{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T08:12:32Z","timestamp":1777882352381,"version":"3.51.4"},"reference-count":48,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Rare Disease"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>Paroxysmal nocturnal haemoglobinuria (PNH) is an ultra-orphan disease, which until 15\u2009years ago had limited treatment options. Eculizumab, a monoclonal antibody that inhibits C5 in the terminal complement cascade, has revolutionised treatment for this disease, near normalising life expectancy and improving quality of life for patients. The treatment landscape of PNH is now evolving, with ravulizumab a second longer acting intravenous C5 inhibitor now licenced by the FDA and EMA. With different therapeutic targets in the complement cascade and difference modalities of treatment, including subcutaneous, oral and intravenous therapies being developed, increasing independence for patients and reducing healthcare requirements. This review discusses the current and future therapies for PNH.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Lay summary<\/jats:title>\n                    <jats:p>Review of current and future treatments for patients with Paroxysmal Nocturnal Haemoglobinuria What is Paroxysmal Nocturnal Haemoglobinuria? Paroxysmal nocturnal haemoglobinuria (PNH) is a very rare disease. It arises from PNH stem cells in the bone marrow. In a normal bone marrow these are inactive; however, if there has been a problem in the bone marrow, the PNH stem cells can expand and make PNH red blood cells, white blood cells and platelets. The problem with these cells is that they lack the cell surface markers that usually protect them. Red blood cells are broken down in the circulation rather than the spleen, which gives rise to PNH symptoms such as abdominal pain, difficulty swallowing, erectile dysfunction and red or black urine (known as haemoglobinuria). The white blood cells and platelets are \u2018stickier\u2019 increasing the risk of blood clots. Previously life expectancy was reduced as there were limited treatment options available. What was the aim of this review? To provide an overview of current and future treatment options for PNH Which treatments are available? \u2022\u2003Eculizumab is an treatment given through a vein (intravenous) every week for 5\u2009weeks then every 2\u2009weeks after this, and has been available for 13\u2009years, improving life expectancy to near normal. \u2022\u2003Ravulizumab is a newer intravenous treatment similar to eculizumab but is given every 8\u2009weeks instead of every 2\u2009weeks. In clinical studies it was comparable with eculizumab. \u2022\u2003Future Treatments - There is new research looking at different methods of treatment delivery, including injections under the skin (subcutaneous) that patients can give themselves, treatments taken by mouth (oral) or a combination of an intravenous and oral treatment for those patients who are not optimally controlled on eculizumab or ravulizumab. What does this mean? PNH is now treatable. For years, the only drug available was eculizumab, but now different targets and drug trials are available. Ravulizumab is currently the only second licenced product available, in USA and Europe, there are other medications active in clinical trials. Why is this important? The benefit for patients, from treatment every 2\u2009weeks to every 8\u2009weeks is likely to be improved further with the development of these new treatments, providing patients with improved disease control and independence. As we move into an era of more patient-friendly treatment options, the PNH community both physicians and patients look forward to new developments as discussed in this article.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/2633004020959349","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T07:47:22Z","timestamp":1603352842000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["A review of the treatment landscape in paroxysmal nocturnal haemoglobinuria: where are we now and where are we going?"],"prefix":"10.1177","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4287-0595","authenticated-orcid":false,"given":"Morag","family":"Griffin","sequence":"first","affiliation":[{"name":"Department of Haematology, Bexley Wing, St James University Hospital, Leeds, LS9 7TF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Haematology, Bexley Wing, St James University Hospital, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Pike","sequence":"additional","affiliation":[{"name":"University of Leeds, Leeds, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"bibr1-2633004020959349","doi-asserted-by":"publisher","DOI":"10.1002\/9781444323160"},{"key":"bibr2-2633004020959349","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S3334"},{"key":"bibr3-2633004020959349","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199511093331904"},{"key":"bibr4-2633004020959349","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-01-133918"},{"key":"bibr5-2633004020959349","doi-asserted-by":"publisher","DOI":"10.1007\/BF03165111"},{"key":"bibr6-2633004020959349","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06240.x"},{"key":"bibr7-2633004020959349","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199401273300404"},{"key":"bibr8-2633004020959349","doi-asserted-by":"publisher","DOI":"10.1001\/jama.293.13.1653"},{"key":"bibr9-2633004020959349","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08096.x"},{"key":"bibr10-2633004020959349","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0009"},{"key":"bibr11-2633004020959349","unstructured":"U.S. Food and Drug Administration. 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