Effectiveness and safety of secukinumab in ankylosing spondylitis and psoriatic arthritis: a 52-week real-life study in an Italian cohort

Colella, Francesco Molica; Zizzo, Gaetano; Parrino, Vincenzo; Filosa, Maria Teresa; Cavaliere, Riccardo; Fazio, Francesco; Colella, Aldo Biagio Molica; Mazzone, Antonino

doi:10.1186/s42358-023-00295-2

person Francesco Molica Colella *

Patient recruitment · data collection · Manuscript review · read and approved the final version submitted

schoolUnit of Rheumatology, Department of Internal Medicine, Azienda Ospedaliera (A.O.) “Papardo”, Messina, ItalyschoolRheumatology Unit, A.O. Papardo, Messina 98158, Italy † These authors have contributed equally to this work.

person Gaetano Zizzo *

Statistical analysis, tables and figures · Literature search · manuscript writing · read and approved the final version submitted

schoolSection of Rheumatology, Department of Internal Medicine, Azienda Socio Sanitaria Territoriale (ASST) Ovest Milanese, Legnano Hospital, Milan, ItalyschoolRheumatology Section, ASST Ovest Milanese, Milan 20025, Italy † These authors have contributed equally to this work.

0000-0002-6971-4576

person Vincenzo Parrino

Manuscript review · read and approved the final version submitted

schoolDepartment of Chemical, Biological, Pharmaceutical, and Environmental Sciences, Messina University, Messina, Italy

person Maria Teresa Filosa

Patient recruitment · data collection · Manuscript review · read and approved the final version submitted

schoolUnit of Rheumatology, Department of Internal Medicine, Azienda Ospedaliera (A.O.) “Papardo”, Messina, Italy

person Riccardo Cavaliere

Manuscript review · read and approved the final version submitted

schoolDepartment of Adult and Developmental Human Pathology “Gaetano Barresi”, Messina University, Messina, Italy

person Francesco Fazio

Manuscript review · read and approved the final version submitted

schoolDepartment of Veterinary Sciences, “Polo Universitario dell’Annunziata”, Messina University, Messina, Italy

person Aldo Biagio Molica Colella

Study conception · design · Patient recruitment · data collection · Manuscript review · Supervision · read and approved the final version submitted

schoolUnit of Rheumatology, Department of Internal Medicine, Azienda Ospedaliera (A.O.) “Papardo”, Messina, Italy

person Antonino Mazzone

Manuscript review · Supervision · read and approved the final version submitted

schoolSection of Rheumatology, Department of Internal Medicine, Azienda Socio Sanitaria Territoriale (ASST) Ovest Milanese, Legnano Hospital, Milan, Italy

person*Correspondence: Francesco Molica Colella,
francesco.molica3@gmail.com Gaetano Zizzo,
gaetano.zizzo@hotmail.it

†

These authors have contributed equally to this work.

Competing interests

The authors declare that they have no competing interests.

Figures (3)
Tables (3)

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Fig. 1 Disease activity scores and treatment responses in patients with AS or PsA during therapy with secukinumab. a) Mean values (± standard deviation) of ASDAS-CRP and DAS28-CRP at baseline and at 8, 24 and 52 weeks of treatment in patients with AS and PsA, respectively. *P < 0.05, ****P < 0.0001 (compared to week 0); ^##P < 0.01, ^####P < 0.0001 (week 24 vs. 8); ⁺⁺P < 0.01, ⁺⁺⁺P < 0.001 (week 52 vs. 24). b) Numbers and percentages of AS or PsA patients with different disease activity states according to ASDAS and DAS28 cut-offs. VHDA, very high disease activity (ASDAS > 3.5); HDA, high disease activity (2.1 ≤ ASDAS < 3.5 or DAS28 > 5.1); MDA, moderate disease activity (3.2 < DAS28 ≤ 5.1); LDA, low disease activity (ASDAS < 2.1 or DAS28 ≤ 3.2); inactive disease or remission (ASDAS < 1.3 or DAS28 < 2.6). *P < 0.05 (LDA at week 8 in AS vs. PsA). c) Median changes of ASDAS-CRP and DAS28-CRP at the various time points in patients with AS and PsA, respectively. ΔASDAS ≥ 1.1, clinically important improvement; ΔASDAS ≥ 2, major improvement; ΔDAS28 > 1.2, moderate response with current DAS28 > 3.2 or good response with current DAS28 ≤ 3.2. **P < 0.01, ****P < 0.0001 (compared to week 0); ^##P < 0.01, ^####P < 0.0001 (week 24 vs. 8); ⁺P < 0.05 (week 52 vs. 24). d) Numbers and percentages of AS or PsA patients with different treatment responses according to ASAS and EULAR criteria (see above cut-offs). *P < 0.05 (significant responses at week 8 in PsA vs. AS).

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Fig. 2 Influence of baseline disease activity and body weight on response to secukinumab. a) Differences in median changes (+ interquartile range) of DAS28-CRP and ASDAS-CRP at 8, 24 and 52 weeks between patients with the highest vs. lower disease activity scores at baseline. **P < 0.01, ***P < 0.001, ****P < 0.0001. b) Significant correlations between baseline disease activity and disease activity score changes at the various time points (Note: events in the fourth graph appear to be fewer than the number of patients analyzed due to overlapping dots). c) Differences in median changes (+ interquartile range) of DAS28-CRP and ASDAS-CRP at 8, 24 and 52 weeks between patients with body weights above and below median values. *P < 0.05.

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Fig. 3 Impact of gender on response to secukinumab. a) Percentages of male and female patients with AS or PsA achieving different outcomes at 52 weeks of treatment. CII, clinically important improvement. *P < 0.05 (males vs. females). b) Kaplan-Meier drug survival curves of male and female patients during one year of follow-up. c) Percentages (and numbers) of male and female patients who experienced poor outcomes during follow-up (i.e., primary and secondary failures or suboptimal responses accounting for subsequent drug discontinuation), in the whole cohort and separately in the AS and PsA groups.

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Table 1 Baseline characteristics of the patients

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Table 2 Outcomes after 8, 24 and 52 weeks of treatment with Secukinumab

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Table 3 Multiple logistic regression aimed to identify possible independent predictors of achievement of inactive disease (ASDAS-ID: ASDAS < 1.3) or remission (DAS28 < 2.6) after 52 weeks of treatment with Secukinumab in the whole cohort of patients with AS or PsA.

	All patients	AS patients	PsA patients
N.	85	29	56
Gender, F/M	62/23	20/9	42/14
Age (years), mean ± SD	55.5 ± 12	50.5 ± 14	58 ± 10
(median ± IQR)	(56 ± 17)	(52 ± 16)	(57 ± 15.5)*
Body weight (Kg), mean ± SD	75 ± 17	72 ± 14	77 ± 18
(median ± IQR)	(75 ± 25)	(72 ± 23)	(76 ± 26)
Disease duration (years),	6.7 ± 1.3	6.6 ± 1.35	6.8 ± 1.2
mean ± SD (median ± IQR)	(7 ± 2)	(6 ± 3)	(7 ± 2)
HLA-B27 carriers, N. (%)	N/A	23 (79)	N/A
Highest disease activity status at baseline, N. (%)	68 (80)	22 (76)	46 (82)
Baseline ASDAS-CRP or DAS28-CRP,	–	3.7 ± 0.3	5.8 ± 0.7
mean ± SD (median ± IQR)		(3.7 ± 0.2)	(5.7 ± 0.8)
Concomitant csDMARDs, N. (%)	61 (72)	7 (24)	54 (96)****
Concomitant MTX, N. (%)	58 (68)	7 (24)	51 (91)****
Concomitant NSAIDs, N. (%)	N/A	26 (90)	N/A
TNFi-experienced, N. (%)	13 (15)	4 (14)	9 (16)

	All patients	AS patients	PsA patients
Effectiveness
Week 8
ASDAS-CRP or DAS28-CRP value, mean ± SD (median ± IQR)	–	2.5 ± 0.8 (2.1 ± 1.5)	4.2 ± 0.85 (4 ± 0.6)
(at least) Low disease activity, N. (%)	15 (18)	11 (38)	4 (7)**
Inactive disease or Remission, N. (%)	0 (0)	0 (0)	0 (0)
Change in ASDAS-CRP or DAS28-CRP, mean ± SD (median ± IQR)		-1.1 ± 0.75 (-1.5 ± 1.6)	-1.6 ± 0.9 (-1.6 ± 0.95)
(at least) CII or Moderate response, N. (%)	67 (79)	19 (65.5)	48 (86)*
Major improvement or Good response, N. (%)	4 (5)	0 (0)	4 (7)
*Week 24*
ASDAS-CRP or DAS28-CRP value, mean ± SD (median ± IQR)	–	1.7 ± 0.8 (1.2 ± 0.6)	2.7 ± 0.8 (2.5 ± 0.85)
(at least) Low disease activity, N. (%)	58 *(68)*	19 *(65.5)*	39 *(70)*
Inactive disease or Remission, N. (%)	39 *(46)*	13 *(45)*	26 *(46)*
Change in ASDAS-CRP or DAS28-CRP, mean ± SD (median ± IQR)	–	-2 ± 0.8 (-2.3 ± 0.65)	-3.1 ± 1.1 (-3.1 ± 1.3)
(at least) CII or Moderate response, N. (%)	70 (82)	21 (72)	49 (87.5)
Major improvement or Good response, N. (%)	55 (65)	16 (55)	39 (70)
*Week 52*
ASDAS-CRP or DAS28-CRP value, mean ± SD (median ± IQR)	–	1.3 ± 0.5 (1.2 ± 0)	2.2 ± 0.7 (2.2 ± 0.45)
(at least) Low disease activity, N. (%)	64 *(75)*	20 *(69)*	44 *(79)*
Inactive disease or Remission, N. (%)	57 *(67)*	19 *(65.5)*	38 *(68)*
Change in ASDAS-CRP or DAS28-CRP, mean ± SD (median ± IQR)	–	-2.3 ± 0.6 (-2.4 ± 0.3)	-3.6 ± 0.9 (-3.6 ± 1.2)
(at least) CII or Moderate response, N. (%)	67 (79)	20 (69)	47 (84)
Major improvement or Good response, N. (%)	63 (74)	19 (65.5)	44 (79)
Retention rate (Drug survival after 52 weeks), N. (%)	64 *(75)*	20 *(69)*	44 *(79)*
Safety
Serious adverse events, N.	0	0	0
Injection-site reactions, N.	4	1	3

Variable	β value	Standard error (SE)	Odds ratio (OR)	95% profile likelihood confidence interval (CI)	P value
Age (above median)	-0.8037	0.5448	0.4477	0.1474 to 1.274	0.1402
Body weight (above median)	-0.1398	0.5536	0.8695	0.2879 to 2.570	0.8006
Disease duration (above median)	-0.8409	0.5687	0.4313	0.1372 to 1.304	0.1392
Male gender	1.641	0.7426	5.161	1.347 to 26.63	0.0271 *()**
Concomitant use of MTX	0.1278	0.7524	1.136	0.2576 to 5.172	0.8651
Previous treatment with TNFi	-0.7003	0.7168	0.4965	0.1201 to 2.101	0.3286
Highest disease activity status at baseline	-0.3904	0.7162	0.6768	0.1491 to 2.626	0.5857
Diagnosis of PsA	0.2529	0.6994	1.288	0.3137 to 5.145	0.7177

[TFN1] Highest disease activity status: ASDAS > 3.5 (AS patients) or DAS28 > 5.1 (PsA patients)

[TFN2] N/A, not available

[TFN2a] (AS vs. PsA)

[TFN3] ^*
P < 0.05 (= 0.0194)

[TFN4] ^****
P < 0.0001