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01-09-2018 | DMARDs | Review | Article

A Practical Approach to the Use of Conventional Synthetic, Biologic and Targeted Synthetic Disease Modifying Anti-Rheumatic Drugs for the Treatment of Inflammatory Arthritis in Patients with a History of Malignancy

Journal: Current Rheumatology Reports

Authors: Peter K. K. Wong, Hanish Bagga, Claire Barrett, Geoff Chong, Patrick Hanrahan, Teja Kodali, Mona Marabani, H. Miles Prince, John Riordan, Phillip Swarbrick, Ray White, Laurel Young

Publisher: Springer US

Abstract

Purpose of Review

Conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) have been used in the treatment of inflammatory arthritis (IA) for many years. More recently, biologic (bDMARDs) and targeted synthetic (tsDMARDs) DMARDs have further improved treatment. Due to increased patient longevity and effective oncology treatment, rheumatologists often encounter patients with IA and previous malignancy. The immunosuppressive effect of DMARDs causes concern regarding impaired tumour surveillance with a potential increased risk of malignancy. We reviewed the literature regarding the risk of malignancy in patients on cs-/b-/tsDMARDS and sought to provide practical advice regarding use of these drugs in patients with previous malignancy.

Recent Findings

Data from randomised controlled trials is limited as patients with pre-existing malignancy are often excluded. Reassuringly, an increasing range of “real world” data from various national b/tsDMARD registries has not provided a convincing signal that these drugs increase tumour recurrence. Nevertheless, awareness of, and adherence to, national screening guidelines for malignancy is important.

Summary

Given the improvement in quality of life achieved with these novel and well-tolerated therapeutic agents, the benefit/risk profile remains overwhelmingly favourable in most patients.
Literature
1.
Singh JA, Saag KG, Bridges SL, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology Guideline for the treatment of rheumatoid arthritis: ACR RA treatment recommendations. Arthritis Care Res. 2016;68:1–25.CrossRef
2.
Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76:960–77.CrossRefPubMed
3.
Pappas DA, Kent JD, Greenberg JD, Mason MA, Kremer JM, Holt RJ. Delays in initiation of disease-modifying therapy in rheumatoid arthritis patients: data from a US-based registry. Rheumatol Ther. 2015;2:153–64.CrossRefPubMedPubMedCentral
4.
Buchbinder R, Van Doornum S, Staples M, Lassere M, March L. Malignancy risk in Australian rheumatoid arthritis patients treated with anti-tumour necrosis factor therapy: analysis of the Australian Rheumatology Association Database (ARAD) prospective cohort study. BMC Musculoskelet Disord [Internet]. 2015 [cited 2017 Oct 29];16. Available from: http://​www.​biomedcentral.​com/​1471-2474/​16/​309
5.
Chan ES, Cronstein BN. Molecular action of methotrexate in inflammatory diseases. Arthritis Res. 2002;4:266–73.CrossRefPubMedPubMedCentral
6.
Dimitrova P, Kalden JR, Schulze-Koops H. Leflunomide: an immunosuppressive drug with multiple effects on T cell function. Mod Rheumatol. 2002;12:195–200.CrossRefPubMed
7.
Töpfer K, Kempe S, Müller N, Schmitz M, Bachmann M, Cartellieri M, et al. Tumor evasion from T cell surveillance. J Biomed Biotechnol. 2011;2011:1–19.CrossRef
8.
Shankaran V, Hiroaki I. IFNg and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature. 2001;410:1107–11.CrossRefPubMed
9.
Swann JB, Smyth MJ. Immune surveillance of tumors. J Clin Invest. 2007;117:1137–46.CrossRefPubMedPubMedCentral
10.
Engels EA, Pfeiffer RM, Fraumeni JF, Kasiske BL, Israni AK, Snyder JJ, et al. Spectrum of cancer risk among US solid organ transplant recipients. JAMA. 2011;306:1891–901.CrossRefPubMedPubMedCentral
11.
Kowalski J, Cholewińska G, Pyziak-Kowalska K, Jabłonowska E, Barałkiewicz G, Grzeszczuk A, et al. The spectrum of malignancies among adult HIV cohort in Poland between 1995 and 2012: a retrospective analysis of 288 cases. Współczesna Onkol. 2015;3:226–35.CrossRef
12.
Matthews N, Watkins JF. Tumour-necrosis factor from the rabbit. I. Mode of action, specificity and physicochemical properties. Br J Cancer. 1978;38:302–9.CrossRefPubMedPubMedCentral
13.
Carswell EA, Old LJ, Kassel R, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci. 1975;72:3666–70.CrossRefPubMedPubMedCentral
14.
Hutchinson D. Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA. Ann Rheum Dis. 2001;60:223–7.CrossRefPubMedPubMedCentral
15.
Chiesa Fuxench ZC, Shin DB, Ogdie Beatty A, Gelfand JM. The risk of cancer in patients with psoriasis: a population-based cohort study in the health improvement network. JAMA Dermatol. 2016;152:282–90.CrossRefPubMedPubMedCentral
16.
Gelfand JM, Shin DB, Neimann AL, Wang X, Margolis DJ, Troxel AB. The risk of lymphoma in patients with psoriasis. J Invest Dermatol. 2006;126:2194–201.CrossRefPubMed
17.
McInnes IB, Mease PJ, Kirkham B, Kavanaugh A, Ritchlin CT, Rahman P, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Lond Engl. 2015;386:1137–46.CrossRef
18.
Keystone EC, Kavanaugh AF, Sharp JT, Tannenbaum H, Hua Y, Teoh LS, et al. Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum. 2004;50:1400–11.CrossRefPubMed
19.
Baeten D, Baraliakos X, Braun J, Sieper J, Emery P, van der Heijde D, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet Lond Engl. 2013;382:1705–13.CrossRef
20.
Ichikawa A, Arakawa F, Kiyasu J, Sato K, Miyoshi H, Niino D, et al. Methotrexate/iatrogenic lymphoproliferative disorders in rheumatoid arthritis: histology, Epstein-Barr virus, and clonality are important predictors of disease progression and regression. Eur J Haematol. 2013;91:20–8.CrossRefPubMed
21.
Bombardier C, Hazlewood GS, Akhavan P, Schieir O, Dooley A, Haraoui B, et al. Canadian Rheumatology Association recommendations for the pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs: part II safety. J Rheumatol. 2012;39:1583–602.CrossRefPubMed
22.
• Mercer LK, Askling J, Raaschou P, Dixon WG, Dreyer L, Hetland ML, et al. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers. Ann Rheum Dis. 2017;76:386–91. Large collaborative European study showing no increased risk of melanoma in patients on bDMARDS. CrossRefPubMed
23.
• Silva-Fernández L, Lunt M, Kearsley-Fleet L, Watson KD, Dixon WG, Symmons DPM, et al. The incidence of cancer in patients with rheumatoid arthritis and a prior malignancy who receive TNF inhibitors or rituximab: results from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis. Rheumatology. 2016;55:2033–9. Useful study looking at risk of cancer recurrence in patients on bDMARD. CrossRefPubMedPubMedCentral
24.
• Raaschou P, Simard JF, Asker Hagelberg C, Askling J. Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden. BMJ. 2016:i262. Large Swedish study showing increased risk of NMSC in bDMARD-naïve RA patients.
25.
Scott FI, Mamtani R, Brensinger CM, Haynes K, Chiesa-Fuxench ZC, Zhang J, et al. Risk of nonmelanoma skin cancer associated with the use of immunosuppressant and biologic agents in patients with a history of autoimmune disease and nonmelanoma skin cancer. JAMA Dermatol. 2016;152:164–72.CrossRefPubMedPubMedCentral
26.
Solomon DH, Kremer JM, Fisher M, Curtis JR, Furer V, Harrold LR, et al. Comparative cancer risk associated with methotrexate, other non-biologic and biologic disease-modifying anti-rheumatic drugs. Semin Arthritis Rheum. 2014;43:489–97.CrossRefPubMed
27.
• Wadström H, Frisell T, Sparén P, Askling J. Do RA or TNF inhibitors increase the risk of cervical neoplasia or of recurrence of previous neoplasia? A nationwide study from Sweden. Ann Rheum Dis. 2016;75:1272–8. Large Swedish study showing increased risk of cervical intraepithelial neoplasia in bDMARD-naive women with RA CrossRefPubMed
28.
Shelton E, Laharie D, Scott FI, Mamtani R, Lewis JD, Colombel J-F, et al. Cancer recurrence following immune-suppressive therapies in patients with immune-mediated diseases: a systematic review and meta-analysis. Gastroenterology. 2016;151:97–109.e4.CrossRefPubMed
29.
Haraoui B. 57 - Leflunomide. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, editors. Rheumatology. Sixth ed. Philadelphia: Elsevier Mosby; 2015. p. 451–8.
30.
Mercer LK, Davies R, Galloway JB, Low A, Lunt M, Dixon WG, et al. Risk of cancer in patients receiving non-biologic disease-modifying therapy for rheumatoid arthritis compared with the UK general population. Rheumatology. 2013;52:91–8.CrossRefPubMed
31.
Silman AJ, Petrie J, Hazleman B, Evans SJ. Lymphoproliferative cancer and other malignancy in patients with rheumatoid arthritis treated with azathioprine: a 20 year follow up study. Ann Rheum Dis. 1988;47:988–92.CrossRefPubMedPubMedCentral
32.
Beaugerie L. Use of immunosuppressants and biologicals in patients with previous cancer. Dig Dis Basel Switz. 2013;31:254–9.CrossRef
33.
Bernatsky S, Clarke AE, Suissa S. Hematologic malignant neoplasms after drug exposure in rheumatoid arthritis. Arch Intern Med. 2008;168:378–81.CrossRefPubMed
34.
van den Borne BE, Landewe RB, Houkes I, Schild F, van der Heyden PC, Hazes JM, et al. No increased risk of malignancies and mortality in cyclosporin A-treated patients with rheumatoid arthritis. Arthritis Rheum. 1998;41:1930–7.CrossRefPubMed
35.
Thomas E, Brewster DH, Black RJ, Macfarlane GJ. Risk of malignancy among patients with rheumatic conditions. Int J Cancer [Internet]. 2000;88. Available from: http://​dx.​doi.​org/​3.​0.​CO;2-J
36.
Other iatrogenic immunodeficiency-associated lymphoproliferative disorders [Internet]. [cited 2018 Apr 21]. Available from: http://​www.​pathologyoutline​s.​com/​topic/​lymphomanonBiatr​oLPD.​html
37.
Inui Y, Matsuoka H, Yakushijin K, Okamura A, Shimada T, Yano S, et al. Methotrexate-associated lymphoproliferative disorders: management by watchful waiting and observation of early lymphocyte recovery after methotrexate withdrawal. Leuk Lymphoma. 2015;56:3045–51.CrossRefPubMed
38.
Yoshida Y, Takahashi Y, Yamashita H, Kano T, Kaneko H, Mimori A. Clinical characteristics and incidence of methotrexate-related lymphoproliferative disorders of patients with rheumatoid arthritis. Mod Rheumatol. 2014;24:763–5.CrossRefPubMed
39.
Mariette X. Lymphomas in rheumatoid arthritis patients treated with methotrexate: a 3-year prospective study in France. Blood. 2002;99:3909–15.CrossRefPubMed
40.
Strangfeld A, Hierse F, Rau R, Burmester G-R, Krummel-Lorenz B, Demary W, et al. Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT. Arthritis Res Ther. 2010;12:R5.CrossRefPubMedPubMedCentral
41.
Staples M, Lassere M, March L, Hill CL, Buchbinder R. O-14 malignancy risk in Australian rheumatoid arthritis patients treated with anti-tumor necrosis factor therapy: an update from the Australian Rheumatology Association Databse (ARAD) Prospective Cohort Study. Intern Med J. 2017;47(Suppl. 2):5–41.
42.
Raaschou P, Simard JF, Holmqvist M, Askling J, for the ARTIS Study Group. Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from Sweden. BMJ. 2013;346:f1939.CrossRefPubMed
43.
Polesie S, Gillstedt M, Sonnergren HH, Osmancevic A, Paoli J. Methotrexate treatment and risk for cutaneous malignant melanoma: a retrospective comparative registry-based cohort study. Br J Dermatol. 2017;176:1492–9.CrossRefPubMed
44.
Chen Y-J, Chang Y-T, Wang C-B, Wu C-Y. The risk of cancer in patients with rheumatoid arthritis: a nationwide cohort study in Taiwan. Arthritis Rheum. 2010;63:352–8.CrossRef
45.
Dixon WG, Watson KD, Lunt M, Mercer LK, British Society For Rheumatology Biologics Register Control Centre Consortium, Hyrich KL, et al. Influence of anti-tumor necrosis factor therapy on cancer incidence in patients with rheumatoid arthritis who have had a prior malignancy: results from the British Society for Rheumatology Biologics Register. Arthritis Care Res. 2010;62:755–63.CrossRef
46.
• Mamtani R, Clark AS, Scott FI, Brensinger CM, Boursi B, Chen L, et al. Association between breast cancer recurrence and immunosuppression in rheumatoid arthritis and inflammatory bowel disease: a cohort study: breast cancer recurrence with immunosuppression in RA and IBD. Arthritis Rheumatol. 2016;68:2403–11. Reassuring study showing no increased risk of breast cancer recurrence in RA patients treated with MTX. CrossRefPubMedPubMedCentral
47.
Kinlen LJ. Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment. Am J Med. 1985;78:44–9.CrossRefPubMed
48.
Mercer LK, Green AC, Galloway JB, Davies R, Lunt M, Dixon WG, et al. The influence of anti-TNF therapy upon incidence of keratinocyte skin cancer in patients with rheumatoid arthritis: longitudinal results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2012;71:869–74.CrossRefPubMed
49.
Elandt K, Aletaha D. Treating rheumatic patients with a malignancy. Arthritis Res Ther. 2011;13:223.CrossRefPubMedPubMedCentral
50.
Manic G, Obrist F, Kroemer G, Vitale I, Galluzzi L. Chloroquine and hydroxychloroquine for cancer therapy. Mol Cell Oncol. 2014;1:e29911.CrossRefPubMedPubMedCentral
51.
• Mercer LK, Lunt M, Low ALS, Dixon WG, Watson KD, Symmons DPM, et al. Risk of solid cancer in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis. Ann Rheum Dis. 2015;74:1087–93. British study showing addition of a TNFi to csDMARDs did not increase malignancy risk CrossRefPubMed
52.
• Hellgren K, Dreyer L, Arkema EV, Glintborg B, Jacobsson LTH, Kristensen L-E, et al. Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: a collaborative study from the ARTIS and DANBIO registers. Ann Rheum Dis. 2017;76:105–11. Large Scandinavian study showing no increase in overall cancer risk in SpA patients treated with a TNFi compared to TNFi-naïve patients. CrossRefPubMed
53.
Wadström H, Frisell T, Askling J, for the Anti-Rheumatic Therapy in Sweden (ARTIS) Study Group. Malignant neoplasms in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors, tocilizumab, abatacept, or rituximab in clinical practice: a nationwide cohort study from Sweden. JAMA Intern Med. 2017;177:1605–12.CrossRefPubMedPubMedCentral
54.
Olsen CM, Green AC. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: an updated meta-analysis. Ann Rheum Dis [Internet]. 2017; Available from: http://​ard.​bmj.​com/​content/​early/​2017/​08/​22/​annrheumdis-2017-212205.​abstract
55.
Rubbert-Roth A, Sebba A, Brockwell L, Kelman A, Porter-Brown B, Pulley J, et al. Malignancy rates in patients with rheumatoid arthritis treated with tocilizumab. RMD Open [Internet]. 2016;2. Available from: http://​rmdopen.​bmj.​com/​content/​2/​1/​e000213.​abstract
56.
Yamamoto K, Goto H, Hirao K, Nakajima A, Origasa H, Tanaka K, et al. Longterm safety of tocilizumab: results from 3 years of followup postmarketing surveillance of 5573 patients with rheumatoid arthritis in Japan. J Rheumatol. 2015;42:1368–75.CrossRefPubMed
57.
Strangfeld A, Pattloch D, Herzer P, Edelmann E, Zinke S. Risk of cancer recurrence or new tumors in RA patients with prior malignancies treated with various biologic agents. Arthritis Rheum. 2013;65:S342.CrossRef
58.
Simon TA, Smitten AL, Franklin J, Askling J, Lacaille D, Wolfe F, et al. Malignancies in the rheumatoid arthritis abatacept clinical development programme: an epidemiological assessment. Ann Rheum Dis. 2009;68:1819–26.CrossRefPubMed
59.
Maneiro JR, Souto A, Gomez-Reino JJ. Risks of malignancies related to tofacitinib and biological drugs in rheumatoid arthritis: systematic review, meta-analysis, and network meta-analysis. Semin Arthritis Rheum. 2017;47:149–56.CrossRefPubMed
60.
van Vollenhoven RF, Fleischmann RM, Furst DE, Lacey S, Lehane PB. Longterm safety of rituximab: final report of the rheumatoid arthritis global clinical trial program over 11 years. J Rheumatol. 2015;42:1761–6.CrossRefPubMed
61.
van de Kerkhof PCM, Griffiths CEM, Reich K, Leonardi CL, Blauvelt A, Tsai T-F, et al. Secukinumab long-term safety experience: a pooled analysis of 10 phase II and III clinical studies in patients with moderate to severe plaque psoriasis. J Am Acad Dermatol. 2016;75:83–98.e4.CrossRefPubMed
62.
Blauvelt A. Safety of secukinumab in the treatment of psoriasis. Expert Opin Drug Saf. 2016;15:1413–20.CrossRefPubMed
63.
Reich K, Mrowietz U, Radtke MA, Thaci D, Rustenbach SJ, Spehr C, et al. Drug safety of systemic treatments for psoriasis: results from the German Psoriasis Registry PsoBest. Arch Dermatol Res. 2015;307:875–83.CrossRefPubMedPubMedCentral
64.
Curtis JR, Lee EB, Kaplan IV, Kwok K, Geier J, Benda B, et al. Tofacitinib, an oral Janus kinase inhibitor: analysis of malignancies across the rheumatoid arthritis clinical development programme. Ann Rheum Dis. 2016;75:831–41.CrossRefPubMed
65.
Dreyer L, Mellemkjær L, Andersen AR, Bennett P, Poulsen UE, Juulsgaard Ellingsen T, et al. Incidences of overall and site specific cancers in TNFα inhibitor treated patients with rheumatoid arthritis and other arthritides – a follow-up study from the DANBIO Registry. Ann Rheum Dis. 2013;72:79–82.CrossRefPubMed
66.
Mercer LK, Low ASL, Galloway JB, Watson KD, Lunt M, Symmons DPM, et al. Anti-TNF therapy in women with rheumatoid arthritis with a history of carcinoma in situ of the cervix. Ann Rheum Dis. 2013;72:143–4.CrossRefPubMed
67.
• Scott FI, Mamtani R, Brensinger CM, Haynes K, Chiesa-Fuxench ZC, Zhang J, et al. Risk of nonmelanoma skin cancer associated with the use of immunosuppressant and biologic agents in patients with a history of autoimmune disease and nonmelanoma skin cancer. JAMA Dermatol. 2016;152:164–72. Large US study showing an increased risk of a second NMSC in RA patients treated with MTX and a TNFi compared to MTX alone. CrossRefPubMedPubMedCentral
68.
• Mercer LK, Askling J, Raaschou P, Dixon WG, Dreyer L, Hetland ML, et al. Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers. Ann Rheum Dis. 2017;76:386–91. Large European study showing no increased risk of invasive melanoma in RA patients following a TNFi CrossRefPubMed
69.
Gale S, Wang J, Nebesky J, Linke A, Berber E. FRI0248 incidence of melanoma in patients with rheumatoid arthritis treated with tocilizumab. Ann Rheum Dis. 2017;76:579.
70.
Moreland LW, Alten R, Van den Bosch F, Appelboom T, Leon M, Emery P, et al. Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion. Arthritis Rheum. 2002;46:1470–9.CrossRefPubMed
71.
Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–23.CrossRefPubMedPubMedCentral
72.
Aaltonen KJ, Joensuu JT, Virkki L, Sokka T, Aronen P, Relas H, et al. Rates of serious infections and malignancies among patients with rheumatoid arthritis receiving either tumor necrosis factor inhibitor or rituximab therapy. J Rheumatol. 2015;42:372–8.CrossRefPubMed
73.
Fabre J, Giustiniani J, Garbar C, Antonicelli F, Merrouche Y, Bensussan A, et al. Targeting the tumor microenvironment: the protumor effects of IL-17 related to cancer type. Int J Mol Sci. 2016;17:1433.CrossRefPubMedCentral
74.
Prabhala RH, Fulciniti M, Pelluru D, Rashid N, Nigroiu A, Nanjappa P, et al. Targeting IL-17A in multiple myeloma: a potential novel therapeutic approach in myeloma. Leukemia. 2016;30:379–89.CrossRefPubMed
75.
Pouplard C, Brenaut E, Horreau C, Barnetche T, Misery L, Richard M-A, et al. Risk of cancer in psoriasis: a systematic review and meta-analysis of epidemiological studies. J Eur Acad Dermatol Venereol. 2013;27(Suppl 3):36–46.CrossRefPubMed
76.
McInnes IB, Kavanaugh A, Gottlieb AB, Puig L, Rahman P, Ritchlin C, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet Lond Engl. 2013;382:780–9.CrossRef
77.
Ritchlin C, Rahman P, Kavanaugh A, McInnes IB, Puig L, Li S, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014;73:990–9.CrossRefPubMed
78.
Papp K, Gottlieb AB, Naldi L, Pariser D, Ho V, Goyal K, et al. Safety surveillance for ustekinumab and other Psoriasis Treatments From the Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Drugs Dermatol. 2015;14:706–14.PubMed