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• W2080772504 abstract "Psoriasis is a common, chronic, inflammatory disease. Psoriasis has been hypothesized to be associated with an increased risk of lymphoma due to its pathophysiology, its treatments, or a combination of these factors. We performed a large population-based cohort study of the risk of lymphoma in psoriasis patients using the General Practice Research Database. We identified 153,197 patients with psoriasis and 765,950 corresponding subjects without psoriasis. Psoriasis patients who received a systemic treatment consistent with extensive disease were classified as severe (N=3,994) and those who did not receive systemic therapies were classified as mild (N=149,203). The analyses were adjusted for age, gender, and person–time using a Cox proportional hazards model. For mild and severe psoriasis patients, the respective adjusted relative risks for lymphoma and its subtypes were as follows: all lymphoma 1.34 (1.16, 1.54) and 1.59 (0.88, 2.89); non-Hodgkin's lymphoma 1.15 (0.97, 1.37) and 0.73 (0.28, 1.96); Hodgkin's lymphoma (HL) 1.42 (1.00, 2.02) and 3.18 (1.01, 9.97); cutaneous T-cell lymphoma (TCL) 4.10 (2.70, 6.23) and 10.75 (3.89, 29.76). Psoriasis is associated with an increased risk of lymphoma. The association is strongest for HL and CTCL. The excess risk of lymphoma attributed to psoriasis was 7.9/100,000 psoriasis patients per year. Although patients with psoriasis have an increased relative risk of lymphoma, the absolute risk attributable to psoriasis is low given that lymphoma is a rare disease and the magnitude of association is modest. Psoriasis is a common, chronic, inflammatory disease. Psoriasis has been hypothesized to be associated with an increased risk of lymphoma due to its pathophysiology, its treatments, or a combination of these factors. We performed a large population-based cohort study of the risk of lymphoma in psoriasis patients using the General Practice Research Database. We identified 153,197 patients with psoriasis and 765,950 corresponding subjects without psoriasis. Psoriasis patients who received a systemic treatment consistent with extensive disease were classified as severe (N=3,994) and those who did not receive systemic therapies were classified as mild (N=149,203). The analyses were adjusted for age, gender, and person–time using a Cox proportional hazards model. For mild and severe psoriasis patients, the respective adjusted relative risks for lymphoma and its subtypes were as follows: all lymphoma 1.34 (1.16, 1.54) and 1.59 (0.88, 2.89); non-Hodgkin's lymphoma 1.15 (0.97, 1.37) and 0.73 (0.28, 1.96); Hodgkin's lymphoma (HL) 1.42 (1.00, 2.02) and 3.18 (1.01, 9.97); cutaneous T-cell lymphoma (TCL) 4.10 (2.70, 6.23) and 10.75 (3.89, 29.76). Psoriasis is associated with an increased risk of lymphoma. The association is strongest for HL and CTCL. The excess risk of lymphoma attributed to psoriasis was 7.9/100,000 psoriasis patients per year. Although patients with psoriasis have an increased relative risk of lymphoma, the absolute risk attributable to psoriasis is low given that lymphoma is a rare disease and the magnitude of association is modest. confidence interval cutaneous T-cell lymphoma General Practice Research Database Hodgkin's lymphoma hazard ratio non-Hodgkin's lymphoma up to standard Psoriasis is a common, chronic disease that affects approximately 2–3% of the adult population (Gelfand et al., 2005Gelfand J.M. Weinstein R. Porter S.B. Neimann A.L. Berlin J.A. Margolis D.J. Prevalence and treatment of psoriasis in the United Kingdom: a population-based study.Arch Dermatol. 2005; 141: 1537-1541Crossref PubMed Scopus (505) Google Scholar). The extent of body surface area (BSA) affected by psoriasis is variable, ranging from limited (i.e., <2% body surface area) disease in approximately 80–85% of patients, to more extensive skin involvement in approximately 15–20% of patients (Gelfand et al., 2004Gelfand J.M. Feldman S.R. Stern R.S. Thomas J. Rolstad T. Margolis D.J. Determinants of quality of life in patients with psoriasis: a study from the US population.J Am Acad Dermatol. 2004; 51: 704-708Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, Gelfand et al., 2005Gelfand J.M. Wang X. Qing L. Neimann A.L. Weinstein R. Margolis D. et al.Epidemiology and treatment patterns of psoriasis in the general practice research database (GPRD).Pharmacoepidemiol Drug Saf. 2005; 14: S23Google Scholar; Stern et al., 2004Stern R.S. Nijsten T. Feldman S.R. Margolis D.J. Rolstad T. Psoriasis is common, carries a substantial burden even when not extensive, and is associated with widespread treatment dissatisfaction.J Investig Dermatol Symp Proc. 2004; 9: 136-139Abstract Full Text Full Text PDF PubMed Scopus (612) Google Scholar). Psoriasis has serious impacts on health-related quality of life, even in patients with limited body surface area involvement (Rapp et al., 1999Rapp S.R. Feldman S.R. Exum M.L. Fleischer Jr, A.B. Reboussin D.M. Psoriasis causes as much disability as other major medical diseases.J Am Acad Dermatol. 1999; 41: 401-407Abstract Full Text Full Text PDF PubMed Scopus (1278) Google Scholar; Gelfand et al., 2004Gelfand J.M. Feldman S.R. Stern R.S. Thomas J. Rolstad T. Margolis D.J. Determinants of quality of life in patients with psoriasis: a study from the US population.J Am Acad Dermatol. 2004; 51: 704-708Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar). The pathophysiology of psoriasis involves an abnormal immune response characterized by increased activity of T cells, antigen-presenting (e.g., dendritic) cells, and Th-1 cytokines (Krueger and Bowcock, 2005Krueger J.G. Bowcock A. Psoriasis pathophysiology: current concepts of pathogenesis.Ann Rheum Dis. 2005; 64: ii30-ii36Crossref PubMed Scopus (404) Google Scholar). Other investigators have also demonstrated increased B lymphocyte activity in patients with psoriasis, which suggests broad immune activation (Muller et al., 1991Muller K.M. Rocken M. Joel D. Bonnefoy J.Y. Saurat J.H. Hauser C. Mononuclear cell-bound CD23 is elevated in both atopic dermatitis and psoriasis.J Dermatol Sci. 1991; 2: 125-133Abstract Full Text PDF PubMed Scopus (19) Google Scholar; Jeffes et al., 1995Jeffes III, E.W. Lee G.C. Said S. Sabahi M. McCullough J.L. Herrod R. et al.Elevated numbers of proliferating mononuclear cells in the peripheral blood of psoriatic patients correlate with disease severity.J Invest Dermatol. 1995; 105: 733-738Crossref PubMed Scopus (33) Google Scholar; Mahmoud et al., 1999Mahmoud F. Abul H. al Saleh Q. Hassab-el Naby H. Kajeji M. Haines D. et al.Elevated B-lymphocyte levels in lesional tissue of non-arthritic psoriasis.J Dermatol. 1999; 26: 428-433Crossref PubMed Scopus (30) Google Scholar). The immunologic nature of psoriasis has raised concern that its pathophysiology may be associated with an increased risk of lymphoma, as has been demonstrated previously for other Th-1 mediated diseases such as rheumatoid arthritis (Gridley et al., 1993Gridley G. McLaughlin J.K. Ekbom A. Klareskog L. Adami H.O. Hacker D.G. et al.Incidence of cancer among patients with rheumatoid arthritis.J Natl Cancer Inst. 1993; 85: 307-311Crossref PubMed Scopus (590) Google Scholar; Ekstrom et al., 2003Ekstrom K. Hjalgrim H. Brandt L. Baecklund E. Klareskog L. Ekbom A. et al.Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first-degree relatives.Arthritis Rheum. 2003; 48: 963-970Crossref PubMed Scopus (232) Google Scholar). Additionally, patients with extensive psoriasis may be treated with systemic therapies such as cyclosporine and methotrexate, which have been associated with the development of lymphoma in psoriasis patients treated with these medications (Koo et al., 1992Koo J.Y. Kadonaga J.N. Wintroub B.V. Lozada-Nur F.I. The development of B-cell lymphoma in a patient with psoriasis treated with cyclosporine.J Am Acad Dermatol. 1992; 26: 836-840Abstract Full Text PDF PubMed Scopus (47) Google Scholar; Kamel et al., 1996Kamel O.W. Weiss L.M. van de Rijn M. Colby T.V. Kingma D.W. Jaffe E.S. Hodgkin's disease and lymphoproliferations resembling Hodgkin's disease in patients receiving long-term low-dose methotrexate therapy.Am J Surg Pathol. 1996; 20: 1279-1287Crossref PubMed Scopus (109) Google Scholar, Kamel, 1997Kamel O.W. Lymphomas during long-term methotrexate therapy.Arch Dermatol. 1997; 133: 903-904Crossref PubMed Google Scholar; Cliff et al., 1999Cliff S. Pettengell R. Gharge S. Marsden R.A. B-cell lymphoma developing in a patient on cyclosporin for recalcitrant psoriasis.Br J Dermatol. 1999; 140: 763-765Crossref PubMed Scopus (29) Google Scholar; Mahe et al., 2003Mahe E. Descamps V. Grossin M. Fraitag S. Crickx B. CD30+ T-cell lymphoma in a patient with psoriasis treated with ciclosporin and infliximab.Br J Dermatol. 2003; 149: 170-173Crossref PubMed Scopus (92) Google Scholar; Lelievre et al., 2005Lelievre J.D. Sacre K. Adle-Biassette H. Molinier-Frenkel V. Gaulard P. Papo T. Epstein-Barr virus-associated lymphoproliferative disease after long-standing cyclosporine therapy for psoriasis: a case of spontaneous regression.J Am Acad Dermatol. 2005; 52: 24-27Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar). Patients with psoriasis are increasingly treated with biologic therapies that target T cells (e.g., efazilumab, alefacept) or cytokines such as tumor necrosis factor-α (infliximab, etanercept, adalimumab). There is theoretical concern that biologic therapies may also increase the risk of lymphoma given their mechanism of action. Large, long-term observational studies of biologics therapies in psoriasis patients are not yet published. Epidemiologic studies in rheumatoid arthritis patients have found increased rates of lymphoma in patients treated with tumor necrosis factor inhibitors (Wolfe and Michaud, 2004Wolfe F. Michaud K. Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients.Arthritis Rheum. 2004; 50: 1740-1751Crossref PubMed Scopus (565) Google Scholar; Geborek et al., 2005Geborek P. Bladstrom A. Turesson C. Gulfe A. Petersson I.F. Saxne T. et al.Tumour necrosis factor blockers do not increase overall tumour risk in patients with rheumatoid arthritis, but may be associated with an increased risk of lymphomas.Ann Rheum Dis. 2005; 64: 699-703Crossref PubMed Scopus (370) Google Scholar); however, it is unclear if this risk is due to the severity of rheumatoid arthritis or the tumor necrosis factor inhibition treatment (e.g., confounding by indication). Lymphomas are divided into two broad categories, non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma (HL). The majority of lymphomas (88%) are NHL with the remaining 12% being HL (Fisher and Fisher, 2004Fisher S.G. Fisher R.I. The epidemiology of non-Hodgkin's lymphoma.Oncogene. 2004; 23: 6524-6534Crossref PubMed Scopus (330) Google Scholar). Studying the risk of lymphoma in psoriasis patients is challenging because lymphoma is statistically rare, and therefore large sample sizes need to be studied to yield robust findings. Although lymphoma is rare, it is of clinical and public health importance given that NHL is the fifth most common cause of cancer in the US, affecting 19/100,000 individuals per year (an incidence similar to melanoma) (Bierman et al., 2004Bierman P.J. Harris N.L. Armitage J.O. Non-Hodgkin's lymphoma.in: Goldman L. Ausiello D. Cecil textbook of medicine. 22nd. WB Saunders Co, Philadelphia, PA2004: 1174-1184Google Scholar). The incidence of NHL has increased approximately 3–4% per year since 1973 and the current overall five year survival is only 53%. Approximately 85% of NHL is B cell in origin (Bierman et al., 2004Bierman P.J. Harris N.L. Armitage J.O. Non-Hodgkin's lymphoma.in: Goldman L. Ausiello D. Cecil textbook of medicine. 22nd. WB Saunders Co, Philadelphia, PA2004: 1174-1184Google Scholar). Cutaneous T-cell lymphoma (CTCL) is the most common form of T-cell lymphoma, affecting approximately 0.5–1.0/100,000 individuals per year (Willemze et al., 1997Willemze R. Kerl H. Sterry W. Berti E. Cerroni L. Chimenti S. et al.EORTC classification for primary cutaneous lymphomas: a proposal from the Cutaneous Lymphoma Study Group of the European Organization for Research and Treatment of Cancer.Blood. 1997; 90: 354-371PubMed Google Scholar; Weinstock and Gardstein, 1999Weinstock M.A. Gardstein B. Twenty-year trends in the reported incidence of mycosis fungoides and associated mortality.Am J Public Health. 1999; 89: 1240-1244Crossref PubMed Scopus (177) Google Scholar; Kim et al., 2005Kim E.J. Hess S. Richardson S.K. Newton S. Showe L.C. Benoit B.M. et al.Immunopathogenesis and therapy of cutaneous T cell lymphoma.J Clin Invest. 2005; 115: 798-812Crossref PubMed Scopus (380) Google Scholar). CTCL is of special interest given that it is a T-cell lymphoma of the skin, and therefore may be related to the pathophysiology of psoriasis. There have been multiple previous studies of the risk of lymphoma in psoriasis patients from both the United States and Europe (Lindelof et al., 1990Lindelof B. Eklund G. Liden S. Stern R.S. The prevalence of malignant tumors in patients with psoriasis.J Am Acad Dermatol. 1990; 22: 1056-1060Abstract Full Text PDF PubMed Scopus (57) Google Scholar; Doody et al., 1992Doody M.M. Linet M.S. Glass A.G. Friedman G.D. Pottern L.M. Boice Jr, J.D. et al.Leukemia, lymphoma, and multiple myeloma following selected medical conditions.Cancer Causes Control. 1992; 3: 449-456Crossref PubMed Scopus (109) Google Scholar; Bhate et al., 1993Bhate S.M. Sharpe G.R. Marks J.M. Shuster S. Ross W.M. Prevalence of skin and other cancers in patients with psoriasis.Clin Exp Dermatol. 1993; 18: 401-404Crossref PubMed Scopus (15) Google Scholar; Hannuksela et al., 1996Hannuksela A. Pukkala E. Hannuksela M. Karvonen J. Cancer incidence among Finnish patients with psoriasis treated with trioxsalen bath PUVA.J Am Acad Dermatol. 1996; 35: 685-689Abstract Full Text PDF PubMed Scopus (51) Google Scholar; Stern and Vakeva, 1997Stern R.S. Vakeva L.H. Noncutaneous malignant tumors in the PUVA follow-up study: 1975–1996.J Invest Dermatol. 1997; 108: 897-900Crossref PubMed Scopus (63) Google Scholar; Frentz and Olsen, 1999Frentz G. Olsen J.H. Malignant tumours and psoriasis: a follow-up study.Br J Dermatol. 1999; 140: 237-242Crossref PubMed Scopus (106) Google Scholar; Hannuksela-Svahn et al., 1999Hannuksela-Svahn A. Sigurgeirsson B. Pukkala E. Lindelof B. Berne B. Hannuksela M. et al.Trioxsalen bath PUVA did not increase the risk of squamous cell skin carcinoma and cutaneous malignant melanoma in a joint analysis of 944 Swedish and Finnish patients with psoriasis.Br J Dermatol. 1999; 141: 497-501Crossref PubMed Scopus (90) Google Scholar, Hannuksela-Svahn et al., 2000Hannuksela-Svahn A. Pukkala E. Laara E. Poikolainen K. Karvonen J. Psoriasis, its treatment, and cancer in a cohort of Finnish patients.J Invest Dermatol. 2000; 114: 587-590Crossref PubMed Scopus (175) Google Scholar; Tavani et al., 2000Tavani A. La Vecchia C. Franceschi S. Serraino D. Carbone A. Medical history and risk of Hodgkin's and non-Hodgkin's lymphomas.Eur J Cancer Prev. 2000; 9: 59-64Crossref PubMed Scopus (125) Google Scholar; Boffetta et al., 2001Boffetta P. Gridley G. Lindelof B. Cancer risk in a population-based cohort of patients hospitalized for psoriasis in Sweden.J Invest Dermatol. 2001; 117: 1531-1537Crossref PubMed Scopus (147) Google Scholar; Margolis et al., 2001Margolis D. Bilker W. Hennessy S. Vittorio C. Santanna J. Strom B.L. The risk of malignancy associated with psoriasis.Arch Dermatol. 2001; 137: 778-783PubMed Google Scholar; Gelfand et al., 2003Gelfand J.M. Berlin J. Van Voorhees A. Margolis D.J. Lymphoma rates are low but increased in patients with psoriasis: results from a population-based cohort study in the United Kingdom.Arch Dermatol. 2003; 139: 1425-1429Crossref PubMed Scopus (225) Google Scholar; Morales et al., 2003Morales M.M. Olsen J. Johansen P. Kaerlev L. Guenel P. Arveux P. et al.Viral infection, atopy and mycosis fungoides: a European multicentre case–control study.Eur J Cancer. 2003; 39: 511-516Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar; Zhang et al., 2004Zhang Y. Holford T.R. Leaderer B. Zahm S.H. Boyle P. Morton L.M. et al.Prior medical conditions and medication use and risk of non-Hodgkin lymphoma in Connecticut United States women.Cancer Causes Control. 2004; 15: 419-428Crossref PubMed Scopus (137) Google Scholar; Becker et al., 2005Becker N. Deeg E. Rudiger T. Nieters A. Medical history and risk for lymphoma: results of a population-based case–control study in Germany.Eur J Cancer. 2005; 41: 133-142Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar). These studies have varied in their design, sample size, population, and outcome (e.g., all lymphoma, NHL, HL, and CTCL) studied. Many of these studies did not report the relative risk of various forms of lymphoma, tended to concentrate on highly selected populations of patients with psoriasis such as those hospitalized for their disease or those treated with psoralen, and were not population-based. The results of these studies have been conflicting, and therefore additional studies are necessary to clarify this association, especially since patients with psoriasis are increasingly being treated on a long-term basis with systemic therapies that selectively target the immune system (i.e., biologics). The purpose of this investigation was to perform a broadly representative, population-based cohort study of the risk of all lymphoma, NHL, HL, and CTCL in patients with psoriasis. We identified 153,197 patients with psoriasis and 765,950 corresponding subjects without psoriasis (Table 1). Psoriasis patients were older than control patients, and mild psoriasis patients were slightly more likely to be females. In unadjusted analyses, both mild and severe psoriasis patients were more likely to have a history of lymphoma at the time the study was initiated. Among psoriasis patients, 2.6% were classified as severe based on having received a systemic treatment for psoriasis. The frequency of use of oral therapies for psoriasis was similar to that reported in other population-based studies from the UK (Nevitt and Hutchinson, 1996Nevitt G.J. Hutchinson P.E. Psoriasis in the community: prevalence, severity and patients' beliefs and attitudes towards the disease.Br J Dermatol. 1996; 135: 533-537Crossref PubMed Scopus (233) Google Scholar). The majority of patients classified with severe psoriasis received methotrexate (58%). Documentation of psoralen and phototherapy use was low (17% of patients with severe disease) and may under-represent the true use of these agents, as they are restricted to dermatologists and their use may not be well captured electronically by the general practitioner.Table 1Description of study groupsVariableControlMild psoriasisSevere psoriasisN (%)765,950149,2033,994Gender Male366,238 (48%)70,742 (47.4%)1,937 (48.5%) Female399,712 (52%)78,461 (52.6%)2,057 (51.5%) Odds ratio (95% CI)—0.98 (0.97, 1.00)1.03 (0.97, 1.09)P=0.0045P=0.3912Age Mean (median, 25th, 75th percentile)35.76 (33, 18, 53)41.51 (40, 26, 57)48.51 (48, 35, 62)P<0.001P<0.001History of lymphoma Yes538 (0.07%)179 (0.12%)11 (0.28%) No765,412 (99.93%)149,024 (99.88%)3,983 (99.72%) Odds ratio (95% CI)—1.71 (1.44, 2.03)3.93 (1.95, 7.09)P<0.0001P=0.0002Systemic therapies (N (%)) Methotrexate——2,314 (57.94%) Psoralen/phototherapy——681 (17.05%) Azathioprine——659 (16.50%) Ciclosporine——414 (10.37%) Etretinate or acitretin——351 (8.79%) Hydroxyurea——224 (5.61%) Mycophenolate mofetil——12 (0.30%)CI, confidence interval.Odds ratios and P-values refer to the comparison of the mild and severe psoriasis groups with the control group. Percentages for systemic therapies do not add to 100 because patients could have received more than one systemic therapy. Open table in a new tab CI, confidence interval. Odds ratios and P-values refer to the comparison of the mild and severe psoriasis groups with the control group. Percentages for systemic therapies do not add to 100 because patients could have received more than one systemic therapy. Psoriasis patients had an increased hazard ratio (HR) (i.e., risk) of lymphoma (Table 2) that persisted when adjusting for age and gender (HR 1.35, 95% CI 1.17, 1.55). The adjusted risk of lymphoma was elevated in mild (HR 1.34, 95% CI 1.16, 1.54) and severe psoriasis (HR 1.59, 95% CI 0.88, 2.89) patients; however, the association did not achieve conventional levels of statistical significance in the severe group. The risk of all lymphoma was slightly greater in our sensitivity analysis, which was restricted to subjects with at least 6 months of follow-up time and who did not have a history of lymphoma or a lymphoma in the first 6 months of observation.Table 2Incidence and relative risk (hazard) of lymphoma in psoriasis patients compared to controlsVariableControlMild psoriasisSevere psoriasisAll psoriasisMean follow-up time (median, 25th, 75th percentile)5.61 (5.25, 2.18, 9.13)4.50 (3.80, 1.64, 7.09)5.77 (5.53, 2.70, 8.96)4.54 (3.84, 1.67, 7.16)Person years (N)4,297,296671,91423,048694,962New lymphoma (N)97023711248Incidence per 10,000 person years (95% CI)2.26 (2.12, 2.40)3.53 (3.09, 4.01)4.77 (2.38, 8.54)3.57 (3.14, 4.04)Primary analysis Unadjusted hazard ratio—1.54 (1.33, 1.77)2.12 (1.17, 3.85)1.56 (1.35, 1.79)P<0.001P=0.013P<0.001 Adjusted hazard ratio1Adjusted for gender, age.—1.34 (1.16, 1.54)1.59 (0.88, 2.89)1.35 (1.17, 1.55)P<0.001P=0.124P<0.001 Attributable risk (excess number of lymphoma cases related to psoriasis)———7.9/100,000 per yearSensitivity analysis2Restricted to subjects with at least 6 months of follow-up time who did not have a history of lymphoma or a lymphoma in the first six months. New lymphoma (N)7111839192 Unadjusted hazard ratio—1.71 (1.45, 2.01)2.37 (1.23, 4.57)1.73 (1.48, 2.03)P<0.001P=0.010P<0.001 Adjusted hazard ratio1Adjusted for gender, age.—1.48 (1.25, 1.74)1.78 (0.92, 3.44)1.49 (1.27, 1.75)P<0.001P=0.085P<0.001CI, confidence interval.1 Adjusted for gender, age.2 Restricted to subjects with at least 6 months of follow-up time who did not have a history of lymphoma or a lymphoma in the first six months. Open table in a new tab CI, confidence interval. The primary analysis for NHL (Table 3, excluding CTCL) found a small increased risk that was not statistically significant for all psoriasis patients (HR 1.14, 95% CI 0.96, 1.35) and for mild patients (HR 1.15, 95% CI 0.97, 1.37). There was no increased risk in the severe group (HR 0.73, 95% CI 0.28, 1.96). Sensitivity analyses slightly increased the degree of association leading to statistical significance in all psoriasis patients (HR 1.26, 95% CI 1.04, 1.52) and mild psoriasis patients (HR 1.27, 95% CI 1.05, 1.54), but not in severe psoriasis patients (HR 0.96, 0.36, 2.57).Table 3Incidence and relative risk (hazard) of NHL in psoriasis patients compared to controlsVariableControlMild psoriasisSevere psoriasisAll psoriasisMean follow-up time (median, 25th, 75th percentile)5.61 (5.25, 2.18, 9.13)4.51 (3.81, 1.65, 7.09)5.77 (5.53, 2.70, 8.96)4.54 (3.84, 1.67, 7.16)Person years (N)4,298,107672,16823,061695,230New NHL (N)7591594163Incidence per 10,000 person years (95% CI)1.77 (1.64, 1.90)2.37 (2.01, 2.76)1.73 (0.47, 4.44)2.35 (2.00, 2.73)Primary analysis Unadjusted hazard ratio—1.33 (1.12, 1.58)0.99 (0.37, 2.63)1.32 (1.11, 1.56)P=0.001P=0.980P=0.001 Adjusted hazard ratio1Adjusted for gender, age.—1.15 (0.97, 1.37)0.73 (0.28, 1.96)1.14 (0.96, 1.35)P=0.103P=0.539P=0.134Sensitivity analysis2Restricted to subjects with at least 6 months of follow-up time who did not have a history of lymphoma or a lymphoma in the first six months. New NHL (N)5811284132 Unadjusted hazard ratio—1.47 (1.21, 1.78)1.29 (0.48, 3.45)1.47 (1.21, 1.77)P<0.001P=0.612P<0.001 Adjusted hazard ratio1Adjusted for gender, age.—1.27 (1.05, 1.54)0.96 (0.36, 2.57)1.26 (1.04, 1.52)P=0.015P=0.939P=0.018CI, confidence interval; NHL, non-Hodgkin's lymphoma.1 Adjusted for gender, age.2 Restricted to subjects with at least 6 months of follow-up time who did not have a history of lymphoma or a lymphoma in the first six months. Open table in a new tab CI, confidence interval; NHL, non-Hodgkin's lymphoma. The adjusted risk of HL (Table 4) was increased in all psoriasis patients (HR 1.48, 1.05, 2.08). The risk of HL was also increased in both the mild (HR 1.42, CI 1.00 2.02) and severe psoriasis (HR 3.18, 95% CI 1.01, 9.97) groups. In sensitivity analyses, the risk of Hodgkin's remained elevated but with borderline statistical significance in all psoriasis patients (HR 1.54, 95% CI 0.99, 2.40) and in patients with mild psoriasis (HR 1.53, 95% CI 0.98, 2.40); however, it was no longer statistically significant in the severe group (HR 1.79, 95% CI 0.25, 12.90).Table 4Incidence and relative risk (hazard) of HL in psoriasis patients compared to controlsVariableControlMild psoriasisSevere psoriasisAll psoriasisMean follow-up time (median, 25th, 75th percentile)5.61 (5.25, 2.19, 9.13)4.51 (3.81, 1.65, 7.10)5.77 (5.52, 2.70, 8.96)4.54 (3.85, 1.67, 7.16)Person years (N)4,299,128672,41823,063695,482New Hodgkin's lymphoma (N)16039342Incidence per 10,000 person years (95% CI)0.37 (0.32, 0.44)0.58 (0.41, 0.79)1.30 (0.27, 3.80)0.60 (0.44, 0.82)Primary analysis Unadjusted hazard ratio—1.48 (1.04, 2.10)3.50 (1.12 10.96)1.54 (1.10, 2.17)P=0.029P=0.032P=0.012 Adjusted hazard ratio1Adjusted for gender, age.—1.42 (1.00, 2.02)3.18 (1.01, 9.97)1.48 (1.05, 2.08)P=0.052P=0.048P=0.025 Attributable risk (excess number of lymphoma cases related to psoriasis)1.8/100,000 per yearSensitivity analysis2Restricted to subjects with at least 6 months of follow-up time who did not have a history of lymphoma or a lymphoma in the first 6 months. New HL (N)9824125 Unadjusted hazard ratio—1.58 (1.01, 2.47)1.91 (0.27, 13.68)1.59 (1.03, 2.47)P=0.045P=0.521P=0.038 Adjusted hazard ratio1Adjusted for gender, age.—1.53 (0.98, 2.40)1.79 (0.25, 12.90)1.54 (0.99, 2.40)P=0.063P=0.561P=0.055HL, Hodgkin's lymphoma; CTCL, cutaneous T-cell lymphoma.1 Adjusted for gender, age.2 Restricted to subjects with at least 6 months of follow-up time who did not have a history of lymphoma or a lymphoma in the first 6 months. Open table in a new tab HL, Hodgkin's lymphoma; CTCL, cutaneous T-cell lymphoma. The strongest association of lymphoma with psoriasis occurred for CTCL (Table 5). The adjusted risk of CTCL in all psoriasis patients was 4.34 (95% CI 2.89, 6.52). The adjusted risk of CTCL was substantially increased in both mild psoriasis (HR 4.10, 95% CI 2.70, 6.23) and severe psoriasis (HR 10.75, 95% CI 3.89, 29.76). Sensitivity analyses found a greater magnitude of association between CTCL and the psoriasis groups.Table 5Incidence and relative risk (hazard) of cutaneous T-cell lymphoma in psoriasis patients compared to controlsVariableControlMild psoriasisSevere psoriasisAll psoriasisMean follow-up time (median, 25th, 75th percentile)5.61 (5.25, 2.19, 9.13)4.51 (3.81, 1.65, 7.10)5.77 (5.53, 2.70, 8.96)4.54 (3.85, 1.67, 7.16)Person years (N)4,299,563672,38323,054695,437New CTCL (N)5139443Incidence per 10,000 person years (95% CI)0.12 (0.09, 0.16)0.58 (0.41, 0.79)1.74 (0.47, 4.44)0.62 (0.45, 0.83)Primary analysis Unadjusted hazard ratio—4.78 (3.15, 7.27)14.60 (5.28, 40.40)5.08 (3.38, 7.64)P<0.001P<0.001P<0.001 Adjusted hazard ratio1Adjusted for gender, age.—4.10 (2.70, 6.23)10.75 (3.89, 29.76)4.34 (2.89, 6.52)P<0.001P<0.001P<0.001Attributable risk (excess number of lymphoma cases related to psoriasis)4.0/100,000 per yearSensitivity analysis2Restricted to subjects with at least 6 months of follow-up time who did not have a history of lymphoma or a lymphoma in the first 6 months. New CTCL (N)3231435 Unadjusted hazard ratio—6.37 (3.88, 10.46)23.21 (8.21, 65.62)6.89 (4.26, 11.15)P<0.001P<0.001P<0.001 Adjusted hazard ratio1Adjusted for gender, age.—5.42 (3.30, 8.89)17.18 (6.07, 48.58)5.84 (3.61, 9.44)P<0.001P<0.001P<0.001CI, confidence interval; CTCL, cutaneous T-cell lymphoma.1 Adjusted for gender, age.2 Restricted to subjects with at least 6 months of follow-up time who did not have a history of lymphoma or a lymphoma in the first 6 months. Open table in a new tab CI, confidence interval; CTCL, cutaneous T-cell lymphoma. In all of the models described above, Poisson models resulted in very similar estimates for all of the observed effects. Additionally, tests for effect modification with respect to age and gender for all models in all psoriasis patients were nonsignificant. To our knowledge, this is the largest study to date to determine the risk of lymphoma in patients with psoriasis. Particular strengths of this study, in addition to its size, include its broadly representative nature and its population-based design, which helps minimize selection and information bias. We have also conducted detailed analyses of subtypes of lymphoma, and conducted sensitivity analyses to determine if the results were robust to different analytical approaches. The risk of all lymphoma was increased in all psoriasis patients and mild psoriasis patients. The risk of all lymphoma was increased slightly in patients with severe psoriasis, but the finding was not statistically significant. The magnitude of association of all lymphoma in the current study is lower than in our previous study, in which we examined only patients who were 65 years of age or older in the General Practice Research Database (GPRD) from 1988 to 1996 (HR 2.94, 95% CI 1.82, 4.74) (Gelfand et al., 2003Gelfand J.M. Berlin J. Van Voorhees A. Margolis D.J. Lymphoma rat" @default.
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• W2080772504 title "The Risk of Lymphoma in Patients with Psoriasis" @default.
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