Question:In people with rheumatoid arthritis, how does golimumab affect outcomes?

Clinical Answer:

There is high quality evidence that, in people with rheumatoid arthritis who have not responded to prior monotherapy with methotrexate or other biologics, golimumab is more effective than placebo when given in combination with methotrexate. Golimumab (at a 50 mg dose every four weeks) in combination with methotrexate improved ACR50 scores, Disease Activity Score (DAS) remission and physical function at 14 weeks compared with placebo in combination with methotrexate. There was no increase in adverse events, serious adverse events, chances of infections and cancers with golimumab plus methotrexate compared with placebo and methotrexate. All the above findings were consistent when golimumab was used at 100 mg every 4 weeks.

Full outcome data is detailed below:

1.Golimumab 50 mg every 4 weeks + methotrexate versus placebo + methotrexate

  • Population, Intervention, Comparator

    Population:

    Patients, primarily women aged 51-57 years, with rheumatoid arthritis (ACR criteria) for 3-10 years and prior methotrexate failure (4 trials) and prior biologic failure (1 trial)

    Intervention:

    Golimumab 50 mg administered via subcutaneous injections at week 0 and every four weeks thereafter + methotrexate (13 or 15 mg/week in 2 trials; not reported in the other two)

    Comparator:

    Injectable placebo + methotrexate (13-15 mg/week in 2 trials; not reported in the other two)

  • OUTCOME 1.1: ACR50 at 14-24 weeks

    Quality of the evidence:

    The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

    Narrative result:

    Four RCTs with 919 participants found that golimumab plus methotrexate increased the proportion of people with ACR50 at 14-24 weeks compared with placebo plus methotrexate. ACR50 is defined as 50% improvement in both tender and swollen joint counts and 50% improvement in three of the five following variables: patient global assessment, physician global assessments, pain scores, Health Assessment Questionnaire (HAQ) score, and acute phase reactants (Erythrocyte Sedimentation Rate (ESR) or C-Reactive Protein (CRP).

    Relative effect or mean difference:

    There was a statistically significant difference between groups, in favor of golimumab (RR 2.57, 95% CI 1.34 to 4.94).

    Forest plot from Cochrane Review

    Absolute effect:

    383 per 1000 people (95% CI 200 to 736) with golimumab compared with 149 per 1000 people with placebo.

    Reference:
    Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
    • OUTCOME 1.2: Disease Activity Score (DAS) remission at 14-24 weeks

      Quality of the evidence:

      The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

      Narrative result:

      Four RCTs with 919 participants found that golimumab increased the proportion of people with DAS remission at 14-24 weeks compared with placebo. The Disease Activity Score (DAS) is a composite index of tender and swollen joint counts, patient global assessment and ESR but no further information is provided by the authors with regards how ‘improvement in DAS’ was assessed.

      Relative effect or mean difference:

      There was a statistically significant difference between groups, in favor of golimumab (RR 5.12, 95% CI 1.67 to 15.66 in Summary of findings table; data not reported in a forest plot).

      Absolute effect:

      220 per 1000 people (95%CI 72 to 673) with golimumab compared with 43 per 1000 with placebo.

      Reference:
      Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
      • OUTCOME 1.3: Physical function measured by Health Assessment Questionnaire (HAQ) scores at 14 weeks

        Quality of the evidence:

        The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

        Narrative result:

        One RCT with 308 participants found that golimumab improved HAQ scores at 14 weeks compared with placebo. The reviewers did not provide further information regarding HAQ so it is unclear what this improvement in scores would mean to a patient.

        Relative effect or mean difference:

        There was a statistically significant difference between groups, in favor of placebo (mean difference -0.20, 95% CI -0.25 to -0.15).

        Forest plot from Cochrane Review

        Reference:
        Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
        • OUTCOME 1.4: Overall adverse events at 16 to 24 weeks

          Quality of the evidence:

          The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

          Narrative result:

          Four RCTs with 918 participants found no statistically significant difference between groups.

          Relative effect or mean difference:

          There was no statistically significant difference between groups (RR 1.05, 95% CI 0.93 to 1.18).

          Forest plot from Cochrane Review

          Absolute effect:

          728 per 1000 (95% CI) with golimumab compared with 693 per 1000 with placebo

          Reference:
          Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
          • OUTCOME 1.5: Serious adverse events at 16 to 24 weeks

            Quality of the evidence:

            The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

            Narrative result:

            Four RCTs with 918 participants found no statistically significant difference between groups. The reviewers did not define the outcome ‘serious adverse events’.

            Relative effect or mean difference:

            There was no statistically significant difference between groups (RR 1.05, 95% CI 0.62 to 1.78).

            Forest plot from Cochrane Review

            Absolute effect:

            59 per 1000 (95% CI 35 to 100) with golimumab compared with 56 per 1000 with placebo.

            Reference:
            Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
            • OUTCOME 1.6: Serious infections at 16 to 24 weeks

              Risk of bias of studies:

              The reviewers did not perform a GRADE assessment of the quality of the evidence. Overall the studies in the systematic review were at low risk of selection bias, as reported adequate methods of allocation concealment and sequence generation and were also at low risk of performance and detection bias. Most studies addressed incomplete outcome data adequately but selective reporting was unclear.

              Narrative result:

              Four RCTs with 918 participants found no statistically significant difference between groups. Serious infections were defined as serious infections leading to hospitalizations or death including tuberculosis (TB), bacterial sepsis, invasive fungal and other opportunistic infections.

              Relative effect or mean difference:

              There was no statistically significant difference between groups (RR 1.06, 95% CI 0.40 to 2.86).

              Forest plot from Cochrane Review

              Absolute effect:

              There was no statistically significant difference between groups.

              Reference:
              Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
              • OUTCOME 1.7: Cancer at 16 to 24 weeks

                Risk of bias of studies:

                The reviewers did not perform a GRADE assessment of the quality of the evidence. Overall the studies in the systematic review were at low risk of selection bias, as reported adequate methods of allocation concealment and sequence generation and were also at low risk of performance and detection bias. Most studies addressed incomplete outcome data adequately but selective reporting was unclear

                Narrative result:

                Four RCTs with 918 participants found no statistically significant difference between groups.

                Relative effect or mean difference:

                There was no statistically significant difference between groups (RR 0.81, 95% CI 0.16 to 4.18).

                Forest plot from Cochrane Review

                Absolute effect:

                There was no statistically significant difference between groups.

                Reference:
                Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                • OUTCOME 1.8: All withdrawals at 14 to 24 weeks

                  Quality of the evidence:

                  The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

                  Narrative result:

                  Four RCTs with 917 participants found that fewer people taking golimumab than placebo withdrew due to lack of efficacy or adverse effects at 14 to 24 weeks.

                  Relative effect or mean difference:

                  There was a statistically significant difference between groups, in favor of golimumab (RR 0.50, 95% CI 0.31 to 0.81).

                  Forest plot from Cochrane Review

                  Absolute effect:

                  3 per 100 people (95% CI 2 to 5) with golimumab compared with 6 per 100 people with placebo

                  Reference:
                  Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                  • OUTCOME 1.9: Withdrawals due to adverse events at 14 to 16 weeks

                    Quality of the evidence:

                    The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

                    Narrative result:

                    Three RCTs with 599 participants found no statistically significant difference between groups.

                    Relative effect or mean difference:

                    There was no statistically significant difference between groups (RR 0.56, 95% CI 0.24 to 1.29).

                    Forest plot from Cochrane Review

                    Absolute effect:

                    28 per 1000 (95% CI 12 to 64) with golimumab compared with 50 per 1000 with placebo.

                    Reference:
                    Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                    • OUTCOME 1.10: Pain; Quality of life

                      Narrative result:

                      The reviewers found no studies assessing these outcomes for this comparison.

                      Reference:
                      Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]

                      2.Golimumab 100 mg every 4 weeks + methotrexate versus placebo + methotrexate

                      • Population, Intervention, Comparator

                        Population:

                        Patients, primarily women aged 51-57 years, with rheumatoid arthritis (ACR criteria) for 3-10 years and prior methotrexate failure (4 trials) and prior biologic failure (1 trial)

                        Intervention:

                        Golimumab 100 mg administered via subcutaneous injections at week 0 and every four weeks thereafter + methotrexate (13 or 15 mg/week in 2 trials; not reported in the other two)

                        Comparator:

                        Injectable placebo + methotrexate (13-15 mg/week in 2 trials; not reported in the other two)

                      • OUTCOME 2.1: ACR50 at 14-24 weeks

                        Risk of bias of studies:

                        The reviewers did not perform a GRADE assessment of the quality of the evidence. Overall the studies in the systematic review were at low risk of selection bias, as reported adequate methods of allocation concealment and sequence generation and were also at low risk of performance and detection bias. Most studies addressed incomplete outcome data adequately but selective reporting was unclear.

                        Narrative result:

                        Four RCTs with 918 participants found that golimumab plus methotrexate increased the proportion of people with ACR50 at 14-24 weeks compared with placebo plus methotrexate. ACR50 is defined as 50% improvement in both tender and swollen joint counts and 50% improvement in three of the five following variables: patient global assessment, physician global assessments, pain scores, Health Assessment Questionnaire (HAQ) score, and acute phase reactants (Erythrocyte Sedimentation Rate (ESR) or C-Reactive Protein (CRP).here was considerable heterogeneity in this analysis (I2=77%), which was due to one study, according to the reviewers. They considered appropriate to pool results as the direction of the effect was same across the studies.

                        Relative effect or mean difference:

                        There was a statistically significant difference between groups, in favor of golimumab (RR 2.43, 95% CI 1.25 to 4.74).

                        Forest plot from Cochrane Review

                        Absolute effect:

                        24 per 100 people (95% CI 12 to 46) with golimumab compared with 10 per 100 people with placebo.

                        Reference:
                        Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                        • OUTCOME 2.2: Disease Activity Score (DAS) remission at 14-24 weeks

                          Risk of bias of studies:

                          The reviewers did not perform a GRADE assessment of the quality of the evidence. Overall the studies in the systematic review were at low risk of selection bias, as reported adequate methods of allocation concealment and sequence generation and were also at low risk of performance and detection bias. Most studies addressed incomplete outcome data adequately but selective reporting was unclear.

                          Narrative result:

                          Four RCTs with 918 participants found that golimumab plus methotrexate increased the proportion of people with DAS remission at 14-24 weeks compared with placebo plus methotrexate. The Disease Activity Score (DAS) is a composite index of tender and swollen joint counts, patient global assessment and ESR (van der Heijde 1993) but no further information is provided by the authors with regard to how DAS was assessed. There was considerable heterogeneity in this analysis (I2=76%), which was due to one study, according to the reviewers. They considered appropriate to pool results as the direction of the effect was same across the studies.

                          Relative effect or mean difference:

                          There was a statistically significant difference between groups, in favor of golimumab (RR 6.28, 95% CI 1.37 to 28.78).

                          Forest plot from Cochrane Review

                          Absolute effect:

                          9 per 100 people (95% CI 2 to 43) with golimumab compared with 2 per 100 people with placebo.

                          Reference:
                          Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                          • OUTCOME 2.3: Physical function measured by Health Assessment Questionnaire (HAQ) scores at 14 weeks

                            Risk of bias of studies:

                            The reviewers did not perform a GRADE assessment of the quality of the evidence. Overall the studies in the systematic review were at low risk of selection bias, as reported adequate methods of allocation concealment and sequence generation and were also at low risk of performance and detection bias. Most studies addressed incomplete outcome data adequately but selective reporting was unclear

                            Narrative result:

                            One RCT with 308 participants found that golimumab plus methotrexate increased the proportion of people with reduced HAQ scores at 14 weeks compared with placebo plus methotrexate. The reviewers did not provide further information regarding HAQ

                            Relative effect or mean difference:

                            There was a statistically significant difference between groups, in favor of placebo (mean difference -0.30, 95% CI -0.36 to -0.24).

                            Forest plot from Cochrane Review

                            Reference:
                            Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                            • OUTCOME 2.4: Adverse events at 16 to 24 weeks

                              Risk of bias of studies:

                              The reviewers did not perform a GRADE assessment of the quality of the evidence. Overall the studies in the systematic review were at low risk of selection bias, as reported adequate methods of allocation concealment and sequence generation and were also at low risk of performance and detection bias. Most studies addressed incomplete outcome data adequately but selective reporting was unclear.

                              Narrative result:

                              Four RCTs with 915 participants found no statistically significant difference between groups.

                              Relative effect or mean difference:

                              There was no statistically significant difference between groups (RR 1.06, 95% CI 0.98 to 1.15).

                              Forest plot from Cochrane Review

                              Absolute effect:

                              There was no statistically significant difference between groups.

                              Reference:
                              Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                              • OUTCOME 2.5: Serious adverse events at 16 to 24 weeks

                                Risk of bias of studies:

                                The reviewers did not perform a GRADE assessment of the quality of the evidence. Overall the studies in the systematic review were at low risk of selection bias, as reported adequate methods of allocation concealment and sequence generation and were also at low risk of performance and detection bias. Most studies addressed incomplete outcome data adequately but selective reporting was unclear.

                                Narrative result:

                                Four RCTs with 915 participants found no statistically significant difference between groups. The reviewers did not define the outcome ‘serious adverse events’.

                                Relative effect or mean difference:

                                There was no statistically significant difference between groups (RR 1.04, 95% CI 0.40 to 2.70).

                                Forest plot from Cochrane Review

                                Absolute effect:

                                There was no statistically significant difference between groups.

                                Reference:
                                Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                                • OUTCOME 2.6: Serious infections at 16 to 24 weeks

                                  Risk of bias of studies:

                                  The reviewers did not perform a GRADE assessment of the quality of the evidence. Overall the studies in the systematic review were at low risk of selection bias, as reported adequate methods of allocation concealment and sequence generation and were also at low risk of performance and detection bias. Most studies addressed incomplete outcome data adequately but selective reporting was unclear.

                                  Narrative result:

                                  Four RCTs with 915 participants found no statistically significant difference between groups. Serious infections were defined as serious infections leading to hospitalizations or death including tuberculosis (TB), bacterial sepsis, invasive fungal, and other opportunistic infection

                                  Relative effect or mean difference:

                                  There was no statistically significant difference between groups (RR 1.80, 95% CI 0.56 to 5.80).

                                  Forest plot from Cochrane Review

                                  Absolute effect:

                                  There was no statistically significant difference between groups.

                                  Reference:
                                  Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                                  • OUTCOME 2.7: Cancer at 16 to 24 weeks

                                    Risk of bias of studies:

                                    The reviewers did not perform a GRADE assessment of the quality of the evidence. Overall the studies in the systematic review were at low risk of selection bias, as reported adequate methods of allocation concealment and sequence generation and were also at low risk of performance and detection bias. Most studies addressed incomplete outcome data adequately but selective reporting was unclear.

                                    Narrative result:

                                    Four RCTs with 915 participants found no statistically significant difference between groups.

                                    Relative effect or mean difference:

                                    There was no statistically significant difference between groups (RR 1.36, 95% CI 0.33 to 5.56).

                                    Forest plot from Cochrane Review

                                    Absolute effect:

                                    There was no statistically significant difference between groups.

                                    Reference:
                                    Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                                    • OUTCOME 2.8: All withdrawals at 14 to 24 weeks

                                      Risk of bias of studies:

                                      The reviewers did not perform a GRADE assessment of the quality of the evidence. Overall the studies in the systematic review were at low risk of selection bias, as reported adequate methods of allocation concealment and sequence generation and were also at low risk of performance and detection bias. Most studies addressed incomplete outcome data adequately but selective reporting was unclear.

                                      Narrative result:

                                      Four RCTs with 917 participants found no statistically significant difference between groups.

                                      Relative effect or mean difference:

                                      There was no statistically significant difference between groups (RR 0.66, 95% CI 0.43 to 1.02).

                                      Forest plot from Cochrane Review

                                      Absolute effect:

                                      There was no statistically significant difference between groups.

                                      Reference:
                                      Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                                      • OUTCOME 2.9: Withdrawals due to adverse events at 14 to 16 weeks

                                        Risk of bias of studies:

                                        The reviewers did not perform a GRADE assessment of the quality of the evidence. Overall the studies in the systematic review were at low risk of selection bias, as reported adequate methods of allocation concealment and sequence generation and were also at low risk of performance and detection bias. Most studies addressed incomplete outcome data adequately but selective reporting was unclear.

                                        Narrative result:

                                        Three RCTs with 598 participants found no statistically significant difference between groups.

                                        Relative effect or mean difference:

                                        There was no statistically significant difference between groups (RR 0.56, 95% CI 0.21 to 1.47).

                                        Forest plot from Cochrane Review

                                        Absolute effect:

                                        There was no statistically significant difference between groups.

                                        Reference:
                                        Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]
                                        • OUTCOME 2.10: Pain; Quality of life

                                          Narrative result:

                                          The reviewers found no studies assessing these outcomes for this comparison.

                                          Reference:
                                          Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]

                                          Additional Information:

                                          DOI

                                          10.1002/cca.204

                                          Publication Dates

                                          1. Published Online: 9 SEP 2013

                                          CCA derived from

                                          Singh JA, Noorbaloochi S, Singh G. Golimumab for rheumatoid arthritis. Cochrane Database of Systematic Reviews 2010, Issue 1. Art. No.: CD008341. DOI: 10.1002/14651858.CD008341. [Review search date: July 2009]

                                          How to Cite

                                          In people with rheumatoid arthritis, how does golimumab affect outcomes? Satish Chandolu (MD, MHA) (on behalf of Cochrane Clinical Answers Editors). Cochrane Clinical Answers 2012. DOI: 10.1002/cca.204.

                                          Further Information

                                          • CCA Associate editor: Satish Chandolu (MD, MHA), Resident physician/Instructor, Michigan State University College of Human Medicine, Michigan, USA.
                                          • CCA Editor: Karen Pettersen. Correspondence to kpettersen@wiley.com.