The Brazilian Society of Rheumatology guidelines for axial spondyloarthritis – 2019

Resende, Gustavo Gomes; Meirelles, Eduardo de Souza; Marques, Cláudia Diniz Lopes; Chiereghin, Adriano; Lyrio, Andre Marun; Ximenes, Antônio Carlos; Saad, Carla Gonçalves; Gonçalves, Célio Roberto; Kohem, Charles Lubianca; Schainberg, Cláudia Goldenstein; Campanholo, Cristiano Barbosa; Bueno Filho, Júlio Silvio de Sousa; Pieruccetti, Lenise Brandao; Keiserman, Mauro Waldemar; Yazbek, Michel Alexandre; Palominos, Penelope Esther; Goncalves, Rafaela Silva Guimarães; Lage, Ricardo da Cruz; Assad, Rodrigo Luppino; Bonfiglioli, Rubens; Anti, Sônia Maria Alvarenga; Carneiro, Sueli; Oliveira, Thauana Luíza; Azevedo, Valderílio Feijó; Bianchi, Washington Alves; Bernardo, Wanderley Marques; Pinheiro, Marcelo de Medeiros; Sampaio-Barros, Percival Degrava

doi:10.1186/s42358-020-0116-2

Gustavo Gomes Resende ^**Correspondence: gustavogomesresende@yahoo.com.br

Universidade Federal de Minas Gerais (UFMG), Alameda Álvaro Celso, 175 / 2° Andar. Santa Efigênia. CEP 30.150-260, Belo Horizonte, MG, Brazil.

https://orcid.org/0000-0001-6566-9280

Eduardo de Souza Meirelles

Universidade De São Paulo (USP), São Paulo, Brazil.

Cláudia Diniz Lopes Marques

Universidade Federal de Pernambuco (UFPE), Recife, Brazil.

Adriano Chiereghin

Pontifície Universidade Católica (PUC) de Sorocaba, Sorocaba, Brazil.

Andre Marun Lyrio

Pontifície Universidade Católica (PUC) de Campinas, Campinas, Brazil.

Antônio Carlos Ximenes

Hospital Estadual Geral de Goiania (HGG), Goiânia, Brazil.

Carla Gonçalves Saad

Universidade De São Paulo (USP), São Paulo, Brazil.

Célio Roberto Gonçalves

Universidade De São Paulo (USP), São Paulo, Brazil.

Charles Lubianca Kohem

Universidade Federal do Rio Grande do Sul (UFRS), Porto Alegre, Brazil.

Cláudia Goldenstein Schainberg

Universidade De São Paulo (USP), São Paulo, Brazil.

Cristiano Barbosa Campanholo

Santa Casa de Misericórdia (SCM) de São Paulo, São Paulo, Brazil.

Júlio Silvio de Sousa Bueno Filho

Departmento de Estatística, Universidade Federal de Lavras (UFLA), Lavras, Brazil.

Lenise Brandao Pieruccetti

Hospital Heliópolis, São Paulo, Brazil.

Mauro Waldemar Keiserman

Pontifície Universidade Católica (PUC) de Porto Alegre, Porto Alegre, Brazil.

Michel Alexandre Yazbek

Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.

Penelope Esther Palominos

Universidade Federal do Rio Grande do Sul (UFRS), Porto Alegre, Brazil.

Rafaela Silva Guimarães Goncalves

Universidade Federal de Pernambuco (UFPE), Recife, Brazil.

Ricardo da Cruz Lage

Universidade Federal de Minas Gerais (UFMG), Alameda Álvaro Celso, 175 / 2° Andar. Santa Efigênia. CEP 30.150-260, Belo Horizonte, MG, Brazil.

Rodrigo Luppino Assad

USP Ribeirão Preto, Ribeirão Preto, Brazil.

Rubens Bonfiglioli

Pontifície Universidade Católica (PUC) de Campinas, Campinas, Brazil.

Sônia Maria Alvarenga Anti

Hospital do Servidor Público do Estado de São Paulo, São Paulo, Brazil.

Sueli Carneiro

Universidade Federal do Rio De Janeiro (UFRJ), Rio de Janeiro, Brazil.

Thauana Luíza Oliveira

Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.

Valderílio Feijó Azevedo

Universidade Federal do Paraná (UFPR), Curitiba, Brazil.

Washington Alves Bianchi

Santa Casa de Misericórdia (SCM) do Rio De Janeiro, Rio de Janeiro, Brazil.

Wanderley Marques Bernardo

Universidade de São Paulo (USP), São Paulo, Brazil.

Marcelo de Medeiros Pinheiro

Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.

Percival Degrava Sampaio-Barros

Universidade de São Paulo (USP), São Paulo, Brazil.

*Correspondence: gustavogomesresende@yahoo.com.br

Authors' contributions

All authors made contributions to the acquisition of data, have been involved in drafting the manuscript or revising it critically for important intellectual content, participated in the voting rounds, gave final approval of the version to be published and have participated sufficiently in the work to take public responsibility for appropriate portions of the content.

Authors' information

Not applicable.

Competing interests

Gustavo Gomes Resende received lecture fees from Abbvie, Janssen, Novartis, Pfizer, and UCB; advisory board from Abbvie, Janssen, and Novartis; Research support from Brazilian Society of Rheumatology, FAPEMIG and UCB; clinical research payments from Abbvie and Pfizer; sponsorship for scientific events from Abbvie, Janssen, Lilly, Novartis, Pfizer, and UCB.

Eduardo de Souza Meirelles received payments as a speaker from Novartis, Abbvie, Abbott and Marjan; research grants from Novartis and Pfizer; support for conferences and courses from Aché, Pfizer, Novartis, Janssen, Abbvie, Roche, and Lilly; Advisory board fee from Novartis and Marjan.

Cláudia Diniz Lopes Marques received lecture fees from Abbvie, Janssen, Pfizer and Novartis; advisory board from Novartis and Abbvie; sponsorship for events from Abbvie, Janssen, Pfizer, Novartis, and Lilly.

Adriano Chiereghin received honoraria as a speaker from Janssen, Novartis, UCB, and Pfizer; support to courses and congresses from Abbvie, Janssen, Novartis, UCB, and Pfizer; advisory board from Novartis and Janssen.

Andre Marun Lyrio received payments from Speaker of Janssen and UCB; support to courses/congresses from Janssen, Abbvie, Pfizer, UBC, Novartis, and Lily.

Antônio Carlos Ximenes received payments for participation in clinical research from Abbvvie, Pfizer, Roche, BMS, and Amgen; on scientific board of Pfizer, and Abbivie; as a lecturer from AbbVie, Pfizer, and Abbott.

Carla Gonçalves Saad has no conflicts of interest.

Célio Roberto Gonçalves has no conflicts of interest.

Charles Lubianca Kohen received financial support for advisory board participation from Novartis; speaker fee from Janssen, Abbvie, Novartis, Pfizer, UCB; support to events from Janssen, Abbvie, Roche, Astra-Zeneca, Novartis. Cláudia Goldenstein Schainberg has participated in the pharmaceutical advisory board of AbbVie, Janssen, Lilly, Novartis, and Pfizer; is a speaker invited by AbbVie, Janssen, Lilly, Novartis, Pfizer; has no stock of these pharmaceutical industries.

Cristiano Barbosa Campanholo received financial support for advisory board participation from Janssen, Abbvie, Bristol, Lilly, Novartis, Pfizer, UCB; speaker fee from Janssen, Abbvie, Lilly, Novartis, and Pfizer, UCB; support to events from Janssen, Abbvie, Bristol, Novartis, and Pfizer.

Júlio Silvio de Sousa Bueno Filho has no conflicts of interest.

Lenise Brandao Pieruccetti has no conflicts of interest.

Mauro Waldemar Keiserman received financial support for lectures, advisory bord and clinical research from Abbvie, Actelion, Biogen, Bristol, Celltrion, Lilly, Human Genome Sceiences, Janssen, Pfizer, Novartis, Roche, Sanofi, and UCB. Michel Alexandre Yazbek received financial support from Abbvie, UCB, Novartis and Lilly.

Penelope Esther Palominos has no conflicts of interest.

Rafaela Silva Guimarães Goncalves received fees for lectures from Janssen, Novertis, Abbvie, Apsen, Bristol, and Pfizer; advisory board from Janssen. Ricardo da Cruz Lage received speakers fee from Abbvie and Novartis; support to scientific events from Janssen, Novartis, Pfizer and Abbvie; clinical research payments from Abbvie.

Rodrigo Luppino Assad received fees for lectures and advisory board from Abbvie, Novartis, Janssen, UCB, Lilly, and Bristol; research support from Abbvie and UCB.

Rubens Bonfiglioli received financial support for clinical research from Roche, Pfizer, Amgen, and Novartis; for scientific advisory from Lilly, Abbvie, Roche, and UCB; for support to events from Roche, Pfizer, Abbvie and Novartis; for symposia and sponsored meetings from Roche, Pfizer, and Janssen.

Sônia Maria Alvarenga Anti received financial support from Abbvie, Jansen, Novartis, Lilly, and UCB.

Sueli Coelho da Silva Carneiro received honorary speaker from Abbvie, Janssen, Lilly, Novartis and Pfizer; support to research from CNPq and FAPERJ; support for congresses from Abbvie, Janssen, Novartis, Pfizer, CNPq and FAPERJ; advisory board from Janssen, Lilly, and Novartis.

Thauana Luíza Oliveira received lecturer fees from Abbvie, Novartis and Janssen; support to congresses from Abbvie and Janssen.

Valderílio Feijó Azevedo is GRAPPA member; Medical diretor of Edumed Biotech; received for clinical research from Pfizer, Roche, Janssen, Bristol, Abbvie, Medimmune, Boehringer, GSK, USB, Sanofi, Takeda, Bird Rock Bio, and NovoNordisk; financial support to events and lectures from Pfizer, Hospira, Roche, MSD, BMS, Merck Senoro, Janssen, Novertis, Celltrion, UCB, and AztraZeneca.

Washington Alves Bianchi has no conflicts of interest.

Wanderley Marques Bernardo has no conflicts of interest.

Marcelo de Medeiros Pinheiro received financial support for advisory board from Novartis and Janssen; by lectures from Novartis, Janssen, Abbvie. Percival Degrava Sampaio-Barros received for participation in lectures, boards or scientific events from laboratories Abbvie, Janssen, Novartis, Pfizer and UCB.

Universidade Federal de Minas Gerais (UFMG), Alameda Álvaro Celso, 175 / 2° Andar. Santa Efigênia. CEP 30.150-260, Belo Horizonte, MG, Brazil.

Universidade De São Paulo (USP), São Paulo, Brazil.

Universidade Federal de Pernambuco (UFPE), Recife, Brazil.

Pontifície Universidade Católica (PUC) de Sorocaba, Sorocaba, Brazil.

Pontifície Universidade Católica (PUC) de Campinas, Campinas, Brazil.

Hospital Estadual Geral de Goiania (HGG), Goiânia, Brazil.

Universidade Federal do Rio Grande do Sul (UFRS), Porto Alegre, Brazil.

Santa Casa de Misericórdia (SCM) de São Paulo, São Paulo, Brazil.

Departmento de Estatística, Universidade Federal de Lavras (UFLA), Lavras, Brazil.

Hospital Heliópolis, São Paulo, Brazil.

Pontifície Universidade Católica (PUC) de Porto Alegre, Porto Alegre, Brazil.

Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.

USP Ribeirão Preto, Ribeirão Preto, Brazil.

Hospital do Servidor Público do Estado de São Paulo, São Paulo, Brazil.

Universidade Federal do Rio De Janeiro (UFRJ), Rio de Janeiro, Brazil.

Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.

Universidade Federal do Paraná (UFPR), Curitiba, Brazil.

Santa Casa de Misericórdia (SCM) do Rio De Janeiro, Rio de Janeiro, Brazil.

Universidade de São Paulo (USP), São Paulo, Brazil.

Clinical question	Recommendation	Level of evidence	Strength of recommendation	Degree of agreement
1- What are the clinical criteria for considering someone affected by a spondyloarthritis?	The 2009 ASAS criteria should be used to classify patients with axial spondyloarthritis. The diagnosis should be performed by an experienced physician or a rheumatologist.	1B	A (strong)	9.2
2- What is the role of magnetic resonance imaging (MRI) in the initial evaluation of axial SpA?	In patients with clinically suspected axial SpA, in which sacroiliac radiography is not conclusive, sacroiliac joints (SIJ) MRI is recommended.	1A	A (strong)	9.0
	SIJ MRI scans should be acquired in T1W and STIR and/or T2 fat saturation (FATSAT) sequences. Intravenous MRI contrast (gadolinium) is not recommended routinely.	2B	B (moderate)	9.5
	Spine MRI scans are not recommended on a routine basis for the diagnosis of patients with suspected axial SpA and no sacroiliitis on images.	1B	A (strong)	8.5
3 - What is the role of the HLA-B27 in spondyloarthritis?	HLA-B27 test is recommended for patients with clinically suspected axial SpA for prognostic reasons (more severe axial involvement, higher risk of anterior uveitis and family history of axial SpA). Although it is frequently used as a diagnostic tool in our population, there is very limited evidence of its value.	2A	B (moderate)	9.2
4 - What is the evidence for the use of physical rehabilitation in patients with axial SpA?	Physical rehabilitation programs should be indicated and offered to all patients diagnosed with axial spondyloarthritis during all stages of the disease.	1A	A (strong)	9.8
	Programs specifically focused on improving mobility are primarily recommended, although programs focused on improving endurance and cardiorespiratory fitness are also beneficial.	2A	A (strong)	9.6
5 - What is the evidence for the use of glucocorticoids in patients with axial SpA?	Long-term use of systemic glucocorticoids to treat axial spondyloarthritis is not recommended.	5	D (very weak)	9.6
	Patients with symptomatic peripheral enthesitis can undergo peritendinous glucocorticoid injections. Caution advised because the procedure may increase the risk of rupture, particularly in the Achilles tendon.	2A	B (moderate)	9.2
	Patients with isolated buttock pain who are unresponsive to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) may experience short-term benefits from an intra-articular injection of triamcinolone acetate in the sacroiliac joints.	2C	B (moderate)	8.5
6 - In which situations is the continuous use of NSAIDs recommended for patients with axial SpA?	NSAIDs should be indicated as the first-line treatment for active and symptomatic axial SpA.	1A	A (strong)	9.8
	There is no evidence that a specific NSAID can be considered superior to the other NSAIDs.	1A	A (strong)	9.3
	Evidence on the effect of NSAIDs on reducing radiographic progression in patients with axial SpA is conflicting.	1B	B (moderate)	9.3
7 - What is the evidence for the use of synthetic disease-modifying antirheumatic drugs (methotrexate, sulfasalazine and leflunomide) in patients with axial SpA?	The use of methotrexate and sulfasalazine is recommended for the treatment of patients with axial SpA when peripheral arthritis is present or in the absence of another pharmacological treatment option due to toxicity, intolerance or contraindications.	2A	B (moderate)	8.4
	The routine use of methotrexate or sulfasalazine as a co-medication in patients with axial SpA who are using biologics is not recommended.	2B	B (moderate)	9.6
8 - What evidence of efficacy supports indications for the use of biologics in patients with axial SpA?	Based on the opinion of the rheumatologist, the use of biologics (TNFα inhibitors or interleukin-17 inhibitors) to treat active (BASDAI≥4 or ASDAS≥2.1) and symptomatic axial SpA is recommended when the initial treatment with NSAIDs fails (disease persistence, toxicity or contraindications).	1A	A (strong)	8.9
	Biologics should be used to treat axial SpA when objective signs of inflammation are detected, such as elevated C-reactive protein (CRP) levels and/or the presence of sacroiliitis on MRI, as these parameters predict the response, particularly in the context of non-radiographic axial SpA.	1B	A (strong)	9.6
	Anti-TNF inhibitors (adalimumab, etanercept, golimumab and certolizumab pegol) are recommended for the treatment of non-radiographic axial SpA since they had an evidence-based approval.	1B	A (strong)	9.7
9 - Are there any differences regarding efficacy among the biologic agents to treat axial SpA patients?	The biologics TNFα inhibitors and the IL17A inhibitors exhibit similar effect sizes for controlling inflammatory activity in patients with axial SpA.	1A	A (strong)	8.9
10 - Does the safety of biologics differ in patients with axial SpA?	The biologics TNFα inhibitors and the IL17A inhibitors have similar effect sizes for the risk of adverse effects and short-term discontinuation.	1A	A (strong)	9.1
11 - Is the use of biological therapy able to reduce structural damage (radiographic progression) in patients with axial SpA?	The reduction in the progression rate of structural damage (observed on spinal radiographies) in patients with axial SpA can be observed in the long-term use of TNF inhibitors.	2B	B (moderate)	8.2
	A similar effect on radiographic progression seems to be observed with the continuous use of anti-IL17 (secukinumab) but need to be confirmed in long-term studies.	2C	B (moderate)	9.6
12 - What is the evidence regarding efficacy of biologic agents on extra-articular manifestations in patients with axial SpA?	In the case of recurrent anterior uveitis or active inflammatory bowel disease in the setting of axial SpA, anti-TNF monoclonal antibodies (infliximab, adalimumab, golimumab, and certolizumab pegol) have shown the best response rates among the biologics. Therefore, it is recommended to choose it, preferably to others.	2A	B (moderate)	9.4
	Monoclonal anti-TNF inhibitors (infliximab, adalimumab, golimumab, and certolizumab pegol) and ant-IL17 inhibitors have shown be the most effective, among the biologics, for the control of active psoriasis in the setting of axial SpA. Therefore, it is recommended to choose it, preferably to others.	2B	B (moderate)	9.4
13- What is the evidence that supports the switching among biologic agents in patients with axial SpA?	Patients with axial SpA who fail to show an initial response to a biological therapy (primary treatment failure), loss of efficacy (secondary treatment failure) or adverse effects may switch to another approved biologic, regardless mechanism of action.	2A	B (moderate)	9.4
	After the first biologic switch, the response rates decrease slightly but remain significant. The little available evidence on the second biologic switch suggest response rates even lower than the second-line treatment.	2A	B (moderate)	9.1
14 - For how long should a biologic be used during the follow-up of a patient with axial SpA?	In those who have reached the proposed treatment target, for at least 6 months, an attempt may be made to reduce the anti-TNFα dose or increase the interval between doses. Data on other mechanisms of action remains insufficient. However, the risk of long-term radiographic progression should be considered.	1B	B (moderate)	8.9
15 - Is there evidence for the use of biologics and/or target-specific small molecules with other mechanisms of action in patients with axial SpA?	The use of other biologics and/or target-specific small molecules (abatacept, tocilizumab, rituximab, sarilumab, ustekinumab and apremilast) is not recommended for the treatment of patients with axial SpA.	1B	A (strong)	9.5
	The Janus kinase (JAK) inhibitors tofacitinib and filgotinib showed promising clinical results in the treatment of ankylosing spondylitis, but more definitive evidence (phase III randomized clinical trials) is still needed prior to their recommendation.	2B	B (moderate)	9.1

In patients with back pain ≥ 3 months and age at onset < 45 years
Sacroiliitis on image Active (acute) inflammation on MRI highly suggestive of sacroiliitis associated with SpA or definitive radiographic sacroiliitis according to mod. New York criteria	or	HLA-B27 positive
plus ≥ 1 SpA feature	or	plus ≥ 2 SpA features
SpA features: Inflammatory back pain Arthritis Enthesitis (heel) Uveitis Dactylitis Psoriasis Crohn's disease / ulcerative colitis Good response to NSAID Family history for SpA HLA-B27 Elevated CRP

Outcome	ASAS20				ASAS40				ASAS PR
	Follow-up time (weeks)
	12 to 16		24		12 to 16		24		12 to 16		24
Drug	%	NNT (95% CI)	%	NNT (95% CI)	%	NNT (95% CI)	%	NNT (95% CI)	%	NNT (95% CI)	%	NNT (95% CI)
Infliximab [¹¹¹111. van der Heijde D, Dijkmans B, Geusens P, Sieper J, DeWoody K, Williamson P, et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum. 2005;52(2):582–91.]	–	–	42	2.4 (1.9–3.2)	–	–	35	2.9 (2.2–4.0)	–	–	21	4.7 (3.7–6.7)
Etanercept [¹¹³113. Davis JC Jr, Van Der Heijde D, Braun J, Dougados M, Cush J, Clegg DO, et al. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum. 2003;48(11):3230–6., ¹¹⁹119. Calin A, Dijkmans BA, Emery P, Hakala M, Kalden J, Leirisalo-Repo M, et al. Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis. Ann Rheum Dis. 2004;63(12):1594–600., ¹²⁰120. Dougados M, Braun J, Szanto S, Combe B, Elbaz M, Geher P, et al. Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomised double-blind placebo-controlled study (SPINE). Ann Rheum Dis. 2011;70(5):799–804., ¹²³123. Dougados M, van der Heijde D, Sieper J, Braun J, Maksymowych WP, Citera G, et al. Symptomatic efficacy of etanercept and its effects on objective signs of inflammation in early nonradiographic axial spondyloarthritis: a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2014;66(8):2091–102.]	27	3.7 (2.9–5.1)	34	2.9 (2.2–4.3)	18	5.5 (3.6–11.7)	–	–	13	7.5 (3.7-∞)	13	7.6 (4.9–16.9)
Adalimumab [¹²⁶126. van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis:results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006;54(7):2136–46., ¹³⁰130. Haibel H, Rudwaleit M, Listing J, Heldmann F, Wong RL, Kupper H, et al. Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two. Arthritis Rheum. 2008;58(7):1981–91., ¹³¹131. Sieper J, van der Heijde D, Dougados M, Mease PJ, Maksymowych WP, Brown MA, et al. Efficacy and safety of adalimumab in patients with nonradiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis. 2013;72(6):815–22.]	27	3.7 (2.8–5.2)	–	–	26	3.8 (3.0–5.2)	26	3.8 (2.8–5.8)	16	6.4 (4.8–9.5)	17	6.1 (4.2–10.7)
Golimumab [¹³³133. Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008;58(11):3402–12., ¹³⁷137. Sieper J, van der Heijde D, Dougados M, Maksymowych WP, Scott BB, Boice JA, et al. A randomized, double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2015;67(10):2702–12., ¹³⁸138. Deodhar A, Reveille JD, Harrison DD, Kim L, Lo KH, Leu JH, et al. Safety and Efficacy of Golimumab Administered Intravenously in Adults with Ankylosing Spondylitis: Results through Week 28 of the GO-ALIVE Study. J Rheumatol. 2018;45(3):341–8.]	37	2.7 (2.3–3.4)	–	–	40	2.5 (2.1–3.2)	28	3.6 (2.5–6.0)	–	7.5 (4.8–16.3)	–	–
Certolizumab pegol [¹³⁹139. Landewé R, Braun J, Deodhar A, Dougados M, Maksymowych WP, Mease PJ, et al. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study. Ann Rheum Dis. 2013;73:39–47.]	22	4.5 (3.0–9.1)	–	–	28	3.6 (2.6–5.5)	–	–	20	5.0 (3.7–7.5)	–	–
Secukinumab [¹⁴²142. Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, et al. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015;373(26):2534–48.]	36	2.8 (2.2–3.8)	–	–	30	3.3 (2.5–4.6)	–	–	12	8.1 (5.4–16.0)	–	–

Outcome	Serious adverse effects		Discontinuation for any cause
	Follow-up time (weeks)
	12 to 24
Drug	Relative risk	95% CI	Relative risk	95% CI
Infliximab [¹¹¹111. van der Heijde D, Dijkmans B, Geusens P, Sieper J, DeWoody K, Williamson P, et al. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum. 2005;52(2):582–91.]	1.30	0.28–6.12	0.78	0.14–4.15
Etanercept [¹¹³113. Davis JC Jr, Van Der Heijde D, Braun J, Dougados M, Cush J, Clegg DO, et al. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Arthritis Rheum. 2003;48(11):3230–6., ¹¹⁹119. Calin A, Dijkmans BA, Emery P, Hakala M, Kalden J, Leirisalo-Repo M, et al. Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis. Ann Rheum Dis. 2004;63(12):1594–600., ¹²⁰120. Dougados M, Braun J, Szanto S, Combe B, Elbaz M, Geher P, et al. Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomised double-blind placebo-controlled study (SPINE). Ann Rheum Dis. 2011;70(5):799–804., ¹²³123. Dougados M, van der Heijde D, Sieper J, Braun J, Maksymowych WP, Citera G, et al. Symptomatic efficacy of etanercept and its effects on objective signs of inflammation in early nonradiographic axial spondyloarthritis: a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2014;66(8):2091–102.]	0.84	0.37–1.91	0.81	0.47–1.42
Adalimumab [¹²⁶126. van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis:results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006;54(7):2136–46., ¹³⁰130. Haibel H, Rudwaleit M, Listing J, Heldmann F, Wong RL, Kupper H, et al. Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two. Arthritis Rheum. 2008;58(7):1981–91., ¹³¹131. Sieper J, van der Heijde D, Dougados M, Mease PJ, Maksymowych WP, Brown MA, et al. Efficacy and safety of adalimumab in patients with nonradiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis. 2013;72(6):815–22.]	1.59	0.49–5.06	1.49	0.65–3.39
Golimumab [¹³³133. Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008;58(11):3402–12., ¹³⁷137. Sieper J, van der Heijde D, Dougados M, Maksymowych WP, Scott BB, Boice JA, et al. A randomized, double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2015;67(10):2702–12., ¹³⁸138. Deodhar A, Reveille JD, Harrison DD, Kim L, Lo KH, Leu JH, et al. Safety and Efficacy of Golimumab Administered Intravenously in Adults with Ankylosing Spondylitis: Results through Week 28 of the GO-ALIVE Study. J Rheumatol. 2018;45(3):341–8.]	0.94	0.35–2.56	1.19	0.52–2.75
Certolizumab pegol [¹³⁹139. Landewé R, Braun J, Deodhar A, Dougados M, Maksymowych WP, Mease PJ, et al. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study. Ann Rheum Dis. 2013;73:39–47.]	1.18	0.43–3.36	0.74	0.34–1.58
Secukinumab [¹⁴²142. Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, et al. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015;373(26):2534–48.]	0.81	0.34–1.92	0.55	0.26–1.16

Outcome	mSASSS variation (units)
	Follow-up time (years)
	0 to 2		0 to 4
Drug	Δ mSASSS	95% CI	Δ mSASSS	95% CI
Infliximab [¹⁷¹171. van der Heijde D, Landewe R, Baraliakos X, Houben H, van Tubergen A, Williamson P, et al. Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum. 2008;58(10):3063–70., ¹⁷²172. Baraliakos X, Listing J, Brandt J, Haibel H, Rudwaleit M, Sieper J, et al. Radiographic progression in patients with ankylosing spondylitis after 4 yrs of treatment with the anti-TNF-alpha antibody infliximab. Rheumatology (Oxford). 2007;46(9):1450–3.]	0.9	0.54–1.26	1.60	1.1–2.1
Etanercept [¹⁷³173. van der Heijde D, Landewe R, Einstein S, Ory P, Vosse D, Ni L, et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthritis Rheum. 2008;58(5):1324–31.]	0.91	0.62–1.21
Adalimumab [¹⁷⁴174. van der Heijde D, Salonen D, Weissman BN, Landewe R, Maksymowych WP, Kupper H, et al. Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthritis Res Therapy. 2009;11(4):R127.]	0.9	0.51–1.09
Golimumab [¹⁷⁵175. Braun J, Baraliakos X, Hermann KG, Deodhar A, van der Heijde D, Inman R, et al. The effect of two golimumab doses on radiographic progression in ankylosing spondylitis: results through 4 years of the GO-RAISE trial. Ann Rheum Dis. 2014;73(6):1107–13.]	0.9	0.38–1.40	1.30	0.9–1.7
Certolizumab pegol [¹⁷⁶176. van der Heijde D, Baraliakos X, Hermann KA, Landewe RBM, Machado PM, Maksymowych WP, et al. Limited radiographic progression and sustained reductions in MRI inflammation in patients with axial spondyloarthritis: 4-year imaging outcomes from the RAPID-axSpA phase III randomised trial. Ann Rheum Dis. 2018;77(5):699–705.]	0.67	0.21–1.13	0.98	0.34–1.63
Secukinumab [¹⁴⁵145. Braun J, Baraliakos X, Deodhar A, Baeten D, Sieper J, Emery P, et al. Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study. Ann Rheum Dis. 2017;76(6):1070–7., ¹⁷⁷177. Braun J, Baraliakos X, Deodhar A, Poddubnyy D, Emery P, Delicha EM, et al. Secukinumab shows sustained efficacy and low structural progression in ankylosing spondylitis: 4-year results from the MEASURE 1 study. Rheumatology (Oxford). 2019;58(5):859–868.]	0.5	0.11–0.89	1.2	0.29–2.11

Outcome	Incidence (events/100 PY)
Drug	AAU Incidence	95% CI	IBD Incidence	95% CI
Infliximab [¹⁷⁹179. Braun J, Baraliakos X, Listing J, Sieper J. Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum. 2005;52(8):2447–51., ¹⁸⁹189. Braun J, Baraliakos X, Listing J, Davis J, van der Heijde D, Haibel H, et al. Differences in the incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti-tumor necrosis factor alpha agents. Arthritis Rheum. 2007;57(4):639–47.]	3.4	0.5–6.4	0.2	0–0.9^* * 95% CI reported by the authors of the original study.
Etanercept [¹⁷⁹179. Braun J, Baraliakos X, Listing J, Sieper J. Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept. Arthritis Rheum. 2005;52(8):2447–51., ¹⁸⁹189. Braun J, Baraliakos X, Listing J, Davis J, van der Heijde D, Haibel H, et al. Differences in the incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti-tumor necrosis factor alpha agents. Arthritis Rheum. 2007;57(4):639–47.]	7.9	5.4–10.5	1.3	0–4.2^* * 95% CI reported by the authors of the original study.
Adalimumab [¹⁸⁰180. Rudwaleit M, Rodevand E, Holck P, Vanhoof J, Kron M, Kary S, et al. Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study. Ann Rheum Dis. 2009;68(5):696–701., ¹⁸⁹189. Braun J, Baraliakos X, Listing J, Davis J, van der Heijde D, Haibel H, et al. Differences in the incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti-tumor necrosis factor alpha agents. Arthritis Rheum. 2007;57(4):639–47.]	7.4	4.7–10.1	0.8	0.6–2.5^* * 95% CI reported by the authors of the original study.
Golimumab [¹³³133. Inman RD, Davis JC Jr, Heijde D, Diekman L, Sieper J, Kim SI, et al. Efficacy and safety of golimumab in patients with ankylosing spondylitis: results of a randomized, double-blind, placebo-controlled, phase III trial. Arthritis Rheum. 2008;58(11):3402–12., ¹³⁸138. Deodhar A, Reveille JD, Harrison DD, Kim L, Lo KH, Leu JH, et al. Safety and Efficacy of Golimumab Administered Intravenously in Adults with Ankylosing Spondylitis: Results through Week 28 of the GO-ALIVE Study. J Rheumatol. 2018;45(3):341–8., ¹⁸⁷187. van Bentum RE, Heslinga SC, Nurmohamed MT, Gerards AH, Griep EN, Koehorst C, et al. Reduced Occurrence Rate of Acute Anterior Uveitis in Ankylosing Spondylitis Treated with Golimumab - The GO-EASY Study. J Rheumatol. 2019;46(2):153–159.]	2.2	0–5.2	0^ No new case or reactivation was reported in the study with golimumab IV. The incidence of this event was not described in studies with SC golimumab injections	–
Certolizumab pegol [¹⁴¹141. van der Heijde D, Dougados M, Landewe R, Sieper J, Maksymowych WP, Rudwaleit M, et al. Sustained efficacy, safety and patient-reported outcomes of certolizumab pegol in axial spondyloarthritis: 4-year outcomes from RAPID-axSpA. Rheumatology (Oxford). 2017;56(9):1498–509., ¹⁸⁶186. Rudwaleit M, Rosenbaum JT, Landewe R, Marzo-Ortega H, Sieper J, van der Heijde D, et al. Observed Incidence of Uveitis Following Certolizumab Pegol Treatment in Patients With Axial Spondyloarthritis. Arthritis Care Research. 2016;68(6):838–44.]	4.9	3.0–6.9	0.1	0–0.3
Secukinumab [¹⁴²142. Baeten D, Sieper J, Braun J, Baraliakos X, Dougados M, Emery P, et al. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015;373(26):2534–48.]	1.0	0.3–1.8	0.7	0.1–1.3

Outcome	PASI50		PASI75		PASI90
	Follow-up time (weeks)
	24		24		24
Drug	%	NNT (95% CI)	%	NNT (95% CI)	%	NNT (95% CI)
Infliximab [¹⁹⁵195. Kavanaugh A, Krueger GG, Beutler A, Guzzo C, Zhou B, Dooley LT, et al. Infliximab maintains a high degree of clinical response in patients with active psoriatic arthritis through 1 year of treatment: results from the IMPACT 2 trial. Ann Rheum Dis. 2007;66(4):498–505.]	66.7	1.5 (1.3–1.8)	58.8	1.7 (1.4–2.1)	38.4	2.6 (2.0–3.6)
Etanercept [¹⁹⁶196. Mease PJ, Kivitz AJ, Burch FX, Siegel EL, Cohen SB, Ory P, et al. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum. 2004;50(7):2264–72., ¹⁹⁷197. Mease PJ, Goffe BS, Metz J, VanderStoep A, Finck B, Burge DJ. Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. Lancet. 2000;356(9227):385–90.]	27.0	3.7 (2.6–6.3)	20.8	4.8 (3.5–7.8)	–	–
Adalimumab [¹⁹⁸198. Mease PJ, Gladman DD, Ritchlin CT, Ruderman EM, Steinfeld SD, Choy EH, et al. Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum. 2005;52(10):3279–89.]	62.5	1.5 (1.2–1.8)	58.8	1.7 (1.4–2.2)	41.7	2.4 (1.9–3.3)
Golimumab [¹⁹⁹199. Kavanaugh A, McInnes I, Mease P, Krueger GG, Gladman D, Gomez-Reino J, et al. Golimumab, a new human tumor necrosis factor alpha antibody, administered every four weeks as a subcutaneous injection in psoriatic arthritis: Twenty-four-week efficacy and safety results of a randomized, placebo-controlled study. Arthritis Rheum. 2009;60(4):976–86.]	66.7	1.5 (1.3–1.8)	55.5	1.8 (1.6–2.2)	32.2	3.1 (2.4–4.3)
Certolizumab pegol [²⁰⁰200. Mease PJ, Fleischmann R, Deodhar AA, Wollenhaupt J, Khraishi M, Kielar D, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a Phase 3 double-blindrandomisedplacebo-controlledstudy (RAPID-PsA). AnnRheum Dis. 2014;73(1):48–55.]	45.5	2.2 (1.7–2.9)	45.5	2.2 (1.8–2.8)	35.7	2.8 (2.2–3.7)
Secukinumab [²⁰¹201. Mease PJ, McInnes IB, Kirkham B, Kavanaugh A, Rahman P, van der Heijde D, et al. Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis. N Engl J Med. 2015;373(14):1329–39., ²⁰²202. 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. 2015;386(9999):1137–46.]	–	–	37.0	2.1 (1.8–2.6)	35.7	2.7 (2.2–3.4)

[1] *Correspondence: gustavogomesresende@yahoo.com.br

Brasil

Brasil

The Brazilian Society of Rheumatology guidelines for axial spondyloarthritis – 2019

Abstract