Psoriatic arthritis

ORIGINAL RESEARCH

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Secukinumab provides sustained
improvement in signs and symptoms
and low radiographic progression in
patients with psoriatic arthritis: 2-year
(end-of-study) results from the FUTURE
5 study

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Philip J Mease ,1 Robert Landewé ,2,3 Proton Rahman,4 Hasan Tahir,5
Atul Singhal, Elke Boettcher, Sandra Navarra,8 Aimee Readie,9
6 7

Shephard Mpofu,10 Eumorphia Maria Delicha,10 Luminita Pricop,9

11
Desirée van der Heijde

To cite: Mease PJ, Landewé R, ABSTRACT

Rahman P, et al. Secukinumab Objective Secukinumab provided sustained efficacy,
Key messages
provides sustained improvement low radiographic progression and consistent safety over
in signs and symptoms and
52 weeks in patients with psoriatic arthritis (PsA) in the
What is already known about this subject?
low radiographic progression ► Secukinumab, a human monoclonal antibody that
FUTURE 5 study. Here, we report 2-year (end-of-study)
in patients with psoriatic directly inhibits interleukin-17A, demonstrated sus-
arthritis: 2-year (end-of- results from this study.
Methods Adults with active PsA were randomised tained efficacy, low rate of radiographic progression
study) results from the
2:2:2:3 to receive subcutaneous secukinumab 300 mg and consistent safety over 52 weeks in patients with
FUTURE 5 study. RMD Open
load (300 mg), 150 mg load (150 mg), 150 mg no load psoriatic arthritis (PsA) in the FUTURE 5 study.
2021;7:e001600. doi:10.1136/
rmdopen-2021-001600 or placebo at baseline; weeks 1, 2, 3 and 4; and every 4 What does this study add?
weeks thereafter. Secukinumab could be escalated from ► This large phase III study in patients with active PsA
► Additional supplemental 150 mg to 300 mg starting at week 52, if active signs of showed that subcutaneous secukinumab 300 mg
material is published online only. disease were observed based on physician’s assessment.
and 150 mg, with or without loading dose, provided
To view, please visit the journal Assessments at week 104 (2 years) included clinical end sustained clinical efficacy, low radiographic progres-
online (http://dx.doi.org/10. points and radiographic damage (mean change in van der
1136/rmdopen-2021-001600). sion and consistent safety over 2 years of treatment,
Heijde-modified total Sharp score (vdH-mTSS)). Safety
demonstrating the long-term clinical benefit of
analysis included all patients who received ≥1 dose of
secukinumab treatment.
study medication.
Received 25 January 2021 ► The unique aspects of this study are the loading or
Accepted 12 May 2021 Results Of the 996 patients randomised, 783 patients
no loading regimes with option of dose escalation
(78.6%) completed 2 years of treatment. Improvement
after 52 weeks. Improvement in American College of
in clinical end points was sustained through 2 years. The
Rheumatology responses was observed in patients
vdH-mTSS (mean change (SD)) was 0.10 (1.74; 300 mg),
who escalated from secukinumab 150 mg to 300
0.52 (2.66; 150 mg) and 0.41 (2.20; 150 mg no load) at
mg, indicating a potential benefit for dose escala-
2 years. The proportion of patients with no radiographic
progression (change from baseline in vdH-mTSS ≤0.5) at tion in patients whose symptoms are not adequately
2 years was 89.5% (300 mg), 82.3% (150 mg) and 81.1% controlled with the lower dose.
(150 mg no load). How might this impact on clinical practice or
Conclusion Secukinumab with and without loading further developments?
© Author(s) (or their
employer(s)) 2021. Re-use regimen provided sustained clinical efficacy and low ► The findings from this 2-year study strengthen the
permitted under CC BY-NC. No radiographic progression through 2 years in patients with
existing evidence on the safety and efficacy of long-
commercial re-use. See rights PsA. No new safety findings were reported.
and permissions. Published
term secukinumab treatment in patients with PsA.
Trial registration number NCT02404350.
by BMJ. There can be a potential benefit in dose escalation if
For numbered affiliations see
signs and symptoms of PsA are not controlled ade-
end of article. quately with the lower dose.

Correspondence to INTRODUCTION arthritis, axial disease, dactylitis, enthesitis,

Professor Philip J Mease; Psoriatic arthritis (PsA) is a chronic multi- and nail and skin psoriasis.1 2 Patients with
[email protected] faceted disease characterised by peripheral PsA are affected by irreversible joint damage

Mease PJ, et al. RMD Open 2021;7:e001600. doi:10.1136/rmdopen-2021-001600 1

RMD Open

and disability, which have a substantial impact on quality of anti-TNF therapy status (ie, patients who were naïve to
of life.3–7 Structural damage in patients with PsA is char- anti-TNF therapy (anti-TNF-naïve) and those who were
acterised by bone erosions, joint space narrowing and inadequate responders or stopped treatment due to safety

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new bone formation, which lead to increased disability.2 or intolerance to an anti-TNF therapy (hereafter collec-
Destruction of bone and cartilage with pathological tively referred as anti-TNF-IR)). The study was planned to
new bone formation is one of the distinctive features enrol no more than 30% of anti-TNF-IR patients.
of PsA. The evidence of bone loss including eccentric Following a protocol amendment, the secukinumab
erosions, joint space narrowing and new bone forma- dose could be escalated from 150 mg to 300 mg every
tion is often seen in radiographs of peripheral joints.7 8 4 weeks at the beginning of week 52, if active signs of
In PsA, radiographic progression has been observed in disease were observed in patients based on the physi-
the early course of the disease, and it has been reported cian’s judgement. Patients were not allowed to switch to a
that 67% of patients have at least one joint erosion at lower dose once dose escalation occurred. After week 52,
their first visit to the clinic9 10 and 47% of patients have patients were unblinded to the original randomised treat-
bone erosions within the first 2 years of disease onset.7 11 ment assignment at randomisation. In addition, treat-

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Secukinumab, a human monoclonal antibody that ment was given as open-label, and patients continued
directly inhibits interleukin-17A, has demonstrated rapid to receive the same active dose of secukinumab as open-
and sustained efficacy in patients with PsA across the label treatment, administered until week 100. A follow-up
phase III FUTURE studies,12–15 and recently published visit was performed 12 weeks after last study treatment
recommendations for the management of PsA include administration for all patients, regardless of whether they
secukinumab as a first-line biological treatment option completed the entire study as planned or discontinued
after failure of conventional synthetic disease-modifying prematurely.
antirheumatic drugs.16 In the FUTURE 1 study, secuk- The study was conducted in accordance with the Decla-
inumab 150 mg provided a low rate of radiographic ration of Helsinki and was approved by institutional review
progression over 3 years and sustained clinical responses boards or independent ethics committees at each partic-
over 5 years.17 Secukinumab 300 mg and 150 mg reported ipating centre. Written informed consent was obtained
sustained efficacy, low rate of radiographic progression from all enrolled patients. Data were collected in accor-
and consistent safety over 52 weeks in the FUTURE 5 dance with Good Clinical Practice guidelines by the study
study.13 18 Here, we report the 2-year (end-of-study) effi- investigators and were analysed by the sponsor.19
cacy, radiographic progression and safety results of secuk-
inumab from the FUTURE 5 study.
Assessments
Assessments at week 104 included the American College
METHODS of Rheumatology (ACR) 20/50/70 responses, Psoriasis
Study design and patients Area and Severity Index 90 and 100 responses, change in
FUTURE 5 is a randomised, double-blind, placebo- 28-joint Disease Activity Score using C reactive protein,
controlled, multicentre, 2-year phase III study. The Health Assessment Questionnaire–Disability Index
detailed inclusion and exclusion criteria and study scores, and resolution of dactylitis and enthesitis. In
design have been reported previously.13 The key exclu- addition, the change in proportion of patients after dose
sion criteria included active/history of ongoing infec- escalation from any secukinumab 150 mg to 300 mg was
tion, use of ≥3 anti-tumour necrosis factor (TNF) agents, evaluated at week 104 for each category of ACR response
active inflammatory disease other than PsA and prior use (defined as no response: ACR <20; low response:
of a biologic other than an anti-TNF agent. All eligible 20≤ACR<50; moderate response: 50≤ACR<70; and high
patients (≥18 years of age) with active PsA for at least 6 response: ACR ≥70).
months, who were stratified by prior anti-TNF (anti-TNF- Radiographic structural damage was assessed by
naïve or inadequate response (IR)) use, were randomised mean change from baseline in van der Heijde-modified
(2:2:2:3) to one of the four treatment groups to receive total Sharp score (vdH-mTSS; sum of bone erosion
subcutaneous secukinumab 300 mg with loading dose (0–5 in the hands and 0–10 in the feet) and joint space
(300 mg), 150 mg with loading dose (150 mg), 150 mg narrowing (0–4) scores) for PsA.20 21 The vdH-mTSS
without loading dose (150 mg no load) or placebo at assessment was based on hand/wrist/foot radiographs
baseline; weeks 1, 2 and 3; and every 4 weeks starting at obtained at baseline and weeks 16 (non-responders),
week 4. At week 16, non-responders in the placebo group 24, 52 and 104, assessed by two blinded readers inde-
(<20% improvement from baseline in tender and swollen pendently (plus an adjudicator if required) who were
joint counts) were switched to receive either secuki- blinded to all patient information, treatment alloca-
numab 300 mg or 150 mg, and all the remaining patients tion and order of radiographs. The total radiographic
in the placebo group (responders) were switched at week score (hands and feet combined) ranged from 0 to 528,
24. Patients, investigators and assessors remained blinded with higher scores indicating more articular damage.
to the treatment allocation until all patients reached A change from baseline in vdH-mTSS ≤0.5 or ≤0.0 was
week 52. Stratification was done according to prior use defined as no structural progression, as recommended

2 Mease PJ, et al. RMD Open 2021;7:e001600. doi:10.1136/rmdopen-2021-001600

 Psoriatic arthritis

by van der Heijde et al.20 Overall safety and tolerability extreme values. Safety analyses included all patients who
of secukinumab over 104 weeks were assessed by moni- received ≥1 dose of secukinumab and were summarised
toring adverse events (AEs), serious AEs (SAEs), labo- descriptively.

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ratory assessments and vital signs.

Statistical analyses RESULTS

Data are presented for patients originally randomised Of the 996 patients randomised at baseline, 783 patients
to secukinumab including placebo switchers up to week (78.6%) completed 2 years (104 weeks) of treatment. A
104. Clinical efficacy and radiographic results up to week total of 84.7% (188/222), 82.3% (181/220) and 75.2%
104 are reported as observed data (evaluable patients). (167/222) patients originally randomised to secuki-
For all patients originally randomised to secukinumab, numab 300 mg, 150 mg and 150 mg no loading dose,
ACR20 and ACR50 responses up to week 104 using respectively, completed 2 years of treatment (figure 1).
multiple imputation (MI) are also reported. Available Of the 664 patients originally randomised to secuki-
data after dose escalation were used (not censored) and numab, 128 patients (19.3%) discontinued before or

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missing responses were imputed using MI in a visit-by- at week 104. The most common reason for premature
visit manner. At each visit, a logistic regression model discontinuation was patient/guardian decision: 6.8% in
was used for imputation with a covariate of weight, base- the 300 mg group, 5.9% in the 150 mg group and 7.7% in
line factors treatment and anti-TNF response status, and the 150 mg no load group. Lack of efficacy was reported
postbaseline factors of responses from previous visits in 1.4% of patients in 300 mg group, 1.8% of patients in
and dose escalation status (yes or no) from previous and 150 mg group and 7.7% of patients in 150 mg no load
current visits. This regression model used a missing-at- group.
random assumption, and multiply imputed data sets were The disposition of patients up to week 104 is presented
combined according to Rubin’s rule. Cumulative proba- in figure 1; disposition up to week 52 was reported previ-
bility plot was generated to show the vdH-mTSS for all ously.13 18 Overall, 39% (86/220) of patients from secuki-
patients according to dose group from baseline to week numab 150 mg load group and 41% (92/222) of patients
104. Subgroup analyses stratified by anti-TNF therapy from secukinumab 150 mg no load group were escalated
status (anti-TNF-naïve or anti-TNF-IR) were prespeci- to secukinumab 300 mg beginning at week 52. Demo-
fied. Radiographic analysis included evaluable patients at graphics and baseline disease characteristics of patients
baseline and weeks 24, 52 and 104. A sensitivity analysis of were balanced between treatment groups and have been
the radiographic data was performed after the statistical reported previously.13 At baseline, approximately 50% of
analysis of the data revealed that one patient exhibited patients were receiving concomitant methotrexate across

Figure 1 Patients’ disposition through week 104.

Twenty-six patients from placebo groups discontinued on or before week 16 and were not classified as responders or non-
responders.

Mease PJ, et al. RMD Open 2021;7:e001600. doi:10.1136/rmdopen-2021-001600 3

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Figure 2 ACR20 and ACR50 responses through 2 years.
All data through week 104 calculated using (A) observed and (B) multiple imputation for patients originally randomised to
secukinumab 300 mg, 150 mg and 150 mg no loading dose. *In observed data (A), ‘150 mg group’ included patients who were
originally randomised and those who had dose escalation and ‘150 mg No load’ group included patients who were originally
randomised and those who had dose escalation from week 60 to week 104, where available data after dose escalation
were used (not censored). ACR, American College of Rheumatology. n, number of patients in the treatment group with ACR
evaluation.

all treatment groups, and nearly one-third of patients 60.3% (ACR20) and 27.6% (ACR50) to 75% (ACR20)
were on anti-TNF-IR across all treatment groups. and 40.3% (ACR50), respectively, from week 60 to week
104. The Sankey-style plot presented in figure 3 shows
Clinical efficacy the proportion of patients with different levels of ACR
Clinical improvements reported at week 16 were response before and up to 36–40 weeks after dose esca-
sustained through 2 years in those patients who were lation among patients with ACR assessment within all
originally randomised to secukinumab and continued to corresponding week intervals. The proportion of ACR
receive secukinumab treatment through 2 years (figure 2 responders increased from 60% before dose escalation
and table 1). to 71% after 36–40 weeks following escalation from
An increase in ACR20 (56.5% to 72.7%) and ACR50 secukinumab 150 mg to 300 mg. Improvements in the
(33.9% to 48.1%) responses was observed from week 60 proportions of ACR responders increased in both anti-
to week 104 in patients who had dose escalation from TNF-naïve and anti-TNF-IR subgroups (online supple-
secukinumab 150 mg no load to 300 mg (figure 2A). mental tables 3 and 4).
At week 104, ACR20/50 response rates using MI in the
secukinumab 300 mg, 150 mg, and 150 mg no load groups Radiographic progression
were 75.3%/50.1%, 74.0%/50.9% and 72.2%/53.6%, Sustained low rates of radiographic progression were
respectively (figure 2B). Clinical efficacy in placebo observed through week 104. Mean changes from baseline
switchers (patients originally randomised to placebo who in vdH-mTSS through 2 years in the overall population
switched to secukinumab) was also sustained through 2 and by anti-TNF status are shown in figure 4. At week
years (online supplemental table 1). Sustained efficacy 52, mean changes from baseline in vdH-mTSS (observed
was observed in both anti-TNF-naïve and anti-TNF-IR data (SD)) were −0.04 (1.02), 0.20 (1.83) and 0.28 (1.34)
patients (online supplemental table 2). In patients in the secukinumab 300 mg, 150 mg and 150 mg no load
whose dose was escalated from secukinumab 150 mg to groups, respectively, in the overall population. At week
300 mg, ACR20 and ACR50 responses increased from 104, mean changes from baseline in vdH-mTSS (observed

4 Mease PJ, et al. RMD Open 2021;7:e001600. doi:10.1136/rmdopen-2021-001600

 Psoriatic arthritis

Table 1 Summary of clinical efficacy through week 104, data as observed

Week 16 Week 52 Week 104

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150 mg no 150 mg no
Efficacy end 300 mg 150 mg load 300 mg 150 mg load 300 mg 150 mg* group 150 mg* no load
points (N=222) (N=220) (N=222) (N=222) (N=220) (N=222) (N=222) (N=220) group (N=222)
ACR70 21.2 (212) 19.0 (211) 15.6 (211) 31.8 (201) 29.1 (196) 28.9 (190) 34.8 (187) 33.1 (175) 44.0 (168)
response, % (n)
PASI 90 54.6 (108) 38.0 (121) 32.7 (113) 61.8 (102) 52.7 (112) 47.1 (102) 70.1 (97) 59.2 (103) 62.6 (91)
response†,
% (n)
PASI 100 34.3 (108) 22.1 (122) 19.5 (113) 48.0 (102) 36.3 (113) 35.3 (102) 49.5 (97) 44.2 (104) 40.7 (91)
response†,
% (n)
DAS28-CRP −1.5±1.3 −1.4±1.2 −1.3±1.2 −1.9±1.2 −1.8±1.1 −1.9±1.3 −2.1±1.2 (182) −2.1±1.1 −2.2±1.1 (165)
score, mean (209) (208) (210) (201) (194) (189) (172)
change from

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BL±SD (n)
HAQ-DI score, −0.55±0.57 −0.46±0.55 −0.49±0.57 −0.58±0.6 −0.53±0.6 −0.60±0.7 −0.58±0.6 (186) −0.57±0.6 (177) −0.62±0.7 (169)
mean change (211) (210) (211) (199) (195) (190)
from BL±SD (n)
Enthesitis 56.5 (138) 56.2 (137) 44.3 (122) 78.0 (127) 69.0 (129) 68.7 (115) 78.0 (118) 80.3 (117) 69.5 (95)
resolution‡,
% (n)
Dactylitis 66.7 (81) 58.2 (79) 58.0 (100) 80.6 82.9 81.6 (87) 82.8 (64) 85.5 89.3 (75)
resolution‡, (72) (70) (62)
% (n)

Results are reported as observed data.

*150 mg groups include patients who escalated to 300 mg.
†Analysis performed in randomised patients with psoriasis (psoriasis subset) affecting ≥3% body surface area at baseline; n=110 (300 mg), 125 (150 mg) and 117 (150 mg no load).
‡Resolution of enthesitis and dactylitis is shown for patients with symptoms at baseline.
%, percentage of responses; ACR, American College of Rheumatology response criteria; BL, baseline; DAS28-CRP, 28-joint Disease Activity Score using C reactive protein; HAQ-DI,
HAQ–Disability Index; n, number of patients in the treatment group with evaluation at weeks 16, 52 and 104; N, number of randomised patients; PASI, Psoriasis Area and Severity
Index.

data (SD)) were 0.10 (1.74), 0.52 (2.66) and 0.41 (2.20) In patients with prior anti-TNF therapy status, mean
in the secukinumab 300 mg, 150 mg and 150 mg no load changes from baseline in vdH-mTSS followed a similar
groups, respectively. The proportion of patients with no trend of low radiographic progression (figure 4). The
radiographic progression (change from baseline in vdH- anti-TNF-naïve group showed lower radiographic
mTSS ≤0.5) with secukinumab at 104 weeks was 89.5% progression than the anti-TNF-IR group. At week 104,
(300 mg), 82.3% (150 mg) and 81.1% (150 mg no load), no radiographic progression (change from baseline
respectively. The proportion of patients with change from in vdH-mTSS ≤0.5) was observed in 92.8% (300 mg),
baseline in vdH-mTSS ≤0.0 was 81.2% (300 mg), 69.1% 83.9% (150 mg) and 84.7% (150 mg no load) of anti-
(150 mg) and 73.4% (150 mg no load), respectively. TNF-naïve patients and in 80.8% (300 mg), 77.3%
(150 mg) and 71.1% (150 mg no load) of anti-TNF-IR
patients, respectively. The proportion of patients with
change from baseline in vdH-mTSS ≤0.0 was 83.5%
(300 mg), 70.8% (150 mg) and 75% (150 mg no load)
in anti-TNF-naïve patients and 75% (300 mg), 63.6%
(150 mg) and 68.9% (150 mg no load) in anti-TNF-IR
patients, respectively.
Cumulative probability plots in vdH-mTSS change
from baseline to week 104 showed the scores of the indi-
vidual patients in different secukinumab doses over 104
weeks of treatment. The structural progression of indi-
vidual patients at week 104 is presented in figure 5. In the
Figure 3 ACR response up to 36–40 weeks after dose 300 mg dose group, there was one outlier (anti-TNF-IR
escalation from 150 mg to 300 mg. ACR, American College patient) with a very high mTSS change from baseline to
of Rheumatology.
week 104 (change from baseline was 52.67). The outlier in
Before dose-escalation is defined as the last assessment
the secukinumab 300 mg group drove the mean change
done on or before a patient took the 300 mg dose. The
colors flowing in the background indicate the proportion from baseline for this group at week 104 compared with
of patients changing the response over time. Number of weeks 24 and 52. The mean vdH-mTSS change at week
subjects evaluated, n=137. First dose-escalation observed at 104 from baseline with the patient included is 1.56 and
study week 52. without the patient included is 0.56.

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Figure 5 Cumulative probability plot of vdH-mTSS at week
104. TNF-IR, tumour necrosis factor inadequate response;
vdH-mTSS, van der Heijde-modified total Sharp score.
300 mg (N=222), 150 mg (N=220), 150 no load (N=222); N:

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randomised patients; n: number of patients with evaluable X-
rays at both baseline and week 104. 150 mg and 150 mg no
load groups included 77 and 79 patients with radiographic
results, respectively, who had dose escalation at week 52 or
later.

events were reported. One patient in any secukinumab

300 mg group was adjudicated as spontaneous myocardial
infarction. Of the two patients who were reported to have
(possible) stroke and identified for adjudication, one
patient in any secukinumab 300 mg group was reported
to have a cerebral haemorrhage that was confirmed as a
stroke, and another patient in any secukinumab 150 mg
group was reported to have a lacunar infarction that was
adjudicated as not a stroke. One patient in any secuki-
numab 150 mg was reported to have cardiopulmonary
arrest that was confirmed as a sudden cardiovascular
Figure 4 Mean changes in vdH-mTSS scores from baseline death. Inflammatory bowel disease was reported in five
through week 104. (A) Overall population, (B) anti-TNF-naïve patients; two patients reported Crohn’s disease (one with
and (C) anti-TNF-IR. a history of Crohn’s disease and another with a history of
Analyses at weeks 24, 52 and 104 were done by observed colitis), one with a new diagnosis of ulcerative colitis, one
data. In the 300 mg dose group there was one outlier (anti- colonic abscess and one ulcerative proctitis. Oesophageal
TNF-IR patient) with a very high mTSS change from baseline candidiasis was reported in one patient in secukinumab
(week 104 analysis). Analysis was based on the patients with 150 mg group. A total of three deaths were reported, one
evaluable X-rays at both baseline and week 104. n, number
in any secukinumab 300 mg due to sepsis and two in any
of patients with evaluable X-rays at both baseline and week
secukinumab 150 mg due to acute myocardial infarc-
104. At each time point, only patients with a value at both
baseline and that time point are included. TNF, tumour tion and cardiorespiratory arrest; none were considered
necrosis factor; vdH-mTSS, van der Heijde-modified total related to study drug as assessed by the investigator. The
Sharp score. safety profile of secukinumab in this study showed no
new or unexpected safety signals.
Safety
Over the entire treatment period, the mean secuki- DISCUSSION
numab exposure was 667.4 days (1761.5 patient-years). In this large phase III study in patients with active PsA,
The rate of discontinuation due to any AE was low and secukinumab 300 mg and 150 mg, with or without loading
similar between secukinumab 300 mg (4.4%) and 150 mg dose, provided sustained clinical efficacy, low radiographic
(4.6%) dose groups. Exposure-adjusted incidence rates progression and consistent safety over 2 years of treatment,
(EAIRs) for treatment emergent SAEs were 8.0 in secuki- demonstrating the long-term clinical benefit of secukinumab
numab 300 mg group and 8.6 in secukinumab 150 mg treatment. The majority (78.6%) of patients remained in
group. The most frequently reported AEs in any secuki- the study for the full 2 years. A slightly lower completion rate
numab group (EAIR ≥5) were nasopharyngitis and upper was observed in the 150 mg no load group with patient/
respiratory tract infection (table 2). guardian decision and lack of efficacy the main reasons for
The EAIRs of selected AEs of interest observed with discontinuation. After secukinumab dose escalation from
secukinumab are shown in table 2. A total of three MACE 150 mg to 300 mg, the proportion of ACR20 and ACR50

6 Mease PJ, et al. RMD Open 2021;7:e001600. doi:10.1136/rmdopen-2021-001600

 Psoriatic arthritis

Table 2 Safety with secukinumab during the entire treatment period through week 104
Any secukinumab Any secukinumab Any secukinumab

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Parameter 300 mg (N=607) 150 mg (N=593) (N=964)
Exposure
Mean, days±SD 542.2±214.76 529.9±224.86 667.4±184.35
Pt-yrs 901.1 860.3 1761.5
AEs, n (EAIR/100 pt-yrs) 448 (129.2) 478 (163.0) 792 (139.8)
SAEs, n (EAIR/100 pt-yrs) 68 (8.0) 70 (8.6) 131 (7.9)
AEs leading to discontinuation, n (%) 27 (4.4) 27 (4.6) 54 (5.6)
Deaths, n (%) 1 (0.2) 2 (0.3) 3 (0.3)
Most frequent AEs, n (EAIR/100 pt-yrs)*
Nasopharyngitis 73 (8.9) 80 (10.3) 148 (9.4)

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Upper respiratory tract infection 57 (6.7) 71 (9.0) 121 (7.5)
AEs of special interest, n (EAIR/100 pt-yrs)
Neutropenia 5 (0.6) 10 (1.2) 15 (0.9)
Oral candidiasis 8 (0.9) 3 (0.4) 11 (0.6)
MACE 2 (0.2) 1 (0.1) 3 (0.2)
Crohn’s disease† 1 (0.1) 2 (0.2) 2 (0.1)
Ulcerative colitis 0 1 (0.1) 1 (0.1)

The ‘any secukinumab’ group includes patients who experienced AEs at least once on either of the doses.
Patient-years (pt-yrs) is calculated as a sum of individual patient durations in days divided by 365.25. If a patient experienced
an AE after dose escalation, the corresponding AE was counted in 300 mg group.
*AEs that occurred with an EAIR of at least 5.0 cases per 100 pt-yrs in either any secukinumab 300 mg or 150 mg mg group
over the entire treatment period
†There is one patient in 150 mg no load arm who reported Crohn’s disease. After the dose escalated to 300 mg, the same
patient reported Crohn’s disease again. So essentially the same patient counted in any 300 mg group and in any 150 mg
group.
AEs, adverse events; EAIR, exposure-adjusted incidence rates; MACE, major adverse cardiovascular event; SAEs, serious
adverse events.

responders increased. Notably, the percentage of patients status, so these data need to be interpreted with caution.
with ACR response ≥50 (ACR50 and ACR70 responders) Furthermore, minimal clinically important differences
increased after dose escalation in both anti-TNF-naïve and are not reported in the article, which may limit the value
anti-TNF-IR subgroups. of results in clinical practice.
Sustained improvement was observed in secukinumab- In conclusion, subcutaneous secukinumab 300 mg and
treated patients across efficacy end points through 2 years, 150 mg with and without loading dose provided sustained
which is in agreement with the findings of previous secuki- improvement in clinical responses and low rates of
numab studies in PsA.15 17 22–25 The majority (81.1%–89.5%) radiographic progression through 2 years of therapy in
of secukinumab-treated patients in the overall population patients with PsA who remain on the treatment for 2
showed no radiographic progression (change from base- years. Improvement in ACR responses was observed in
line in vdH-mTSS ≤0.5) at 2 years. Low rates of radiographic patients who escalated from secukinumab 150 mg to 300
progression were observed in secukinumab-treated patients
mg, indicating a potential benefit for dose escalation in
with PsA regardless of the previous anti-TNF treatment
patients whose symptoms were not adequately controlled
status, with lower radiographic progression observed in the
with the lower dose. Secukinumab was well tolerated with
anti-TNF-naïve subgroup than in the anti-TNF-IR subgroup.
no new or unexpected safety signals reported. Overall,
These results are consistent with previous results with secuk-
inumab.13 17 18 26 the findings from this study strengthen the existing
The safety profile was consistent with previous reports evidence on the efficacy of long-term secukinumab treat-
from secukinumab trials and with the results of a retro- ment in patients with PsA.
spective safety analysis of 21 secukinumab clinical trials
Author affiliations
across different indications.12–15 27 1
Rheumatology Research Division, Providence St. Joseph Health and University of
This study was not designed to compare between treat- Washington, Swedish Medical Center, Seattle, Washington, USA
ment regimens (secukinumab load vs no load) or to 2
Department of Rheumatology, University of Amsterdam, Amsterdam, The
assess treatment differences by previous anti-TNF therapy Netherlands

Mease PJ, et al. RMD Open 2021;7:e001600. doi:10.1136/rmdopen-2021-001600 7

 RMD Open
3
Department of Rheumatology, Atrium Medical Centre, Amsterdam, The 5 Coates LC, Kavanaugh A, Mease PJ, et al. Group for research
Netherlands and assessment of psoriasis and psoriatic arthritis 2015 treatment
4
Faculty of Medicine, Memorial University of Newfoundland, St. John's, recommendations for psoriatic arthritis. Arthritis Rheumatol

RMD Open: first published as 10.1136/rmdopen-2021-001600 on 30 July 2021. Downloaded from https://rmdopen.bmj.com on 21 September 2025 by guest.
2016;68:1060–71.
Newfoundland, Canada 6 Bond SJ, Farewell VT, Schentag CT, et al. Predictors for radiological
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Rheumatology, Whipps Cross University Hospital, London, UK damage in psoriatic arthritis: results from a single centre. Ann
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Southwest Rheumatology, Dallas, Texas, USA Rheum Dis 2007;66:370–6.
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Rheumazentrum, Favoriten Hospital, Vienna, Austria 7 Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J
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Section of Rheumatology, University of Santo Tomas Hospital, Manila, Philippines Med 2017;376:957–70.
9 8 Poggenborg RP, Østergaard M, Terslev L. Imaging in psoriatic
Rheumatology, Novartis Pharmaceuticals Corp, East Hanover, New Jersey, USA
10 arthritis. Rheum Dis Clin North Am 2015;41:593–613.
Rheumatology, Novartis AG, Basel, Basel-Stadt, Switzerland 9 Gladman DD, Shuckett R, Russell ML, et al. Psoriatic arthritis (PSA)--
11
Rheumatology, Leiden University Medical Center, Leiden, The Netherlands an analysis of 220 patients. Q J Med 1987;62:127–41.
10 Alonso JCT, Perez AR, Castrillo JMA, et al. Psoriatic arthritis (PA):
Acknowledgements We thank the patients who participated in this study and a clinical, immunological and radiological study of 180 patients.
the study investigators for their contributions. Rajeeb Ghosh (Novartis) provided Rheumatology 1991;30:245–50.
medical writing support and John Gallagher (Novartis) provided medical and 11 Kane Det alA prospective, clinical and radiological study of early
psoriatic arthritis: an early synovitis clinic experience. Rheumatology
editorial guidance in accordance with Good Publication Practice guidelines.
2003;42:1460–8.
Funding This study was supported by Novartis Pharma AG, Switzerland. 12 McInnes IB, Mease PJ, Kirkham B, et al. Secukinumab, a human

Protected by copyright, including for uses related to text and data mining, AI training, and similar technologies.
anti-interleukin-17A monoclonal antibody, in patients with psoriatic
Competing interests PJM has received research grants, consulting and speaking
arthritis (FUTURE 2): a randomised, double-blind, placebo-
fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB; research controlled, phase 3 trial. Lancet 2015;386:1137–46.
grants and consulting fees from Bristol-Myers Squibb, Galapagos, Gilead and 13 Mease P, van der Heijde D, Landewé R, et al. Secukinumab improves
Sun; and consulting fees from Boehringer Ingelheim and GlaxoSmithKliine. RBL active psoriatic arthritis symptoms and inhibits radiographic
has received consulting fees from AbbVie, Novartis, EliLilly, UCB, Pfizer, Galapagos progression: primary results from the randomised, double-blind,
and Gilead. PR has received research grants from Janssen and Novartis, and phase III FUTURE 5 study. Ann Rheum Dis 2018;77:890–7.
consulting and speaking fees from AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, 14 Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab inhibition
Merck, Novartis, Pfizer and UCB. HT, AS and EB have nothing to disclose. SN has of interleukin-17A in patients with psoriatic arthritis. N Engl J Med
received research grants from Novartis and Johnson & Johnson, and consulting 2015;373:1329–39.
fees from Novartis, Johnson & Johnson and Pfizer. AR is an employee of Novartis, 15 Nash P, Mease PJ, McInnes IB, et al. Efficacy and safety of
with Novartis stock. SM is an employee of Novartis, with Novartis stock. EMD was secukinumab administration by autoinjector in patients with
an employee of Novartis and LP is an employee of Novartis. DvdH has received psoriatic arthritis: results from a randomized, placebo-controlled trial
consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BMS, Boehringer (FUTURE 3). Arthritis Res Ther 2018;20:47.
Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith- 16 Gossec L, Baraliakos X, Kerschbaumer A, et al. EULAR
Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda and UCB recommendations for the management of psoriatic arthritis
Pharma. DvdH is a Director of Imaging Rheumatology with pharmacological therapies: 2019 update. Ann Rheum Dis
2020;79:700.1–12.
Patient consent for publication Not required. 17 Mease PJ, Kavanaugh A, Reimold A, et al. Secukinumab in the
treatment of psoriatic arthritis: efficacy and safety results through 3
Provenance and peer review Not commissioned; externally peer reviewed.
years from the year 1 extension of the randomised phase III FUTURE
Data availability statement The data sets generated and/or analysed during this 1 trial. RMD Open 2018;4:e000723.
study are not publicly available. Novartis is committed to sharing with qualified 18 van der Heijde D, Mease PJ, Landewé RBM, et al. Secukinumab
external researchers the access to patient-level data and supporting clinical provides sustained low rates of radiographic progression in
documents from eligible studies. These requests are reviewed and approved psoriatic arthritis: 52-week results from a phase 3 study, FUTURE 5.
on the basis of scientific merit. All data provided are anonymised to respect the Rheumatology 2020;59:1325–34.
privacy of patients who have participated in the trial, in line with applicable laws 19 World Medical Association. World Medical association Declaration
and regulations. The data may be requested from the corresponding author of the of Helsinki: ethical principles for medical research involving human
manuscript. subjects. JAMA 2013;310:2191–4.
20 van der Heijde D, Landewé R, Klareskog L, et al. Presentation and
Open access This is an open access article distributed in accordance with the analysis of data on radiographic outcome in clinical trials: experience
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which from the tempo study. Arthritis Rheum 2005;52:49–60.
permits others to distribute, remix, adapt, build upon this work non-commercially, 21 van der Heijde D. How to read radiographs according to the Sharp/
and license their derivative works on different terms, provided the original work is van Der Heijde method. J Rheumatol 1999;26:261–3.
properly cited, appropriate credit is given, any changes made indicated, and the 22 McInnes IB, Mease PJ, Kivitz AJ, et al. Long-Term efficacy and
use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/. safety of secukinumab in patients with psoriatic arthritis: 5-year
(end-of-study) results from the phase 3 FUTURE 2 study. Lancet
ORCID iDs Rheumatol 2020;2:e227–35.
Philip J Mease http://orcid.org/0000-0002-6620-0457 23 Kivitz AJ, Nash P, Tahir H, et al. Efficacy and Safety of Subcutaneous
Robert Landewé http://orcid.org/0000-0002-0577-6620 Secukinumab 150 mg with or Without Loading Regimen in Psoriatic
Desirée van der Heijde http://orcid.org/0000-0002-5781-158X Arthritis: Results from the FUTURE 4 Study. Rheumatol Ther
2019;6:393–407.
24 McInnes IB, Mease PJ, Ritchlin CT, et al. Secukinumab sustains
improvement in signs and symptoms of psoriatic arthritis: 2
year results from the phase 3 FUTURE 2 study. Rheumatology
2017;56:1993–2003.
25 Kavanaugh A, Mease PJ, Reimold AM, et al. Secukinumab for
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