Latest news with #immunosuppressants
BBC News
17-05-2025
- Health
- BBC News
Oxford patients with sarcoidosis in lungs given new drug
The first new drug approved for 50 years to treat a rare condition that creates swollen tissue on the lungs has been administered to Hunter became the first person with pulmonary sarcoidosis to receive infliximab as part of her treatment for the condition at the John Radcliffe Hospital in Oxford. Infliximab is currently used to treat inflammatory conditions, such as Crohn's disease, and has now been commissioned by the NHS for use in pulmonary condition causes granulomas - lumps made up of clusters of cells involved in inflammation - to develop in organs, and most commonly affects the lungs. Sarcoidosis can affect people of all ages and can be particularly severe in some cases - with patients often requiring multiple immunosuppressants to treat the affects about 1 in 10,000 people in the UK, according the charity Sarcoidosis well as the lungs it can also affect the skin, eyes, joints, nervous system, heart and other parts of the of pulmonary sarcoidosis include shortness of breath and a persistent dry cough, according to the NHS. Infliximab reduces the need for patients to rely on immunosuppressants - which can increase the risk of infections and further complications - by targeting a protein produced by overactive immune Hunter said she was "excited about the possibility of reducing the number of medications I need"."I have been on various immunosuppressants for a long time, and the side effects have started to surface," she said."The commissioning of this drug is very welcome news."Prof Ling-Pei Ho, who is a consultant in respiratory medicine at Oxford University Hospitals (OUH), was involved in the work that led to the drug's commissioning."We are very pleased to be able to offer a new medicine for our patients with severe lung sarcoidosis," she medical officer at OUH Prof Andrew Brent said that the new drug was "fantastic news" for patients."The commissioning of this drug is a great example of our teams' dedication to continually improving patient care," he added. You can follow BBC Oxfordshire on Facebook, X (Twitter), or Instagram.
Medscape
14-05-2025
- Health
- Medscape
Lupus Drug Withdrawal: Immunosuppressants or Steroids First?
In patients with systemic lupus erythematosus (SLE) who had been in remission for at least 1 year, immunosuppressant withdrawal was noninferior to glucocorticoid withdrawal, with no significant differences in the proportion of patients who experienced flares or in flare severity at 1- and 2-year follow-ups. METHODOLOGY: Researchers conducted a randomized noninferiority trial at a tertiary hospital in India (between May 2021 and December 2023) to compare the outcomes of immunosuppressant withdrawal with those of glucocorticoid withdrawal in adult patients with SLE in remission. They included 117 patients with SLE who had received treatment for at least 3 years, had been in remission for at least 1 year, and were receiving glucocorticoids (≤ 7.5 mg/d of prednisolone) along with one maintenance immunosuppressant. Patients were randomly assigned to one of the two groups: One tapered off prednisolone over 3 months while continuing immunosuppressants (n = 58; median age, 35 years; 98.3% women) and the other tapered off immunosuppressants while maintaining low-dose prednisolone (n = 59; median age, 36 years; 93.2% women). All patients continued receiving hydroxychloroquine. The primary outcome was the proportion of patients who experienced a flare, as defined by the SELENA-SLEDAI Flare Index, at any time up to 52 weeks, with follow-up extending up to and beyond 104 weeks. Noninferiority of immunosuppressant over glucocorticoid withdrawal was confirmed if the upper limit of the 95% CI for the between-group difference in the proportion of patients who experienced a flare was < 10%. TAKEAWAY: At 52 weeks and at maximum follow-up, the proportion of patients who experienced a flare did not differ significantly between the immunosuppressant and glucocorticoid withdrawal groups, with the risk difference between the groups indicating the noninferiority of immunosuppressant withdrawal. At the maximum follow-up, 55.2% of patients in the glucocorticoid withdrawal group and 67.8% of those in the immunosuppressant withdrawal group did not experience a flare. Among those who did, mild to moderate flares were most common. Damage accrual did not differ significantly between the two groups at maximum follow-up. Low baseline complement C3 levels were identified as a predictor of flares at both 52 weeks (hazard ratio [HR], 3.698; P = .012) and at maximum follow-up (HR, 3.785; P = .001). IN PRACTICE: 'Our results suggest that low-dose GCs [glucocorticoids], combined with HCQ [hydroxychloroquine], may be a viable long-term maintenance option for managing SLE patients in sustained remission,' the authors wrote. 'Based on our findings, it is evident that a one-size-fits-all approach to IS [immunosuppressant] or GC withdrawal may not be ideal. Instead, a personalized tapering approach considering patient risk profile, prior damage, and steroid exposure may help mitigate adverse events while maintaining disease control,' they added. SOURCE: This study was led by Aishwarya Gopal, MD, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India. It was published online on March 24, 2025, in Rheumatology . LIMITATIONS: This study had an open-label design and lacked a control arm that continued all medications. Adrenal insufficiency upon flares was not tested in patients who underwent steroid withdrawal. Remote access to glucocorticoids could not be ruled out. DISCLOSURES: This study received funding from Jawaharlal Institute of Postgraduate Medical Education and Research. The authors declared having no conflicts of interest.
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.
