The efficacy and safety of olokizumab for rheumatoid arthritis: a systematic review, pairwise, and network meta-analysis
Olokizumab (OKZ) is a novel IL-6 inhibitor that directly targets IL-6 rather than its receptor. We aim to evaluate the efficacy and safety of OKZ for patients with rheumatoid arthritis (RA) and to investigate the optimal treatment regimen. A systematic review, pairwise, and network meta-analysis syn...
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| Veröffentlicht in: | Clinical rheumatology 2023-06, Vol.42 (6), p.1503-1520 |
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| creator | Abuelazm, Mohamed Ghanem, Ahmed Mahmoud, Abdelrahman Brakat, Aml M. Elzeftawy, Mohamad A. Mamdouh Fayoud, Aya Awad, Ahmed K. Abdelazeem, Basel |
| description | Olokizumab (OKZ) is a novel IL-6 inhibitor that directly targets IL-6 rather than its receptor. We aim to evaluate the efficacy and safety of OKZ for patients with rheumatoid arthritis (RA) and to investigate the optimal treatment regimen. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, CENTRAL, SCOPUS, EMBASE, and PubMed until August 31, 2022. We used the risk ratio (RR) and mean difference (MD) for dichotomous and continuous outcomes, respectively, presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID:
CRD42022358082
. Five RCTs with 2277 patients were included. OKZ significantly improved the American College of Rheumatology criteria (ACR) 20 (RR: 1.97 with 95% CI [1.49, 2.58],
P
= 0.00001), ACR50 (RR: 3.83 with 95% CI [2.13, 6.87],
P
= 0.00001), ACR70 (RR: 3.83 with 95% CI [2.13, 6.87],
P
= 0.00001), disease activity score 28 based on C-reactive protein (DAS28-CRP) (RR: 3.91 with 95% CI [2.65, 5.79],
P
= 0.00001), clinical disease activity index (CDAI) (RR: 2.80 with 95% CI [1.43, 5.48],
P
= 0.003), and health assessment questionnaire disability index (HAQ-DI) (MD: − 0.28 with 95% CI [− 0.38, − 0.18],
P
= 0.00001) after 12 weeks, compared to placebo. However, OKZ was also associated with a higher incidence of any adverse events (AEs) (RR: 1.15 with 95% CI [1.06, 1.25], P = 0.0005) and AEs leading to drug discontinuation (RR: 1.86 with 95% CI [1.05, 3.29], P = 0.03). OKZ is effective and with acceptable safety profile when administrated with methotrexate in patients with RA not adequately controlled by tumor necrosis factor inhibitors; however, more large-scale RCTs are still required to investigate the optimal dosing, long-term effects, and comparative efficacy versus established biological DMARDs.
Key Points
•
OKZ is effective especially with methotrexate in RA patients. |
| doi_str_mv | 10.1007/s10067-023-06519-6 |
| format | Article |
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CRD42022358082
. Five RCTs with 2277 patients were included. OKZ significantly improved the American College of Rheumatology criteria (ACR) 20 (RR: 1.97 with 95% CI [1.49, 2.58],
P
= 0.00001), ACR50 (RR: 3.83 with 95% CI [2.13, 6.87],
P
= 0.00001), ACR70 (RR: 3.83 with 95% CI [2.13, 6.87],
P
= 0.00001), disease activity score 28 based on C-reactive protein (DAS28-CRP) (RR: 3.91 with 95% CI [2.65, 5.79],
P
= 0.00001), clinical disease activity index (CDAI) (RR: 2.80 with 95% CI [1.43, 5.48],
P
= 0.003), and health assessment questionnaire disability index (HAQ-DI) (MD: − 0.28 with 95% CI [− 0.38, − 0.18],
P
= 0.00001) after 12 weeks, compared to placebo. However, OKZ was also associated with a higher incidence of any adverse events (AEs) (RR: 1.15 with 95% CI [1.06, 1.25], P = 0.0005) and AEs leading to drug discontinuation (RR: 1.86 with 95% CI [1.05, 3.29], P = 0.03). OKZ is effective and with acceptable safety profile when administrated with methotrexate in patients with RA not adequately controlled by tumor necrosis factor inhibitors; however, more large-scale RCTs are still required to investigate the optimal dosing, long-term effects, and comparative efficacy versus established biological DMARDs.
Key Points
•
OKZ is effective especially with methotrexate in RA patients.</description><identifier>ISSN: 0770-3198</identifier><identifier>EISSN: 1434-9949</identifier><identifier>DOI: 10.1007/s10067-023-06519-6</identifier><identifier>PMID: 36792848</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Antirheumatic Agents - adverse effects ; Arthritis, Rheumatoid - chemically induced ; Arthritis, Rheumatoid - drug therapy ; C-reactive protein ; Clinical trials ; Humans ; Interleukin 6 ; Long-term effects ; Medicine ; Medicine & Public Health ; Meta-analysis ; Methotrexate ; Methotrexate - therapeutic use ; Network Meta-Analysis ; Patients ; Review ; Review Article ; Rheumatoid arthritis ; Rheumatology ; Safety ; Systematic review ; Treatment Outcome</subject><ispartof>Clinical rheumatology, 2023-06, Vol.42 (6), p.1503-1520</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-29a653f1fc071d068d75d347ce3a82d2a2c421cd93b2c526bf345cb10c9fe08f3</citedby><cites>FETCH-LOGICAL-c475t-29a653f1fc071d068d75d347ce3a82d2a2c421cd93b2c526bf345cb10c9fe08f3</cites><orcidid>0000-0001-6647-1866 ; 0000-0003-4139-8812 ; 0000-0001-9786-2237 ; 0000-0001-5619-9803 ; 0000-0002-2919-6196 ; 0000-0001-7514-1623 ; 0000-0002-2514-0689 ; 0000-0002-1547-7886</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10067-023-06519-6$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10067-023-06519-6$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36792848$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abuelazm, Mohamed</creatorcontrib><creatorcontrib>Ghanem, Ahmed</creatorcontrib><creatorcontrib>Mahmoud, Abdelrahman</creatorcontrib><creatorcontrib>Brakat, Aml M.</creatorcontrib><creatorcontrib>Elzeftawy, Mohamad A.</creatorcontrib><creatorcontrib>Mamdouh Fayoud, Aya</creatorcontrib><creatorcontrib>Awad, Ahmed K.</creatorcontrib><creatorcontrib>Abdelazeem, Basel</creatorcontrib><title>The efficacy and safety of olokizumab for rheumatoid arthritis: a systematic review, pairwise, and network meta-analysis</title><title>Clinical rheumatology</title><addtitle>Clin Rheumatol</addtitle><addtitle>Clin Rheumatol</addtitle><description>Olokizumab (OKZ) is a novel IL-6 inhibitor that directly targets IL-6 rather than its receptor. We aim to evaluate the efficacy and safety of OKZ for patients with rheumatoid arthritis (RA) and to investigate the optimal treatment regimen. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, CENTRAL, SCOPUS, EMBASE, and PubMed until August 31, 2022. We used the risk ratio (RR) and mean difference (MD) for dichotomous and continuous outcomes, respectively, presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID:
CRD42022358082
. Five RCTs with 2277 patients were included. OKZ significantly improved the American College of Rheumatology criteria (ACR) 20 (RR: 1.97 with 95% CI [1.49, 2.58],
P
= 0.00001), ACR50 (RR: 3.83 with 95% CI [2.13, 6.87],
P
= 0.00001), ACR70 (RR: 3.83 with 95% CI [2.13, 6.87],
P
= 0.00001), disease activity score 28 based on C-reactive protein (DAS28-CRP) (RR: 3.91 with 95% CI [2.65, 5.79],
P
= 0.00001), clinical disease activity index (CDAI) (RR: 2.80 with 95% CI [1.43, 5.48],
P
= 0.003), and health assessment questionnaire disability index (HAQ-DI) (MD: − 0.28 with 95% CI [− 0.38, − 0.18],
P
= 0.00001) after 12 weeks, compared to placebo. However, OKZ was also associated with a higher incidence of any adverse events (AEs) (RR: 1.15 with 95% CI [1.06, 1.25], P = 0.0005) and AEs leading to drug discontinuation (RR: 1.86 with 95% CI [1.05, 3.29], P = 0.03). OKZ is effective and with acceptable safety profile when administrated with methotrexate in patients with RA not adequately controlled by tumor necrosis factor inhibitors; however, more large-scale RCTs are still required to investigate the optimal dosing, long-term effects, and comparative efficacy versus established biological DMARDs.
Key Points
•
OKZ is effective especially with methotrexate in RA patients.</description><subject>Antirheumatic Agents - adverse effects</subject><subject>Arthritis, Rheumatoid - chemically induced</subject><subject>Arthritis, Rheumatoid - drug therapy</subject><subject>C-reactive protein</subject><subject>Clinical trials</subject><subject>Humans</subject><subject>Interleukin 6</subject><subject>Long-term effects</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Meta-analysis</subject><subject>Methotrexate</subject><subject>Methotrexate - therapeutic use</subject><subject>Network Meta-Analysis</subject><subject>Patients</subject><subject>Review</subject><subject>Review Article</subject><subject>Rheumatoid arthritis</subject><subject>Rheumatology</subject><subject>Safety</subject><subject>Systematic review</subject><subject>Treatment Outcome</subject><issn>0770-3198</issn><issn>1434-9949</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUtvFSEYhonR2GP1D7gwJG5cdJTbwOCmMU29JE3c1DVhmI8e2pnhCJwex19f2lPrZeEGSN6HB768CL2k5C0lRL3LdZWqIYw3RLZUN_IRWlHBRaO10I_RiihFGk51d4Ce5XxJCGGdpk_RAZdKs050K_TjfA0YvA_OugXbecDZeigLjh7HMV6Fn9vJ9tjHhNMa6rnEMGCbyjqFEvJ7bHFecoEaBIcTXAfYHeGNDWkXMhzdGWcou5iu8ATFNna245JDfo6eeDtmeHG_H6JvH0_PTz43Z18_fTn5cNY4odrSMG1lyz31jig6ENkNqh24UA647djALHOCUTdo3jPXMtl7LlrXU-K0B9J5foiO997Ntp9gcDCXZEezSWGyaTHRBvN3Moe1uYjXhhJGmFaiGt7cG1L8voVczBSyg3G0M8RtNkwpJYgkSlb09T_oZdymOnGlOqoYpVzqSrE95VLMOYF_-A0l5rZZs2_W1GbNXbPmVv3qzzkervyqsgJ8D-QazReQfr_9H-0NexmxKA</recordid><startdate>20230601</startdate><enddate>20230601</enddate><creator>Abuelazm, Mohamed</creator><creator>Ghanem, Ahmed</creator><creator>Mahmoud, Abdelrahman</creator><creator>Brakat, Aml M.</creator><creator>Elzeftawy, Mohamad A.</creator><creator>Mamdouh Fayoud, Aya</creator><creator>Awad, Ahmed K.</creator><creator>Abdelazeem, Basel</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6647-1866</orcidid><orcidid>https://orcid.org/0000-0003-4139-8812</orcidid><orcidid>https://orcid.org/0000-0001-9786-2237</orcidid><orcidid>https://orcid.org/0000-0001-5619-9803</orcidid><orcidid>https://orcid.org/0000-0002-2919-6196</orcidid><orcidid>https://orcid.org/0000-0001-7514-1623</orcidid><orcidid>https://orcid.org/0000-0002-2514-0689</orcidid><orcidid>https://orcid.org/0000-0002-1547-7886</orcidid></search><sort><creationdate>20230601</creationdate><title>The efficacy and safety of olokizumab for rheumatoid arthritis: a systematic review, pairwise, and network meta-analysis</title><author>Abuelazm, Mohamed ; 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We aim to evaluate the efficacy and safety of OKZ for patients with rheumatoid arthritis (RA) and to investigate the optimal treatment regimen. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, CENTRAL, SCOPUS, EMBASE, and PubMed until August 31, 2022. We used the risk ratio (RR) and mean difference (MD) for dichotomous and continuous outcomes, respectively, presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID:
CRD42022358082
. Five RCTs with 2277 patients were included. OKZ significantly improved the American College of Rheumatology criteria (ACR) 20 (RR: 1.97 with 95% CI [1.49, 2.58],
P
= 0.00001), ACR50 (RR: 3.83 with 95% CI [2.13, 6.87],
P
= 0.00001), ACR70 (RR: 3.83 with 95% CI [2.13, 6.87],
P
= 0.00001), disease activity score 28 based on C-reactive protein (DAS28-CRP) (RR: 3.91 with 95% CI [2.65, 5.79],
P
= 0.00001), clinical disease activity index (CDAI) (RR: 2.80 with 95% CI [1.43, 5.48],
P
= 0.003), and health assessment questionnaire disability index (HAQ-DI) (MD: − 0.28 with 95% CI [− 0.38, − 0.18],
P
= 0.00001) after 12 weeks, compared to placebo. However, OKZ was also associated with a higher incidence of any adverse events (AEs) (RR: 1.15 with 95% CI [1.06, 1.25], P = 0.0005) and AEs leading to drug discontinuation (RR: 1.86 with 95% CI [1.05, 3.29], P = 0.03). OKZ is effective and with acceptable safety profile when administrated with methotrexate in patients with RA not adequately controlled by tumor necrosis factor inhibitors; however, more large-scale RCTs are still required to investigate the optimal dosing, long-term effects, and comparative efficacy versus established biological DMARDs.
Key Points
•
OKZ is effective especially with methotrexate in RA patients.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>36792848</pmid><doi>10.1007/s10067-023-06519-6</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0001-6647-1866</orcidid><orcidid>https://orcid.org/0000-0003-4139-8812</orcidid><orcidid>https://orcid.org/0000-0001-9786-2237</orcidid><orcidid>https://orcid.org/0000-0001-5619-9803</orcidid><orcidid>https://orcid.org/0000-0002-2919-6196</orcidid><orcidid>https://orcid.org/0000-0001-7514-1623</orcidid><orcidid>https://orcid.org/0000-0002-2514-0689</orcidid><orcidid>https://orcid.org/0000-0002-1547-7886</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0770-3198 |
| ispartof | Clinical rheumatology, 2023-06, Vol.42 (6), p.1503-1520 |
| issn | 0770-3198 1434-9949 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10202974 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Antirheumatic Agents - adverse effects Arthritis, Rheumatoid - chemically induced Arthritis, Rheumatoid - drug therapy C-reactive protein Clinical trials Humans Interleukin 6 Long-term effects Medicine Medicine & Public Health Meta-analysis Methotrexate Methotrexate - therapeutic use Network Meta-Analysis Patients Review Review Article Rheumatoid arthritis Rheumatology Safety Systematic review Treatment Outcome |
| title | The efficacy and safety of olokizumab for rheumatoid arthritis: a systematic review, pairwise, and network meta-analysis |
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