P = .026). Conversely, the presence of anti–Scl-70 was associated with reduced odds of developing PAH (OR, 0.15; P = .009). The fact that MMF was associated with a reduced odds of developing SSc-PAH fits with other data, Rodolfi said. The drug has been shown to alleviate thickening of pulmonary arterial walls and inhibit abnormal vascular remodeling in a mouse model of PAH, and its efficacy has been reported in cases of PAH associated with other connective tissue diseases other than SSc. Mortality Impact For the second part of the analysis that examined the possible effect of immunosuppression on mortality in SSc-PAH, two groups of 'ever' (n = 30) or 'never' (n = 42) users of immunosuppression were formed. Rodolfi reported that more patients in the 'ever' than 'never' group had diffuse cutaneous SSc (20% vs 0%) and ILD (60% vs 14.6%), but fewer had anticentromere antibodies (55.2% vs 86.1%). Over a median follow-up of 7 years, 22 patients (73%) died in the 'ever' group and 30 died (71%) in the 'never' group. The median duration of survival from the time of PAH diagnosis was 7 years and 4 years, respectively, in the two groups (OR, 0.41; P = .045). 'When analyzing the impact of single agents, hydroxychloroquine was associated with reduced mortality risk,' Rodolfi said. Of the nine patients who had been treated with hydroxychloroquine, two died 17 years after their PAH diagnosis (hazard ratio, 0.04; P = .004). 'Once again, this is corroborated by preclinical evidence,' Rodolfi said, adding that it's not the first time either that hydroxychloroquine has been shown to have a possible beneficial clinical effect. Although a different endpoint was used, prior data have shown that treatment with hydroxychloroquine given in the first 18 months of SSc onset may reduce the risk for developing PAH. It is 'not quite the same finding as we had. Our signal was towards a benefit in survival, but still, something to corroborate the role of hydroxychloroquine in this setting.' Are There Any Practice Implications? But are the findings enough to have an impact on practice as it stands today? Consultant rheumatologist Carmel Stober, MD, PhD, who works for Cambridge University Hospitals NHS Trust, Cambridge, England, told Medscape Medical News that the results could potentially have an impact on how some patients with systemic sclerosis were treated. 'For example, if someone has got limited cutaneous systemic sclerosis, you would not necessarily get them on immunosuppression,' but you might give hydroxychloroquine if it has an effect on risk for PAH and there is a risk-benefit advantage for it, she said. The hypothesis is that PAH is modifiable by immunosuppression, Stober said, noting that the second part of the study looked at people who were already receiving immunosuppression and whether that decreased their risk for PAH. But the answer as to whether immunosuppression truly has that effect lies perhaps in a randomized controlled trial. Rodolfi noted that an ongoing multicenter, open-label, randomized trial of about 120 patients with limited cutaneous SSc in the United Kingdom is aiming to determine if MMF plus standard of care can slow down disease progression vs standard of care alone. The study's findings have been previously presented as a poster at the American College of Rheumatology (ACR) 2024 Annual Meeting. The study was independently supported. Rodolfi and Stober had no financial conflicts of interest to report. Denton reported receiving no financial relationships on the abstract but has in the past received speaker or advisory fees, research support, or clinical trial funding from various pharmaceutical companies, including Actelion, Pfizer, GlaxoSmithKline, Sanofi-Aventis, and Novartis.
